1066 Thorax 1998;53:1066–1074

Occasional reviews Thorax: first published as 10.1136/thx.53.12.1066 on 1 December 1998. Downloaded from

Review of psychosocial stress and asthma: an integrated biopsychosocial approach

Rosalind J Wright, Mario Rodriguez, Sheldon Cohen

Although consensus has emerged from the albeit equally important, determinants of clinical, social science, psychological, and asthma morbidity—for example, by influencing biological literature that psychosocial factors how children and their families perceive and aVect asthma morbidity in children, their role manage their asthma. Although no clear causal in the genesis, incidence, and symptomatology link between psychosocial stress and asthma has of asthma remains controversial since mecha- been established, this review provides a multi- nisms are not well understood. Three recent disciplinary transactional infrastructure that trends in medical research have led both clini- may guide future research priorities. cians and investigators to reconsider the role of psychosocial stress in asthma. Firstly, eVorts to Historical perspective define the aetiological risk factors for the The hypothesis of an association between stress development and expression of disease have and asthma emerges from a wide range of intensified in the face of rising trends in the clinical observation and evolving research. The prevalence and severity of asthma observed 1 general concept of the role of and the worldwide. Thus far, focus on traditional social environment in disease is as old as medi- environmental risk factors has not fully ex- cine itself. Early references to the importance plained these trends. Secondly, evidence of emotional and psychological processes were evolved over the last two decades of important put forth in a treatise on asthma by Maimo- interactions among behavioural, neural, endo- nides, an influential medieval Rabbi, philos- crine, and immune processes provides fresh opher, and physician.9 Sir William Osler http://thorax.bmj.com/ insight into means by which psychosocial referred to asthma as “a neurotic aVection” in stressors may influence the development and his medical textbook which served as a corner- 23 expression of inflammatory diseases. This stone of medical teaching in the latter part of insight emerged in parallel with our increased 10 Channing Laboratory, the 19th century. Indeed, before we under- Department of understanding of the complex cellular and stood the inflammatory basis of asthma, it was Medicine, Brigham molecular basis of asthma as a chronic inflam- among the disorders believed to be “purely” 4 and Women’s Hospital, matory disorder. Finally, hypotheses about the psychogenic in origin and was commonly and the Pulmonary/ substantial role of the social environment and referred to as asthma nervosa. Critical Care Division, social integration in and disease in gen- on September 24, 2021 by guest. Protected copyright. Boston’s Beth Israel Scientific support for an association between eral have gained significant emphasis over the psychological factors and asthma has its begin- Deaconess Medical 56 Center, Harvard last decade. In particular, prospective epide- nings in the first part of the 20th century and Medical School, miological studies have demonstrated associa- derives from research in widely disparate fields. Boston, tions between life stress, social position or sta- Early research suggesting that asthma had a Massachusetts, USA tus, and quality of social relationships—that is, psychosomatic component was strongly domi- R J Wright social networks, an individual’s ties to friends, nated by psychoanalytical theory, an extension Department of family, work, and community through social of the Freudian idea that symptoms were a 67 Medicine, Allegheny and religious groups—and health. All have symbolic expression of unconscious conflicts University of the led to a paradigm shift that reconsiders the and repressed desires.11 The so called specific Health Sciences, overlap between biological determinates and emotion theory, developed in large part by Philadelphia, psychosocial factors in understanding the Alexander and colleagues12 at the Chicago Pennsylvania, USA 8 M Rodriguez rising asthma burden. Institute of Psychoanalysis beginning in the This review highlights significant insights 1930s, was among the most influential work of Department of into this field from a multidisciplinary (psycho- this era. Concurrently, learning theorists ar- , Carnegie analytical, behavioural, psychosocial, epidemio- gued that particular emotional experiences Mellon University, logical, and immunological) perspective rather may have reinforced pulmonary physiological , than being an exhaustive overview of the responses, thus increasing the likelihood of Pennsylvania, USA 13 S Cohen subject. We examine behavioural, neural, and them recurring in the same context. More immunological pathways, underscoring recip- recently, published clinical studies have dem- Correspondence to: rocal relations that might link psychological onstrated the benefit of psychotherapy in treat- Dr R J Wright, Channing factors to both the onset of asthma and exacer- ing asthmatic patients,14 and relaxation tech- Laboratory, 181 Longwood Avenue, Boston, bation of established disease. We also focus on niques have been associated with improvement Massachusetts 02115, USA. stress and psychological factors as indirect, in respiration.15 Review of psychosocial stress and asthma 1067

25 Eventually, purely psychoanalytical and be- stimuli. Key to recent advances in the field of Thorax: first published as 10.1136/thx.53.12.1066 on 1 December 1998. Downloaded from havioural formulations gave way to physiologi- asthma is an emerging understanding of cal studies providing more objective support asthma and allergic disease as chronic inflam- for the idea that play an important matory processes regulated through compli- role in asthma. Stress and psychological factors cated immune phenomena in which many cells have been associated with asthma symptoma- (mast cells, eosinophils, and T lymphocytes) tology16 and with bronchoconstriction and and associated cytokines play a part. Mecha- reduction in pulmonary flow rates in asthmatic nisms of airway inflammation involve a cascade children.17 When subjected to stressful experi- of events that include the release of immuno- ences such as performing mental arithmetic logical mediators triggered by both IgE de- tasks,18 watching emotionally charged films,19 pendent and independent mechanisms. Pro- and listening to stressful interactions,20 15– cesses regulated through cytokines of the T 30% of asthmatic subjects respond with helper cell (Th2 phenotype) such as interleukin increased bronchoconstriction. (IL)-4, IL-5, and IL-13 are thought to promote Taken together, these data clearly support an recruitment of inflammatory cells which may association with stress, although mechanisms initiate and/or potentiate allergic inflammation linking stress and asthma remain poorly and the release of mediators that cause defined. To explore potential mechanisms link- contraction of smooth muscle and influence ing stress and asthma, it is helpful first to con- mucus production.26 The leukotrienes (LTs), sider how environmental and social stressors including LTC4, LTD4, and LTE4, are known may influence disease in general and, second, potent constrictors of human airways,27 have to frame these hypotheses within the current been observed to play a part in mucus asthma paradigm. secretion,28 and are thought to have an impor- tant role in asthma. A substantial body of Life stress model evidence supports the role of complex neural A general model of the link between environ- mechanisms and alterations of autonomic mental demands as psychological stressors and nervous system control in the pathophysiology health is reproduced in fig 1. When confronting and symptomatology of asthma.29 30 Autonomic environmental demands, individuals cogni- nerves can impact airway calibre and function tively appraise whether the event is threatening via eVects on airway smooth muscle, bronchial or potentially overwhelming to their existing vessels, and mucus glands. Hormones and 21 coping resources. If environmental demands neuropeptides released into the circulation are found to be taxing or threatening, and at when individuals experience stress are also the same time coping resources are viewed to thought to be involved in regulating both be inadequate, we perceive ourselves as being inflammatory and airway responses.31 There- under stress. This perception is presumed to fore, consideration of recent advances in the result in negative emotional states including field of psychoneuroimmunology—linking psy- fear, anger, anxiety, and depression. Changes in chosocial stress, the central nervous system, http://thorax.bmj.com/ behavioural and emotional states that accom- and alterations in immune and endocrine pany the perception of, and the eVort to adapt function—provide plausible biological path- to, environmental circumstances are accompa- nied by complex patterns of neuroendocrine and immunological changes.22 Both the duration and the frequency of Environmental demands experienced stress are important determinants (stressors or life events) of its impact on health and illness.22 23 Psycho- logical stress and its biological concomitants on September 24, 2021 by guest. Protected copyright. can last for a few minutes or for years. Appraisal of demands Chronicity is to some degree based on the and of adaptive capacities ongoing presence of external stimuli that trigger the stress response—for example, ongo- ing unemployment, poverty, living in a danger- Perceived Benign ous environment—but is also dependent on the stress appraisal long term success of individual coping re- sources. Moreover, events that last a very short time can have very long term stress eVects and lasting physiological responses thought to be Negative emotional responses maintained by recurrent “intrusive” thoughts about past events. Variable response to acute challenges superimposed on chronic stressors mayhavediVerent implications on disease Physiological or behavioural expression.24 responses

Current asthma paradigm Asthma is currently defined by the American Increased risk of Thoracic Society as a disease characterised by physical disease (1) airway obstruction that is, to a variable degree, reversible, either spontaneously or with Figure 1 Biopsychosocial model of the stress process designed to illustrate the potential integration of the treatment, (2) airway inflammation, and (3) psychological and biological eVects of environmental increased airway responsiveness to a variety of demands. Modified from reference 22. 1068 Wright, Rodriguez, Cohen

ways through which stress may impact on ated, leading to increased secretion of inflamma- Thorax: first published as 10.1136/thx.53.12.1066 on 1 December 1998. Downloaded from asthma expression.32 33 tory cytokines typically counterregulated by Furthermore, self-management of disease is cortisol. Some populations with post-traumatic a cornerstone of current asthma guidelines.34 stress disorder (PTSD), for example, have lower Poor self-management has been linked to poor mean basal plasma cortisol levels throughout the asthma outcomes,35 and studies of mediators circadian cycle and lower mean 24 hour urinary with a potential adverse impact on asthma cortisol excretion.43 Furthermore, a state of management have drawn a great deal of atten- stress induced HPA hyporesponsiveness in some tion. Indeed, the ability of the patient to adhere research subjects has been associated with other to a prescribed treatment regimen is viewed as inflammatory disorders.44 A hyporesponsive one of the most important pathways through HPA axis may explain stress induced exacerba- which many risk factors impact on asthma tions of asthma in certain subgroups of asthmat- morbidity. Factors important to adherence ics and increased association of asthma with include asthma knowledge, skills, and manage- particular psychological states. ment behaviour.36 In addition, these variables activates the HPA axis are known to be aVected by mental health resulting in the release of cortisol, which has (both adults and children), family functioning, known anti-inflammatory eVects. However, , cognitive functioning, the per- other regulatory pituitary (i.e. corticotrophin) sonality and self-concept of the subject, and and hypothalamic hormones (i.e. CRH and personal health beliefs and behaviours. Stress arginine vasopressin (AVP)) of the HPA axis and coping may also influence health beliefs, have systemic immunopotentiating and proin- health behaviour, social support, symptom flammatory eVects. Recently, Theohanides and perception, and adherence which, in turn, have colleagues have shown that acute psychological an impact on asthma morbidity. stress (immobilization in rats) results in skin To simplify the discussion we have arbitrarily mast cell degranulation, an eVect inhibited by chosen to review the relations between stress, anti-CRH serum administered prior to stress.45 psychological dysfunction, endocrine function, Although hormones of the sympathetic and neural function, immune function, social con- adrenal medullary and HPA systems are those nectedness, and behaviour separately in order most often discussed as the biochemical to explore the influence of environmental stress substances involved in stress responses, altera- on asthma morbidity. We recognise that this is tions in a range of other hormones, neurotrans- a rudimentary approach, as contemporary mitters, and neuropeptides found in response attempts to apply the biopsychosocial model to to stress may also play a part in the health disease emphasise that a unidirectional model eVects of stress. For example, stressor associ- is too simplistic; causality is at least bidirec- ated increases in growth hormone and prolac- tional or reciprocal and more probably cyclic in tin secreted by the pituitary gland and in the complexity.37 natural opiate â-endorphins and enkephalins released in the brain are also thought to play a http://thorax.bmj.com/ Psychological stress and the endocrine role in immune regulation.46 system Psychological stressors have been associated Psychological distress and asthma with the activation of the sympathetic and Asthmatic subjects frequently have associated adrenomedullary system and the hypothalamic- underlying psychological distress (depression pituitary-adrenocortical (HPA) axis. These sys- and anxiety). Development of psychological tems respond to psychological stress with distress in children has been associated with increased output of adrenaline (epinephrine) asthma that is more diYcult to manage, and noradrenaline (norepinephrine) from the requiring higher doses of steroids,47 more on September 24, 2021 by guest. Protected copyright. adrenal medulla.38 The hormonal responses of frequent and prolonged admissions to hospi- the HPA axis have long been thought to tal,48 and greater functional disability.49 Asth- represent a non-specific physiological reaction matics with comorbid psychological symptoms to excessive stimulation,39 particularly the emo- are more often non-compliant.50 Psychological tional arousal associated with appraising situa- morbidity has been linked to asthmatic mor- tions as stressful.40 The hypothalamus produces tality.51 52 Mechanisms linking psychological corticotrophin releasing hormone (CRH) which morbidity and asthma morbidity and mortality triggers the anterior pituitary gland to secrete are complex and remain largely undefined. adrenocorticotrophic hormone (ACTH), which Asthmatic subjects have been characterised in turn activates the adrenal cortex to secrete by â adrenergic hyporesponsiveness and corticosteroids (primarily cortisol in humans). á-adrenergic and cholinergic hyperresponsive- More recent work suggests that negative emo- ness.53 Defects in the function of the autonomic tional responses disturb the regulation of the nervous system have also been demonstrated in HPA system. For example, relatively pro- psychological states including depression, nounced HPA activation is common in depres- PTSD, and psychomotor agitation.54–56 In sion with episodes of cortisol secretion being depression and PTSD, studies of central more frequent and of longer duration among mediators in the brain also demonstrate depressed than among other psychiatric patients parasympathetic hyperresponsiveness and â and normal subjects.41 Shifts in the circadian adrenergic hyporesponsiveness.56 Whereas in- rhythm of cortisol have also been found among creased á adrenergic and cholinergic respon- persons in stressful situations.42 Chronic stress siveness distal from the airway has also been may induce a state of hyporesponsiveness of the demonstrated in asthmatic patients,57 a similar HPA axis whereby cortisol secretion is attenu- imbalance to the autonomic nervous system in Review of psychosocial stress and asthma 1069

the central nervous system among asthmatic should relax airway smooth muscle and that Thorax: first published as 10.1136/thx.53.12.1066 on 1 December 1998. Downloaded from populations has not been demonstrated. These acute psychological stress, which is accompa- data raise the question of common biological nied by a rapid increase in circulating catecho- pathways. lamines, should consequently cause bronchodi- lation. However, the stress induced response of Stress and autonomic control of airways the autonomic nervous system is more complex The argument that psychological stress influ- and variable. Once the acute stressor is termi- ences autonomic control of the airways is based nated, levels of adrenaline and noradrenaline primarily on the fact that many of the same quickly return to normal or below normal.60 The autonomic mechanisms thought to play a role relative strength of sympathetic versus parasym- in asthma are involved in the activation and pathetic control in response to certain forms of regulation of physiological responses to stress. stress diVers with the individual, with some These mechanisms include the release of sym- showing a predominantly parasympathetic re- pathetic nervous system mediators and the sponse. Such individuals may be particularly action of adrenergic (sympathetic) and cholin- susceptible to stress induced bronchoconstric- ergic (parasympathetic) nerves, and the neuro- tion.16 It is possible that sympathetic activation transmitters and neuropeptides they produce. itself might contribute to asthma symptoms. For The parasympathetic nervous system inner- example, increases in circulating levels of vates the airways via eVerent fibres from the adrenaline and noradrenaline are known to alter vagus nerve and synapse in ganglia in the airway a number of immune parameters that might wall with short postsynaptic fibres directly sup- contribute to inflammation of the airways. Some plying the airway smooth muscle and submu- evidence suggests long term increases or poten- cosal glands.29 Increased activity of the para- tiation of the catecholamine response with sympathetic nervous system was once thought chronic stress.23 Prolonged increases in catecho- to be the dominant mechanism responsible for lamine levels under chronic stress may also con- the exaggerated reflex bronchoconstriction in tribute to asthma severity. Chronic daily use of â asthmatic subjects, although more recent work agonists by mild to moderate asthmatics with a challenges this idea.58 In the initial phases, nar- specific genetic predisposition may increase rowing of the airways in asthma is thought to severity by downregulating â receptors,61 and it result primarily from inflammation. Current is possible that chronically increased stress theory holds that bronchial constriction is due induced catecholamines do the same among to some combination of vagal input plus genetically susceptible subgroups. In addition, inflammation, with the relative importance of in those with chronic life stress the physiological these factors being dependent upon genetic and response to acute stressors may result in more environmental influences. sustained eVects on the immune system, even Recent experimental studies in which asth- following sympathetic recovery.24 matic patients are exposed to stressful situa- Collectively, these data showing that stress tions have focused on stress induced vagal and psychological dysfunction have been asso- http://thorax.bmj.com/ reactivity as a mediator of emotionally induced ciated with modulation of many of the bronchoconstriction.16 Preliminary evidence hormones, neurotransmitters, and neuropep- shows that children with asthma who respond tides involved in autonomic control and to stressful stimuli with high vagal activation inflammation of the airways (potential com- (associated with increased cholinergic activity) mon biological mediators) suggest potential have greater impairment of airway reactivity in common underlying biological mechanisms. response to methacholine.19 Further study of the “balance” among func- Although human airway smooth muscle is tional parasympathetic and functional sympa- not functionally innervated by adrenergic thetic activity in relation to stress and emo- on September 24, 2021 by guest. Protected copyright. axons, studies have shown adrenergic innerva- tional stimuli in asthmatic populations is tion of submucosal glands, bronchial blood needed. vessels, and airway ganglia.59 Adrenergic nerves may influence cholinergic neurotransmission Stress and immune function via prejunctional á and â receptors.29 Depend- A focus on the inflammation of the airways in ing on the type of agonist (â or á) involved, asthma has drawn attention to the possibility these changes can variably aVect airway that stress induced alterations in immune smooth muscle, release of inflammatory me- response have implications for development, diators, cholinergic neurotransmission, mucus exacerbation, and triggering of asthma.833 A secretion, and possibly mucociliary clearance, substantial literature demonstrating that psy- resulting in either bronchodilation or broncho- chological stress can influence cell traYcking, constriction. Adrenoceptors are regulated by cell function including mitogen stimulated noradrenaline which is released locally from blastogenesis and natural killer cell cytotoxic- sympathetic nerves, and by adrenaline and ity, and lymphocyte production of cytokines noradrenaline secreted by the adrenal medulla. has been recently reviewed.22 Stress can modu- The regulatory eVects of adrenaline and late immune response through nerve pathways noradrenaline on adrenoceptors suggest a connecting the autonomic nervous and im- plausible mechanism by which stress induced mune systems, by triggering the release of hor- activation of the sympathetic nervous system mones and neuropeptides that interact with might influence bronchomotor tone. immune cells, and through the impact on It seems paradoxical that activation of the behaviours such as smoking and drinking alco- sympathetic nervous system by stress, resulting hol that are adopted as ways of coping with in release of mediators with a â agonist eVect, stress.62 1070 Wright, Rodriguez, Cohen

Subjects exposed to cognitive or social labo- has been speculated that stress triggers hor- Thorax: first published as 10.1136/thx.53.12.1066 on 1 December 1998. Downloaded from ratory stressor tasks lasting only a few minutes mones in the early months of life which may show suppression of T cell mitogenesis and influence Th2 cell predominance, perhaps increased numbers of circulating T suppressor/ through a direct influence of stress hormones cytotoxic (CD8) cells and natural killer cells.63 on the production of cytokines that are thought This phenomenon includes stress elicited to modulate the direction of diVerentiation. alteration of the production of the cytokines Simultaneous investigation of both host sus- IL-1â, IL-2, and IFNã.64 65 These eVects are ceptibilty factors and the eVect of environmen- thought to be mediated by the autonomic tal exposures, including psychosocial stressors, nervous system because they occur quite on the selection process for immunological rapidly and have been shown to be associated memory may provide fresh insight into the with increased heart rate, blood pressure, and pathogenesis of atopic disorders. circulating catecholamines,66 and are blocked by administration of an adrenoceptor antago- nist.67 Living near the Three Mile Island Stress and infection nuclear power plant at the time of the accident, The strongest suggestion from the current taking care of a relative with Alzheimer’s literature is that psychological stress may influ- disease, and taking medical school examina- ence the pathophysiology of asthma by increas- tions have all been shown to influence both the ing the risk of respiratory infections. The role of numbers and functions of various populations respiratory tract infection in asthma is fairly well of lymphocytes. characterised with current evidence indicating Stress is not expected to have the same that viral, as opposed to bacterial, infections are eVects on immune function in all people. As the most important infectious agents.75 Early noted earlier, individual diVerences in response life viral lower respiratory infections may be to stressful events are attributable to interpret- associated with an increased risk of developing ation of the event, access to coping resources, asthma.76 Further evidence supports a more and presence of antecedent chronic stress. complex pathogenetic role for viral infections73 However, there is also evidence of stable and suggests that the eVects of infection may individual diVerences in immune response that depend on which pathogen infects the host early occur independent of psychological response in immune development.77 to the stressor. When exposed to multiple acute A number of mechanisms may be involved in laboratory stressors over time, some subjects explaining the exacerbation of asthma, especially consistently demonstrate stress elicited altera- wheezing and increased airway responsiveness, tions in immunity, while others do not.68 by viral respiratory infections. Firstly, viral respi- As highlighted previously, airway inflamma- ratory infections damage the airway epithelium tion and hyperresponsiveness are thought to be causing inflammation. Another mechanism in- orchestrated by activated T lymphocytes and volves the stimulation of virus specific IgE anti- the cytokines they produce. The T helper cell body. Respiratory syncytial and parainfluenza http://thorax.bmj.com/ Th2 cytokine phenotype promotes IgE pro- viruses may potentiate the allergic response to duction with subsequent recruitment of in- allergens by increasing the release of inflamma- flammatory cells that may initiate and/or tory mediators from mast cells and the subse- potentiate allergic inflammation.69 Prospective quent cascade of inflammatory events character- seroepidemiological studies have shown that istic of asthma.78 Lastly, viral respiratory the newborn period is dominated by Th2 reac- infections may also result in the appearance of a tivity in response to allergens,70 and it is also late asthmatic response to inhaled antigen.79 evident that the Th1 memory cells selectively Thus there is evidence that viral infections are an develop shortly after birth (at 3–6 months of “adjuvant” to the inflammatory response and on September 24, 2021 by guest. Protected copyright. age) and persist into adulthood in non-atopic promote the development of airway injury by subjects.71 For most children who become enhancing airway inflammation. allergic or asthmatic, the polarisation of their A potential consequence of stress induced immune system into an atopic phenotype changes in immune response is suppression of probably occurs during early childhood.72 host resistance to infectious agents, particularly These findings have sparked oV vigorous agents that cause upper respiratory disease. investigation into the potential influence of The primary evidence for such eVects comes early life environmental risk factors for asthma from studies of psychological stress as a risk and allergy on the maturation of the immune factor for respiratory infections. Increased inci- system, in the hopes of understanding which dence of upper respiratory infections under factors will potentiate (or protect from) this stress in these epidemiological studies may be polarisation. For example, Martinez and col- attributable either to stress induced increases leagues73 suggest that certain lower respiratory in exposure to infectious agents or to stress tract infections in early life (primarily croup) induced changes in host resistance. Control for enhance the production of IFNã by non- exposure is provided by studies in which specifically stimulated lymphocytes, believed to volunteers are intentionally exposed to a be an expression of the Th1 phenotype. virus—that is, viral challenge trials. In these Although there is no direct evidence for the prospective studies psychological stress is influence of stress on Th phenotype diVeren- assessed before volunteers are exposed to an tiation in the developing immune system, there upper respiratory virus and monitored in quar- is evidence that parental reports of life stress antine for infection and illness. Using this are associated with subsequent onset of wheez- paradigm, psychological stress has been associ- ing in children between birth and one year.74 It ated with the incidence of infection and Review of psychosocial stress and asthma 1071

80 81 96 illness, with increasing stress related in a shedding. Furthermore, these authors found Thorax: first published as 10.1136/thx.53.12.1066 on 1 December 1998. Downloaded from dose response manner to increasing risk of that susceptibility to colds decreased in a dose infection.82 dependent manner with increasing diversity of In summary, these data provide provocative their social networks. evidence that stress is associated with reduced Social support/networks may facilitate host resistance to respiratory infectious agents asthma management and general coping which, and implicates this as a possible causal in turn, may enhance the asthma status and mechanism in the stress-asthma paradigm. reduce disruptive eVects of environmental stressors. Data from the Neighborhood Asthma Stress and social connectedness Coalition (NAC), developed as a collaborative Ecological views on health promotion under- eVort to promote community (neighbour to score the significance of the social context neighbour) support and encouragement of within which individuals live and the im- asthma management, more directly suggest that portance of social relationships.83 In the study social isolation is important in asthma manage- of social relationships and health, the former ment and morbidity. These investigators found has been conceptualised in terms of social net- that children of socially isolated parents (those works (a person centred web of social relation- below the median on both support from family ships) and social support (a measure of the and from friends) were reported to have more functional content of these relationships). Lack frequent days/nights with asthma symptoms, of social relationships has been linked to an more days of activity limitation, poorer asthma array of adverse health outcomes7 and physi- management practices, and more emergency ological eVects including altered immuno- department visits than those of non-isolated logical functioning.84 Social support may re- parents/care givers.97 Furthermore, subsequent duce or buVer the deleterious eVects of stress interventions orchestrated through the NAC, by altering the perception of a situation or which emphasises neighbourhood and commu- facilitating more appropriate coping.85 Greater nity organisation strategies and social support diversity has been related to less to help asthmatic families, have resulted in anxiety, depression, and non-specific psycho- reductions in acute care for asthmatic logical distress.86 Social supports may operate children.98 through influence on health promoting behav- Future studies which examine the role of a iours such as abstaining from cigarette smok- broad range of social ties and diversity of social ing, moderating alcohol consumption, improv- networks on disease expression and asthma ing diet, exercise, and sleep quality.87 On the management are needed to understand the other hand, social support can be deleterious as influence of social connectedness in this field. well as health promoting. For example, support Social support and social networks may impact that encourages dependency may not have a on physical and mental health through various positive impact.88 Parental attitudes that reflect mechanisms. For example, social relationships exaggerated concern in protecting the child’s can be examined as having a direct influence in http://thorax.bmj.com/ health89 and overdependency on medical sup- the causal pathway or may be considered as a port90 have been demonstrated, especially buVering system which impacts on the eVects among severe asthmatic subjects. of environmental stressors. For children the family as a support network has significant influence on chronic disease. Environmental stress and health Family function is an important correlate of behaviours health outcomes in general and this has been Because self-management is so critical in asthma shown to be the case for asthma as well. The care, it is important to consider how stress may role of disturbed family interaction could be aVect self-management strategies and adherence on September 24, 2021 by guest. Protected copyright. either direct by increasing the psychological to prescribed treatment plans. Social learning stress in the child, or indirect by providing poor theory provides a useful model which examines methods for coping with stress in the family the interaction among individuals, environ- system.91 Family structure is also an important ments, and health behaviours.99 Perceived con- correlate of health outcomes. Relationships trol has been identified among factors that between severity of illness and maladjustment mediate the experience of chronic illness.100 vary significantly within diVerent family struc- There have been a number of conceptual tures.92 93 Many of the psychosocial factors approaches taken to the individual’s perceived implicated in the rise in asthma morbidity and control of his or her own behaviour. Popular mortality—for example, childhood anxiety and among these have been self-eYcacy, locus of depression, noncompliance, family conflict94 95 control, and learned helplessness. Interactions —are dependent on family structure and func- between individuals and the environment are tion. key to the development of perceived control. For Social support/networks may buVer direct example, the experience of positive conse- eVects of stress on biological functioning and quences following task performance leads to thus impact on asthma. For example, there is self-eYcacy.101 Individuals repeatedly exposed to evidence that social networks influence the aversive events they cannot predict or control— immune system and may play a role in suscep- for example, poverty, adverse life events, living in tibility of the host to infection. Cohen and col- an unsafe or unpredictable environment—may leagues recently demonstrated an association learn to become helpless.102 Both perceived of social ties with reduced susceptibility to the control103 and appraisals of self-eYcacy104 are common cold, decreased mucus secretion, predictive of health outcomes. In animal studies more eVective ciliary clearance, and less viral there is evidence that controllable shocks have 1072 Wright, Rodriguez, Cohen

less deleterious eVects on T cell functioning Life stress, socioeconomic status, and Thorax: first published as 10.1136/thx.53.12.1066 on 1 December 1998. Downloaded from than uncontrollable shocks, which suggests that race the controllability of stressors may be critical in In the USA asthma morbidity disproportion- modulating immune functioning.105 Recently, ately impacts on poor urban minority popula- Katz and colleagues106 have developed a disease tions.115 EVorts to identify factors related to specific brief Perceived Control of Asthma these disparities are needed. The adverse associ- Questionnaire (PCAQ) (11 items) to examine ation between poverty and ethnic minority the association of perceived control and asthma status and asthma outcomes may in part be due outcomes. They found that a lower PCAQ score to diVerential exposure to and perception of life was associated with an increased risk of admis- stress as has been postulated for other health outcomes.116 In a recent review by Taylor and sion to hospital and frequent activity restriction, 6 which suggests that lower levels of perceived colleagues multiple characteristics of commu- control are associated with more adverse nity, work, and family environments were considered which may lead to chronic stress in outcomes in this population of adult asthmatic high risk groups. Some unique factors pur- subjects. However, this was not a prospective ported to cause chronic stress in communities of study and therefore perceived control may have low socioeconomic status include poverty, mi- been influenced by the adverse events of the nority ethnicity, the real or perceived threat of past year associated with the participant’s crime and violence, and poor transportation and asthma, such as admission to hospital. refused services such as taxi and ambulance. Although the major impact of psychological Preliminary evidence suggests that exposure to functioning on adherence has been shown in violence is associated with the occurrence of 107 108 the context of other diseases, few studies asthma/wheeze syndromes and prescription have examined this issue in asthma. Chris- bronchodilator use among inner city children.117 109 tiaanse and co-workers examined compli- Frequency of adverse life events and level of ance with theophylline therapy in asthmatic perceived stress show an inverse relationship to children and found that psychological adjust- socioeconomic status, while degree of perceived ment and level of family conflict versus control and social support decrease as the socio- cohesiveness were predictive of compliance economic gradient decreases.116 118 Pervasive life determined by mean theophylline levels. Most experiences such as racism and sexism may be work to date has examined the role of family important life stressors with health implications. dysfunction in adherence to the medical Among minority populations, more attention is regimen in asthma management.50 The rela- being given to the study of racism and sexism as tionship between stress, feelings of hoplessness stressors that impact on health status.119 120 or lack of control, and adherence with medical While there is general consensus regarding the treatment remains virtually unexplored in the importance of the physical environment in field of asthma research. The National Coop- asthma morbidity, the significance of such char- erative Inner City Asthma Study (NCICAS), a acteristics of the psychosocial environment has http://thorax.bmj.com/ multicentre study, has launched an initiative received little attention in asthma research. designed to examine many domains including psychosocial stress, believed to be important to asthma morbidity, in order to guide more Summary eVective asthma intervention programmes in Environmental stressors may impact asthma the inner city.110 A preliminary description of morbidity through neuroimmunological mech- the psychosocial factors explored in this study anisms which are adversely impacted and/or 111 buVered by social networks, social support, and

has recently been published. on September 24, 2021 by guest. Protected copyright. Another critical premise of the self- psychological functioning. In addition, life management approach is the ability to identify stress may impact on health beliefs and behav- accurately symptoms and pulmonary function iours that may aVect asthma management. Whereas earlier psychosomatic models have compromise. It has been speculated that supported a role for psychological stress in accuracy of perceived symptoms in paediatric contributing to variable asthma morbidity asthma may be influenced by physiological fac- among those with existing disease, a growing tors such as disease severity as well as appreciation of the interactions between behav- psychological factors such as defensive style, ioural, neural, endocrine, and immune proc- although empirical evidence is scarce.112 113 114 esses suggest a role for these psychosocial fac- Boxer and colleagues found a relationship tors in the genesis of asthma as well. While a between paediatric admissions to hospital for causal link between stress and asthma has not asthma and family dysfunction through the lack been established, this review provides a frame- of symptom recognition and poor management work in which we can begin to see links of exacerbations. between these systems that might provide new As with previously discussed psychosocial insights to guide future explorations. The com- factors, lack of perceived control and/or the plexity of these interactions underscore the environmental circumstances which lead to it need for a multidisciplinary approach which may therefore act through two pathways. There combines the idea that the origin of asthma is may be direct eVects on biological functions— purely psychogenic in nature with the antitheti- for example, uncontrollable shock on T cal consideration that the biological aspects are cells—or lack of perceived control may under- all important. These distinctions are artificial, mine symptom perception and disease man- and future research that synthesises biological, agement eVorts. psychological, sociocultural, and family param- Review of psychosocial stress and asthma 1073

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