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Background and aims: Epidemiological evidence examining the role of atopy and/or allergy in the pathogenesis of otitis media with effusion (OME) is inconclusive. The aim of this study was to assess any increased risk for OME attributable to allergy-related factors, in a well-characterized population using a case-control design and multivariate analysis.
Subjects and methods: Eighty-eight 1–7-year-old children with OME, diagnosed by clinical and tympanometric evaluation and 80 matched controls were enrolled. A standardized questionnaire was completed, in order to assess factors related to OME and allergy-related symptoms and diagnoses using strict clinical definitions. Specific IgE was measured by skin-prick tests and/or CAP-FEIA.
Results: The patient and control groups were well matched. Factors conferring increased risk for OME in the univariate analysis included IgE sensitization, dyspnea, wheezing, asthma, paroxysmal sneezing, rhinitis, eczema, ‘any allergic disease,’ family history of otitis media, and family history of allergy. After multivariate analysis IgE sensitization, wheezing, nasal obstruction, family history of otitis, and child-care attendance remained as independent risk factors for development of OME.
Conclusion: IgE sensitization and respiratory allergy symptoms are independent risk factors for the development of OME, suggesting that both immunological and mechanical pathways may contribute to the development of the disease. Otitis heritability provides additional risk, as well as frequent exposure to viral upper respiratory tract infections in children attending daycare. Treatment and/or prevention of OME using anti-allergic medications should be further examined.
Otitis media with effusion (OME) involves the accumulation of middle ear effusion (MEE) behind an intact tympanic membrane (TM) without signs or symptoms of acute infection. Otitis media with effusion is affecting up to 80% of preschool children at some time (1) and is the commonest cause of hearing loss in children in developed countries (2), potentially leading to language deficits (3). Therefore, effective prevention and treatment is considered imperative. However, current management options have been relatively suboptimal (3), leading many researchers during the last decades to attempt clarifying its unclear pathophysiology.
The possibility that allergy contributes to OME has been extensively discussed, but not conclusively ascertained (3–6). Analyses of the effusion content have consistently revealed significantly elevated levels of allergy-related mediators (IL-4, IL-5, IL-6, RANTES, ECP, tryptase, IgE), as well as differences between atopic and nonatopic patients with OME (7–10). However, epidemiological studies on OME have been controversial in this respect, showing increased (11, 12), or not affected (13, 14) prevalence of atopy and/or allergic diseases in OME patients. It has also been uncertain whether IgE sensitization per se, or clinical allergic disease(s) associated with mechanical eustachian tube (ET) dysfunction are involved in any reported associations (15–17). Factors that may explain this confusion include discrepancies in the definition of allergy, atopy, and IgE sensitization among different studies, nonhomogeneous patient populations, noncontrolled study designs, and lack of power.
We hypothesized that IgE sensitization, allergic diseases or both predispose to the development of OME. The aim of this study was to assess any increased risk for OME attributable to the above factors, in a well-characterized population using a case-control design and multivariate analysis.
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- Subjects and methods
To our knowledge, this is the first study to describe concurrent and independent associations of OME with IgE sensitization, allergy-related symptoms and otitis heritability, conclusively confirming previously suggested relationships between allergic disease and OME.
A number of studies have attempted in the past to assess possible links between IgE-mediated allergy and OME (11, 12, 14, 16, 25–27). However, in none of these studies there was an adjustment for the effects of possible confounders and none made an attempt to differentiate between the components of atopic disease: IgE sensitization, symptoms, and heritability.
A high incidence of atopic disease among children with OME was initially reported in 1983 (11). An association between OME and IgE sensitization was described a decade later (12). However, in other similar studies the results were conflicting (13, 14). These discrepancies may be attributed to study design, including diagnostic criteria for allergy and differing populations.
Such potential problems were taken into account in the design of the present study. The population sample was restricted to the sensitive age range of 1–7 years; cases and controls were well matched; adenoidal hypertrophy, a factor associated with OME and possibly with allergy (24, 28), was also matched between the groups. Among exposure parameters, only daycare attendance was found to be more common in children with OME, remaining marginally significant after being included in the multivariate model. This is most probably related to increased frequency of viral respiratory infections, which are also the main triggers of rhinitis and acute asthma exacerbations (29).
The most important finding of this study is the demonstration of independent risk components associated with OME. It is not surprising that symptoms of respiratory allergy were independent risk factors for OME, while eczema was not. Several epidemiological studies, as also this one, have documented associations between OME and allergic rhinitis (14–16). Experimental studies have shown a transient tubal dysfunction, evoked by nasal allergic reactions in sensitized animal models or patients with allergic rhinitis, without however resulting in MEE or histological change in the tympanic cavity (15, 17). On the other hand, anti-genic challenge into the tympanic cavity results in mucosal changes and mucociliary clearance impairment (17). Middle ear effusion can be produced after transtympanic injection of ovalbumin in sensitized rats, reduced after pretreatment with diphenhydramine (30). These observations suggested that allergic rhinitis-associated mechanical ET dysfunction might not be sufficient for the accumulation of MEE.
This is also supported by our finding that history of wheezing was in this study the strongest factor associated with OME development, independent of IgE sensitization and rhinitis. A mechanical effect of wheezing on ET function could be proposed as an explanation, however, this is not very likely, as wheezing in this age group is usually intermittent and of short duration. It is possible that additional mechanisms, such as epithelial dysfunction or defective responses to viral infections (31, 32) observed in asthmatic individuals, may also affect the middle ear, although these hypotheses require further evaluation.
In this respect, it is also interesting to note that associations with OME were stronger when IgE-mediated diagnoses were analyzed. The fact that IgE sensitization is independently associated with OME shows that immunological parameters, unrelated to mechanical obstruction, are associated with the disease: this supports previous suggestions that the middle ear may serve as a target organ for allergic reactions (33) and/or that the consequences of atopy, related to defective reactions to external stimuli, may also affect the middle ear.
Consequently, an augmented inflammatory response in the middle ear mucosa and a disruptive effusion clearance may act together for the development of OME.
An association of food allergy with OME has been reported in the past (25). This was not confirmed in our study, however, the etiology of reported food reactions was not properly evaluated in this study; it is well documented that only a small proportion of reported food reactions are true food allergy, or even hypersensitivity reactions (21).
A heritable predisposition for OME was also observed, as increased risk by both family history of OM and family history of allergy, of which the former was stronger and remained significant in the multivariate analysis. This is in agreement with previous epidemiological reports (34, 35), and it may represent additional factors, such as, e.g. anatomical variability, however, it may certainly be a composition of several heritability predispositions, including susceptibility to viral infection and/or allergic disease.
The main limitation of this study is the fact that it did not include objective measures for allergic disease diagnosis. However, objective measures of asthma and rhinitis at this age group are rather cumbersome and not completely reliable, while objective assessment of food and drug allergy requires double-blind challenges, which were out of the scope of this study. An objective measure (tympanogram) was used for the diagnosis of OME.
In conclusion, our results demonstrate that OME is independently associated with IgE sensitization, symptoms of respiratory allergy, and otitis heritability. Additionally, they are suggestive of an interaction of allergy and viral infections in the upper airways, leading to an increased risk of MEE development. Among the above factors, symptoms of respiratory allergy are the most straightforward targets for possible intervention; the effectiveness of relevant medications in preventing and/or treating OME should now be scrutinized.