Journal of Otology & Rhinology.ISSN: 2324-8785

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Commentary, J Otol Rhinol Vol: 4 Issue: 5

Pathophysiology of Otitis Media with Effusion: Consequences for Treatment and Research

Alexander de Ru*
Department of Otorhinolaryngology-Head and Neck Surgery, Central Military Hospital, Utrecht, The Netherlands
Corresponding author : Dr. Alexander de Ru
Department of Otorhinolaryngology-Head and Neck Surgery, Central Military Hospital, Utrecht, The Netherlands
E-mail: [email protected]
Received: December 29, 2014 Accepted: July 02, 2015 Published: July 06, 2015
Citation: De Ru JA(2015) Pathophysiology of Otitis media with Effusion: Consequences for Treatment and Research. J Otol Rhinol 4:4. doi:10.4172/2324-8785.1000235

Abstract

Otitis media with effusion (OME) is highly prevalent among young children. The precise pathophysiological mechanism, the long-term consequences, and the best treatment of OME remain unclear. The most important factor in overcoming OME seems to be maturation. Literature shows evidence of an infectious etiology of OME. But often articles are contradictory with regard to singular causative factors. So, although OME is correlated with various patient characteristics and socio-economic factors, none of these has been identified as the sole causative factor. This could be due to the fact that many studies have lumped all forms of OME together, instead of applying differentiation based on varying causative factors.

The objective of this manuscript is to support the hypothesis that the thick glue, that is the predominant sign of OME, is not a disease in itself, but a barrier that may actually protect the middle ear against invading bacteria. This would render OME a mere defence reaction - a necessary consequence following a variety of infectious causes - instead of the disease itself. In this new way of thinking the thick glue that is actively secreted by the middle ear mucosa, ensures that an antimicrobial milieu is locally present. Therefore, resolving the glue itself is not a prerequisite; the underlying gap in the defence - which necessitates glue formation - should be closed.

Various consequences of the idea that OME is part of the middle ear defence are common practice and concur with the guidelines on this subject. Since OME is generally self-limiting and resolves with age; restrictive management is indicated. Treatment, especially of the underlying cause, should be tailor-made for each individual child.

Keywords: Otitis media; Pathogenesis; Therapy; Hearing loss; Adenoidectomy; Ventilation tube

Keywords

Otitis media; Pathogenesis; Therapy; Hearing loss; Adenoidectomy; Ventilation tube

Opinion

OME versus OMA
It has been stated that ‘otitis media’ continues to be one of the most common childhood diseases [1]. I would like to state that there is not just one ‘otitis media’. Otitis media acuta (OMA) and otitis media with effusion (OME) have been described as different stages of the otitis media continuum and I agree with that statement [2].
However, both ends of the spectrum differ so much that we should differentiate between OME on the one hand, and OMA on the other. OMA is a disease that causes both pain and fever, and it may lead to both extra- and/or intracranial complications. Without any doubt a clinical infection.
OME, on the other hand, can be the residual phenomenon following OMA – a spectrum in time. However, from the moment that OME exists, the clinical picture usually improves significantly. Fever and pain make place for an annoying, but rather innocent, conductive hearing loss.
Multifactorial origin of OME
OME is a frequently occurring ‘disorder’; the point prevalence of middle ear effusion on screening tests in young children is about 20%. OME is an often-mentioned reason for a visit to the doctor’s office and the subsequent prescription of antibiotics [1,3-5]. The annual cost estimate of OME in the United States is 4 billion dollars [1].
Recent guidelines from otologists, paediatricians, and allergists describe OME as a multifactorial disease related to the dysfunction of the Eustachian tube that is generally related to upper respiratory tract infections, adenoid hypertrophy, and craniofacial malformations such as cleft palate deformities and Down syndrome. Clinical evidence also supports an important role of atopy in the development of OME [6].
Accordingly, it has been stated that OME is a multi-factorial disease; the resulting consequence of interaction between the microbial load and the immune response [1]. All factors known to cause otitis media are related to these two core elements [1]. This statement however- though I agree with the multi-factorial origin - applies to all infectious diseases and does therefore not provide any clarity with regard to the etiology nor to the advisability of treatment.
The immaturity of both the immune system and the local defence system appear to be the most important contributing factors to OME. In the past it has been suggested that OME could function in defence - an immune response by the body in childhood - in order to protect the middle ear [7]. Once children reach age 5 to 7 the incidence decreases drastically. The glue that is formed contains the best antimicrobial elements that the human body can produce such as lactoferrin, lysozyme, immunoglobulins and complement components [7]. These are actively secreted. Thus, we may conclude that it is a most hostile environment for bacteria, and more than likely the best treatment against infection that the middle ear can produce.
Clinical support for this premise is found in the following remarks: “the only cure is a continued development of a child’s immune system” [8]. Until that time, we will have to rely on “parental education and avoidance of unproven therapies” [8].
The aforementioned articles were critical with regard to the effects of currently available treatments to ‘cure’ OME, also questioning the necessity of treatment in itself [7,8]. Since the publication of these articles the dust has far from settled [9]. In light of the large impact that OME has on the overall cost of the health care system, it seems worthwhile to revisit this discussion.
OME the defensive consequence following a variety of infectious causes
In my opinion, OME appears to be a necessary defence reaction provoked by many different factors that make the middle ear more susceptible to infection. In this scenario the thick glue may also function as a barrier to ascending bacteria from the nasopharynx [10].
Instead of large studies that lump all OME together, I suggest that we differentiate between OME based on the various possible underlying causes. This may lead to many different treatment options for as many different patients, instead of one consistent therapy for all.
In my opinion, it is questionable whether OME is really an ongoing infection that we need to deal with. Bacterial cultures of middle ear fluid do not provide us with a pathogen in over fifty percent of all cases, and antibiotics only provide a minimally healing effect. This strengthens my belief in the hypothesis that the development of OME is a ‘defensive reaction’ in order to protect the middle ear, when other components of the human immune system and defence (both regional and systemic) have failed to prevent infection [7]. Various levels of resistance could be implicated in this failure, such as inadequate antibody formation, craniofacial deformities, Down syndrome, or Kartagener syndrome [11]. Other contributing factors – among others - are Eustachian tube dysfunction, persistent upper respiratory tract infections, and chronic inflammation [1,4,5]. The need to secrete the ‘glue’ might be increased due to other local factors that cause damage to the mucosa such as allergy and reflux that leave the middle ear more susceptible to infection. Extrinsic factors like exposure to tobacco smoke; exposure to day care, and a lack of access to adequate medical care also play a role. All of these completely different causes and factors would, as a consequence, require totally different forms of treatment [11].
Thus, it would be very important to discriminate the one patient with OME from the other, as it simply is not a singular ‘disease’. OME appears to be a mere sign of the reaction that takes place due to a failing ‘defence’ (or higher microbial load) at another ‘level or levels’. So, in many cases a policy of watchful waiting until the child has strengthened those other parts of the defence system appears to be wholly justified.
OME and biofilm
One of the newer insights is the existence of a bacterial bio-film in the middle ear [12]. This bio-film may explain why using the PCRmethod allows the measurement of active bacteria in a middle ear secretion that otherwise yields a negative culture. Such a bio-film would also be responsible for the increased resistance to antibiotics that these bacteria display, which would supposedly make them, better equipped to evade the body’s natural immune response.
However, the fact that research shows the existence of bacteria in a bio-film is not actually significant in itself, especially not, when we consider that this bio-film apparently cannot cause serious infection. It may, however, provide us with sufficient cause to reverse our thinking [11]. In other words, the body is capable of building such a strong defence, i.e. the effusion that bacteria -trapped in the thick glue- can only survive in a ‘bio-film’.
Adenoidectomy
If treatment is at all necessary, adenoidectomy appears to be one of the best forms of treatment. Adenoidectomy will reduce the number of infections, as well as the source of those infections [13]. However, as OME is a multifactorial sign it stands to reason that not all patients will be cured by means of an adenoidectomy (perhaps a mere 10%) and of course, only those patients with chronic adenoiditis/ adenoid hypertrophy as an underlying cause. This procedure, like any other treatment for OME, cannot guarantee non-recurrence. This as a consequence of adenoid re-growth or persistent adenoiditis - the adenoid is never removed in total. The recurrence of this ‘disorder’ can also be due to all of the other causative factors – such as allergy for example- as described above.
Antibiotics
Antibiotics can partially resolve the problem by eliminating some of the bacterial load. However, the clinical effect is only marginal [14]. Recently, it was postulated that a long-term therapy of antibiotics might be appropriate for specific patient populations suffering from OME. In that study, a group of patients was treated for a 24-week period. In view of the fact that within this ethnic patient population eardrum perforation occurred in 25 percent of the children, it seems appropriate to try and decrease this percentage in order to improve the long-term socio-economic status of this specific group (Aboriginal children in Australia) [15].
However, the benefits of treatment with antibiotics appear to be limited, which leaves us with the question whether the slight advantage outweighs the risk of developing resistance to antibiotics as a consequence of long-term treatment [11]. Especially, when one takes into account that the large perforations due to otitis media do not occur as frequently in Western Europe or the United States. Moreover, it has been established that the patient population of the previously mentioned study was exposed to parental smoking, and that formal childcare was largely unavailable [15]. This again leaves us with the question whether perhaps parental education would result in a more significant beneficial effect.
I concur with a significant reduction in the prescription of antibiotics as treatment for OME. More so, as prescribing antibiotics for OME leads to more frequent visits to the doctor’s office on account of recurring ear infections, which exerts even more pressure on the already overloaded health care system [16].
Gastro-intestinal reflux
In the meantime, there is mounting evidence that gastrointestinal reflux may be a contributing factor to OME, which is based on the established presence of bile salts in the middle ear fluid [17,18]. And although reflux most definitely could contribute to the pathogenesis, it is perfectly clear that most of the currently used treatments (antibiotics, grommets, and adenoidectomy) will neither prevent reflux from occurring, nor will they prevent the subsequent damage to the mucosa.
This finding does lend more credence, in particular, to the premise that once children start spending more time in an upright position rather than supine, OME is mostly self-limiting. One wonders whether treatment with acid inhibitors might be an option [11]. However, positive results with this kind of treatment are still scarce.
Allergy
What about allergy and its treatment? Allergies are mentioned in greatly varying percentages; anywhere from 24% to 80%. It might be one of the most common underlying factors in children with no apparent other infections [6]. As for a treatment option, we know that a nasal spray was successfully administered in the one study; however, another study could not duplicate these results [19-21]. This could be due to the differences in patients that were included in these studies. A number of patients included in the study that reported successful treatment with corticosteroid nasal spray were scheduled for grommets and adenoidectomy, which suggests that these patients had more rhinological (allergic) symptoms and were, therefore, more likely to benefit from said treatment. The patients in the study with a negative result belonged to a small subgroup of patients with nonresolving bilateral OME [11].
Personally, I think that anti-reflux and anti-allergic therapy can be helpful treatment options in some children. We do however, need to clearly differentiate between those children that might benefit from these various forms of treatment and the ones that do not. I am sure that not all patients with OME suffer from this disease as a consequence of reflux. Thus, administering a therapy aimed at reflux to an entire study population is not a logical procedure. Likewise, patients with an allergic rhinitis as a co-factor might benefit from a corticosteroid nasal spray. However, again, this therapy should not be used for every patient. Moreover, including every patient with OME in a study on anti-reflux medication or corticosteroids does not make any sense either. If we want to study the possible effects of allergy treatment on OME, we need to include patients with both an allergy and OME. And it follows that we should differentiate patients similarly for any other type of treatment.
Ventilation tubes
Furthermore, it has been established that over time the insertion of ventilation tubes in childhood causes more hearing loss than an expectant observational policy [22].
The natural course of most eardrum pathology associated with otitis media tends to be favorable, however, tympanosclerosis (myringosclerosis), which is predominantly associated with the insertion of grommets, shows the least tendency towards recovery [23].
Moreover, the acoustic reflex is impaired in patients that have previously been treated with grommets [24]. Hypothetically, this could mean that inner ear protection against loud sound is diminished in children after the insertion of tympanostomy tubes, theoretically leading to long-term hearing loss. In my view, the insertion of tympanostomy tubes is a surgical intervention that should be very carefully considered. In the past, groups of patients that might benefit from tubes have been ‘identified’. These groups mostly consist of children with language and learning problems. I agree that even a short-term benefit may be desirable in these patients. However, only a very marginal benefit from tube insertion has been established until now [25]. So, tympanostomy tubes improve the annoying hearing loss and can therefore be considered in patients with a definite need for improved hearing, however, this should be carefully assessed for each individual patient. Perhaps we should rather consider hearing aids as an alternative treatment option? We must not forget that grommet insertion is also associated with the development of otorrhoea, which in my opinion is a sign of an actual infection [9,26]. Could this be a natural consequence of ruining a well-balanced defence system?
Future treatment options?
In a recent study a nasal spray with Streptococcus sanguinis constitutes an interesting new therapy that has shown good initial results and few adverse effects [27]. This therapy may possibly offer a boost to the immune system. Whether this is actually the case still remains to be proven. I have high expectations for this and other types of ‘probiotics’ in the future.
In the future, more evidence will be available on the genetics and hereditary aspects of OME. I think that it will be very important to differentiate between true hereditary factors and socio-economic factors. And even if true hereditary factors are found, the question remains whether these patients actually inherited a better or a worse middle ear defence system. Is OME perhaps a form of coping and dealing with a compromised, less than optimal, functioning of other parts of the immune system? Is it actually a hereditary, optimally functioning defensive reaction that prevents further complications from an OMA?
Personalized care
In summary, the severity and the long-term consequences of OME in children fortunately appear to be minimal. A-symptomatic children with persistent OME discovered during screening, only benefit minimally from surgical intervention [1]. For any particular child, surgery is appropriate only if the objective benefits are significant, particularly with regard to language, learning and overall development [1]. The duration of OME should not be the single operative criterion. Optimal treatment outcomes are most likely when a particular child is perfectly matched with the appropriate intervention for that particular child [1]. In line with this, Ruben recently called for personalized medicine [28]. I could not agree more, and in light of that statement, I hope to provide the reader with a different background and theory for the well-known phenomenon glue ear; a step forward towards a paradigm shift in our thinking with regard to OME.
Selection of the right therapy for each individual child is undoubtedly difficult, yet that should, nonetheless, always be our goal. Let’s suppose, for example, that only 10% of children have allergy as a co-factor. Treating all patients (even in a study population) with antihistamines and corticosteroids - instead of looking at only those patients with a possible allergy- would result in a 90% failure beforehand. In my work at a military hospital, I would call that unjustifiable ‘collateral damage’.

Conclusions

I suggest that the development of OME is a sign of ‘defence’, and that the glue is not the disease in itself. So, both in practice and in research, we need not only to differentiate between OME and OMA. But, also we need to discriminate the one patient with OME from the other based on the causative factors that necessitate glue formation. Research should be performed in subgroups, based on probable underlying causes, instead of in generalized large study populations in which all patients with OME are lumped together. When confronted with OME in children the focus is a matter of aiming the right therapy at the right child.

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