Chronic rhinosinusitis: An enhanced immune response to ubiquitous airborne fungi

Chronic rhinosinusitis (CRS) is one of the most common long-term illnesses in the United States. The etiology of CRS is unknown, and no effective treatment has been established. We investigated the hypothesis that abnormal immunologic responses to ubiquitous airborne fungi contribute to the pathogenesis of this disease. The proliferative and cytokine responses of PBMCs to extracts from 4 common airborne fungi - including Alternaria, Aspergillus, Cladosporium, and Penicillium - were examined by in vitro culture. Serum specimens were tested for specific IgE and IgG to these fungi. PBMCs from approximately 90% of the patients with CRS, but not those from normal individuals, produced both IL-5 and IL-13 when exposed to Alternaria. Furthermore, PBMCs from patients with CRS produced significantly more IFN-γ than PBMCs from normal individuals in response to Alternaria (median, 553 pg/mL vs 98 pg/mL; P <. 01). Levels of serum IgG antibodies to Alternaria and Cladosporium were clearly increased in patients with CRS compared with normal individuals (P <. 01). Less than 30% of the patients with CRS had specific IgE antibodies to Alternaria or Cladosporium. The increased humoral (serum IgG) response strongly correlated with the increased cellular (IL-5 production) response to Alternaria (r = 0.619; P <. 01). Patients with CRS show exaggerated humoral and cellular responses, both T _h1 and T _h2 types, to common airborne fungi, particularly Alternaria. The anomalous immune and inflammatory responses to ubiquitous fungi may explain the chronicity of airway inflammation in CRS.