Poor asthma control is often linked to treatment nonadherence and the presence of comorbidities such as respiratory infections and congestive heart failure,1 as well as psychological disorders.2 In fact, patients with asthma have demonstrated an elevated risk for anxiety and depression that may be twice that of the general population, according to various findings.3

These comorbidities are associated with worse asthma control, greater functional disability, lower quality of life, and more frequent hospitalizations and physician’s visits.2,4

As emerging evidence has begun to elucidate asthma phenotypes and endotypes in a push toward precision medicine for asthma treatment, findings suggest that certain phenotypes are linked to higher rates of psychiatric comorbidity. In a 2018 cross-sectional study published in the Journal of Asthma, researchers from the University of Osijek in Croatia explored this connection and the potential effects of depression and anxiety on asthma control in 201 adult patients.2

Using cluster analysis, they identified 5 asthma phenotypes within the sample: allergic (AA; 43.8%), aspirin-exacerbated respiratory disease (21.9%), late-onset (LOA; 18.9%), obesity-associated (10.0%), and respiratory infection-associated asthma (5.5%). Multivariate analysis revealed significant associations among the following variables:

  • Anxiety with LOA and comorbid hypertension (odds ratio [OR], 2.12 and 2.37, respectively; P =.012)
  • Depression with AA, respiratory infection-associated asthma, hypertension, and Asthma Control Questionnaire score (OR, 6.07, 4.73, 5.67, and 1.87, respectively; P <.001)
  • Comorbid anxiety/depression with AA, LOA, respiratory infection-associated asthma, hypertension, and Asthma Control Questionnaire score (OR, 10.15, 2.98, 6.29, 5.15, and 1.90, respectively; P <.001)

In sum, anxiety and depression “were significantly associated with AA, LOA, and infection-associated asthma, together with comorbid hypertension and the level of asthma control,” the authors concluded.2

“This can have a significant effect on management and treatment of asthma in these specific phenotypes in adult patients.”

Researchers have explored the bidirectional nature of the connection between asthma and mental health disorders, as in a 2016 case-control study that compared 96 adult patients with asthma with 96 sociodemographically matched control individuals.5 The results showed a significant association between asthma and lifetime anxiety disorders (OR, 3.03; P =.003), but no other psychiatric disorder. In addition, asthma severity was linked to lifetime and current anxiety (P <.003 and P =.001, based on age), with asthma preceding anxiety in 48% of patients and anxiety preceding asthma in 52% of cases.

Other evidence suggests that a shared genetic pathway may underlie the relationship between asthma and psychiatric illness, as Pulmonology Advisor recently reported. In a large twin registry, Kelli Lehto, PhD, and colleagues at the Karolinska Institute in Sweden identified questionnaire-based associations between asthma and major depression (OR, 1.67; 95% CI, 1.50-1.86), anxiety (OR, 1.45; 95% CI, 1.30-1.61), and high neuroticism (OR, 1.60; 95% CI, 1.40-1.82).3

Genetic analyses demonstrated that genetic “susceptibility for neuroticism explained the variance in asthma with a dose response effect; that is, study participants in the highest neuroticism quartile [based on polygenic risk scores] were more likely to have asthma than those in the lowest quartile (OR, 1.37, 95% CI, 1.17-1.61),” according to Dr Lehto and colleagues. In addition, the results revealed genetic correlations between asthma and depression (rg=0.17), but not anxiety or neuroticism.

The authors concluded that the “observed comorbidity between asthma and the affective traits is in part due to genetic influences on the affective traits, and a moderate shared genetic risk of importance for both asthma and depression and neuroticism but not anxiety.”5

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To further explore this topic, Pulmonology Advisor interviewed Dr Lehto and her coinvestigator Bronwyn K. Brew, PhD, MPH, as well as Paul Lehrer, PhD, a professor emeritus of psychiatry at Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey, who has conducted numerous studies on the psychological aspects of asthma.

Pulmonology Advisor: What is known thus far about the connection between asthma and psychiatric symptoms and disorders?

Dr Lehrer: Acute sadness produces bronchoconstriction in asthmatic children, along with vagus nerve activation. Many people with depression show activation of the vagal system (accompanies passivity and fatigue), and vagal stimulation causes bronchoconstriction.6,7 Stress-induced asthma is common, and people with asthma tend to show a vagal bias in their stress response rather than a fight-flight pattern. Some children with asthma tend to show a more passive behavioral response to stress — internalizing emotions rather than acting them out, which may be accompanied by a vasovagal component. In addition, parents with depression and children with asthma tend to show poorer asthma control in their children.

Depression makes uncomfortable feelings more salient, so depressed people tend to have more asthma symptoms for a given amount of pulmonary impairment. Some studies find that the severity of asthma is linked to depression. In epidemiologic studies, asthma is significantly associated with depression, but not generalized anxiety, although there is a large association with panic disorder, where symptom confusion between the 2 disorders can lead to mistreatment of both. Also, the stress response and chronic depression are accompanied by a general inflammatory response, which also may exacerbate asthma.

Dr Lehto and Dr Brew: The prevalence of depression and anxiety disorders is higher in adult patients with asthma compared with the population average. Similarly, patients with asthma show higher neuroticism, which is a stable personality trait that reflects a tendency to experience more emotional instability, worry, and fear. But it is currently unclear what is driving these associations and what the direction of effect is: Is asthma causing psychiatric problems, or vice versa?

Pulmonology Advisor: What are the proposed mechanisms underlying these associations? 

Dr Lehrer: There are many: the vagal connection mentioned here, cognitive bias toward magnifying symptoms, poor motivation in depressed people to take adequate asthma self-care measures, and that having a chronic disease is depressing. Severe asthma can lead to oxygen desaturation and fatigue, which is a symptom of depression. Mild asthma can lead to hyperventilation, which causes multiple psychological symptoms.

Pulmonology Advisor: What do your findings add to our understanding of this link?

Dr Lehto and Dr Brew: In our genetic investigation into the association between asthma and affective traits, we found evidence for shared genetic influences between asthma and depression and neuroticism. This suggests the potential involvement of shared biological pathways underlying both asthma and depression. As inflammation is a key player in both asthma and depression, the involvement of inflammatory pathways controlled by genes may be plausible.

Pulmonology Advisor: What are some relevant treatment recommendations for clinicians?

Dr Lehrer: Good diagnosis of depression and panic in asthma is important, as well as diagnosis of asthma in patients with depression and panic. Have a good asthma education program in place, with regular home peak flow measures, to distinguish asthma symptoms from emotional symptoms and treat the appropriate condition. Family therapy is indicated for children with asthma with a stressful family environment, as these children are particularly vulnerable to stress. Antidepressant treatment of parents or caregivers sometimes improves children’s asthma.

Dr Lehto and Dr Brew: According to our results, clinicians should be aware that patients with asthma might suffer from affective problems more frequently, partly because of common underlying pathways, and not necessarily because one disease is causing the other. Affective problems in patients should be noticed, acknowledged, and managed. Better understanding of the biological drivers behind asthma and psychiatric comorbidities will enable us to move toward improved treatment and management in patients with comorbid affective problems. 

Pulmonology Advisor: What are the remaining needs in this area, in terms of research or otherwise?

Dr Lehrer: More research is needed on treatment models for emotional/asthma comorbidities, as well as the relationship among emotional factors/stress, inflammation, and asthma. Better standardization of depression measures in children is needed. More education is needed for the existence and treatment of asthma/mood disorder comorbidities for families, patients with asthma, and physicians.

Dr Lehto and Dr Brew: Researchers now need to specifically identify the shared genes and biological pathways between asthma and affective traits, which will enable more targeted treatment options and increase patients’ well-being.

References

  1. Braido F, Brusselle G, Guastalla D, et al. Determinants and impact of suboptimal asthma control in Europe: The international cross-sectional and longitudinal assessment on asthma control (LIAISON) study. Respir Res. 2016;17(1):51.
  2. Labor M, Labor S, Jurić I, Fijačko V, Popović Grle S, Plavec D. Mood disorders in adult asthma phenotypes. J Asthma. 2018;55:(1):57-65.
  3. Lehto K, Pedersen NL, Almqvist C, Lu Y, Brew BK. Asthma and affective traits in adults: a genetically informative study. Eur Respir J. 2019;53(6):1802142.
  4. Patel PO, Patel MR, Baptist AP. Depression and asthma outcomes in older adults: results from the National Health and Nutrition Examination Survey. J Allergy Clin Immunol. 2017;5(6):1691-1697.
  5. Del Giacco SR, Cappai A, Gambula L, et al. The asthma-anxiety connection. Respir Med. 2016;120:44-53.
  6. Han L, Limjunyawong N, Ru F, et a. Mrgprs on vagal sensory neurons contribute to bronchoconstriction and airway hyperresponsiveness. Nat Neurosci. 2018;21(3):324-328.
  7. Mazzone SB, Undem BJ. Vagal afferent innervation of the airways in health and disease. Physiol Rev. 2016;96(3):975-1024.

This article originally appeared on Pulmonology Advisor