Login | Register

Comparison of Immune Reactivity to Respiratory Challenges in Asthmatics with and without Panic Disorder


Comparison of Immune Reactivity to Respiratory Challenges in Asthmatics with and without Panic Disorder

Elhalwi, Alexandre (2014) Comparison of Immune Reactivity to Respiratory Challenges in Asthmatics with and without Panic Disorder. Masters thesis, Concordia University.

Text (application/pdf)
Elhalwi_MSc_F2014.pdf - Accepted Version
Available under License Spectrum Terms of Access.


Asthma and panic disorder (PD) are highly comorbid conditions. The objective of this study was to examine if PD altered immune reactivity in asthmatics to two acute respiratory stress challenges. We hypothesized that asthmatics with PD would have increased proportions of sputum eosinophils compared to asthmatics without PD in reaction to both challenges.

Eleven participants (7 PD, 4 non-PD) inhaled methacholine (which produces an asthma attack) on a first day, and on a second, two gases in randomized order: compressed air and a 35% carbon dioxide (CO2) solution (the latter produces a ‘simulated’ panic attack). Following each challenge, we induced sputum to assess immune cell profiles.

ANCOVA-like GLMs demonstrated that the PD group had a significantly lower proportion of sputum lymphocytes (β=-0.75, 95% CIs = -1.30–0.20) than the non-PD group in response to methacholine. A trend also emerged for the PD group reacting with more eosinophils (β=5.03, 95% CIs = -0.73–10.79). The presence of PD conferred no effect on neutrophils (β=-11.72, 95% CIs = -34.64–11.18) or macrophages (β=0.10, 95% CIs = -22.63–22.82). Analyses did not reveal a significant effect of PD on immune reactivity to CO2.

PD appears to influence immunological responses in asthmatics by decreasing the proportion of sputum lymphocytes following a methacholine challenge, but does not seem to alter the immunological responses to CO2 inhalation. Additional studies are indicated to characterize the immunological interrelations between these conditions; these discoveries could allow clinicians to select more targeted treatments for this population.

Divisions:Concordia University > Faculty of Arts and Science > Exercise Science
Item Type:Thesis (Masters)
Authors:Elhalwi, Alexandre
Institution:Concordia University
Degree Name:M. Sc.
Program:Exercise Science
Date:28 August 2014
Thesis Supervisor(s):Bacon, Simon L.
Keywords:Panic disorder, asthma, eosinophil, lymphocyte, stress, panic induction
ID Code:978890
Deposited On:11 Nov 2014 14:55
Last Modified:18 Jan 2018 17:47


1. Statistics Canada. Asthma, 2012. 2013 [updated 2013-06-19; cited 2013 November 26]; Available from: http://www.statcan.gc.ca/pub/82-625-x/2013001/article/11834-eng.htm.
2. Asthma Society of Canada. What Is Asthma? 2013 [cited 2013 November 26]; Available from: http://www.asthma.ca/adults/about/whatIsAsthma.php.
3. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2012 [updated December; cited 2013 November 26]; Available from: http://www.ginasthma.org/documents/4.
4. Global Initiative for Asthma (GINA). General information about asthma. [cited 2013 November 26]; Available from: http://www.ginasthma.org/FAQs.
5. Cookson W. The alliance of genes and environment in asthma and allergy. Nature. 1999;402:B5-11.
6. Malo JL, Chan-Yeung M. Agents causing occupational asthma. J Allergy Clin Immunol. 2009;123:545-50.
7. Busse WW, Lemanske RF, Jr. Asthma. N Engl J Med. 2001;344:350-62.
8. Chung KF, Barnes PJ. Cytokines in asthma. Thorax. 1999;54:825-57.
9. Anderson GP. The immunobiology of early asthma. The Medical journal of Australia. 2002;177 Suppl:S47-9.
10. Xu J, Jiang F, Nayeri F, Zetterstrom O. Apoptotic eosinophils in sputum from asthmatic patients correlate negatively with levels of IL-5 and eotaxin. Respir Med. 2007;101:1447-54.
11. Venge P, Peterson CGB. Eosinophil biochemistry and killing mechanisms. In: Mosbey J, Colditz I, editors. Eosinophils in asthma. New York: Academic Press; 1989. p. 163-77.
12. Gleich GJ, Flavahan NA, Fujisawa T, Vanhoutte PM. The eosinophil as a mediator of damage to respiratory epithelium: a model for bronchial hyperreactivity. J Allergy Clin Immunol. 1988;81:776-81.
13. Rothenberg ME, Hogan SP. The eosinophil. Annual review of immunology. 2006;24:147-74.
14. Chen Y, Johansen H, Thillaiampalam S, Sambell C. Asthma. Health Reports. 2005;16:43-37.
15. McIvor RA, Boulet LP, FitzGerald JM, Zimmerman S, Chapman KR. Asthma control in Canada: no improvement since we last looked in 1999. Can Fam Physician. 2007;53:672-7.
16. Roy-Byrne PP, Davidson KW, Kessler RC, Asmundson GJ, Goodwin RD, Kubzansky L, Lydiard RB, Massie MJ, Katon W, Laden SK, Stein MB. Anxiety disorders and comorbid medical illness. Gen Hosp Psychiatry. 2008;30:208-25.
17. Nascimento I, Nardi AE, Valenca AM, Lopes FL, Mezzasalma MA, Nascentes R, Zin WA. Psychiatric disorders in asthmatic outpatients. Psychiatry Res. 2002;110:73-80.
18. Kuehn BM. Asthma linked to psychiatric disorders. JAMA. 2008;299:158-60.
19. Katon WJ, Richardson L, Lozano P, McCauley E. The relationship of asthma and anxiety disorders. Psychosom Med. 2004;66:349-55.
20. Scott KM, Von Korff M, Ormel J, Zhang MY, Bruffaerts R, Alonso J, Kessler RC, Tachimori H, Karam E, Levinson D, Bromet EJ, Posada-Villa J, Gasquet I, Angermeyer MC, Borges G, de Girolamo G, Herman A, Haro JM. Mental disorders among adults with asthma: results from the World Mental Health Survey. Gen Hosp Psychiatry. 2007;29:123-33.
21. Nejtek VA, Brown ES, Khan DA, Moore JJ, Van Wagner J, Perantie DC. Prevalence of mood disorders and relationship to asthma severity in patients at an inner-city asthma clinic. Ann Allergy Asthma Immunol. 2001;87:129-33.
22. Lavoie KL, Bacon SL, Barone S, Cartier A, Ditto B, Labrecque M. What is worse for asthma control and quality of life: depressive disorders, anxiety disorders, or both? Chest. 2006;130:1039-47.
23. Urrutia I, Aguirre U, Pascual S, Esteban C, Ballaz A, Arrizubieta I, Larrea I. Impact of anxiety and depression on disease control and quality of life in asthma patients. J Asthma. 2012;49:201-8.
24. Ouellet K, Bacon SL, Boudreau M, Plourde A, Moullec G, Lavoie KL. Individual and combined impact of cigarette smoking, anxiety, and mood disorders on asthma control. Nicotine Tob Res. 2012;14:961-9.
25. Dhabhar FS. Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation. 2009;16:300-17.
26. Liu LY, 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;165:1062-7.
27. Marin TJ, Chen E, Munch JA, Miller GE. Double-exposure to acute stress and chronic family stress is associated with immune changes in children with asthma. Psychosom Med. 2009;71:378-84.
28. Chen E, Miller GE. Stress and inflammation in exacerbations of asthma. Brain, behavior, and immunity. 2007;21:993-9.
29. Van Lieshout RJ, Macqueen GM. Relations between asthma and psychological distress: an old idea revisited. Chem Immunol Allergy. 2012;98:1-13.
30. Reiss S, Peterson RA, Gursky DM, McNally RJ. Anxiety sensitivity, anxiety frequency and the prediction of fearfulness. Behav Res Ther. 1986;24:1-8.
31. Avallone KM, McLeish AC, Luberto CM, Bernstein JA. Anxiety sensitivity, asthma control, and quality of life in adults with asthma. J Asthma. 2012;49:57-62.
32. Favreau H, Bacon SL, Labrecque M, Lavoie KL. Prospective impact of panic disorder and panic-anxiety on asthma control, health service use, and quality of life in adult patients with asthma over a 4-year follow-up. Psychosom Med. 2014;76:147-55.
33. Plehn K, Peterson RA. Anxiety sensitivity as a predictor of the development of panic symptoms, panic attacks, and panic disorder: a prospective study. J Anxiety Disord. 2002;16:455-74.
34. American Psychological Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC1994.
35. Ramage-Morin PL. Panic disorder and coping. Health Rep. 2004;15 Suppl:31-43.
36. Feldman JM, Lehrer PM, Borson S, Hallstrand TS, Siddique MI. Health care use and quality of life among patients with asthma and panic disorder. J Asthma. 2005;42:179-84.
37. Ritz T, Steptoe A, DeWilde S, Costa M. Emotions and stress increase respiratory resistance in asthma. Psychosom Med. 2000;62:401-12.
38. Ritz T, Steptoe A. Emotion and pulmonary function in asthma: reactivity in the field and relationship with laboratory induction of emotion. Psychosom Med. 2000;62:808-15.
39. Molfino NA, Slutsky AS, Julia-Serda G, Hoffstein V, Szalai JP, Chapman KR, Rebuck AS, Zamel N. Assessment of airway tone in asthma. Comparison between double lung transplant patients and healthy subjects. Am Rev Respir Dis. 1993;148:1238-43.
40. Brambilla F, Bellodi L, Perna G. Plasma levels of tumor necrosis factor-alpha in patients with panic disorder: effect of alprazolam therapy. Psychiatry Res. 1999;89:21-7.
41. Tukel R, Arslan BA, Ertekin BA, Ertekin E, Oflaz S, Ergen A, Kuruca SE, Isbir T. Decreased IFN-gamma and IL-12 levels in panic disorder. J Psychosom Res. 2012;73:63-7.
42. Hoge EA, Brandstetter K, Moshier S, Pollack MH, Wong KK, Simon NM. Broad spectrum of cytokine abnormalities in panic disorder and posttraumatic stress disorder. Depress Anxiety. 2009;26:447-55.
43. Liebowitz MR, Fyer AJ, Gorman JM, Dillon D, Appleby IL, Levy G, Anderson S, Levitt M, Palij M, Davies SO, et al. Lactate provocation of panic attacks. I. Clinical and behavioral findings. Arch Gen Psychiatry. 1984;41:764-70.
44. Charney DS, Heninger GR, Jatlow PI. Increased anxiogenic effects of caffeine in panic disorders. Arch Gen Psychiatry. 1985;42:233-43.
45. Nardi AE, Valenca AM, Lopes FL, Nascimento I, Mezzasalma MA, Zin WA. Clinical features of panic patients sensitive to hyperventilation or breath-holding methods for inducing panic attacks. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica [et al]. 2004;37:251-7.
46. Rapee RM, Brown TA, Antony MM, Barlow DH. Response to hyperventilation and inhalation of 5.5% carbon dioxide-enriched air across the DSM-III-R anxiety disorders. J Abnorm Psychol. 1992;101:538-52.
47. Strohle A, Graetz B, Scheel M, Wittmann A, Feller C, Heinz A, Dimeo F. The acute antipanic and anxiolytic activity of aerobic exercise in patients with panic disorder and healthy control subjects. Journal of psychiatric research. 2009;43:1013-7.
48. Papp LA, Goetz R, Cole R, Klein DF, Jordan F, Liebowitz MR, Fyer AJ, Hollander E, Gorman JM. Hypersensitivity to carbon dioxide in panic disorder. Am J Psychiatry. 1989;146:779-81.
49. Pain MC, Biddle N, Tiller JW. Panic disorder, the ventilatory response to carbon dioxide and respiratory variables. Psychosom Med. 1988;50:541-8.
50. Nardi AE, Valenca AM, Lopes FL, de-Melo-Neto VL, Freire RC, Veras AB, Nascimento I, King AL, Soares-Filho GL, Mezzasalma MA, Zin WA. Caffeine and 35% carbon dioxide challenge tests in panic disorder. Hum Psychopharmacol. 2007;22:231-40.
51. Papp LA, Martinez JM, Klein DF, Coplan JD, Norman RG, Cole R, de Jesus MJ, Ross D, Goetz R, Gorman JM. Respiratory psychophysiology of panic disorder: three respiratory challenges in 98 subjects. Am J Psychiatry. 1997;154:1557-65.
52. Sanderson WC, Wetzler S. Five percent carbon dioxide challenge: valid analogue and marker of panic disorder? Biol Psychiatry. 1990;27:689-701.
53. Griez EJ, Lousberg H, van den Hout MA, van der Molen GM. CO2 vulnerability in panic disorder. Psychiatry Res. 1987;20:87-95.
54. Klein DF. False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry. 1993;50:306-17.
55. Gorman JM, Papp LA, Coplan JD, Martinez JM, Lennon S, Goetz RR, Ross D, Klein DF. Anxiogenic effects of CO2 and hyperventilation in patients with panic disorder. Am J Psychiatry. 1994;151:547-53.
56. Griez EJ, Colasanti A, van Diest R, Salamon E, Schruers K. Carbon dioxide inhalation induces dose-dependent and age-related negative affectivity. PLoS One. 2007;2:e987.
57. van Duinen MA, Schruers KR, Kenis GR, Wauters A, Delanghe J, Griez EJ, Maes MH. Effects of experimental panic on neuroimmunological functioning. J Psychosom Res. 2008;64:305-10.
58. Chinen J, Shearer WT. Basic and clinical immunology. J Allergy Clin Immunol. 2005;116:411-8.
59. Wills-Karp M. Interleukin-13 in asthma pathogenesis. Immunol Rev. 2004;202:175-90.
60. Amini-Vaughan ZJ, Martinez-Moczygemba M, Huston DP. Therapeutic strategies for harnessing human eosinophils in allergic inflammation, hypereosinophilic disorders, and cancer. Curr Allergy Asthma Rep. 2012;12:402-12.
61. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J, Force AET. Standardisation of spirometry. Eur Respir J. 2005;26:319-38.
62. Brown TA, Di Nardo PA, Barlow DH. Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV). Albany, NY: Graywind; 1994.
63. Hunsley J, Mash EJ. A guide to assessments that work. New York, NY US: Oxford University Press; 2008.
64. Grisham JR, Brown TA, Campbell LA. The Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV). In: Hilsenroth MJ, Segal DL, editors. Comprehensive handbook of psychological assessment, Vol 2: Personality assessment. Hoboken, NJ US: John Wiley & Sons Inc; 2004. p. 163-77.
65. Brown TA, Di Nardo PA, Lehman CL, Campbell LA. Reliability of DSM-IV anxiety and mood disorders: Implications for the classification of emotional disorders. Journal of Abnormal Psychology. 2001;110:49-58.
66. Dillon DJ, Gorman JM, Liebowitz MR, Fyer AJ, Klein DF. Measurement of lactate-induced panic and anxiety. Psychiatry Res. 1987;20:97-105.
67. van Beek N, Perna G, Schruers K, Verburg K, Cucchi M, Bellodi L, Griez E. Vulnerability to 35% CO2 of panic disorder patients with a history of respiratory disorders. Psychiatry Res. 2003;120:125-30.
68. van Beek N, Griez E. Reactivity to a 35% CO2 challenge in healthy first-degree relatives of patients with panic disorder. Biol Psychiatry. 2000;47:830-5.
69. Pin I, Gibson PG, Kolendowicz R, Girgis-Gabardo A, Denburg JA, Hargreave FE, Dolovich J. Use of induced sputum cell counts to investigate airway inflammation in asthma. Thorax. 1992;47:25-9.
70. Canadian Thoracic Society. Sputum Examination for Indices of Airway Inflammation: Laboratory Procedures. Lund, Sweden: Astra Draco AB; 1997.
71. Rubin DB. Multiple Imputation for Nonresponse in Surveys New York: John Wiley & Sons; 1987.
72. Harrell FE. Regression Modeling Strategies. New York: Springer; 2001.
73. Shavelson RJ. Statistical reasoning for the behavioral sciences. 2nd ed. Needham Heights, MA: Allyn and Bacon, Inc.; 1988.
74. Schleich FN, Manise M, Sele J, Henket M, Seidel L, Louis R. Distribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation. BMC pulmonary medicine. 2013;13:11.
75. Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology. 2006;11:54-61.
76. Carr RE, Lehrer PM, Hochron SM, Jackson A. Effect of Psychological Stress on Airway Impedance in Individuals With Asthma and Panic Disorder. Journal of Abnormal Psychology. 1996;105:5.
77. Aboussafy D, Campbell TS, Lavoie K, Aboud FE, Ditto B. Airflow and autonomic responses to stress and relaxation in asthma: the impact of stressor type. International journal of psychophysiology : official journal of the International Organization of Psychophysiology. 2005;57:195-201.
78. Fleet R, Lesperance F, Arsenault A, Gregoire J, Lavoie K, Laurin C, Harel F, Burelle D, Lambert J, Beitman B, Frasure-Smith N. Myocardial perfusion study of panic attacks in patients with coronary artery disease. The American journal of cardiology. 2005;96:1064-8.
79. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis. 1983;127:725-34.
All items in Spectrum are protected by copyright, with all rights reserved. The use of items is governed by Spectrum's terms of access.

Repository Staff Only: item control page

Downloads per month over past year

Back to top Back to top