Otitis media with effusion in an allergic animal model: A functional and morphological study

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Abstract

Objectives

Allergy is considered as one of important etiologic factor of otitis media with effusion (OME). In present study, we evaluated the causal effect of allergy on OME in an animal model, and investigated the secondary effect of bacterial infection.

Methods

Allergy and control animals were subdivided into groups with and without intratympanic injection of lipopolysaccharide (IT-LPS). Allergic otitis media was induced via intraperitoneal ovo-albumin injection with intranasal challenge. We assessed the occurrence of OME in allergic animals and the effect of IT-LPS on allergic otitis media. We also investigated the Th1 and Th2 responses in the middle-ear mucosa. Hearing of the animals was measured by ABR and DPOAE.

Results

OME was observed in 75% of the allergic animals. After IT-LPS, 100% of the control and allergy groups showed otitis media. Light microscopy revealed that the middle-ear mucosa of animals of both groups also was significantly increased after IT-LPS, and the Th1 response (IL-2 and IFN-γ) and Th2 response (IL-5 and IL-13) cytokines were expressed at higher levels in the allergy group with IT-LPS than in control group with IT-LPS. Hearing tests between the allergy and control group with IT-LPS did not reveal any differences.

Conclusion

Our findings may be direct evidence of an allergic causal effect on OME. Th2 response cytokines were strongly expressed in allergic OME, and the inflammatory reaction to LPS was more intense in the allergic group, which indicates that otitis media related to allergy can be severely aggravated by an inflammatory reaction to bacterial infection.

Introduction

Otitis media with effusion (OME) is the most prevalent ear disease in children, and is a common cause of hearing impairment. Among the host factors associated with the onset of OME are bacterial infections, Eustachian tube dysfunction, allergic and immunologic factors, genetic factors, breast feeding, gender, and race, OME may also be associated with environmental factors, including communal living and unhygienic habits, and anatomical and physiologic factors, including cleft palate and Down's syndrome, which often accompany Eustachian tube dysfunction [1].

As an etiologic factor of OME, the relationship between allergic rhinitis (AR) and OME has been investigated widely. In many epidemiologic surveys of OME and AR, AR was an important risk factor for OME [2]. Kwon et al. [3] in 2013 found a prevalence of AR of 33.8% in a group of 370 patients affected by OME, which was significantly higher than the 16% prevalence in a control group of 100 children without OME. Tomonaga et al. [4] revealed that among 259 pediatric patients diagnosed with OME, 50% had comorbid AR, defined as having two or more of the following: positive SPT, nasal eosinophilia, or elevated serum IgE following nasal provocation test.

However, the mechanism by which AR causes or aggravates OME, or whether OME related to AR has a different reaction to bacterial infections with OME related other etiologic factors, have not yet been fully elucidated. In this study, we generated an animal model of otitis media with upper airway allergy using ovo-albumin, and investigated the rate of occurrence of otitis media. We also investigated the immunologic reactions to lipopolysaccharide (LPS) following its intratympanic injection. Our findings improve our understanding of the relationship between OME and allergy.

Section snippets

Design of experiments

Firstly, we investigated whether allergic reactions occur in the middle ear after allergy induction in the upper airway, and secondly, we evaluated the reaction to LPS injected intratympanically in both the allergy-induced and control groups.

We also evaluated the occurrence and severity of otitis media in animals using an oto-endoscope to inspect the tympanic membrane, and performed audiologic tests including distortion product optoacoustic emission (DPOAE) and auditory brainstem responses

Otitis media occurrence with allergy induction

In the nasal mucosa of both groups, allergy induction by OVA in the allergy group was confirmed by significantly higher mean eosinophil counts than in the control group (Fig. 3).

After allergy induction, five ears from the allergy group showed redness of the tympanic membranes (62.5%), and six ears showed effusion in the middle ear (75%) among eight ears of the allergy group. In audiologic tests, the mean threshold in ABR of the allergy group was higher, and the mean response in DPOAE of the

Discussion

In the present study, otitis media occurred only following upper airway allergy induction. 75% of ears in the allergy group showed infection or effusion in the middle ear, which confirmed that otitis media with effusion could be induced by upper airway allergy (Fig. 3, Fig. 4, Fig. 5). Bluestone [7] suggested four possible mechanisms by which allergy could be responsible for production of OME: (1) the middle ear functioning as a “shock organ,” (2) inflammatory swelling of the ET, (3)

Acknowledgments

This study was supported by a grant from the Department of Otolaryngology and Head and Neck Surgery Fund of the Catholic University of Korea in the program year of 2013, a grant from the Basic Science Research Program of the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (2013-011870), and a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future

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