Airway surface mycosis in chronic T_H2-associated airway disease

Background Environmental fungi have been linked to T_H2 cell-related airway inflammation and the T_H2-associated chronic airway diseases asthma, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. Objective To determine the frequency of fungus isolation and fungus-specific immunity in patients with T_H2-associated and non-T _H2-associated airway disease. Methods Sinus lavage fluid and blood were collected from sinus surgery patients (n = 118) including patients with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non-CRS/nonasthmatic control patients. Asthma status was determined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked immunocell spot assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared with fungus-specific IgE levels measured from plasma by ELISA. Results Filamentous fungi were significantly more commonly cultured in patients with T_H2-associated airway disease (asthma, CRSwNP, or AFRS: n = 68) than in control patients with non-T _H2-associated disease (n = 31): 74% vs 16%, respectively (P <.001). Both fungus-specific IL-4 enzyme-linked immunocell spot (n = 48) and specific IgE (n = 70) data correlated with T_H2-associated diseases (sensitivity 73% and specificity 100% vs 50% and 77%, respectively). Conclusions The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with T _H2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients.