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Severe Asthma with Fungal Sensitization

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Abstract

A new phenotype of asthma has been described recently, namely severe asthma with fungal sensitization (SAFS). SAFS can be conceptualized as a continuum of fungal sensitization, with asthma at one end and allergic bronchopulmonary aspergillosis at the other. It is diagnosed by the presence of severe asthma, fungal sensitization, and exclusion of allergic bronchopulmonary aspergillosis. Because of the paucity of data and ambiguity in diagnostic criteria, SAFS is currently more of a diagnosis of exclusion than a specific entity. Treatment of SAFS initially should be similar to that of severe asthma, including the use of omalizumab. The potential role of itraconazole as a specific therapy in SAFS requires more evidence before it can be incorporated in routine practice. An urgent need exists for data regarding the prevalence, natural history, and clinical relevance of SAFS so that its exact characterization and importance as a specific subtype of asthma can be clearly defined. This review summarizes the current understanding of the pathogenesis, diagnosis, and management of SAFS.

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References

Papers of particular interest, published recently, have been highlighted as:• Of importance

  1. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Available at http://www.ginasthma.com/Guidelineitem.asp??l1=2&l2=1&intId=1561, 2009 update.

  2. Moore WC, Bleecker ER, Curran-Everett D, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119:405–13.

    Article  PubMed  Google Scholar 

  3. Antonicelli L, Bucca C, Neri M, et al. Asthma severity and medical resource utilisation. Eur Respir J. 2004;23:723–9.

    Article  PubMed  CAS  Google Scholar 

  4. Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med. 2000;162:2341–51.

    Google Scholar 

  5. Langley SJ, Goldthorpe S, Craven M, et al. Exposure and sensitization to indoor allergens: association with lung function, bronchial reactivity, and exhaled nitric oxide measures in asthma. J Allergy Clin Immunol. 2003;112:362–8.

    Article  PubMed  CAS  Google Scholar 

  6. Kalliel JN, Goldstein BM, Braman SS, et al. High frequency of atopic asthma in a pulmonary clinic population. Chest. 1989;96:1336–40.

    Article  PubMed  CAS  Google Scholar 

  7. Miles J, Cayton R, Ayres J. Atopic status in patients with brittle and non-brittle asthma: a case-control study. Clin Exp Allergy. 1995;25:1074–82.

    Article  PubMed  CAS  Google Scholar 

  8. Denning DW, O’Driscoll BR, Hogaboam CM, et al. The link between fungi and severe asthma: a summary of the evidence. Eur Respir J. 2006;27:615–26.

    Article  PubMed  CAS  Google Scholar 

  9. • Agarwal R, Gupta D. Severe asthma and fungi: current evidence. Med Mycol. 2011;49 Suppl 1:S150–7. This is a good review, especially with regard to the link between Aspergillus spp and severe asthma.

    Article  PubMed  Google Scholar 

  10. Salvaggio J, Seabury J, Schoenhardt FA. New Orleans asthma. V. Relationship between Charity Hospital asthma admission rates, semiquantitative pollen and fungal spore counts, and total particulate aerometric sampling data. J Allergy Clin Immunol. 1971;48:96–114.

    Article  PubMed  CAS  Google Scholar 

  11. Jenkins PF, Mullins JK, Davies BH, et al. The possible role of aero-allergens in the epidemic of asthma deaths. Clin Allergy. 1981;11:611–20.

    Article  PubMed  CAS  Google Scholar 

  12. Targonski PV, Persky VW, Ramekrishnan V. Effect of environmental molds on risk of death from asthma during the pollen season. J Allergy Clin Immunol. 1995;95:955–61.

    Article  PubMed  CAS  Google Scholar 

  13. Neas LM, Dockery DW, Burge H, et al. Fungus spores, air pollutants, and other determinants of peak expiratory flow rate in children. Am J Epidemiol. 1996;143:797–807.

    PubMed  CAS  Google Scholar 

  14. Delfino RJ, Zeiger RS, Seltzer JM, et al. The effect of outdoor fungal spore concentrations on daily asthma severity. Environ Health Perspect. 1997;105:622–35.

    Article  PubMed  CAS  Google Scholar 

  15. Newson R, Strachan D, Corden J, et al. Fungal and other spore counts as predictors of admissions for asthma in the Trent region. Occup Environ Med. 2000;57:786–92.

    Article  PubMed  CAS  Google Scholar 

  16. Douwes J, Pearce N. Invited commentary: is indoor mold exposure a risk factor for asthma? Am J Epidemiol. 2003;158:203–6.

    Article  PubMed  Google Scholar 

  17. Schwartz HJ, Citron KM, Chester EH, et al. A comparison of the prevalence of sensitization to Aspergillus antigens among asthmatics in Cleveland and London. J Allergy Clin Immunol. 1978;62:9–14.

    Article  PubMed  CAS  Google Scholar 

  18. O’Hollaren M, Yunginger J, Offord K, et al. Exposure to an aeroallergen as a possible precipitating factor in respiratory arrest in young patients with asthma. N Engl J Med. 1991;324:359–63.

    Article  PubMed  Google Scholar 

  19. Peat JK, Tovey E, Mellis CM, et al. Importance of house dust mite and Alternaria allergens in childhood asthma: an epidemiological study in two climatic regions of Australia. Clin Exp Allergy. 1993;23:812–20.

    Article  PubMed  CAS  Google Scholar 

  20. Nelson HS, Szefler SJ, Jacobs J, et al. The relationships among environmental allergen sensitization, allergen exposure, pulmonary function, and bronchial hyperresponsiveness in the Childhood Asthma Management Program. J Allergy Clin Immunol. 1999;104:775–85.

    Article  PubMed  CAS  Google Scholar 

  21. Neukirch C, Henry C, Leynaert B, et al. Is sensitization to Alternaria alternata a risk factor for severe asthma? A population-based study. J Allergy Clin Immunol. 1999;103:709–11.

    Article  PubMed  CAS  Google Scholar 

  22. Roux P, Smit M, Weinberg EG. Seasonal and recurrent intensive care unit admissions for acute severe asthma in children. S Afr Med J. 1993;83:177–9.

    PubMed  CAS  Google Scholar 

  23. Niedoszytko M, Chelminska M, Jassem E, et al. Association between sensitization to Aureobasidium pullulans (Pullularia sp) and severity of asthma. Ann Allergy Asthma Immunol. 2007;98:153–6.

    Article  PubMed  Google Scholar 

  24. Matsuoka H, Niimi A, Matsumoto H, et al. Specific IgE response to trichophyton and asthma severity. Chest. 2009;135:898–903.

    Article  PubMed  CAS  Google Scholar 

  25. Fairs A, Agbetile J, Hargadon B, et al. IgE sensitisation to Aspergillus fumigatus is associated with reduced lung function in asthma. Am J Respir Crit Care Med. 2010;182:1362–8.

    Article  PubMed  Google Scholar 

  26. Agarwal R, Noel V, Aggarwal AN, et al. Clinical significance of Aspergillus sensitization in bronchial asthma. Mycoses. 2011; doi:10.1111/j.1439-0507.2010.01971.x.

  27. • Menzies D, Holmes L, McCumesky G, et al. Aspergillus sensitization is associated with airflow limitation and bronchiectasis in severe asthma. Allergy. 2011;66:679–85. This article describes the association between Aspergillus sensitization and asthma.

    Article  PubMed  CAS  Google Scholar 

  28. Maurya V, Gugnani HC, Sarma PU, et al. Sensitization to Aspergillus antigens and occurrence of allergic bronchopulmonary aspergillosis in patients with asthma. Chest. 2005;127:1252–9.

    Article  PubMed  Google Scholar 

  29. Zureik M, Neukirch C, Leynaert B, et al. Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community Respiratory Health Survey. BMJ. 2002;325:411–4.

    Article  PubMed  Google Scholar 

  30. O’Driscoll BR, Hopkinson LC, Denning DW. Mold sensitization is common amongst patients with severe asthma requiring multiple hospital admissions. BMC Pulm Med. 2005;5:4.

    Article  PubMed  Google Scholar 

  31. Black PN, Udy AA, Brodie SM. Sensitivity to fungal allergens is a risk factor for life-threatening asthma. Allergy. 2000;55:501–4.

    Article  PubMed  CAS  Google Scholar 

  32. Agarwal R, Nath A, Aggarwal AN, et al. Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with acute severe asthma in a respiratory intensive care unit in North India. Mycoses. 2010;53:138–43.

    Article  PubMed  CAS  Google Scholar 

  33. Agarwal R, Gupta D, Aggarwal AN, et al. Allergic bronchopulmonary aspergillosis: lessons from 126 patients attending a chest clinic in north India. Chest. 2006;130:442–8.

    Article  PubMed  Google Scholar 

  34. Agarwal R, Gupta D, Aggarwal AN, et al. Clinical significance of hyperattenuating mucoid impaction in allergic bronchopulmonary aspergillosis: an analysis of 155 patients. Chest. 2007;132:1183–90.

    Article  PubMed  Google Scholar 

  35. Agarwal R, Gupta D, Aggarwal AN, et al. Clinical significance of decline in serum IgE levels in allergic bronchopulmonary aspergillosis. Respir Med. 2010;104:204–10.

    Article  PubMed  Google Scholar 

  36. • Agarwal R, Khan A, Gupta D, et al. An alternate method of classifying allergic bronchopulmonary aspergillosis based on high-attenuation mucus. PLoS One. 2010;5:e15346. This is an outstanding paper describing a new evidence-based radiologic classification of ABPA.

    Article  PubMed  CAS  Google Scholar 

  37. Akhunova AM. Infectious-allergic bronchopulmonary paecilomycosis. Ter Arkh. 1991;63:19–24.

    PubMed  CAS  Google Scholar 

  38. Gondor M, Michaels MG, Finder JD. Non-aspergillus allergic bronchopulmonary mycosis in a pediatric patient with cystic fibrosis. Pediatrics. 1998;102:1480–2.

    Article  PubMed  CAS  Google Scholar 

  39. • Agarwal R. Allergic bronchopulmonary aspergillosis. Chest. 2009;135:805–26. This is an in-depth review on ABPA.

    Article  PubMed  Google Scholar 

  40. Agarwal R, Chakrabarti A. Epidemiology of allergic bronchopulmonary aspergillosis. In: Pasqualotto AC, editor. Aspergillosis: from diagnosis to prevention. New York: Springer; 2009. p. 671–88.

    Chapter  Google Scholar 

  41. • Agarwal R, Aggarwal AN, Gupta D, et al. Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with bronchial asthma: systematic review and meta-analysis. Int J Tubercul Lung Dis. 2009;13:936–44. This is a meta-analysis on the prevalence of Aspergillus sensitization and ABPA in bronchial asthma.

    CAS  Google Scholar 

  42. Renz H, Smith HR, Henson JE, et al. Aerosolized antigen exposure without adjuvant causes increased IgE production and increased airway responsiveness in the mouse. J Allergy Clin Immunol. 1992;89:1127–38.

    Article  PubMed  CAS  Google Scholar 

  43. Gulbenkian AR, Egan RW, Fernandez X, et al. Interleukin-5 modulates eosinophil accumulation in allergic guinea pig lung. Am Rev Respir Dis. 1992;146:263–6.

    PubMed  CAS  Google Scholar 

  44. Corry DB, Grunig G, Hadeiba H, et al. Requirements for allergen-induced airway hyperreactivity in T and B cell-deficient mice. Mol Med. 1998;4:344–55.

    Article  PubMed  CAS  Google Scholar 

  45. Agarwal R. Allergic bronchopulmonary aspergillosis: lessons learnt from genetics. Indian J Chest Dis Allied Sci. 2011;53:137–40.

    Google Scholar 

  46. Eaton TE, Weiner Miller P, Garrett JE, et al. Cystic fibrosis transmembrane conductance regulator gene mutations: do they play a role in the aetiology of allergic bronchopulmonary aspergillosis? Clin Exp Allergy. 2002;32:756–61.

    Article  PubMed  CAS  Google Scholar 

  47. Carvalho A, Pasqualotto AC, Pitzurra L, et al. Polymorphisms in Toll-like receptor genes and susceptibility to pulmonary aspergillosis. J Infect Dis. 2008;197:618–21.

    Article  PubMed  CAS  Google Scholar 

  48. Vicencio AG, Chupp GL, Tsirilakis K, et al. CHIT1 mutations: genetic risk factor for severe asthma with fungal sensitization? Pediatrics. 2010;126:e982–5.

    Article  PubMed  Google Scholar 

  49. Vicencio AG, Muzumdar H, Tsirilakis K, et al. Severe asthma with fungal sensitization in a child: response to itraconazole therapy. Pediatrics. 2010;125:e1255–8.

    Article  PubMed  Google Scholar 

  50. Chauhan B, Knutsen A, Hutcheson PS, et al. T cell subsets, epitope mapping, and HLA-restriction in patients with allergic bronchopulmonary aspergillosis. J Clin Invest. 1996;97:2324–31.

    Article  PubMed  CAS  Google Scholar 

  51. Aron Y, Bienvenu T, Hubert D, et al. HLA-DR polymorphism in allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol. 1999;104:891–2.

    Article  PubMed  CAS  Google Scholar 

  52. Chauhan B, Santiago L, Hutcheson PS, et al. Evidence for the involvement of two different MHC class II regions in susceptibility or protection in allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol. 2000;106:723–9.

    Article  PubMed  CAS  Google Scholar 

  53. Knutsen AP, Vijay HM, Kumar V, et al. Mold-sensitivity in children with moderate-severe asthma is associated with HLA-DR and HLA-DQ. Allergy. 2010;65:1367–75.

    Article  PubMed  CAS  Google Scholar 

  54. Horner WE, Helbling A, Salvaggio JE, et al. Fungal allergens. Clin Microbiol Rev. 1995;8:161–79.

    PubMed  CAS  Google Scholar 

  55. Crameri R, Glaser AG, Vilhelmsson M, et al. Overview of Aspergillus allergens. In: Pasqualotto AC, editor. Aspergillosis: from diagnosis to prevention. New York: Springer; 2009. p. 655–70.

    Chapter  Google Scholar 

  56. Kheradmand F, Kiss A, Xu J, et al. A protease-activated pathway underlying Th cell type 2 activation and allergic lung disease. J Immunol. 2002;169:5904–11.

    PubMed  CAS  Google Scholar 

  57. Porter P, Susarla SC, Polikepahad S, et al. Link between allergic asthma and airway mucosal infection suggested by proteinase-secreting household fungi. Mucosal Immunol. 2009;2:504–17.

    Article  PubMed  CAS  Google Scholar 

  58. Gudmundsson G, Hunninghake GW. Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis. J Clin Invest. 1997;99:2386–90.

    Article  PubMed  CAS  Google Scholar 

  59. Tomee JF, Wierenga AT, Hiemstra PS, et al. Proteases from Aspergillus fumigatus induce release of proinflammatory cytokines and cell detachment in airway epithelial cell lines. J Infect Dis. 1997;176:300–3.

    Article  PubMed  CAS  Google Scholar 

  60. Tomee JF, Kauffman HF, Klimp AH, et al. Immunologic significance of a collagen-derived culture filtrate containing proteolytic activity in Aspergillus-related diseases. J Allergy Clin Immunol. 1994;93:768–78.

    Article  PubMed  CAS  Google Scholar 

  61. Hogaboam CM, Blease K, Schuh JM. Cytokines and chemokines in allergic bronchopulmonary aspergillosis (ABPA) and experimental Aspergillus-induced allergic airway or asthmatic disease. Front Biosci. 2003;8:e147–56.

    Article  PubMed  CAS  Google Scholar 

  62. Kauffman HK, Tomee JFC. Inflammatory cells and airway defense against Aspergillus fumigatus. Immunol Allergy Clin North Am. 1998;18:619–40.

    Article  Google Scholar 

  63. Kauffman HF, Tomee JF, van de Riet MA, et al. Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. J Allergy Clin Immunol. 2000;105:1185–93.

    Article  PubMed  CAS  Google Scholar 

  64. British guideline on the management of asthma. Thorax. 2008;63 Suppl 4:iv1–121.

  65. National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007;120:S94–S138.

    Article  Google Scholar 

  66. Liang KL, Su MC, Jiang RS. Comparison of the skin test and ImmunoCAP system in the evaluation of mold allergy. J Chin Med Assoc. 2006;69:3–6.

    Article  PubMed  Google Scholar 

  67. O’Driscoll BR, Powell G, Chew F, et al. Comparison of skin prick tests with specific serum immunoglobulin E in the diagnosis of fungal sensitization in patients with severe asthma. Clin Exp Allergy. 2009;39:1677–83.

    Article  PubMed  CAS  Google Scholar 

  68. Malo JL, Paquin R. Incidence of immediate sensitivity to Aspergillus fumigatus in a North American asthmatic population. Clin Allergy. 1979;9:377–84.

    Article  PubMed  CAS  Google Scholar 

  69. Behera D, Guleria R, Jindal SK, et al. Allergic bronchopulmonary aspergillosis: a retrospective study of 35 cases. Indian J Chest Dis Allied Sci. 1994;36:173–9.

    PubMed  CAS  Google Scholar 

  70. Chakrabarti A, Sethi S, Raman DS, et al. Eight-year study of allergic bronchopulmonary aspergillosis in an Indian teaching hospital. Mycoses. 2002;45:295–9.

    Article  PubMed  CAS  Google Scholar 

  71. Agarwal R, Hazarika B, Gupta D, et al. Aspergillus hypersensitivity in patients with chronic obstructive pulmonary disease: COPD as a risk factor for ABPA? Med Mycol. 2010;48:988–94.

    Article  PubMed  Google Scholar 

  72. Wang JL, Patterson R, Rosenberg M, et al. Serum IgE and IgG antibody activity against Aspergillus fumigatus as a diagnostic aid in allergic bronchopulmonary aspergillosis. Am Rev Respir Dis. 1978;117:917–27.

    PubMed  CAS  Google Scholar 

  73. Kurup VP, Banerjee B, Hemmann S, et al. Selected recombinant Aspergillus fumigatus allergens bind specifically to IgE in ABPA. Clin Exp Allergy. 2000;30:988–93.

    Article  PubMed  CAS  Google Scholar 

  74. Crameri R, Hemmann S, Ismail C, et al. Disease-specific recombinant allergens for the diagnosis of allergic bronchopulmonary aspergillosis. Int Immunol. 1998;10:1211–6.

    Article  PubMed  CAS  Google Scholar 

  75. Crameri R. Recombinant Aspergillus fumigatus allergens: from the nucleotide sequences to clinical applications. Int Arch Allergy Immunol. 1998;115:99–114.

    Article  PubMed  CAS  Google Scholar 

  76. Crameri R, Lidholm J, Gronlund H, et al. Automated specific IgE assay with recombinant allergens: evaluation of the recombinant Aspergillus fumigatus allergen I in the Pharmacia Cap System. Clin Exp Allergy. 1996;26:1411–9.

    Article  PubMed  CAS  Google Scholar 

  77. Bowyer P, Blightman O, Denning DW. Relative reactivity of Aspergillus allergens used in serological tests. Med Mycol. 2006;44 Suppl 1:23–8.

    Article  CAS  Google Scholar 

  78. Bateman ED. A new look at the natural history of Aspergillus hypersensitivity in asthmatics. Respir Med. 1994;88:325–7.

    Article  PubMed  CAS  Google Scholar 

  79. Greenberger PA, Miller TP, Roberts M, et al. Allergic bronchopulmonary aspergillosis in patients with and without evidence of bronchiectasis. Ann Allergy. 1993;70:333–8.

    PubMed  CAS  Google Scholar 

  80. Skov M, Main KM, Sillesen IB, et al. Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide. Eur Respir J. 2002;20:127–33.

    Article  PubMed  CAS  Google Scholar 

  81. Kim JH, Ahn YK. The effects of itraconazole on the immune responses in ICR mice. J Toxicol Sci. 1994;19:7–15.

    PubMed  CAS  Google Scholar 

  82. Agarwal R, Khan A. ABPA or AFAA: that is the question? Am J Respir Crit Care Med 2011;183:1281.

    Google Scholar 

  83. Denning DW, Van Wye JE, Lewiston NJ, et al. Adjunctive therapy of allergic bronchopulmonary aspergillosis with itraconazole. Chest. 1991;100:813–9.

    Article  PubMed  CAS  Google Scholar 

  84. Agarwal R, Khan A, Aggarwal AN, et al. Is the SMART approach better than other treatment approaches for prevention of asthma exacerbations? A meta-analysis. Monaldi Arch Chest Dis. 2009;71:161–9.

    PubMed  CAS  Google Scholar 

  85. Brusselle G, Michils A, Louis R, et al. “Real-life” effectiveness of omalizumab in patients with severe persistent allergic asthma: the PERSIST study. Respir Med. 2009;103:1633–42.

    Article  PubMed  CAS  Google Scholar 

  86. Walker S, Monteil M, Phelan K, et al. Anti-IgE for chronic asthma in adults and children. Cochrane Database Syst Rev. 2006:CD003559.

  87. van der Ent CK, Hoekstra H, Rijkers GT. Successful treatment of allergic bronchopulmonary aspergillosis with recombinant anti-IgE antibody. Thorax. 2007;62:276–7.

    Article  PubMed  Google Scholar 

  88. Kanu A, Patel K. Treatment of allergic bronchopulmonary aspergillosis (ABPA) in CF with anti-IgE antibody (omalizumab). Pediatr Pulmonol. 2008;43:1249–51.

    Article  PubMed  Google Scholar 

  89. Zirbes JM, Milla CE. Steroid-sparing effect of omalizumab for allergic bronchopulmonary aspergillosis and cystic fibrosis. Pediatr Pulmonol. 2008;43:607–10.

    Article  PubMed  Google Scholar 

  90. Lebecque P, Leonard A, Pilette C. Omalizumab for treatment of ABPA exacerbations in CF patients. Pediatr Pulmonol. 2009;44:516.

    Article  PubMed  Google Scholar 

  91. Quintas Vazquez LM, Ortiz Piquer M, Perez de Llano LA. [Effective anti-immunoglobulin-E antibody treatment of a patient with allergic bronchopulmonary aspergillosis.]. Arch Bronconeumol. 2009;45:207.

    Google Scholar 

  92. Randhawa I, Chin T, Nussbaum E. Resolution of corticosteroid-induced diabetes in allergic bronchopulmonary aspergillosis with omalizumab therapy: a novel approach. J Asthma. 2009;46:445–7.

    Article  PubMed  CAS  Google Scholar 

  93. Thomas MF. Life-threatening allergic bronchopulomnary aspergillosis treated with methylprednisolone and anti-IgE monoclonal antibody. J R Soc Med. 2009;102 Suppl 1:49–53.

    Article  PubMed  Google Scholar 

  94. Brinkmann F, Schwerk N, Hansen G, et al. Steroid dependency despite omalizumab treatment of ABPA in cystic fibrosis. Allergy. 2010;65:134–5.

    Article  PubMed  CAS  Google Scholar 

  95. Lin RY, Sethi S, Bhargave GA. Measured immunoglobulin E in allergic bronchopulmonary aspergillosis treated with omalizumab. J Asthma. 2010;47:942–5.

    Article  PubMed  CAS  Google Scholar 

  96. Wark PA, Gibson PG, Wilson AJ. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev. 2003:CD001108.

  97. Ward Jr GW, Woodfolk JA, Hayden ML, et al. Treatment of late-onset asthma with fluconazole. J Allergy Clin Immunol. 1999;104:541–6.

    Article  PubMed  CAS  Google Scholar 

  98. • Denning DW, O’Driscoll BR, Powell G, et al. Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: The Fungal Asthma Sensitization Trial (FAST) study. Am J Respir Crit Care Med. 2009;179:11–8. This was the first trial to evaluate itraconazole in the treatment of SAFS.

    Article  PubMed  CAS  Google Scholar 

  99. Varis T, Kaukonen KM, Kivisto KT, et al. Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole. Clin Pharmacol Ther. 1998;64:363–8.

    Article  PubMed  CAS  Google Scholar 

  100. Varis T, Kivisto KT, Neuvonen PJ. The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone. Eur J Clin Pharmacol. 2000;56:57–60.

    Article  PubMed  CAS  Google Scholar 

  101. Abruzzo GK, Fromtling RA, Turnbull TA, et al. Effects of bifonazole, fluconazole, itraconazole, and terbinafine on the chemiluminescence response of immune cells. J Antimicrob Chemother. 1987;20:61–8.

    Article  PubMed  CAS  Google Scholar 

  102. Pawelec G, Jaschonek K, Ehninger G. The anti-fungal agent itraconazole exerts immunosuppressive effects on alloreactivity but not on natural immunity in vitro. Int J Immunopharmacol. 1991;13:875–9.

    Article  PubMed  CAS  Google Scholar 

  103. Pawelec G, Ehninger G, Rehbein A, et al. Comparison of the immunosuppressive activities of the antimycotic agents itraconazole, fluconazole, ketoconazole and miconazole on human T-cells. Int J Immunopharmacol. 1991;13:299–304.

    Article  PubMed  CAS  Google Scholar 

  104. Kanda N, Enomoto U, Watanabe S. Anti-mycotics suppress interleukin-4 and interleukin-5 production in anti-CD3 plus anti-CD28-stimulated T cells from patients with atopic dermatitis. J Invest Dermatol. 2001;117:1635–46.

    Article  PubMed  CAS  Google Scholar 

  105. Ausaneya U, Kawada A, Aragane Y. Itraconazole suppresses an elicitation phase of a contact hypersensitivity reaction. J Invest Dermatol. 2006;126:1028–35.

    Article  PubMed  CAS  Google Scholar 

  106. Simitsopoulou M, Roilides E, Likartsis C, et al. Expression of immunomodulatory genes in human monocytes induced by voriconazole in the presence of Aspergillus fumigatus. Antimicrob Agents Chemother. 2007;51:1048–54.

    Article  PubMed  CAS  Google Scholar 

  107. Pasqualotto AC, Powell G, Niven R, et al. The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis. Respirology. 2009;14:1121–7.

    Article  PubMed  Google Scholar 

  108. Tucker RM, Haq Y, Denning DW, et al. Adverse events associated with itraconazole in 189 patients on chronic therapy. J Antimicrob Chemother. 1990;26:561–6.

    Article  PubMed  CAS  Google Scholar 

  109. Lebrun-Vignes B, Archer VC, Diquet B, et al. Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects. Br J Clin Pharmacol. 2001;51:443–50.

    Article  PubMed  CAS  Google Scholar 

  110. Main KM, Skov M, Sillesen IB, et al. Cushing’s syndrome due to pharmacological interaction in a cystic fibrosis patient. Acta Paediatr. 2002;91:1008–11.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, 160012, India

    Ritesh Agarwal

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Agarwal, R. Severe Asthma with Fungal Sensitization. Curr Allergy Asthma Rep 11, 403–413 (2011). https://doi.org/10.1007/s11882-011-0217-4

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