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.