Laboratory Evidence and biomarkers linking allergic inflammation to increased risk of middle ear inflammation.
Several authors have tried to show an association between allergy and middle ear inflammation by animal studies as well as experimental human models. The phenotype more frequently involved in these studies was OME as reported in table 1. The inflammatory substrate observed in atopic OME patients seems to be similar to that of the late phase of allergic response in AR and asthma patients.Several authors15-17have demonstrated a higher percentage of TH-2 mediators, (eosinophils, T-lymphocytes, IL-4 and IL-5), as well as a hyper-expression of major basic protein and eosinophilic cationic protein in the middle ear fluid, adenoid tissue, and middle ear mucosa in atopic versus non-atopic children with OME. Several other cytokines as tumor necrosis factor alfa, IL-1b, IL-13, IL-6, and IL-8 are elevated in middle ear fluid in children with OME.18 Smirnova et al. have demonstrated that these cytokines might play a role as molecular regulators of middle ear inflammation switching the acute phase of inflammation to the chronic stage.19Furthermore, histologic studies have demonstrated that there is an increased level of IL-4, IL-5, and eosinophils not only in middle ear fluid but also at both ends of the ET suggesting again the possibility of activating an allergic mechanism in sensitized children.20Accordingly, some authors observed a significantly lower rate of neutrophils and IFN-gamma (predominant in TH-1 inflammatory response) in atopic vs non-atopic OME.16
Previous authors have demonstrated that allergic inflammation in the ear of children with OME is similar to that of other target organs confirming the hypothesis that ear is part of unified airway.21, 22In addition, animal models demonstrated that middle ear effusion can be preventedby inhibiting allergy cytokines.22
Experimental evidence showed that trans-tympanic histamine challenge compromise muco-ciliary clearance and ventilating function of ET in rat models.23In particular, Hardy et al.24 demonstrated that late-phase allergy leads to significant ET dysfunction and subsequent formation of effusion by impairing the ventilatory and clearance function of the ET. Furthermore, Pollok et al.25 demonstrated that the late-phase allergic inflammatory response and middle ear effusion may be prevented by pre-treatment with soluble interleukin (IL)-4 receptors (sIL-4R) and more modestly with IL-5 antibodies (IL-5Ab).
The most relevant articles included in the qualitative analyses are summarized in table 1. The majority of articles supports the link between allergy and otitis media with effusion.