Background: Fungal exposure is associated with particularly severe asthma. Nevertheless, the effects of anti-fungal treatments on fungus-exacerbated asthma need to be determined. Objectives: The present study aimed to compare the effects of itraconazole (ITCZ) and dexamethasone (Dex) on Aspergillus fumigatus (Af)-exacerbated preexisting Dermatophagoides farinae (Df) allergen-sensitized allergic airway inflammation. Methods: Four groups of BALB/c mice were prepared: control, Df-sensitized plus Af-infected mice (Df-Af), and Df-Af mice treated with Dex (Df-Af-Dex) or with ITCZ (Df-Af-ITCZ). Pulmonary pathology and cytokine profiles in the airway were evaluated. In a different set of experiments, the effects of Dex on alveolar macrophage (AM) phagocytosis of Af conidia were determined in Df-sensitized mice. Results:Af infection significantly increased the level of eosinophils and neutrophils in the airway of Df- sensitized mice. While Dex significantly decreased eosinophils, ITCZ significantly decreased both eosinophils and neutrophils in Df-Af mice. Dex significantly decreased IL-5, whereas ITCZ significantly reduced MIP-2 in the airway. Compared to controls, AM isolated from Df-sensitized mice had significantly reduced phagocytotic activity of Af conidia. However, Dex significantly improved phagocytotic activity of AM in Df-sensitized mice. Conclusions: The present study showed that Dex and ITCZ differently regulated Af-exacerbated allergic airway inflammation; the former inhibits eosinophilic inflammation and the latter inhibits neutrophilic as well as eosinophilic inflammation by regulating different cytokines. Additionally, Dex enhanced the phagocytotic activity of AM in allergic asthma. Thus, a combination of Dex and ITCZ might be effective for the management of fungus-exacerbated asthma.

1.
Boyce JA, Bochner B, Finkelman FD, Rothenberg ME: Advances in mechanisms of asthma, allergy, and immunology in 2011. J Allergy Clin Immunol 2011;129:335-341.
2.
Hamid Q: Pathogenesis of small airways in asthma. Respiration 2012;84:2-11.
3.
Lemanske RF Jr: Viruses and asthma: inception, exacerbation, and possible prevention. J Pediatr 2003;142:S3-S7.
4.
Nicholson KG, Kent J, Ireland DC: Respiratory viruses and exacerbations of asthma in adults. Br Med J 1993;342:1494-1495.
5.
Contoli M, Caramori G, Mallia P, Johnson S, Papi A: Mechanisms of respiratory virus-induced asthma exacerbations. Clin Exp Allergy 2005;35:137-145.
6.
O'Driscoll BR, Powell G, Chew F, Niven RM, Miles JF, Vyas A, Denning DW: 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;39:1677-1683.
7.
Zureik M, Neukirch C, Leynaert B, Liard R, Bousquet J, Neukirch F, European Community Respiratory Health Survey: Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey. BMJ 2002;325:411-414.
8.
Agarwal R: Severe asthma with fungal sensitization. Curr Allergy Asthma Rep 2011;11:403-413.
9.
Agarwal R: Allergic bronchopulmonary aspergillosis. Chest 2009;133:805-826.
10.
Denning DW, O'Driscoll BR, Hogaboam CM, Bowyer P, Niven RM: The link between fungi and severe asthma: a summary of the evidence. Eur Respir J 2006;27:615-626.
11.
Stevens DA, Schwartz HJ, Lee JY, Moskovitz BL, Jerome DC, Catanzaro A, Bamberger DM, Weinmann AJ, Tuazon CU, Judson MA, Platts-Mills TA, DeGraff AC Jr: A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med 2000;342:756-762.
12.
Wark PA, Hensley MJ, Saltos N, Boyle MJ, Toneguzzi RC, Epid GD, Simpson JL, McElduff P, Gibson PG: Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: a randomized controlled trial. J Allergy Clin Immunol 2003;111:952-957.
13.
Denning DW, O'Driscoll BR, Powell G, Chew F, Atherton GT, Vyas A, Miles J, Morris J, Niven RM: 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;179:11-18.
14.
Pasqualotto AC, Powell G, Niven R, Denning DW: The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis. Respirology 2009;14:1121-1127.
15.
Gruning G, Kurup VP: Animal models of allergic bronchopulmonary aspergillosis. Front Biosci 2003;8:157-171.
16.
Hogaboam CM, Blease K, Mehrad B, Steinhauser ML, Standiford TJ, Kunkel SL, Lukacs NW: Chronic airway hyperreactivity, goblet cell hyperplasia, and peribronchial fibrosis during allergic airway disease induced by Aspergillus fumigatus. Am J Pathol 2000;156:723-732.
17.
Fukushima C, Matsuse H, Fukahori S, Tsuchida T, Kawano T, Kohno S: Aspergillus fumigatus synergistically enhances mite-induced allergic airway inflammation. Med Sci Monitor 2010;16:BR197-BR202.
18.
Pelikan Z: Delayed asthmatic response to bronchial challenge with allergen-mediators, eicosanoids, eosinophil and neutrophil constituents in the blood and urine. Respiration 2011;82:225-236.
19.
Gibson PG, Simpson JL, Saltos N: Heterogeneity of airway inflammation in persistent asthma: evidence of neutrophilic inflammation and increased sputum interleukin-8. Chest 2001;119:1329-1336.
20.
Fairs A, Agbetile J, Hargadon B, Bourne M, Monteiro WR, Brightling CE, Bradding P, Green RH, Mutalithas K, Desai D, Pavord ID, Wardlaw AJ, Pashley CH: IgE sensitization to Aspergillus fumigatus is associated with reduced lung function in asthma. Am J Respir Crit Care Med 2010;182:1362-1368.
21.
Park SJ, Wiekowski MT, Lira SA, Mehrad B: Neutrophils regulate airway responses in a model of fungal allergic airways disease. J Immunol 2006;176:2538-2545.
22.
Wenzel SE, Schwartz LB, Langmack EL, Halliday JL, Trudeau JB, Gibbs RL, Chu HW: Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Respir Crit Care Med 1999;160:1001-1008.
23.
Berry M, Morgan A, Shaw DE, Parker D, Green R, Brightling C, Bradding P, Wardlaw AJ, Pavord ID: Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax 2007;62:1043-1049.
24.
Cosmi L, Liotta F, Maggi E, Romagnani S, Annunziato F: Th17 cells: new players in asthma pathogenesis. Allergy 2011;66:989-998.
25.
Fitzpatrick AM, Holguin F, Teague WG, Brown LA: Alveolar macrophage phagocytosis is impaired in children with poorly controlled asthma. J Allergy Clin Immunol. 2008;121:1372-1378.
26.
Philippe B, Ibrahim-Granet O, Prévost MC, Gougerot-Pocidalo MA, Sanchez Perez M, Van der Meeren A, Latgé JP: Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates. Infect Immun 2003;71:3034-3042.
27.
Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG: Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care Med 2008;17:148-155.
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