The middle ear The inflammatory response in children with otitis media with effusion and the impact of atopy : clinical and histochemical studies

Abstract: Otitis media with effusion (OME) is the major form of chronic relapsing inflammatory disease of the middle ear, constitutes the most common diagnosis for children under 15 years old and is the major cause of auditory dysfunction in pre-school children. OME is a disease more commonly found in allergic children. These studies sought to investigate the inflammatory response in the middle ear of patients and test the hypothesis that an allergic-like response might occur in the ear. Atopy was diagnosed by standard in vitro tests. Immunochemical techniques used to study classic allergic rhinitis and asthma were extrapolated to the evaluation of OME children whose effusion persisted beyond 2 months. Not only eosinophil cationic protein (ECP), tryptase, CD3-positive and IL-5 producing cells, but also myeloperoxidase (MPO) was found in middle ear fluid and/or mucosa in the majority of patients with OME and atopy. Initially, levels of ECP, MPO, and tryptase were measured in effusions from 97 random OME patients whose atopic status was determined by in vitro testing to 12 inhalants and 5 foods. The response of eosinophils, neutrophils and mast cells in the middle ear was distinctly different between atopic and non-atopic patients (p<0.001) with higher levels of the cell markers in the atopic group of patients. This suggested that 1) perhaps OME was predominantly a disease of atopics and that 2) they differed in their response from non-atopics.Tryptase was measured in middle ear effusions from 38 patients with OME, 94.7% of whom were atopic by in vitro testing. Tryptase was elevated only in the effusion of atopic patients as compared to 5 controls (p<0.01). Biopsies stained histochemically for tryptase showed evidence of mast cells in the mucosa and submucosa from 6 of 8 OME ears but absent in 4 normals.Middle ear biopsies, embedded in a plastic resin to improve the structural preservation, from 5 patients with OME and 5 normals were evaluated for the presence of eosinophils and neutrophils with monoclonal antibodies against 4 specific granule proteins. Eosinophils and neutrophils were present in the mucosa and mucus in significantly higher numbers than in the control group.In an effort to determine whether the middle ear itself might be involved in allergic disease, evidence that some of the cells, mediators and cytokines associated specifically with a Th-2 response were sought for in the middle ear mucosa of these children. Middle ear biopsies from 7 atopic patients with OME and 4 controls demonstrated the presence of activated eosinophils, CD-3+ T cells and IL-5 mRNA cells only in the mucosa from atopic OME children. Conclusion: Effusion and mucosal biopsies containing ECP, tryptase, and/or IL-5 mRNA cells, CD3+ T cells, eosinophils, and mast cells indicate that many of the mediators and cells essential to the production of a Th-2 immune mediated response are present in ears with chronic effusion. The increased levels of MPO in atopic patients further suggest that the general inflammatory response to putative inciting agents such as bacterial and viral products may be altered in atopy. These studies support the hypothesis that the exaggerated inflammation within the middle ear associated with most cases of OME is possibly the result of an atopic response within the middle ear itself.