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Epidemiologic studies suggest that increased concentrations of airborne spores of Aspergillus fumigatus closely relate to asthma aggravation. Chronic exposure to A. fumigatus aggravates airway inflammation, remodeling, and airway hyperresponsiveness in asthmatic rats. The effects of chronic exposure to A. fumigatus on epidermal growth factor receptor (EGFR) expression in the airway epithelial cells of asthmatic rats remain unclear. This study aimed to investigate the effects of chronic exposure to A. fumigatus on injury and shedding of airway epithelium, goblet cell metaplasia, and EGFR expression in the airway epithelial cells of asthmatic rats. A rat model of chronic asthma was established using ovalbumin (OVA) sensitization and challenge. Rats with chronic asthma were then exposed to long-term inhalation of spores of A. fumigatus, and the dynamic changes in injury and shedding of airway epithelium, goblet cell metaplasia, and EGFR expression were observed and analyzed. Chronic exposure to A. fumigatus could aggravate airway epithelial cell damage, upregulate the expression of EGFR and its ligands EGF and TGF-α, promote goblet cell metaplasia, and increase airway responsiveness in rats with asthma. Chronic exposure to A. fumigatus upregulates the expression of EGFR and its ligands in asthmatic rats. The EGFR pathway may play a role in asthma aggravation induced by exposure to A. fumigatus.

Objective: To explore the effects of chronic Aspergillus fumigatus (Af) exposure on the expression of mucin 5AC (MUC5AC) in the airways of asthmatic rats., Methods: Fifty-six male Wistar rats were randomly divided into 8 groups: chronic asthma (group A), chronic asthma plus Af spores inhalation for 1 week (group B), 3 weeks (group C) and 5 weeks (group D), chronic asthma plus saline inhalation for 5 weeks (group E), OVA-sensitized and-saline-challenged group (group F) and OVA-sensitized and-saline-challenged plus Af spores inhalation for 5 weeks (group G) (each n = 8). The airway resistance (Raw) and the change rate of Raw after acetylcholine provocation were detected using a computerized system. The level of MUC5AC mRNA in the lung tissue was measured by RT-PCR, and the expression of MUC5AC in airway epithelial cells were demonstrated by immunohistochemistry. The concentration of IL-13 in BALF was measured by ELISA. The extent of goblet cell hyperplasia was evaluated on periodic acid-Schiff stain (PAS) lung sections., Results: In group B, C, and D, the level of MUC5AC mRNA (MUC5AC mRNA/β-actin mRNA) (1.9 ± 0.4, 2.3 ± 0.6, 2.9 ± 0.8, respectively), the integrated optical density (value A) of MUC5AC positive stain in airway epithelial cells (278 ± 58, 566 ± 64, 891 ± 80, respectively), the concentration of IL-13 in BALF (µg/L) (96 ± 16, 136 ± 22, 197 ± 34, respectively), and the ratio of goblet cell area to epithelial cell area(%) (16 ± 5, 23 ± 7, 36 ± 9, respectively), were higher than those in group A, E, F and G (all P < 0.05). The change rate of Raw(%) in group C and D (61.91 ± 5.26 and 84.69 ± 6.38) were higher than that in group A, E, F and G (all P < 0.05). The level of MUC5AC mRNA and the value A of MUC5AC were positively correlated with the ratio of goblet cell area to epithelial cell area (r = 0.578, P < 0.05;r = 0.614, P < 0.05, respectively) and the change rate of Raw (r = 0.638, P < 0.05;r = 0.564, P < 0.05, respectively) in group B, C and D., Conclusion: Chronic Aspergillus fumigatus exposure upregulated the expression of MUC5AC in the airway epithelial cells and induced goblet cell hyperplasia, resulting in increased airway hypersensitivity in rats with chronic asthma.

Background: Airway mucus hypersecretion is associated with increased morbidity and mortality in patients with asthma. Chronic Aspergillus fumigatus (A. fumigatus) exposure leads to aggravation of airway inflammation and remodeling, including goblet cell hyperplasia (GCH) and mucus hypersecretion in a rat model of asthma. The effects of chronic A. fumigatus exposure on the expression of airway mucin 5AC (MUC5AC) are unknown., Methods: The rat model of chronic asthma was set up by systemic sensitization and repeated challenge to ovalbumin (OVA). The asthmatic rats were exposed to chronic intranasal inhalation of A. fumigatus spores. The changes of MUC5AC expression, the extent of GCH, and airway hyperreactivity (AHR) were measured after exposure to the fungus., Results and Conclusions: Chronic exposure to A. fumigatus upregulates the expression of MUC5AC, and induces GCH in the airways of asthma rats, and the remodeling changes of the airway epithelium was positively correlated with AHR. Upregulation of MUC5AC and induction of GCH may be mechanisms by which chronic A. fumigatus exposure promotes the progression of asthma.

Background and Objective: Epidemiological evidence indicates a close link between exposure to fungi and deterioration of asthma. However, the role of fungi as an exogenous precipitant for initiation and progression of asthma has been incompletely explored. In this study, the effects of Aspergillus fumigatus exposure on airway inflammation and remodelling in a rat model of chronic asthma were investigated., Methods: The rat model of chronic asthma was established by systemic sensitization and repeated challenge with ovalbumin (OVA). The asthmatic rats were exposed to chronic intranasal inhalation of A. fumigatus spores. Changes in airway inflammation, remodelling and BHR were measured after exposure to the fungus., Results: Chronic inhalation of A. fumigatus spores elevated the production of T helper 2 (Th2) cytokines, increased the concentration of total serum IgE, and resulted in the recruitment of eosinophils and lymphocyte infiltration into the airways of asthmatic rats. Goblet cell hyperplasia, mucus hyperproduction and subepithelial collagen deposition were also induced by inhalation of the fungus. The remodelling changes induced by inhalation of the fungus paralleled the changes in BHR in this rat model of asthma., Conclusions: Chronic exposure to A. fumigatus aggravated Th2 airway inflammation, promoted airway remodelling and increased BHR in OVA-sensitized and -challenged rats.