Asthma and mental health among youth: etiology, current knowledge and future directions

Abstract

Asthma and mental health problems, such as depression, anxiety and behavior disorders, are common among youth and are significant sources of morbidity. There is a consistent association between asthma and anxiety/depression and a less consistent association between asthma and behavior disorders. Possible biological and psychological mechanisms may include inflammatory processes as well as the stress of having to live with a life-threatening condition. Future studies are warranted with longitudinal designs to establish temporality as well as measures of potential confounds. Biological and psychological measures would complement the longitudinal design to further establish causality. In addition, more information on the degree to which asthma and mental health have reciprocal influences on each other over time – and the mechanisms of these relationships – are needed in order to develop more effective intervention strategies to improve asthma control and mental health among those with both.

Keywords::

• anxiety
• asthma
• depression
• epidemiology
• youth

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Editor

Elisa Manzotti

Publisher, Future Science Group, London, UK

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CME Author

Charles P. Vega, MD

Health Sciences Clinical Professor; Residency Director, Department of Family Medicine, University of California, Irvine, CA, USA

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Authors and Credentials

Renee D. Goodwin, PhD, MPH

Department of Epidemiology, Mailman School of Public Health, Columbia University, NY, USA

Disclosure: Renee D. Goodwin, PhD, MPH, has disclosed no relevant financial relationships.

Frank C. Bandiera, MPH

Department of Epidemiology and Public Health, Miller School of Medicine, University of Miami, FL, USA

Disclosure: Frank C. Bandiera, MPH, has disclosed no relevant financial relationships.

Dara Steinberg, MS

Ferkauf Graduate School of Psychology, Yeshiva University, NY, USA

Disclosure: Dara Steinberg, MS, has disclosed no relevant financial relationships.

Alexander N. Ortega, PhD

UCLA Fielding School of Public Health, Los Angeles, CA, USA

Disclosure: Alexander N. Ortega, PhD, has disclosed no relevant financial relationships.

Jonathan M. Feldman, PhD

Ferkauf Graduate School of Psychology, Yeshiva University, NY, USA; Department of Epidemiology and Population Health, Albert Einstein College of

Medicine, Bronx, NY, USA

Disclosure: Jonathan M. Feldman, PhD, has disclosed no relevant financial relationships.

Child & adolescent asthma morbidity & mental health: a major public health problem

Asthma is the most common chronic condition affecting children in the USA [1]. Specifically, estimates show that asthma affects approximately 4.4 million children and accounts for 2.9 million visits to pediatricians each year [2]. Depending on the disease level, with proper asthma management children with asthma can live symptom-free [3], avoiding the significant functional limitations otherwise imposed. However, despite the current availability of highly effective treatment strategies for asthma in youth [4], asthma morbidity continues to be a very common and serious public health problem. Childhood asthma morbidity is responsible for missed school days [5], time taken away from classroom activities [6], lost work productivity for parents who must care for their children [7] and limitations on after-school activities [8]. Inner cities have the highest reported levels of childhood asthma in the USA [9].

Child and adolescent mental disorders have a significant impact on individual suffering and on the economic productivity of communities [10]. Child and adolescent mental disorders are associated with significant costs on education, criminal justice and social services systems [10]. In the National Comorbidity Survey Replication – Adolescent Supplement, an epidemiologic study of over 10,000 participants, the prevalence of lifetime anxiety disorders, behavior disorders, mood disorders and substance use disorders was 31.9, 19.1, 14.3 and 11.4%, respectively.

Pathways/risk factors for child asthma morbidity

The literature points to several possible explanations for children’s excess asthma burden. These factors include genetics, environment, family health beliefs and disparities in healthcare use. Increasingly, studies have also suggested that comorbid psychiatric problems, particularly anxiety and depression in caregivers and anxiety in children, could be responsible for a significant portion of the excess asthma morbidity [11–16].

Asthma & mental health among youth

Anxiety & asthma in youth

Data from several cross-sectional [16–21]; and longitudinal [22–25] community-based studies of youth show a consistent link between asthma and other respiratory symptoms and anxiety disorders among youth. Clinical data has also shown that anxiety is associated with increased severity of asthma symptomatology, health service use, functional impairment and poorer asthma control, compared with that among youth without anxiety [24,26–31].

Depression & asthma in youth

Evidence from several cross-sectional, representative community based-epidemiologic studies suggests that young persons (aged 14–21 years) with asthma are more likely to have depression compared with those without asthma [19,23,32–35]. A number of small clinically selected studies have also found higher than expected rates of depressive symptoms among pediatric asthma patient samples [19,21,23]. Research has also shown a cross-sectional association between depressive symptoms and asthma severity among youth who are 7–17 years of age [35–37]. One study of adolescents aged 11–17 years in a health maintenance organization found a cross-sectional relationship between depression and asthma-related functional impairment [26]. Although some studies have failed to find a link between asthma and depression in children (e.g., Ortega et al. [16]), the majority of studies support a link.

Disruptive/behavioral disorders & asthma among youth

Findings in the literature have been inconsistent on this association. In 2004, Ortega et al. detected an association between parent-reported lifetime diagnosis of asthma and any disruptive disorder (odds ratio: 1.6; 95% CI: 1.1–2.3) and asthma attack and oppositional defiant disorder (odds ratio: 1.9; 95% CI: 1.2–3.0) among Puerto Rican children [19]. However, the same study found no association between hospitalization for asthma and disruptive disorders [19], and Ortega et al. found no association between parent-reported lifetime asthma and disruptive disorders among youth in US community samples [20]. Alati et al. found no relationship between asthma at 6 years of age and externalizing disorders in a birth cohort in Australia [22]. The reason for these discrepancies is not clear. It could be due to differences in sample size, sample composition, use of different measures for assessing mental health/behavioral problems and/or measurement of asthma. Previous clinical studies have also found relationships between asthma and other externalizing type/disruptive behaviors [18], suggesting that the weight of evidence to date would support an association between asthma and both internalizing and externalizing problems.

Possible mechanisms

A number of studies have investigated the potential mechanisms underlying the relationships between asthma and mental disorders, and between asthma morbidity and mental disorders. In the following sections we review evidence to date and discuss areas for further investigation.

Causal relationship

One possibility is that there is a causal relationship between asthma morbidity and mental disorders. It is conceivable that having a chronic health condition with symptoms that are distressing, uncomfortable and interfere with daily functioning could result in feelings of hopelessness and discouragement that could lead to depression. It is also possible that living with the knowledge that one has a life-threatening condition could result in the development of some types of anxiety disorders – or that having a life-threatening episode could lead to severe anxiety. For instance, Kean et al. found a relationship between severe life-threatening asthma attacks and increased post-traumatic stress disorder symptoms among an adolescent clinical sample in a tertiary care setting [38]. More recent studies have shown that moderate and severe current asthma is associated with mental disorders in young persons, and that remitted/mild asthma does not appear to increase vulnerability to mental health problems [39]. Feldman et al. found that children with a history of asthma attacks at baseline had greater odds of having an internalizing disorder at 1-year follow-up after accounting for sociodemographic factors [24]. However, not enough work has been done to confirm or rule out a causal relationship of this nature.

It is alternatively conceivable that having a mental disorder could lead to greater asthma morbidity. For instance, depression has been associated with poor medication and treatment plan adherence in the management of a wide range of chronic diseases (e.g., heart disease and diabetes) [40,41]. Therefore, it is possible that depression interferes with optimal asthma treatment plan adherence, which then results in greater asthma morbidity. Similarly, it is conceivable that oppositional or defiant behaviors could contribute to poorer treatment adherence, as has been found in adolescents with diabetes [42]. Furthermore, it is possible that physiological changes related to mental disorders (e.g., alterations in the autonomic nervous system and HPA axis) could increase vulnerability to asthma onset; this will be discussed in greater depth in further sections. Future research is needed to better understand the potentially causal pathways through which mental disorders may affect asthma morbidity. Since mental disorders are a modifiable risk factor, this is a particularly promising area. Interventions that can impact mental health problems could have positive outcomes on mental health of youth, as well as improved asthma control/respiratory functioning.

Uncontrolled confounding factors

It is possible that the relationship between asthma morbidity and mental disorders is due to uncontrolled factors that could be common risk factors for both. A birth cohort study in New Zealand found that the relationship between anxiety disorders and asthma was no longer statistically significant after adjusting for a wide range of potentially confounding factors [23]. This study adjusted for demographics, poverty/income, maternal education, exposure to adverse early life events (e.g., childhood abuse), smoking and other physical health problems. However, the analyses could not reveal what specific factors played a role in this association – only that unmeasured factors that were closely related to those that were measured were responsible. Results of this analysis are consistent with the hypothesis that the co-occurrence of asthma and mental disorders may be due to exposure to a common cause for both – rather than a causal relationship between the two. There are a number of potentially confounding factors not previously examined that should be looked at in future analyses in a single study. These include prenatal smoking, secondhand smoke (SHS) exposure, poor family functioning and inflammation.

Asthma morbidity & cigarette smoking

There is extensive research suggesting that cigarette smoking plays a role in both childhood and adult asthma [43,44]. SHS is a risk factor for asthma onset in infants and children, and is a trigger for asthma morbidity in youth [45,46]. Cigarette smoking is a risk factor for asthma onset in adults. Youth and adults with asthma smoke more than their counterparts who do not have asthma [47]. The pathways through which smoking, mental health problems and asthma morbidity may reciprocally influence one another remain unclear.

Prenatal smoking

Prenatal smoke exposure is associated with an increased risk of asthma early in life [48]. There is also increased evidence that exposure to prenatal smoking is associated with mental health problems in young children [49]. One recent study found that the relationship between asthma and mental health problems was no longer statistically significant in Puerto Rican youth after adjusting for exposure to prenatal smoking [50]. The possible role of exposure to prenatal smoking in the asthma–mental disorders link may be worth exploring further. Recent data suggest that prenatal smoking is associated with an increased risk of asthma in youth [51], as well as higher levels of mental disorders among offspring [52]. As such, exposure to prenatal smoking appears to be a potential risk factor for both asthma and mental disorders in youth.

SHS exposure

As previously mentioned, SHS exposure may be a risk factor for the onset of new asthma and exacerbation of existing asthma. Recently, there have been studies reporting that both prenatal and postnatal SHS exposure may affect mental health. There is some evidence that prenatal exposure to SHS is associated with conduct disorder, anxiety and depression from cross-sectional and longitudinal evidence. Furthermore, studies in animals have suggested that prenatal exposure to nicotine and early postnatal exposure to nicotine may lead to anxiety-like states in mice and rats [53].

In terms of postnatal SHS exposure, there is a growing body of literature suggesting that SHS exposure is associated with conduct disorder, attention-deficit/hyperactive disorder, depressive disorders and anxiety disorders among children and adolescents in cross-sectional study designs. Although the findings between prenatal/postnatal SHS exposure and mental health are provocative and interesting, causality is not known. Specifically, there are few or no studies that establish how SHS exposure may lead to poor mental health outcomes through neurobiological and immunological pathways. Furthermore, this association is complicated by potential confounders such as psychological distress and family functioning. Nevertheless, prenatal/postnatal SHS exposure may link asthma with mental health outcomes as a shared etiological factor.

Family functioning & asthma morbidity

There is extensive research suggesting that family functioning plays a role in childhood asthma [43,44]. Previous studies have found that asthma symptoms in children that are associated with emotional triggers improve when the child is separated from the family [54]. Adolescents with higher levels of parental criticism respond better to treatment in an inpatient program (i.e., when separated from their parents) [55], and family conflict is associated with a greater number of hospitalizations for asthma [56]. In addition, several studies have yielded results suggesting that family functioning may play a role in the relationship between depression and asthma severity in pediatric asthma patients [36]. Suboptimal family functioning is also associated with increased mental health problems among youth [57]. Previous researchers have suggested that using a combination of family and psychobiological mechanisms/underpinnings to understand the relationship between asthma and depression would be a useful next step [36].

Parental mental health & cigarette smoking

Several studies have found links between parental mental health problems and increased asthma among youth [50,58,59]. As noted earlier, parental cigarette smoking is also a risk factor for onset (and exacerbation) of childhood asthma through exposure to SHS [60–62]. Numerous studies have shown links between mental disorders (e.g., depression and anxiety) among adults and increased cigarette smoking [63]. Therefore, an additional possibility is that the co-occurrence of parental mental health problems and smoking may lead to increased likelihood of comorbidity of asthma and mental health problems among youth [64]. One recent study tested this pathway and found that parental smoking appeared to explain much of the relationship between childhood asthma and depression/anxiety disorders, although parental mental health did not appear to have a significant influence on the relationship [65].

Mediators

Asthma medicine use/mismanagement

Oral steroids such as prednisone, prelone and prednisolone are often used to treat acute asthma exacerbations. Research has indicated the efficacy of oral steroid use in treating acute asthma symptoms, reducing hospital stays and decreasing physicians’ visits for asthma in children [66–68]. However, there is 
some indication that anxiety and increased behavioral issues may result from the use of oral steroids. In a sample of children 
(aged 3–16 years; n = 10) with steroid-sensitive nephrotic syndrome, there were eight children whose behavior was rated as normal on the Child Behavior Checklist, a parent-report measure. After taking high doses of prednisone, their anxious/depressive behavior and/or aggressive behavior was rated in the 95th percentile. At this percentile, children typically are referred to mental healthcare providers [69]. Dosages of medications may also impact the manifestation of psychological symptoms. A study of children (aged 2–16 years) with mild persistent asthma compared differences between children taking 2 versus 1 mg/kg of oral steroids (prednisone or prednisolone) during an acute asthma exacerbation. Greater behavioral side effects, including anxiety and aggressive behavior, were seen in children taking 2 mg/kg compared with those taking the smaller dose, yet the benefits of the dosages were similar. These behavioral effects ended when the course of treatment was finished [70]. A qualitative analysis of in-depth interviews with adults who were prescribed prednisolone for asthma revealed that the adults felt that they had no other 
option but to take the oral steroids. Side effects they reported experiencing included nervousness, restlessness and trouble sleeping [71].

Overuse of quick-relief medication (e.g., albuterol) can lead to a cycle of asthma and anxiety. Due to overlap in symptoms, there is the potential to confuse asthma and anxiety. If anxiety is mistaken for asthma, individuals might take their quick-relief medications, which can increase various physiological symptoms, including heart rate, and lead to catastrophic thoughts. In turn, this might be mistaken as asthma, thus perpetuating the cycle. Abuse or overuse of quick-relief medications can result in psychological symptoms. Research on albuterol inhaler misuse (i.e., using the inhaler at a greater rate than prescribed) amongst residents of the Missouri Division of Youth Services showed that those who used their inhalers at greater rates than prescribed had greater levels of psychiatric distress, fearlessness, impulsivity, substance abuse and suicidality than those who did not misuse their inhalers [72].

Inflammation

In other chronic diseases, such as heart disease, it has been shown that depression is associated with poorer outcomes for reasons that remain unclear. One possibility is that both depression and such chronic diseases are associated with elevated inflammation and that there are biological mechanisms through which depression adversely affects asthma outcomes as well. More work in this area is needed to better understand these potential pathways.

Inflammation & depression

There is evidence that immunological markers are associated with increased vulnerability to major depression. Evidence of an association between inflammation and depression comes from animal models [73–75] and clinical samples, including findings that up to 50% of individuals treated with IL-2 and IFN-α as part of cancer or hepatitis C treatment develop depression [76–79]. Biological 
data has found at least four pathways through which localized inflammation or peripheral circulating cytokines may influence brain signaling and thereby induce depression: direct stimulation of primary afferent nerves (e.g., vagal nerves); stimulation of Toll-like receptors on macrophages residing in the circumventricular organs; cytokine transporters on the blood–brain barrier and IL-1 receptors on various cells within the brain venules [80]. Observational studies have also found associations between increased levels of various proinflammatory cytokines (including IL-1, IL-6 and TNF-α) or acute phase proteins (including C-reactive protein) among depressed compared with nondepressed individuals. Importantly, while clinical samples consistently find elevated levels of proinflammatory cytokines or acute phase proteins in depressed individuals [81–87], community-based samples tend to find that differences in the inflammatory markers are driven by a minority of participants with very high levels of the particular inflammatory marker under study, suggesting a threshold effect [88,89]. However, the majority of these studies are cross-sectional and have not examined the relationship between inflammation and depression over time [80,90], suggesting the need for further investigation.

Asthma & inflammation

Asthma is an inflammatory disease of the airways [91–93]. During an attack, whether allergic or nonallergic, the airways are infiltrated by T-helper cells leading, through various pathways, to the release of several proinflammatory cytokines including IL-6 and TNF-α [94]. Higher levels of inflammatory markers have been observed in both adults and children with asthma [95,96]. Given a common link between depression and asthma, and a link between both depression and asthma and inflammation, it is possible that immune markers may play a mediating role in the relationship between depression and asthma morbidity.

Limitations of research to date

While an increasing number of studies suggest an association between asthma and mental disorders among youth [19,21,23,32–35,97–100], several methodological shortcomings limit the usefulness of this information. First, the majority of studies that have examined the relationship between mental health and asthma morbidity in children have been based on cross-sectional studies. While these studies suggest that depression or other mental health problems appear to be associated with increased asthma among children, it has not been possible to examine the temporal relationship between depression and asthma morbidity. This is important because if depression leads to poorer asthma management, incorporating treatment for depression may be a key toward improving asthma control. Second, measurement of depression and/or mental health problems in previous studies has been imprecise. For instance, some studies have reported that ‘any psychopathology’, based on mental health service use or report by family members is associated with childhood asthma morbidity [19]. Other studies have looked at either anxiety/depression and respiratory disease (not asthma specifically) in children or depressive symptoms (not major depression) and asthma [101]. Third, the time period during which the depression and/or asthma morbidity occurred has been unspecified. Therefore, it is not clear, for instance, whether individuals with early-onset asthma who ‘outgrow’ it by adolescence or adulthood are still at increased risk for mental health problems subsequently, or whether the association is only evident when the two occur concurrently. Fourth, the samples used in the previous studies have been somewhat unique populations (e.g., Puerto Rican youth) or clinical samples that may not be widely generalizable. As such, no previous study has examined both depression and youth asthma morbidity using prospective data in a community (unselected) sample. Fifth, previous studies have been limited in the extent to which they were able to control for specific factors that may help to explain the mechanism of these relationships such as atopic status, level of exposure to other environmental factors, family factors and socioeconomic status. Sixth, all previous studies have relied on self-report or parent-report diagnoses of asthma and have been unable to examine asthma morbidity over time. This is important to understand in terms of the potential impact of mental health problems, conceptualized as modifiable risk factors, on asthma morbidity over time because this presents the potential opportunity to reduce asthma morbidity through interventions on mental health. Seventh, while asthma and mental health disorders are both disproportionately common among lower income, urban populations, previous studies have not examined these associations in such a high-risk sample. Therefore, whether and to what degree the problem exists in this vulnerable population is unclear. Finally, a key methodological problem with most, if not all, studies trying to examine the relationship between mental health problems and ‘severity’ of asthma is that these studies are not able to disentangle or differentiate ‘asthma severity’ from ‘asthma control’. This is particularly important as it relates to mental health, since asthma control can surely be affected by mental health. Studies that assess asthma severity at diagnosis, prior to initiation of treatment, are needed to clarify the potential impact of asthma severity on mental health. Future research into the relationship between asthma and mental disorders that can overcome these limitations is needed to move the field forward.

Conclusion

Both asthma and mental health conditions are common in youth and are related to increased morbidity. In the literature, there is a consistent cross-sectional association between asthma and mental health outcomes; however, there is a scarcity of longitudinal research. Furthermore, the etiology of the association between asthma and mental health is not clear. It is possible that mental health outcomes, such as depression, lead to asthma through inflammation; or it is possible that asthma leads to mental health outcomes due to the physical burden of illness. The association between asthma and mental health can be confounded by shared etiological factors such as SHS exposure, prenatal cigarette exposure and poor family functioning. In conclusion, it is not clear whether the association between asthma and mental health outcomes is causal. Future longitudinal research among family and youth with measures of family functioning and tobacco exposure are needed.

Expert commentary

There is fairly consistent evidence that asthma is associated with mental health problems in youth. However, there is relatively little known about the role of asthma severity, asthma control or the persistence of asthma in this relationship. Furthermore, little is known about possible mechanisms or the specificity of this relationship in terms of mental disorders (i.e., is it specific to anxiety or is asthma associated with a wide range of mental health problems) and how this changes throughout various developmental periods.

Five-year view

More work is needed to understand the nature of the relationship between asthma and mental health problems over time, across developmental periods, across various mental disorders and possible mechanisms. Understanding how severity of asthma and asthma control are related to mental health is also critical. In addition, a persistent problem that plagues this work is the confounding of asthma severity and asthma control in relation to mental health. Studies that can examine the relationship between mental health and asthma at diagnosis may be somewhat helpful in sorting this out. Given the high prevalence of asthma among youth, understanding the extent to which youth with asthma are at an increased risk for mental health problems and identifying the mechanisms is essential if effective prevention and intervention strategies are to be developed for both clinical and community settings.

Key issues

• • Asthma appears to be associated with increased mental health problems among youth.

• • The role of asthma control, asthma severity and whether and to what degree the relationship between asthma and mental disorders is specific to certain mental health problems remains to be determined.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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Asthma and mental health among youth: etiology, current knowledge and future directions

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Activity Evaluation: Where 1 is strongly disagree and 5 is strongly agree

	1	2	3	4	5
1. The activity supported the learning objectives.
2. The material was organized clearly for learning to occur.
3. The content learned from this activity will impact my practice.
4. The activity was presented objectively and free of commercial bias.

1. You are seeing a 14-year-old female adolescent with her parents. The reason for the visit is to better control frequent exacerbations of her moderate persistent asthma, but the parents tell you that the patient is more detached and not herself over the past month. Which of the following mental health diagnoses is most related to asthma?

• □ A Schizoid personality disorder

• □ B Anxiety disorders

• □ C Attention deficit disorder

• □ D Borderline personality disorder

What should you consider regarding the research linking asthma and mental health outcomes among children and adolescents?

• □ A Even remitted, mild asthma is associated with higher rates of depression and anxiety disorders

• □ B There is no evidence that other confounders might influence conclusions regarding the association between asthma and mental health disorders

• □ C Family conflict is associated with a higher number of hospitalizations for asthma

• □ D There is a clear temporal relationship between worsening depression and asthma morbidity

3. You inquire as to this patient's exposure to cigarette smoke, and she has a strong history of exposure to tobacco. What should you consider regarding the relationship between smoking and asthma?

• □ A Prenatal smoking increases the risk of asthma among mothers but not their children

• □ B Secondhand smoke exposure is not associated with a higher risk of asthma

• □ C Secondhand smoke exposure is not associated with mental health disorders

• □ D Prenatal exposure to secondhand smoke may increase the risks of depression and anxiety during childhood and adolescence

4. You review this patient's asthma medication history, which is extensive. Which of the following medications for asthma might be most likely to promote anxiety or depression?

• □ A Long-acting inhaled beta-agonists

• □ B Inhaled corticosteroids

• □ C Oral corticosteroids

• □ D Leukotriene receptor blockers