This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buske-Kirschbaum, A. Articles by Hellhammer, D. Search for Related Content PubMed PubMed Citation Articles by Buske-Kirschbaum, A. Articles by Hellhammer, D. Related Collections Neuroendocrine Pulmonary Stress and Coping

Blunted Cortisol Responses to Psychosocial Stress in Asthmatic Children: A General Feature of Atopic Disease?

From the Department of Psychobiology, University of Trier (A.B.-K., D.H.), Trier, Germany; Department of Child Psychiatry, Mutterhaus der Borromäerinnen (K. von-A.), Trier, Germany; and Department of Pediatrics, Mutterhaus der Borromäerinnen (S.K., S.W., W.R.), Trier, Germany.

Address reprint requests to: Angelika Buske-Kirschbaum, PhD, Center for Psychobiological and Psychosomatic Research, University of Trier, Universitätsring 15, D-54286 Trier, Germany. E-mail: buske{at}uni-trier.de

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
OBJECTIVE: Atopy is defined by the individual predisposition to develop a group of inflammatory disorders in response to certain food or environmental substances that are otherwise innocuous for the host. In previous studies we could demonstrate a reduced responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis to psychosocial stress in young and adult patients with atopic dermatitis (AD), a chronic atopic skin disorder. With respect to the important immunoregulatory role of the HPA axis, especially under stress, this observation could be of clinical relevance and may at least partly explain stress-induced exacerbation of AD. The present study was designed to investigate whether attenuated responsiveness of the HPA axis to stress represents a characteristic feature of AD or whether it can also be found in other chronic manifestations of atopy.

METHODS: Children (aged 7–12) with allergic asthma (AA; N = 17) and age- and sex-matched healthy controls (N = 18) were exposed to the "Trier Social Stress Test for Children"(TSST-C), which mainly consists of a free speech and mental arithmetic tasks in front of an audience. Salivary cortisol was measured in ten-minute intervals before and after the TSST-C, while heart rate was monitored continuously. In addition, early morning cortisol levels (after awakening, +10, +20, +30 minutes) were assessed on three consecutive days.

RESULTS: Data analysis yielded a significant increase of cortisol concentrations (F (9297)= 16.79; p < .001) and heart rates (F(32,992)= 9.16; p < .001) after the stressor with no between-group difference in heart rate responses. However, AA children showed a significantly blunted cortisol response to the TSST-C when compared with the control group (F(9297)= 2.95; p < .01). Awakening in the morning was accompanied by a significant rise of cortisol levels on all three experimental days in AA and control subjects (all p < .001) that was not different between the two groups.

CONCLUSIONS: These findings suggest that a blunted adrenocortical response to stress may represent a common feature of chronic allergic inflammatory processes that may be relevant in different forms of chronic manifestation of atopy.

Key Words: allergic asthma, • atopy, • hypothalamus-pituitary-adrenal (HPA) axis, • stress.

Abbreviations: AA = allergic asthma; AD = atopic dermatitis; HPA = hypothalamus-pituitary-adrenal; TSST-C = Trier Social Stress Test for Children

	INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
Atopy is a genetically and environmentally determined condition predisposing to different forms of atopy such as atopic dermatitis (AD), allergic asthma (AA), and allergic rhinitis (AR) (1). The main symptoms of AA are episodic occurrence of coughing, dyspnea, wheezing, and chest tightness, while AD is characterized by dry skin, erythematous papules, lichenification, and an intense pruritus (2, 3). AR is characterized by nasal congestion, sneezing, and itching of the eyes, nose, and throat (4). Atopic disorders affect approximately 20 to 30% of the general population and there is broad consensus that the prevalence of atopy has significantly increased in western countries (5). Due to the increasing prevalence, the physical and psychological suffering of the patients, and the considerable financial burden on the community, there is a growing interest in a better understanding of the pathophysiology of the disease (6).

Multiple genetic and environmental factors (eg, climate, allergens, microbial organisms such as Staphylococcus aureus) are thought to be critical for the determination of atopic conditions (7). Research in the past decade further indicates that immunoregulatory abnormalities play a pivotal role in the pathophysiology of atopic disease. The atopic immune system is characterized by a hypersecretion of immunoglobulin-E (IgE) that stimulates the release of proinflammatory mediators (ie, histamine, leukotriene) by mast cells and basophils eliciting the immediate hypersensitivity reactions of atopic conditions. Further, IgE enables allergen processing and subsequent activation of CD4⁺T helper type 2 (TH₂) lymphocytes. TH2 cells orchestrate the allergic inflammation by secretion of a series of cytokines, mainly interleukin-4 (IL-4) and interleukin-5 (IL-5). Both cytokines are key molecules inducing chronic atopy. IL-4 is the major factor regulating IgE production by B cells while IL-5 induces eosinophilia known to be responsible for tissue damage seen in AD and in AA (8, 9) .

In addition to these immunological abnormalities, our group has demonstrated reduced cortisol levels in response to psychosocial stress in AD children pointing to a dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis (10). It is well accepted that the HPA axis represents a major immunoregulatory system that plays an important role in balancing the immune response especially under stressful conditions. Animal data strongly suggest that an appropriate responsiveness of the HPA axis may be necessary to control immunological processes, and to prevent an immune response from reaching a level that may damage the host (11, 12). Based on these findings it may be assumed that the failure of AD patients to generate a sufficient glucocorticoid response to acute psychosocial stress may be pathologically significant. Thus it could be postulated that a blunted HPA axis response may increase the risk for aberrant immune processes (eg, an ongoing allergic inflammatory reaction especially under stressful conditions). This model agrees with clinical observations suggesting that stress is closely related to exacerbation of skin atopy (13, 14). In fact, in a more recent study we observed that attenuated cortisol and ACTH responses to stress in adult AD sufferers are accompanied by distinct atopy-relevant immunological changes (ie, increased IgE-levels, decreased IL-4 and elevated IFN- levels, increased eosinophil number) and exacerbation of symptomatology (15, 16).

The specific goal of the present study was to investigate whether attenuated responsiveness of the HPA axis represents a characteristic feature of AD or whether it may also be found in other chronic manifestations of atopy.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
Subjects
Children with asthma (N = 17; 8 females, 9 males) aged 7 to 12 years (mean age: 11.8 ± 1.9 years) were recruited in the allergy unit of the Department of Pediatrics of the General Hospital "Mutterhaus der Borromäerinnen" in Trier. They were informed that "the effect of psychosocial stress on physiological processes in childhood asthma should be investigated." All children were classified as having moderate allergic asthma as indicated by clinical history and physical examination by the pediatrician. The children showed AA symptoms occasionally and in these cases bronchodilator use was recommended. The children’s minimum history of asthma was 5 years. To ensure that all AA children were suffering from allergic asthma, they had to bring their "allergy passports". In Germany, this document indicates that the bearer has tested positive for allergy and allergic symptoms, and provoking allergens are listed. Based on the parents’ reports seven children were on sympathomimetics, four on anticholinergics, four on theophylline, and 12 on cromoglycine. Because there are some reports indicating that steroid treatment has an impact on HPA axis functioning (17), AA children requiring current steroid medication were excluded from the study. All children had been without steroid treatment for at least 3 months.

To establish an appropriately matched control group in terms of age, sex, and educational background, the asthma children were asked to bring their best same-sex friend. The control group included 18 children aged 7 to 13 years (9 males; 9 females; mean age: 11.3 ± 2.0 years). None of the control children had ever suffered from atopy or had a family history of atopy. Control children who had any current or chronic medical problem were excluded from the study. The two groups did not differ with respect to age, sex, or educational status (school type)(all p values > .5).

Experimental Protocol
Experimental sessions were run between 3:00 PM and 4:30 PM with one asthmatic and one control child participating per day.

After arriving, a questionnaire assessing socioeconomic and medical data were completed by the accompanying parent of the children. After having completed the questionnaire, the parent left the experimental setting. After 45 minutes the children were guided to the experimental room and confronted with the "Trier Social Stress Test for Children" (TSST-C), which has been described and evaluated elsewhere (10). Briefly, in an experimental room, a tape recorder, a video camera, and a microphone were installed. Before the beginning of the stress test, the children heard the beginning of a story and were asked to finish the story in a manner as exciting as possible in front of an audience (two adults). The children were prompted to perform better than the other participants. They then had a rest period of 10 minutes to prepare the speech. After the preparation period the children were exposed 4 minutes to the speaking task. The committee then asked the children to serially subtract the number 7 from 758 (7–10 years) or the number 13 from 1023 (11–12 years) as fast and as accurately as possible. On every failure, the subjects had to restart. The TSST-C represents an adapted version of the "Trier Social Stress Test" (TSST) that has been developed and evaluated in our laboratory (18).

The TSST-C was followed by a 10-minute feedback period in which the children had the opportunity to ask questions. Importantly, all children were told that she or he did an excellent job in their free speech and that he or she performed as well as all the other subjects. Finally, the children completed a 10-item, 5-point manipulation check of how stressfully they experienced the free speech and the mental arithmetic tasks. In addition, a visual analogue scale asking for the momentary well being of the children ("How do you feel at the moment?" [bad, o.k., fine, very good, excellent]) was completed before and after the TSST-C.

The experimental protocol was approved by the local ethics committee, and written informed consent was obtained from the subjects and their parents before participating in the experiment. The children received a compensation of DM 50 on completion of the experimental protocol.

Cortisol Analysis
To assess cortisol levels, saliva samples were obtained 35 (t1), 25 (t2), 15 (t3), and 1 (t4) minute(s) before and 1 (t5), 10 (t6), 20 (t7), 30 (t8), 40 (t9) and 60 (t10) minute(s) after the TSST-C using the Salivette sampling device (Sarstedt, Rommelsdorf, Germany). Additionally, saliva cortisol was determined in the morning on three consecutive days (one day before, and one and two days after the TSST), on awakening and 10, 20, and 30 minutes after waking up, respectively.

For analysis, the samples were thawed and spun at 3000 rpm for 5 minutes to obtain a clear, watery supernatant with low viscosity. For cortisol determination 100 µl saliva were removed for duplicate analysis of cortisol levels using a time-resolved fluorescence immunoassay (DELFIA) that has been previously described in detail (19). The lower detection limit of this assay is 0.43 nmol/l with interassay and intraassay coefficients of variance of < 10% across the expected range of cortisol levels.

Heart Rates
Heart rates were monitored continuously at 1-minute intervals with EKC precision using a wireless signal transmission device (Sport Profi, Polar Instruments, Germany).

Statistical Analysis
For all physiological parameters (cortisol, morning cortisol, heart rates), ANOVAs were computed on the absolute levels to the TSST-C for stress-induced alterations (‘time-effect’), overall differences between AA patients and controls (‘group-effect’), or different response profiles between the two groups (‘group x time effects’). Socioeconomic status, family history, and educational background of the two groups were compared by ² tests. Furthermore, Spearman rank correlations were computed for assessment of associations between subjective stress ratings and cortisol and heart rate responses, respectively. The cortisol response to the TSST was defined as the increase from base-line level (1 minute before the TSST) to the individual peak level (cort_diff= cort peak - cort t4). Accordingly, the heart rate response was defined as the increase from the mean heart rate during the rest period to the mean heart rate during the TSST (heart rate_diff=(mean heart rate t19 to t28) - (mean heart rate t1 to t5).

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
Analysis of variance of the cortisol data on the experimental day yielded a significant time (F (9,297)= 16.79; p < .0001) and a significant group x time effect (F(9,297)= 2.95; p < .01). As illustrated in Figure 1, subjects showed significantly increased cortisol levels when exposed to the TSST-C. However, while there was no difference in basal cortisol concentrations, a significantly reduced cortisol response to the TSST-C was found in AA children 10, 20, and 30 minutes after being stressed (Newman Keuls tests; p < .001). The blunted cortisol response to the TSST-C in AA children was also reflected by a significantly diminished area under the response curve (AUC) in the patient group (t = 2.22; df = 33; p = .03; see insert Fig. 1).

View larger version (21K): [in this window] [in a new window]   Fig. 1. Cortisol responses to psychosocial stress ("Trier Social Stress-Test"; TSST) in children with allergic asthma (AA) and nonatopic control children. Figure insert: cortisol response (area under the curve, AUC) to the TSST in AA children and nonatopic controls. *p < .05.

View larger version (32K): [in this window] [in a new window]   Fig. 2. Heart rate responses to psychosocial stress ("Trier Social Stress-Test"; TSST) in children with allergic asthma (AA) and nonatopic control children.

View larger version (13K): [in this window] [in a new window]   Fig. 3. Morning cortisol levels after waking up and 10, 20, and 30 minutes after awakening one day before the TSST (A) and one day (B) and two days (C) after the TSST.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
The specific goal of the present study was to investigate whether an attenuated responsiveness of the HPA axis as previously described in young and adult AD sufferers (10, 15) could also be observed in other atopic conditions. It was found that children with AA, a chronic bronchial inflammatory condition of the "atopic triad" show significantly attenuated cortisol responses to psychosocial stress. This finding suggests that hyporesponsiveness of the HPA axis in fact may represent a general feature of chronic manifestation of atopy. Basal cortisol concentrations and morning cortisol levels did not differ between AA children and nonatopic controls. This parallels previous reports of our group (10, 15) and others (20) indicating that a dysfunction of the HPA axis in atopy becomes evident only under stimulated conditions. It may be argued, however, that the attenuated cortisol responses found in our AA children may simply reflect a consequence of past steroid treatment. In fact, there is evidence that a prolonged inhalative steroid medication may lead to impaired HPA axis reactivity (21). It should be noted, however, that a suppressive effect on HPA axis functioning was detected in asthmatics with high-dose inhaled steroid (budesonide) therapy (17) whereas no impairment of the HPA axis response was found at doses recommended for clinical use (22). Additionally, after analyzing 50 studies investigating the effect of inhaled steroid treatment on HPA axis function, Chrousos and Harris (23) concluded that chronic administration of inhalative steroids in clinically recommended doses does not endanger the functioning of the HPA axis. Thus, it can be assumed that the hyporesponsive HPA axis observed in our AA children (suffering from moderate, asymptotic asthma and being without steroid medication for at least 3 months) was not due to previous glucocorticoid therapy. Finally, there is evidence that HPA axis functioning seems to be normal in patients with intrinsic asthma (24). This finding further supports the idea that HPA axis dysfunction as we have found it in our patient group probably does not reflect just a nonspecific phenomenon linked to asthma therapy. Alternatively, it may be speculated that a specific personality profile (ie, high extroversion, depression, anxiety, or aggressiveness) as it has been described in asthmatics (25, 26) may render the individual more vulnerable to stress leading to a potentially altered biological stress response. However, no significant difference was observed between AA and control children in the perceived stress of the TSST-C and how their individual well being was affected by the stressor. These considerations support the idea that chronic manifestation of atopy, regardless of the target organ affected, may be associated with reduced responsiveness of the HPA axis.

The finding of an aberrant HPA axis functioning in asthmatics may be of clinical relevance. It is well accepted that a hyporesponsive HPA axis is linked to increased susceptibility to chronic inflammatory disorders (27–29). In this model it is assumed that the failure to render an adequate (immunoregulatory) HPA axis response increases the risk for aberrant immune functions (eg, an exaggerated ongoing inflammation) that may lead to the aggravation and chronification of inflammatory disease. This may be especially relevant under stressful conditions when both systems, the HPA axis and the immune system, are activated. In fact, a growing number of reports suggest that AA can be exacerbated by stress. Various acute stressors such as watching stressful film sequences (30, 31) or being confronted with stressful interactions (32) has been found to worsen respiratory capacity in AA patients. Moreover, it was reported that asthmatics reporting more negative life events and low levels of social support experience more asthmatic episodes (33). Most recently, Liu et al. (34) highlighted a potential mechanism that may link stress and asthma symptomatology. They demonstrated that during a stressful final exam, antigen challenge resulted in significantly increased airway eosinophilia in students suffering from moderate asthma. These data support the possibility that in asthmatics, stress can lead to an (aberrant) immunological profile (ie, airway eosinophilia) that may promote an inflammatory response.

In conclusion, this study extends previous findings of attenuated cortisol responses to stress in (skin) atopy suggesting that a blunted HPA axis responsiveness may be generally linked to the chronic atopic condition. The potential clinical significance of a reduced cortisol response in the stress-immune network described for AA or AD patients is still speculative and remains to be evaluated.

	ACKNOWLEDGMENTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
This work was supported by the Deutsche Forschungsgemeinschaft (He 1013/13-1). We thank Mrs. Rummel-Frühauf for her excellent technical help.

Received for publication September 3, 2002.

	REFERENCES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION ACKNOWLEDGMENTS REFERENCES

 

1. Nimmagadda SR, Evans R. Allergy: etiology and epidemiology. Pediatr Rev 1999; 20: 111–15.
2. Muro S, Minshall EM, Hamid QA. The pathology of chronic asthma. Clin Chest Med 2000; 21: 2225–44.
3. Werfel T, Kapp A. Environmental and other major provocation factors in atopic dermatitis. Allergy 1998; 53: 731–39.[Medline]
4. Schoenwetter WF. Allergic rhinitis: epidemiology and natural history. Allergy Asthma Proc 2000; 21: 1–6.[Medline]
5. Ring J, Krämer U, Schäfer T, Behrendt H. Why are allergies increasing. Curr Opin Immunol 2001; 13: 701–08.[CrossRef][Medline]
6. Van Moerbeke D. European allergy white paper. Allergic diseases as a public health problem in Europe. Brussels: UCB Institute of Allergy; 1997.
7. Casolaro V, Georas SN, Song Z, Ono SJ. Biology and genetics of atopic disease. Curr Opin Immunol 1996; 8: 796–803.[CrossRef][Medline]
8. Leung DYM. Pathogenesis of atopic dermatitis. J Allergy Clin Immunol 1999; 104: S99–S108.[CrossRef][Medline]
9. Renauld JC. New insights into the role of cytokines in asthma. J Clin Pathol 2001; 54: 577–89.[Abstract/Free Full Text]
10. Buske-Kirschbaum A, Jobst S, Wustmans A, Kirschbaum C, Rauh W, Hellhammer DH. Attenuated free cortisol response to psychosocial stress in children with atopic dermatitis. Psychosom Med 1997; 59: 419–26.[Abstract/Free Full Text]
11. Sternberg EM, Hill JM, Chroussos GP, Kamilaris T, Listwak SJ, Gold PW, Wilder RL. Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats. Proc Natl Acad Sci USA 1989; 86: 2374–78.[Abstract/Free Full Text]
12. Elenkov IJ, Chrousos GP. Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease. TEM 1999; 10: 359–68.[CrossRef][Medline]
13. Buske-Kirschbaum A, Geiben A, Hellhammer D. Psychobiological aspects of atopic dermatitis. Psychother Psychosom 2001; 70: 6–16.[CrossRef][Medline]
14. Tausk FA. Stress and the skin. Arch Dermatol 2001; 137: 78–82.[Free Full Text]
15. Buske-Kirschbaum A, Geiben A, Höllig H, Morschhäuser E, Hellhammer D. Altered responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic adrenomedullary system (SAMS) to stress in patients with atopic dermatitis. J Clin Endocrinol Metabol. In press.
16. Buske-Kirschbaum A, Geiben A, Höllig H, Morschhäuser DH. Stress-induced immunomodulation is altered in patients with atopic dermatitis. J Neuroimmunol 2002; 129: 161–67.[CrossRef][Medline]
17. Clark DJ, Lipworth BJ. Evaluation of corticotropin-releasing factor stimulation and basal markers of hypothalamic-pituitary-adrenal axis suppression in asthmatic patients. Chest 1997; 112: 1248–52.[Abstract/Free Full Text]
18. Kirschbaum C, Pirke KM, Hellhammer DH. The ‘Trier Social Stress Test’–a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiol 1993; 28: 76–81.
19. Dressendörfer RA, Kirschbaum C, Rohde W, Stahl F, Strasburger CJ. Synthesis of a cortisol-biotin conjugate and evaluation as tracer in an immunoassay for salivary cortisol measurement. J Steroid Biochem Mol Biol 1990; 43: 683–92.
20. Rupprecht M, Rupprecht R, Koch HU, Haack D, Müller OA, Hornstein OP. Mulllltihormonal response to dexamethasone: a study in atopic dermatitis and normal controls. Acta Derm Venereol 1990; 71: 214–18.
21. Wolthers OD, Honour JW. Measures of hypothalamic-pituitary-adrenal function in patients with asthma treated with inhaled glucocorticoids: clinical and research implications. J Asthma 1999; 36: 477–86.[Medline]
22. Aaronson D, Kaiser H, Dockhorn R, Findlay S, Korenblat P, Thorsson L, Kallen A. Effects of budesonide by means of the Turbuhaler on the hypothalamus-pituitary-adrenal axis in asthmatic subjects: a dose-response study. J Allergy Clin Immunol 1998; 101: 312–19.[CrossRef][Medline]
23. Chrousos GP, Harris AG. Hypothalamus-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. 2. Review of the literature. Neuroimmunomodulation 1998; 5: 288–308.[CrossRef][Medline]
24. Collins JV, Bellamy D, Britton MG, Townsend J, Brown DJ. Hypothalamo-pituitary-adrenal function in intrinsic non-atopic asthma. Thorax 1975; 30: 578–81.[Abstract/Free Full Text]
25. Mascia A, Frank S, Berkman A, Stern L, Lampl L, Davies M, Yeager T, Birmaaher B, Chieco E. Mortality versus improvement in severe chronic asthma: physiological and psychological factors. Annals Allergy 1989; 62: 311–17.
26. Huovinen E, Kaprio J, Koskenvuo M. Asthma in relation to personality traits, life satisfaction, and stress: a prospective study among 11,000 adults. Allergy 2001; 56: 971–77.[CrossRef][Medline]
27. Chroussos GP. Stress, chronic inflammation, and emotional and physical well-being: concurrent effects and chronic sequelae. J Allergy Clin Immunol 2000; 106: S275–91.[CrossRef][Medline]
28. Sternberg EM, Hill JM, Chroussos GP, Kamilaris T, Listwak SJ, Gold PW, Wilder RL. Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats. Proc Natl Acad Sci USA 1989; 86: 2374–78.
29. Elenkov IJ, Chrousos GP. Stress hormones, Th1/Th2 patterns, pro/antiinflammatory cytokines and susceptibility to disease. Trends Endocrinol Metab 1999; 10: 359–68.
30. Beggs PJ, Curson PH. An integrated environmental asthma model. Arch Environ Health 1995; 50: 87–94.[Medline]
31. Ritz T, Steptoe A, DeWilde S, Costa M. Emotions and stress increase respiratory resistance in asthma. Psychosom Med 2000; 62: 401–12.[Abstract/Free Full Text]
32. Kolbe J, Garrett J, Vamos M, Rea HH. Influences on trends in asthma morbidity and mortality: the New Zealand experience. Chest 1994; 106: 211S–15S.[Free Full Text]
33. Smith A, Nicholson K. Psychosocial factors, respiratory viruses and exacerbation of asthma. Psychoneuroendocrinol 2001; 26: 411–20.[CrossRef][Medline]
34. Liu YL, Coe CL, Swenson CA, Kelly EA, Kita H, Busse WW. School examinations enhance airway inflammation to antigen challenge. Am J Respir Crit Care Med 2002; 165: 1062–67.[Abstract/Free Full Text]

This article has been cited by other articles:

				A. L. Kozyrskyj, G. E. Kendall, S. R. Zubrick, J. P. Newnham, and P. D. Sly Frequent nocturnal awakening in early life is associated with nonatopic asthma in children Eur. Respir. J., December 1, 2009; 34(6): 1288 - 1295. [Abstract] [Full Text] [PDF]

				M. Tegethoff, C. Pryce, and G. Meinlschmidt Effects of Intrauterine Exposure to Synthetic Glucocorticoids on Fetal, Newborn, and Infant Hypothalamic-Pituitary-Adrenal Axis Function in Humans: A Systematic Review Endocr. Rev., December 1, 2009; 30(7): 753 - 789. [Abstract] [Full Text] [PDF]

				A. E Hipwell, K. Keenan, and A. Marsland Exploring Psychophysiological Markers of Vulnerability to Somatic Illnesses in Females J. Pediatr. Psychol., October 1, 2009; 34(9): 1030 - 1039. [Abstract] [Full Text] [PDF]

				F. S. Dhabhar A hassle a day may keep the pathogens away: The fight-or-flight stress response and the augmentation of immune function Integr. Comp. Biol., September 1, 2009; 49(3): 215 - 236. [Abstract] [Full Text] [PDF]

				R. T. Cohen, G. J. Canino, H. R. Bird, and J. C. Celedon Violence, Abuse, and Asthma in Puerto Rican Children Am. J. Respir. Crit. Care Med., September 1, 2008; 178(5): 453 - 459. [Abstract] [Full Text] [PDF]

				G. P. Chrousos, L. O'Dowd, T. Uryniak, B. Simpson, F. Casty, and M. Goldman Basal and Cosyntropin-Stimulated Plasma Cortisol Concentrations, as Measured by High-Performance Liquid Chromatography, in Children Aged 5 Months to Younger than 6 Years J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2125 - 2129. [Abstract] [Full Text] [PDF]

				Y. Chida, N. Sudo, J. Sonoda, T. Hiramoto, and C. Kubo Early-Life Psychological Stress Exacerbates Adult Mouse Asthma via the Hypothalamus-Pituitary-Adrenal Axis Am. J. Respir. Crit. Care Med., February 15, 2007; 175(4): 316 - 322. [Abstract] [Full Text] [PDF]

				T. Kikusui, J. T Winslow, and Y. Mori Social buffering: relief from stress and anxiety Phil Trans R Soc B, December 29, 2006; 361(1476): 2215 - 2228. [Abstract] [Full Text] [PDF]

				M. A. Rosenkranz, W. W. Busse, T. Johnstone, C. A. Swenson, G. M. Crisafi, M. M. Jackson, J. A. Bosch, J. F. Sheridan, and R. J. Davidson From The Cover: Neural circuitry underlying the interaction between emotion and asthma symptom exacerbation PNAS, September 13, 2005; 102(37): 13319 - 13324. [Abstract] [Full Text] [PDF]

				A. S. Kaugars, M. D. Klinnert, and B. G. Bender Family Influences on Pediatric Asthma J. Pediatr. Psychol., October 1, 2004; 29(7): 475 - 491. [Abstract] [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buske-Kirschbaum, A. Articles by Hellhammer, D. Search for Related Content PubMed PubMed Citation Articles by Buske-Kirschbaum, A. Articles by Hellhammer, D. Related Collections Neuroendocrine Pulmonary Stress and Coping