INTRODUCTION
Otitis media with effusion (OME) is a chronic otitis media with inflammatory effusion in the middle ear. Inflammation causes a thickening of the mucosa within the middle ear cleft which, by modifying the gas exchange capacities, is responsible for a decrease in the partial pressure of oxygen facilitating the retraction of the tympanic membrane (TM) (1). In children, inflammation often arises via an infectious origin by contamination of middle ear cavities via the Eustachian tube.
The diagnosis of OME is clinical, by otoscopy and by tympanometry (2). The exact incidence of OME is unknown, due to the nature of the disease which can be asymptomatic. However, it is thought to be up to 50% children under 12 months of age and 60% children at the age of 2 years. A study conducted with systematic screening of children aged 1 to 4 years suggests a prevalence between 15 and 40% (3).
OME can lead to structural changes in the TM (4)(17). Tympanosclerosis plaques are classic and not dangerous, but atrophy of the eardrum can lead to retraction pockets, and then into more significant disease such as cholesteatoma or chronic adhesive otitis media (5) (6). In otoscopy, atrophy appears as a thin, partially or totally transparent eardrum (8). Histologically, the atrophy of the pars tensa is explained by the destruction of type IV collagen fibers of the lamina propria (7), and it has been suggested that the activity of matrix metalloproteinase are involved in destruction of tympanic membrane fibrous layer (9).
An increase in matrix metalloproteinase (MMP) activity may be present in OME. MMPs are a multigenic family (25 members and 7 different classes) of zinc-dependent, secretory or membrane enzymes. They control the activity of extracellular matrix proteins by proteolytic cleavage. Their targets include membrane-bound or soluble molecules involved in the transmission of intercellular signals such as cytokines, chemokines, trophic factors, adherence proteins and different receptors. Correlation has been demonstrated between significant activity of MMP-2 and 9 (gelatinases), MMP-3 (stromelysin 1) and 7 (matrilysin 1) and MMP-8 (collagenase-2) and the viscosity of the effusion (7) (10) (11) (12). Each MMP is specific to one or more component of the extracellular matrix (13). Gelatinases (MMP-2, MMP-9) are the fourth class of MMPs, and their proteolytic activity is directed against denatured interstitial collagen (gelatin) and type IV and V collagens of basal membranes. MMP-9 (gelatinase-B) expression is low or absent in normal tissues and limited to monocytes and macrophages. MMP-7 (matrilysin-1) is part of the matrilysin group, and is specifically expressed by tumoral epithelial cells. Its proteolytic spectra are partially divergent but include fibronectin and gelatin.
In tissues, the proteolytic activity of MMPs is controlled by four inhibitors called TIMPs (tissue inhibitors of metalloproteinases) (14). TIMPs (TIMP-1 to TIMP-4) are endogenous inhibitors of activated MMPs. The MMP/TIMP system controls the cell-cell and cell-matrix interactions involved in many physiological processes, including proliferation, differentiation, migration and cell death. TIMP-2 works as an MMP inhibitor but also as an activator since it inhibits the active form of MMPs and activates proMMPs. Thanks to their C-terminal domain, there is a specificity between MMP and TIMP types, TIMP-2 is an inhibitor that binds specifically to MMP-2.
In France, insertion of VT is the second most frequent ENT surgery procedure after tonsillectomies and/or adenoidectomies. This surgery is indicated for auditory and/or infectious reasons and/or OME complicated with TM atrophy with posterior mesotympanic retraction (2). Studies are inconclusive about the effectiveness of VTs on the development of tympanic atrophy (15) (16). The inter-individual variability of the lytic activity of OME liquids, both in its composition and/or enzymatic concentration, could explain the difficulty to statistically demonstrate the efficacy of VT in preventing the development of atrophy.
The purpose of this study was to assess a correlation between the presence of eardrum atrophy and the level of MMP-2, MMP-9, MMP-7, TIMP-2 in OME effusion. The secondary objective was to determine if there is a relationship between the level of MMPs and TIMP-2 and the patient’s age, gender, history of VT insertion, thickness of the glue (mucous or serous), and hearing loss.