Bronchial Asthma with Psychogenic Trigger

Bronchial Asthma with Psychogenic Trigger I.B. IAMANDESCU 1, ALEXANDRA MIHĂILESCU 2 1 Carol Davila University of Medicine and Pharmacy, Colentina Hospital, Clinic of Allergology, Bucharest, Romania 2 Carol Davila University of Medicine and Pharmacy, Al. Obregia Hospital of Psychiatry, Bucharest, Romania The authors present several personal studies in accordance with other published data which contest the existence of purely psychogenic bronchial asthma, as it was considered 30-50 years ago. Although psychological stimuli could trigger the occurrence of attacks of bronchial asthma, they are not an exclusive etiological factor (Iamandescu, 1980, 1985). In the context of large groups of asthma with allergic or other etiology, forms of asthma that are triggered by an additional psychogenic factor could be identified. These are noted in 62.5% of hospitalized patients, most cases with a prolonged and more severe evolution of the disease, but in only 30% of light and moderately severe cases that are followed up in outpatient (Iamandescu, 1980, 1984). The percent of psychological trigger is maximum (86%) in corticodependent asthma patients (Iamandescu, 1996). Somatic and psychological background of asthma with psychogenic triggering is represented by the following: 1) an obvious relationship between psychological stimuli and the onset of asthma attacks, and a psychological terrain endowed with an increased vulnerability to stress. These patients present a diminished rate of cortisol response to stress compared with asthma patients without psychogenic triggering; 2) reversibility to broncho-dilator agents, in contrast with resistance to systemic corticoid therapy; 3) sensitivity to aspirin; 4) endocrine dysfunctions (high estrogen and thyroid hormones secretion); 5) multi-factorial triggering of the attacks (especially non-specific respiratory irritants, including physical-chemical factors and meteorological changes) (1985); 6) variable response to psychotherapy and psychotropic drugs, suggesting in case of therapeutic failure the predominance of the chronic inflammation determined by other etiologic agents, different from psychological stress. Key words: Bronchial asthma, psychological trigger, stress, depression. 1. BACKGROUND PARTICULARITIES MODALITIES OF PSYCHOGENIC TRIGGERING OF ASTHMA ATTACKS In many cases the bronchial asthma is, at least initially, of allergic or intrinsic (non-allergic) origin, and the psychogenic triggering is a supplemental factor. It should be stressed that the study of the role played by psychogenic factors in the triggering of bronchial asthma attacks has two aspects: The relationship between the psychological stress as a rule extending over a long period of the patient s life, and having a variable intensity and duration and the occurrence of the first bronchial asthma attacks, corresponding to the onset of the disease. The relationship between common, daily psychological excitants and the triggering of asthma attacks after the onset of the disease. The legitimacy of purely psychogenic asthma had been suggested (with some reserves) by authors like Hansen, Findeisen, Seropian, Graham and Mathov, based on clinical observations of BA attacks without any explanation: allergic or infectious (the two main etiologies admitted at that time, 1970 1980). Oehling [1] believed that psychological factors just like physical, chemical or neural factors play a secondary role in inducing disturbances leading to bronchial asthma. Mathov [2] expressed in 1981 a series of reserves with regard to the exclusive psychogenic etiology of asthma, and the so-called psychogenic asthma. The author invoked, just as we do, the fact that patients with psychogenic asthma had either personal or family antecedents of allergy and a high level of total IgE, suffering in fact from allergic asthma. These patients had a quasi-constant evolution of asthma in the spring or in the autumn, and did not respond favorably to anxiolytic medication. Mathov restricts the sphere already limited of purely psychogenic asthma to those cases that are triggered by psychogenic causes in the absence of a demonstrated allergy or infection. Klaper (cited by Klumbies) [3] did not find a single patient with pure psychogenic asthma out ROM. J. INTERN. MED., 2008, 46, 2, 113 118

114 I.B. Iamandescu, Alexandra Mihăilescu 2 of 100 cases, even if a psychogenic etiology was identified in 53 of these. Of the 120 patients that have been investigated in a personal study by Iamandescu (1980) [4], none had pure psychological asthma, which is triggering of asthma attacks exclusively by psychological factors. 89 of these patients had a purely allergic etiology (to dust, pollen, daphnia, moulds) confirmed by challenge testing, while 31 had intrinsic asthma. In the context of large groups of asthma with allergic or other etiology, forms of asthma that are triggered by an additional psychogenic factor could be identified. These are noted in 62.5% of hospitalized patients, most cases with a prolonged and more severe evolution of the disease, but in only 30% of light and moderately severe cases that are followed up in outpatients [4]. The percent of psychological trigger is maximum (86%) in corticodependent asthma patients [5]. To conclude, although psychological stimuli could trigger the occurrence of attacks of bronchial asthma, they are not an exclusive etiological factor [4][6] and this is in accordance with more recent opinions. While contesting a purely psychogenic bronchial asthma, it is necessary to isolate those forms of BA, either allergic or intrinsic, in which the onset of attacks is provoked also by the psychological factors. 2. INCIDENCE With regard to the incidence of psychogenic triggering of allergic asthma attacks, this varies according to the data in the literature in relation with the severity of the disease, but also with the age of the patient [7]. The percentages of old statistics vary from 8% [8] in a group of 441 patients with asthma, to 54% (Pearson, 1958) in a lot of 375 patients. More recently (1992) Richter and Dahme [9] evaluated the appreciations in this regard made by physicians (60%) and psychosomaticians (68%). Since we have examined these problems in the context of a doctoral thesis, and in several later studies (1996, 1998, 2006), we are in a position to present our personal data in the light of experience of the other authors. An analytical study presented in a paper published in 1985 tried to establish the relationship between psychological stress and the trigger of asthma attacks. We studied a sample of 120 asthma patients and two control groups including patients with psychosomatic diseases (60 patients with urticaria and 50 with digestive ulcers). All groups of patients with psychosomatic diseases were compared between them and with a group of healthy controls. The analysis of these results disclosed the following major aspects: 1) The presence of traumatic psychological events in the period preceding the first attacks of asthma was detected in approximately 66% of the asthma patients, a percentage that is significantly different statistically (p<0.01) from the lower percentage found in normal controls (42%) and the higher percentage (83%) found in the group of urticaria while patients with ulcers (70%) did not differ significantly from the one found in asthma patients. One should note that the healthy controls also had a high proportion (42%) of major psychological trauma in the previous 5 years (average of asthma s duration in the asthma patients group), a fact that was mentioned by other Romanian authors that found in a non-sampled population a similar percentage (44.6%) [10]. It appears from the above that it is not psychological stress alone that is involved in the triggering of the disease, and that a psychological resonance, provided by the patient s personality and an organic background (morpho-functional meiopragia) are also necessary to enable the psychological factor to exert its role. 2) With regard to the nature of the psychological traumatic events that have occurred months and weeks before the onset of the first asthma attacks, those that happened in the familial environment are clear in majority, especially the marital conflicts, culminating with the trauma of the divorce. 3) A detailed anamnesis was carried out in hospitalized patients on the incidence of asthma attacks occurring following emotional situations after the onset of the disease. These could be incriminated as the triggering factor in 62.5% of the subjects under study (77% of women and 55% of men), a far higher percentage than that found in ambulatory patients (30% in a previous study), although holding an intermediate position compared with the results noted in patients with ulcers (48%) and in those with urticaria (80%). We could certainly maintain that this percentage is much higher than the median incidence of asthma attacks, because only the more severe cases were hospitalized, generally intrinsic asthma cases.

3 Bronchial asthma with psychogenic trigger 115 After this study we have evidenced a significant increase (86%) of psychogenic triggering of asthma attacks in corticoid dependent patients [5]. It is possible that asthma patients with a severe evolution of the disease have all their attacks triggered by minimal stress. 4) Of the 75 patients with asthma in whom attacks were triggered by emotional factors, 80% had mentioned important psychological stress in the immediate antecedents of the onset of their condition. This should not be unexpected considering the general percentage of 51.4% of asthma patients with stress in their antecedents, and a clear correlation between receptivity to stress, before the onset of the disease, and the additional receptivity to stress due to the traumatic experience of the asthma attacks. 5) The latency time between the stress and the onset of the attacks in the 62.5% of the patients in whom asthma attacks were triggered by psychogenic causes was as follows: in 40% the attacks occurred in less than 5 minutes in 12.5% the attacks occurred between 5 and 30 minutes in 10% the attacks occurred in the following night (after periods during which the patients had not experienced a single attack). It would have been interesting to perform measures of humoral values in these patients, because this would have allowed identifying possible correlations between emotional factors and other etiological ones. These clinical observations since 1980 may be correlated with experimental data obtained by Forsythe et al. (2004) [11] (who have studied on a murine model, the effects of short and long-term distress on the bronchial inflammation), but also with previous data regarding the 2 types of response (early and late response) during type I reaction involved at onset of bronchial asthma. 3. CHARACTERISTICS OF THE SOMATIC AND PSYCHOLOGICAL TERRAIN OF PATIENTS WITH PSYCHOGENIC TRIGGERING OF BRONCHIAL ASTHMA At the conclusion of our studies, and based on the epidemiological and psychological data of these patients (Iamandescu, 1980, 1984, 1985) [4 6], it is appropriate to make the following observations: 1) Psychogenic-triggered bronchial asthma is not purely psychogenic, but also includes cases of bronchial asthma which are clearly triggered by psychological stimuli (usually stress stimuli) in the context of multiple triggers, on the background of bronchial hyperreactivity induced by allergic inflammation or by non-immunological factors. 2) The mechanisms of intervention of psychological stimuli either favor the occurrence of asthma attacks by other triggers (by summation), or induce asthma attacks per se. 3) It is not only the stress stimuli that play a triggering role, but also a series of conditioned excitants, the number of which increases with the duration of illness, such that, even patient s perception about his/her wheezing, will become a stress capable to induce patent asthma attacks [12]. 4) It seems logical to deduce that the intensity of bronchial hyperexcitability, expressed by the decreased thresholds to acetylcholine [13], could be in direct proportion with the possibility of psychogenic triggering of asthma attacks, especially because, in the final stage, efferent corticosubcortical impulses that occur in the psychological stress result in liberation of acetylcholine and other mediators (including also stress hormones ) at the level of the bronchial effector, or in alpha-adrenergic stimulation. 5) This possibility depends on the personality features leading to an increased permeability to stress. In the attempt to count the traits of stress vulnerability, identified by ourselves most often in asthma patients, we will mention firstly the data resulting from the use of the MMPI test, more easily converted into a common medical language. Thus we have encountered in the first place (practically in all our patients) anxiety, followed by paranoid features (tenacity, perseverance, stubbornness, and extreme suspiciousness), an increased introversion, emotional immaturity, obsessive and phobic tendencies, as well as elements of depression (these last were correlated by us to the somato-psychological effect of the illness). It should be noted that, in the asthma patients we have studied with the MMPI test, all the clinical scales had representatives at a higher level as compared with normal controls (the scales with the tallest peaks were Pa, Hy, Hs, D, Pt and Pd). Data obtained by us in 1980, but also in the next years, have been recently confirmed by other

116 I.B. Iamandescu, Alexandra Mihăilescu 4 authors. Thus, with regard to the anxiety, its onset triggers unconscious hyperventilation, and is certainly involved in the psychologically traumatic experience of asthma attacks. With regard to the degree of anxiety, Dirks [14], using an Asthma Symptoms Checklist, has demonstrated in several studies that panic fear traits are predictors for a series of negative aspects of the evolution of bronchial asthma, as well as excessive use of broncho-dilating medicines, difficulties of corticoid weaning, and the high probability of re-hospitalization in the following 6 months. Schmidt-Traub [15] pointed out that one of the exacerbations of anxiety-panic disorder is developed five times more in asthmatic (10%) than in controls (2%). Janson et al. [16] have demonstrated that anxiety and depression, evaluated with the HAD (Hospital Anxiety-Depression) questionnaire, are significantly higher in asthma patients who experience asthma attacks upon waking or during effort. However, these traits are not mandatory for the other categories of asthmatics, especially if they have a less severe evolution of their illness. With regard to the depression, this affective trouble is of a reactive nature, a reaction against the chronic evolution of the illness, or the prospect of new and unexpected attacks. There are also cases (see Iamandescu 1980, 1985, 1994) [4][6][17] where depression precedes (and possibly contributes to) the onset of asthma. As a rule, however, it is frequently encountered after the onset of the illness, as we ourselves have found (scale D of MMPI), and as recorded by Teiramaa (cited by Brush and Mathe [18]) with the Beck Depression Inventory. In a personal statistics [5] of 100 corticoiddependent asthma patients we have used the MMPI and found that 88 % of them were depressed. Many authors (Struck et al., Miller) [19][20] consider depression as one of the lethal risk factors in asthma patients. 6) A series of particularities that we have evidenced, and which include: the female gender, the duration of illness and the tendency to multiintricate forms of asthma, the severity of the attack (this type of psychological triggering of asthma attacks is predominant in patients that are corticodependent) (Iamandescu, 1996)[5] and certain endocrine dysfunctions (high estrogen and thyroid hormones secretion), as well as the multi-factorial triggering of the attacks (especially non-specific respiratory irritants, including physical-chemical factors and meteorological changes) (1985). 7) Sensitivity to aspirin may also be a cause of an asthmatic terrain very receptive to the psychological stress (Iamandescu, 1985). 8) Serghiescu et al. (2006) [21] have noted in a group of asthmatics with psychogenic triggering a diminished rate of cortisol response to stress compared with asthma patients without psychogenic triggering. 9) Clinical features of BAPT are supported by other studies besides those mentioned above (Iamandescu, 1998). These are the following: An obvious relationship between psychological stimuli and the onset of asthma attacks, and a psychological terrain endowed with an increased vulnerability to stress [22]. Reversibility to broncho-dilator agents, in contrast with resistance to systemic corticoid therapy; Variable response to psychotherapy and psychotropic drugs, suggesting in case of therapeutic failure the predominance of the chronic inflammation determined by other etiologic agents, different from psychological stress. 4. THERAPEUTIC APPROACH The knowledge concerning the role of psychological stress in the onset and evolution of asthma attacks as well as in the evolution of the illness (including elements such as the frequency and severity of the attacks, or the symptoms occurring between the attacks) has certainly prophylactic implications in the first place. a) Psychotherapeutical approach. The asthma patient, when informed on the risks represented by psychological stresses for his disease could in some cases prevent the occurrence of stress situations, or reduce their intensity. Between the most frequent and severe psychological stresses one should count the panic experienced by the patients at the onset of the asthma attack, and certainly during the peak of the attack. Thus, a nonmedicinal antidote against psychological stress is the relaxation psycho-therapeutic methods. Simple supportive psychotherapy is at ease to every physician that treats asthma patients. Besides its two fundamental sides encouragement and

5 Bronchial asthma with psychogenic trigger 117 relaxation (discharge of psychological tension) of the patients includes a series of measures with guiding role, regarding compliance to treatment, change of noxious behaviors for the disease (smoking, walks in allergen rich areas, use of drugs that produce or worsen asthma, etc.). These measures are integrated into the larger frame of asthmatic patient s education. It is important to stress out the fact that a well informed patient (about his/her disease s problems) is a powerful human being (paraphrasing the saying about value of information). The achievements of such campaigns against asthma are resulting (Haachtela et al., 2001)[23] in change of prevalence from severe persistent asthma to moderate asthma from 40 to 20%, reduction of hospital admission with 50% as the same percent regarding reduction for annual medical costs. b) Psychopharmacological treatment in asthma patients. With regard to psychotropic medication used in bronchial asthma we have to summarize several concluding observations, accrued over time, including in our own experience caring for asthma patients (Iamandescu, 1980)[4]. The following therapeutic attitudes are traditional: (1) the administration of psychotropic drugs, both between attacks and cautiously during it, dominated as a rule, by anxiety (although with possibilities for breathing assistance); (2) the use of mild sedation for the prevention of secondary psychological excitatory effects induced by bronchodilator medication (xanthines and sympathomymetics). Treatment of depressive and anxiety syndromes associated to bronchial asthma, in most of the cases these being induces (secondary) disturbances in the course of the illness. Antidepressants have therapeutic value in asthma [24]. Antidepressants may have a therapeutic role in asthma by supressing proinflammatory cytokines and preventing their brain effects. They also interfere with cholinergic and serotoninergic pathways, both centrally and peripherally. Most antidepressants also induce adaptive changes in central monoaminergic neurotransmission, which itself might modulate immune reactivity [25]. A newer antidepressant in the tetracyclic antidepressant class, mirtazapine, has an additional antihistaminic effect, and the respiratory side-effects are rare. Antidepressants that combine anti -inflammatory and bronchodilating properties with minor side effects like tianeptine [26][27]could turn out to be promising drugs in treating asthma. Future development of antidepressant drugs based on these observations may actually result in new indications for antidepressants. They could also help in understanding some common pathophysiological mechanisms existing between asthma and depression. Autorii prezintă cercetări personale în acord cu alte date din literatură care contestă existenţa unui astm bronşic pur psihogen aşa cum se considera în urmă cu 3 5 decenii. Deşi stimulii psihologici pot să declanşeze atacurile de astm bronşic, aceştia nu sunt un factor etiologic exclusiv (Iamandescu, 1980, 1985). În contextul studiului unor grupuri mari de pacienţi cu astm cu etiologie alergică, sau de alt fel, formele de astm care sunt declanşate de un factor adiţional psihogenic au putut fi identificate. Acest lucru a fost observat la 62,5% dintre pacienţii spitalizaţi, majoritatea cazurilor cu o evoluţie prelungită şi o mult mai severă evoluţie a bolii, dar numai la 30% dintre cazurile uşoare şi moderate care sunt urmărite în ambulator (Iamandescu, 1980, 1984). Procentul de trigger psihogen este maxim (86%) la pacienţii cu astm corticodependent (Iamandescu, 1996). Fondul somatic şi psihologic al pacienţilor cu astm cu trigger psihogen este reprezentat de următorii factori: 1) o relaţie evidentă între stimulul psihologic şi debutul atacului bronşic, şi un teren psihologic înzestrat cu o vulnerabilitate la stress crescută. Aceşti pacienţi au o rată scăzută de răspuns cortizolic la stress comparativ cu pacienţii astmatici fără trigger psihogen; 2) reversibilitatea la agenţi bronhodilatatori, în contrast cu rezistenţa la terapia sistemică cortizonică; 3) sensibilitate la aspirină; 4) disfuncţii endocrine (secreţie crescută de estrogeni şi hormoni tiroidieni); 5) declanşare multifactorială a atacurilor (în special iritanţi respiratori nespecifici, inclusiv factori fizico-chimici şi schimbări meteorologice); 6) răspuns

118 I.B. Iamandescu, Alexandra Mihăilescu 6 variabil la psihoterapie şi medicamente psihotrope, sugerând în cazul eşecului terapeutic predominanţa unei inflamaţii cronice determinate de alţi agenţi etiologici, diferiţi de stresul psihic. Corresponding author: Prof. I.B. Iamandescu, 35, Banu Manta, 011223 Bucharest Colentina Hospital, 19 21, Şos. Ştefan cel Mare 020125 Bucharest, Romania E-mail: iamandb@yahoo.com REFERENCES 1. OEHLING A., Immunological aspects of the pathogenesis of bronchial asthma. Allergol. et Immunopathol., 1982, 10(6): 417 22. 2. MATHOV E., New classification of bronchial asthma. Alergol. et Immunopathol. (Pamplona Spain), 1981, 28(3): 241 245. 3. KLUMBIES G., Psychoterapie beim Asthma Bronchiale eine Einschatzung der Indikationen und Erfolgsaussichten. Allergie und Asthma, 1963, 9: 126. 4. IAMANDESCU I.B., Corelaţii psiho-somatice în astmul bronşic. 1980, IMF Bucureşti. 5. IAMANDESCU I.B., Mecanisme psihoendocrine invocate în evoluţia astmului bronşic cu trigger psihogen pe baza unor studii asupra astmaticilor corticodependenţi. In: Cong. Nation. I. Psihoneuroendocrinologie. 1996, Bucureşti. 6. IAMANDESCU I.B., Rolul factorilor psihoemoţionali în etiopatogenia astmului bronşic. Viaţa Medicală, 1985, 1: 34 39. 7. WEINER, P. et al., Characteristics of asthma in the elderly. Eur. Respir. J., 1998, 12(3): 564 568. 8. REES L., Aetiological factors in asthma. Hosp. Med., 1989, 9: 1101 1012. 8bis. PEARSON R.S.B., Natural history of asthma. Acta Allergol., 1958, 12: 277. 9. RICHTER R. and DAHME B., High risk asthmatics: Psychological aspects. In: Highlights in Allergy and Clinical Immunology, B. Wuthrich, Editor, 1992, Hogrefe and Huber Bern. 10. PREDESCU V. and NICA UDANGIU St., Epidemiologia nevrozelor în populaţia urbană. Neurologia, 1976. 21(3): 169 178. 11. FORSYTHE P. et al., Opposing effects of short- and long-term stress on airway inflammation. Am. J. Respir. Crit. Care Med., 2004, 169(2): 220 6. 12. KINSMAN, R.A. et al., Observations on Patterns of Subjective Symptomatology of Acute Asthma. Psychosom. Med., 1974, 36(2): 129 143. 13. TIFFENEAU R., Examen pulmonaire de l asthmatique. Presse Medicale, 1960, 23: 864 875. 14. DIRKS, J.F., N.F. JONES, KINSMAN R.A., Panic-fear: a personality dimension related to intractability in asthma. Psychosom. Med., 1977, 39(2): 120 126. 15. SCHMIDT-TRAUB S., The psychoimmunological network of panic disorders, agoraphobia and allergic reactions. Thorax 1995, 52(2): 123 128. 16. JANSON C. et al., Anxiety and Depression in Relation to Respiratory Symptoms and Asthma. Amer. J. Respir. Crit. Care Med., 1994, 149: 903 934. 17. IAMANDESCU I.B., COCULESCU M., Acute and chronic stress in etiopathogeny of allergic asthma. Allergy Clin. Immunol. News, 1994, 2(Suppl. Abstracts): p. 537. 18. BRUSH J., MATHE A., Psychiatric aspects in Bronchial Asthma-Mechanisms and Therapeutics, t.e. Weiss E. and Stein M., Editor, 1993, Little-Brown: Boston (Toronto) London, 1121 1131. 19. STRUCK R.C. et al., Physiologic and psychological characteristics associated with deaths due to asthma in childhood. JAMA 1985, 254: 1193 8.. 20. MILLER B.D., Depression and asthma: a potential lethal mixture. J. Allergy Clin. Immunol., 1987, 80: 481 6. 21. SERGHIESCU I. et al., Salivary cortisol level dynamics after an experimental psycho-social stress test in asthmatics. XXVth Congress of the European Academy of Allergology, 2006, Vienna: abstract no. 1167, Poster session Clinical and Occupational Asthma. 22. IAMANDESCU I.B., STANCULESCU (MIHAILESCU) A. et al., Correlations between vulnerability to stress and quality of life in asthma patients. XXIInd Congress of the European Academy of Allergology and Clinical Immunology, 2003, Paris. 23. HAACHTELA T. et al., Working Group of the Asthma Programme in Finland 1994 2004. Asthma programme in Finland: a community problem needs community solutions. Thorax, 2001, 56: 806 814. 24. VALENCA A.M. et al., The relationship between the severity of asthma and comorbidities with anxiety and depressive disorders. Rev. Bras. Psiquiatr., 2006, 28(3): p. 206 8. 25. KROMMYDAS G. et al., Therapeutic value of antidepressants in asthma. Med. Hypotheses, 2004, 64: p. 938 40. 26. LECHIN F. et al., Neuropharmacologic treatment of bronchial asthma with the antidepressant tianeptine: a double-blind, crossover placebo-controlled study. N. Clin. Pharmacol. Ther., 1998, 64(2): 223 32. 27. LECHIN F., VAN DER DIJS B., and LECHIN A.E., Tianeptine: a new exploratory therapy for asthma. Chest., 2004, 125(1): 348 9. Received March 10, 2008