Psychophysiologic Reactivity in Asthmatic Children: A Cholinergically Mediated Confluence of Pathways

doi:10.1097/00004583-199411000-00004

Journal of the American Academy of Child & Adolescent Psychiatry

Volume 33, Issue 9, November–December 1994, Pages 1236-1245

https://doi.org/10.1097/00004583-199411000-00004 Get rights and content

ABSTRACT

Objective

The purpose of this study was to determine the suitability of a newly developed experimental paradigm, designed to assess relationships among emotional responsivity, physiologic (autonomic) reactivity, airway reactivity, and pulmonary function in asthmatic children under controlled conditions of ecologically valid emotional stimulation.

Method

Twenty-four children, aged 8 through 17, with moderate to severe asthma viewed the movie, E.T., the Extra-Terrestrial, while having their heart and respiration rate and oxygen saturation continuously measured and recorded. Airway reactivity was assessed by the methacholine challenge test, and pre- and postmovie pulmonary function by spirometry. Self-report of emotion was recorded for targeted scenes.

Results

Findings indicated that emotional responsivity and physiologic reactivity to the movie were associated with increased airway reactivity and with decreased pulmonary function.

Conclusions

The pattern of results suggests cholinergically mediated psychophysiologic pathways of emotional influence in the asthmatic process for some asthmatic children. A heuristic biopsychosocial model of these pathways is presented.

REFERENCES (53)

American Thoracic Society
Definitions and classification of chronic bronchitis, asthma, and pulmonary emphysema
Am Rev Respir Dis
(1962)
H Beech et al.
Asthma and aggression: the investigation of a hypothetical relationship employing a new procedure
Br J Soc Clin Psychol
(1965)
DC Beidel
Assessing anxious emotion: a review of psychophysiological assessment in children
Clin Psychol Rev
(1989)
U Bengtsson
Emotions and asthma. I
Eur J Respir Dis
(1984)
WT Boyce et al.
Temperament and the psychobiology of childhood stress
Pediatrics
(1992)
JF Dirks et al.
Clinical prediction of medical rehospitalization: psychological assessment with the battery of illness behavior
J Pers Assess
(1981)
I Florin et al.
Facial expressions of emotion and physiologic reactions in children with bronchial asthma
Psychosom Med
(1985)
GK Fritz
Childhood asthma
Psychosomatics
(1983)
GK Fritz et al.
Psychological factors in fatal childhood asthma
Am J Orthopsychiatry
(1987)
RC Frysinger et al.
Interictal heart rate patterns in partial seizure disorders
Neurology
(1993)

M Hofer

Cardiac and respiratory function during sudden prolonged immobility in wild rodents

Psychosom Med

(1970)

J Hollaender et al.

Expressed emotion and airway conductance in children with bronchial asthma

J Psychosom Res

(1983)

DO Hopp et al.

Genetic analysis of allergic disease in twins

J Allergy Clin Immunol

(1984)

SA Isenberg et al.

The effects of suggestion and emotional arousal on pulmonary function in asthma: a review and a hypothesis regarding vagal mediation

Psychosom Med

(1992)

DS Janowsky et al.

Increased vulnerability to cholinergic stimulation in affective disorder patients (proc)

Psychopharmacol Bull

(1980)

JM Jemerin et al.

Cardiovascular markers of biobehavioral reactivity

J Dev Behav Pediatr

(1992)

J Kagan et al.

Biologic basis of childhood shyness

Science

(1988)

BS Kapp et al.

The amygdala, emotion, and cardiovascular conditioning

RA Kinsman et al.

(PRN) medication use in asthma: usage patterns and patient characteristics

J Psychosom Res

(1980)

MD Klinnert et al.

Marriages with children at medical risk: the transition to parenthood

J Am Acad Child Adolesc Psychiatry

(1992)

LP Kravis et al.

Sudden death in childhood asthma

Adv Asthma Allergy Pulmon Dis

(1978)

PM Lehrer et al.

Asthma and emotion: a review

J Asthma

(1993)

R Levenson

Effects of thematically relevant and general stressors on specificity of responding in asthmatic and nonasthmatic subjects

Psychosom Med

(1979)

D Marx et al.

Expression of emotion in asthmatic children and their mothers

J Psychosom Res

(1986)

DR Miklich et al.

A preliminary investigation of psychophysiological responses to stress among different subgroups of asthmatic children

J Psychosom Res

(1973)

BD Miller

Depression and asthma: a potentially lethal mixture

J Allergy Clin Immunol

(1987)

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Assuming the subjects have been randomly assigned in sufficient numbers to stressor versus control conditions, the researcher can make causal inferences about the influence of the manipulation, without concerns about confounding variables playing a role. One laboratory manipulation suggests that emotional responsivity may mediate the relationship between psychological stress and asthma outcomes.41 As part of this study, youth with asthma watched several segments from the movie, E.T., The Extra-terrestrial.
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This work was supported in part by a Clinical Research Center Grant to Dr. Miller from the National Jewish Center for Immunology and Respiratory Medicine, and in part by funding from the Department of Psychiatry at the University of Rochester School of Medicine and Dentistry. The authors thank Drs. David Mrazek and Bruce Bender for their professional contributions to this effort, William Orr and Isaac George for their technical assistance, and their patients for participation in this study.

Dr. Miller dedicates this paper to the memory of Haroutun M. Babigian, M.D., who as Chairman, mentor, and friend at the University of Rochester provided support and encouragement for this work.

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ArticlesPsychophysiologic Reactivity in Asthmatic Children: A Cholinergically Mediated Confluence of Pathways

ABSTRACT

Objective

Method

Results

Conclusions

Definitions and classification of chronic bronchitis, asthma, and pulmonary emphysema

Am Rev Respir Dis

Asthma and aggression: the investigation of a hypothetical relationship employing a new procedure

Br J Soc Clin Psychol

Assessing anxious emotion: a review of psychophysiological assessment in children

Clin Psychol Rev

Emotions and asthma. I

Eur J Respir Dis

Temperament and the psychobiology of childhood stress

Pediatrics

Clinical prediction of medical rehospitalization: psychological assessment with the battery of illness behavior

J Pers Assess

Facial expressions of emotion and physiologic reactions in children with bronchial asthma

Psychosom Med

Childhood asthma

Psychosomatics

Psychological factors in fatal childhood asthma

Am J Orthopsychiatry

Interictal heart rate patterns in partial seizure disorders

Neurology

Cardiac and respiratory function during sudden prolonged immobility in wild rodents

Psychosom Med

Expressed emotion and airway conductance in children with bronchial asthma

J Psychosom Res

Genetic analysis of allergic disease in twins

J Allergy Clin Immunol

The effects of suggestion and emotional arousal on pulmonary function in asthma: a review and a hypothesis regarding vagal mediation

Psychosom Med

Increased vulnerability to cholinergic stimulation in affective disorder patients (proc)

Psychopharmacol Bull

Cardiovascular markers of biobehavioral reactivity

J Dev Behav Pediatr

Biologic basis of childhood shyness

Science

The amygdala, emotion, and cardiovascular conditioning

(PRN) medication use in asthma: usage patterns and patient characteristics

J Psychosom Res

Marriages with children at medical risk: the transition to parenthood

J Am Acad Child Adolesc Psychiatry

Sudden death in childhood asthma

Adv Asthma Allergy Pulmon Dis

Asthma and emotion: a review

J Asthma

Effects of thematically relevant and general stressors on specificity of responding in asthmatic and nonasthmatic subjects

Psychosom Med

Expression of emotion in asthmatic children and their mothers

J Psychosom Res

A preliminary investigation of psychophysiological responses to stress among different subgroups of asthmatic children

J Psychosom Res

Depression and asthma: a potentially lethal mixture

J Allergy Clin Immunol

Articles
Psychophysiologic Reactivity in Asthmatic Children: A Cholinergically Mediated Confluence of Pathways