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illaries, which effectively happens in relation to water vapor, O2, and CO2 in the middle ear cleft. Under these conditions, when we provoke a perforation in the tympanic membrane, the gaseous content of the middle ear quickly becomes similar to atmospheric air. Just a few moments after the closure of this perforation, the middle ear’s gaseous concentration returns to nd its balance point with the venous capillary system that surrounds it [44]. Assuming that the venous blood draining the middle ear has a gaseous PP and TP composition similar to that of the venous system, a steady state of equilibrium will nally be reached at slightly subatmospheric levels or around 56mmHg (760−704=56). This theoretical composition would result in a pressure difference acting on the tympanic membrane (with an excess of 56 Hg external to it), which would be absolutely undesirable for the perfect functioning of the tympanic-ossicular mechanism. Thus, for the middle ear to obtain a TP equal to the atmospheric pressure, some physiological mechanism must be put into action, which effectively happens in the form of periodic openings of the Eustachian tube, causing the entry of an air bolus into the middle ear from the nasopharynx. As we discussed earlier, water and CO2 moving from the mucosa into the tympanic cavity lumen and diffusing in the opposite direction of O2 quickly equilibrate, leaving it to N2 (which diffuses poorly and remains longer in the CT light) to partially offset this pressure decit of 56mmHg. Due to its diffusion and solubility characteristics, N2 tends to present a higher PP in the middle ear than in blood, thus compensating for the discrepancy produced by the negative O2/CO2 equation. This extra dose of air that lls the middle ear and balances the extra- and intratympanic pressures is a direct consequence of the ventilatory function of the Eustachian tube. The amount of gas admitted (which occurs mainly during swallowing) is so proportionally small, when compared with the total amount of gas present in the light of the middle ear cleft, that the alterations in the PP of H2O, O2, and CO2 resulting from it are practically imperceptible. In other words, the act of swallowing does not signicantly modify the PP of these gases in the middle ear cleft [44]. On the other hand, the gas that penetrates the middle ear in this way is not exactly the same as the atmospheric one (since it is slightly modied by expiration) presenting in its composition: 99mmHg of O2, 36mmHg of CO2, 47mm of H2O, and 578mmHg of N2. Thus, the main gas inhaled by the middle ear at each swallow is N2, which slowly diffuses into the adjacent circulation. As a result, a difference in the PP of N2 is consistently maintained between the middle ear cleft and the circulation with an excess of around 56mmHg for the former. This PP difference (light×circulation) systematically transfers N2 molecules from the middle ear lumen to the circulation, consequently reducing the middle ear PN2 until a new gush of air penetrates via the Eustachian tube, fullling what we call the ventilatory cycle of the middle ear cleft [44].

Normally, this process repeats itself periodically at a rate directly proportional to the diffusion of N2. Even today, much is discussed in relation to the factors that positively or negatively modulate this rhythm. It has been suggested that the ventilatory function of the Eustachian tube is controlled by neuronal feedback circuits with sensory components capable of detecting both TP and PP alterations of the gases present in the middle ear and effector components that modulate the activities responsible for the opening of the Eustachian tube or the variation of peritubal pressures. Consubstantiating this hypothesis, a series of possible chemoreceptors and baroreceptors have been identied to be dispersed in the middle ear cleft. Likewise, afferent and efferent nerve pathways between the tympanic plexus and the respiratory subnucleus of the solitary tract, trigeminal motor nucleus, nucleus ambiguus, and peritubal musculature have been described in rabbits, cats, and chimpanzees [15,

45, 46]. Cantekin etal. [47] demonstrated that stimulation of

the tympanic nerve in the middle ear of monkeys increased the electrical activity veried in the muscle bers of the palate tensor in these animals. Shupak etal. [48], using animal models, conrmed these ndings and showed that this electrical activity could be modied according to the concentration of different gases present in a gaseous mixture offered experimentally to these animals. Without the possibility of periodically renewing the air dispersed inside, all biological air pockets would denitely be doomed to collapse. In the middle ear cleft, a situation of negative pressure would imply, at rst, a more dramatic repercussion on its only nonosseous wall: the tympanic membrane. In the tympanic membrane, these pressure deciencies affect its dimer composition portion or the tympanic pars accida (Shrapnell’s membrane) more strongly. Thus, this small triangular fraction of the tympanic membrane in opposition to the rest of the eardrum, which is highly inelastic under normal conditions, would function as a legitimate mirror of intratympanic pressure variations.

Even today, we have little information regarding the laws that govern the quantitative and qualitative physiological parameters of gas transfer from the nasopharynx to the middle ear. This lack of knowledge becomes critical as we wish to identify and compare operational ventilatory parameters in healthy and diseased ears. The volume of gas admitted in the middle ear cleft (which could be dened as the ventilatory coefcient) is equivalent to the product of the inhaled volume by the number of gaseous admissions per unit of time [44]. In humans, the Eustachian tube has a total length of around 4 cm and roughly resembles two conical portions joined by a narrow ring called the isthmus. The anterior and medial cone is formed by an elastic cartilage, which is collapsed most of the time. The posterior portion is bony and, therefore, rigid, when considered from a physiological point of view as an extension of the middle ear. These two portions

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meet at the isthmus, which is an annular structure 1–2mm long and 0.6–1.2mm in diameter. The cartilaginous portion is actively opened through contraction of the tensor palatini muscle during swallowing, yawning, or lateral movements of the mandible. This opening is in the order of 0.2ms every 1 or 2min (for a total of 3–4min over 24h). In general, a gas moves from one environment to another according to the difference in pressure between these two environments. During its course through the Eustachian tube, the air column coming from the nasopharynx nds its point of maximum obstruction next to the tubal isthmus. For practical purposes, once the air passes the isthmic region, it is already inside the middle ear. As we will see later, the geometry of the Eustachian tube is peculiar in the sense that its ventilatory and drainage functions do not interfere with each other. Drainage is carried out through the ciliary beat that generates a current of mucus that follows from the tympanic cavity to the nasopharynx through the oor of the Eustachian tube, whereas ventilation is processed in the opposite direction and in the middle and upper oors of the Eustachian tube (unless they meet—if blocked by mucus due to acute or subacute inammatory events). The amount of gas that passes through the isthmus is a direct function of the pressure difference existing between the nasopharyngeal and tympanic ends of the Eustachian tube, the time this channel opens, and its dimensions (length × diameter). Elner [49] calculated that, under physiological and stable conditions, around 1–2mL of gas penetrates the middle ear cleft every 24h, a volume that would correspond to the daily gaseous loss from the middle ear lumen to the circulation. Even though there are small pressure uctuations in the nasopharynx when we breathe, these variations are practically insignicant during swallowing and the consequent tube opening (1mm H2O). Thus, the main, if not the only, difference in pressure between the Eustachian tube and the nasopharynx is due to the continuous loss of gas from the middle ear to the adjacent circulation. As seen, if the middle ear transfers between 1 and 2mL of gas into the circulation daily, and around 1000 swallows are performed every 24h, it is calculated that 1–2μL of gas diffuses into the circulation at intervals of 1–2min and that the same volume is retrieved from the nasopharynx with each swallow. It is worth mentioning that not all swallows open the Eustachian tube, and, likewise, even if this occurs, there are occasions when this opening does not transfer air to the CT.The magnitude of the difference in pressure between the middle ear and the nasopharynx (due to the loss of gas by diffusion, as already mentioned) is also directly proportional to the total dimension of the middle ear cleft (Eustachian tube orice, meso-, hypo-, and epitympanum, aditus, antrum, and, mainly, the mastoid cell complex). In a system with the mastoid normally pneumatized (12 cm3), the difference in negative pressure resulting from the subtraction of 1–2μL of gas due to diffusion is in the order of only 1–2mm H2O.This

difference is so small that it provides the ability to passively move an air current across the tubal isthmus (1mm in diameter×2mm in length for a total volume of 1–3μL) in a time interval of only 0.2ms [44]. From these considerations, it is suggested that this transfer of air from the nasopharynx to the middle ear should not be an exclusive consequence of passive events but that active mechanisms may also play a role (supporting or even the main) in this scenario. Sadé [44] even proposed a theoretical model in this sense: when the palate tensor muscle contracts during swallowing or yawning, the cartilaginous portion of the Eustachian tube opens, thus creating a new volume with a pressure lower than that found in the nasopharynx or middle ear, and the air coming from the nasopharynx quickly occupies this new volume. In the second phase, the tubal walls, after muscle contraction, tend to return to their resting state and do so by practically pushing this new air pocket toward the isthmus. Another force that could help in this regard would be the contraction that happens just milliseconds after the palate elevator muscle. In this sense, this muscle (whose function is not yet fully elucidated) is larger than the tensor palate. Furthermore, it is located on the Eustachian tube oor and contracts for a much longer period of time (0.45s).

The existence of more than one operational mechanism in the equalization and maintenance of intra- and extratympanic pressures increases the degree of complexity of these functions. A logical and expected side effect of this renement is the possibility of pathological phenomena interfering in several phases of these operations [2]. In other words, there is a need to identify and test a series of etiological variants (anatomical and/or functional) that are still little explored in the pathophysiology of the Eustachian tube and its most relevant consequences: otitis media.

Drainage

The drainage function allows the ow of middle ear secretions toward the nasopharynx through the Eustachian tube. It is basically exercised by three factors, namely, the mucociliary ow from the middle ear to the nasopharynx, the air renewal mechanism of the ventilatory function that can mobilize secretions in the same direction, and the surface tension of the secretions themselves [41].

All living surfaces of an organism are covered by an epithelium whose purpose is to offer protection to the deeper tissues. The epithelium that is in contact with the outside world is our skin; those that cover the internal organs are the mucous membranes or their analogues. The inner surface of organs such as the intestines and lungs are lined by a modied mucosa with at cells. The life span of the cells that form part of this protective lining is limited, and, when dead, they are automatically removed from the organ in question. In order to keep this epithelial mantle intact, the cells of the deeper layers begin to divide, replacing the rst ones, until

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they themselves mature and descend in a monotonously repetitive cycle. The anterior portion of the middle ear is covered by the respiratory epithelium whose cells live for a short time. Under inammatory conditions, the epithelium differentiates with increased numbers of mucus-producing cells and hair cells. This occurs throughout the respiratory tract: nose, trachea, bronchi, etc. The excess of dead and desquamated cells must be constantly eliminated, otherwise it will accumulate and ll the cavity from where it originated. Nature has conveniently provided the middle ear cleft with a cleansing organ: the Eustachian tube. Both the middle ear cleft and the Eustachian tube are lined by a mucociliary system similar to that found in the trachea and bronchi. A thin layer of mucus produced by the secretory cells remains as a lm on the surface of the cilia. These move synchronously, removing any middle ear debris similarly to a conveyor belt that travels through the Eustachian tube from the middle ear to the nasopharynx. The composition and consistency of this mucus layer is critical to the functioning of this entire selfcleaning mechanism. As an example, if a small particle of charcoal is placed in the anteroinferior part of the headland, through a perforation in the tympanic membrane, one can observe this particle being propelled toward the opening of the Eustachian tube.

Although this mucociliary “belt” system transports mucus unidirectionally from the middle ear via the Eustachian tube to the nasopharynx, some microorganisms can travel in the opposite direction and reach the middle ear cleft from the nasopharynx. The mechanism used by these microorganisms to reach the middle ear is one of the many issues that needs to be completely elucidated in the pathogenesis of otitis media. The resulting inammatory reaction, otitis media, leads to the formation of an inammatory exudate and usually causes cells to synthesize more mucus than usual. Again, this phenomenon is analogous to tracheobronchitis, or nasal secretions, produced during a common cold.

Long-lasting inammation induces the middle ear mucosa to differentiate, through metaplastic processes, into a typically secretory epithelium (cylindrical, ciliated, pseudostratied, rich in goblet cells and submucosal glands), which, in turn, synthesizes greater amounts of mucus than under normal physiological conditions. In fact, some of these histopathological ndings are found even in healthy ears since, at some point in life, they have been subjected to inammatory insults. Only animals reared in germ-free conditions are completely devoid of such glands, cysts, or previous evidence of inammation. This metaplastic alteration, with the consequent increase in mucus production, may cause it to completely ll the middle ear. The excessive presence of mucus in the respiratory tree can be easily eliminated by coughing or, in the case of the nasal cavity, by sneezing. However, through the narrow Eustachian tube, it is not possible to cough or sneeze, and, so, these secretions can accu-

mulate inside the AF for several months. Why large amounts of mucus are not rapidly cleared from the middle ear by ciliary beating is still an intriguing question today, especially since cilia, although microscopic in size, are biologically quite robust organelles. Mechanical (adenoid) and functional tubal obstructions, changes in the rheological characteristics of secretions, primary or secondary ciliary dysfunction, mucus plugging, negative pressure, and vacuum are some of the hypotheses already tested in this regard. It is our conviction that the course developed by middle ear inammatory processes from their most incipient phases to chronication can be compared to a theatrical play with a few main actors, several supporting characters, and countless extras. The latter, when analyzed separately, lack greater importance, but as a whole they acquire signicance and are absolutely essential in triggering the entire process.

Protection

The protective function comprises defending the middle ear from sounds, especially from contaminated secretions from the nasopharynx. This objective is achieved by the fact that the Eustachian tube remains closed, opening only quickly during swallowing. On the other hand, it has an ascending path, making contamination in this direction difcult due to gravity, and a narrow isthmus that by capillarity protects the passage of secretions in the ascending direction. In addition, the air column inside it also makes it difcult for secretions to pass through. As its direction is from the middle ear to the nasopharynx, the mucociliary ow contributes to the protective function. This protective mechanism, however, can be overcome in some circumstances, such as positive pressure in the nasopharynx, which occurs when blowing your nose, sneezing, and crying. It should be remembered that swallowing, in the presence of severe nasal obstruction, also creates positive pressure in the nasopharynx when the palate contracts. Minor Eustachian tube obstructions that create moderately and slowly progressive negative pressure in the middle ear can lead to aspiration of nasopharyngeal secretions into this cavity. This does not happen when the obstruction is complete and of sudden installation because then the negative pressure contributes even more to aggravate the obstruction that caused it. In children, because they have a wider, more horizontal, and shorter Eustachian tube, the protective function is less effective. The fact that children spend more time lying down and younger ones eat in this posture facilitates the reux of secretions and food into the middle ear. The vulnerability of the Eustachian tube in children has been identied as one of the factors responsible for the high incidence of AOM in this age group [41].

Aeration oftheMiddle Ear Cleft

Proctor [50] demonstrated that despite the fact that the middle ear cleft has its aeration ensured by the Eustachian tube,

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the paths taken by the air currents inside the tympanic cavity are narrow and sinuous. A series of mucous folds, ligaments, and parts of the ossicles make up the so-called tympanic diaphragm, practically separating the mesotympanum from the epitympanum and mastoid. This diaphragm comprises the head of the malleus, the body of the incus, the lateral and medial incudal folds, the anterior and lateral malleolar folds, and the tensor tympani fold. Only two narrow passages—the anterior and posterior tympanic isthmuses—pass through this diaphragm. The anterior isthmus is larger and more consistent, lying medially to the body of the incus, passing between the states and the tendon of the tensor tympani. When the medial incudal fold is present, a small posterior isthmus appears between this fold and the posterior tympanic wall. As previously mentioned, in less than 10% of individuals, the anterior epitympanum can be formed from the saccus anticus, opening a second air channel between the two compartments. From the point of view of embryological anatomy, the tympanic isthmus corresponds to an area where the structures of the rst and second branchial arches come together, through which the rst pharyngeal pouch extends to the extrabranchial region.

Epidemiology

AOM has an annual incidence rate of 10.8 episodes per 100 people per year. There are a number of factors that inuence the incidence patterns among different locations, with the most critical one being socioeconomic conditions: developed regions (such as central Europe) have an average AOM incidence of 3.6 episodes per 100 people/year, whereas in less developed areas (such as sub-Saharan West Africa and Central Africa), the incidence rises up to 43.4/100 people/year [4]. Although AOM can affect people of all age groups, the peak of maximum prevalence occurs at the age of 4years. Children are the most at risk in the rst year of life, with an incidence of 45.3 episodes of AOM per 100 children per year [4].

The incidence and prevalence of otitis media with effusion (OME) might be even higher than those of AOM.Studies have shown that by the age of 3 years, virtually all children will have had experienced at least one episode of OME [6,

51, 52]. The peak of incidence/prevalence of chronic suppu-

rative otitis media (CSOM), differently from than AOM and OME, has a less clear pattern: children <5years represent only 22% of new cases every year. The average estimated global rate of new CSOM cases is 4.8 episodes per 1000 people or 31 million new cases every year [4].

In the last few decades, there has been a decrease in the global rates of OM due to two mains factors: the use (and abuse) of antibiotics and the development of strict treatment guidelines for OM, in addition to the introduction of pneumococcal conjugate vaccinations. Before these vaccinations were introduced in the United States, it was estimated that

95% of all children have had one or more middle ear infections before reaching the age of 5 [53]. Even if the overall rates of OM seemed to decrease, the prevalence of CSOM and the rates of complications arising from either AOM and CSOM have not changed signicantly [6], suggesting that other factors may be involved in the pathogenesis of CSOM and the risks of developing such complications.

The rst prevalence peak of AOM and OME (early childhood) is probably explained by the intrinsic aspects of the infant, such as its immunological immaturity and the anatomical and physiological characteristics of the Eustachian tube, which are typical for this age group (smaller, more horizontal and patent). Between the ages of 4 and 7, however, a series of events that are extraneous to the child and specic to the environment are responsible for causing a second peak in prevalence. At these ages, children are introduced to the community, increasing exposure to microbes and bacteria. Among all these circumstances, the most disastrous is socialization in day-care centers, kindergartens, and schools. Not only do children begin to share closed spaces but they also tend to share bottles, paciers, toys, and others; consequently, the risks of developing recurrent cycles of

infections of the upper airways arise. Children with immunodeciencies [54] and adenoid hypertrophy are also at an

increased risk of developing OM.

Recent studies have conrmed the classical estimative of a higher frequency of OM in boys: MacIntyre etal. [55], in a cohort that followed more than 50,000 children in Canada from birth to the age of 3years, found that 51.5% of AOM episodes occurred in male children. Around 20months of age, the difference of prevalence between boys and girls seemed to become less evident. Moreover, the study found that children born in the winter and spring seasons, and those with older siblings, were at an increased risk of developing OM in their rst year of life.

There is seasonal variation in the prevalence of OM, with an increase in incidence in winter and early spring. It is believed that the incidence of OM during winter is four times greater than in summer, coinciding with the increased incidence of respiratory viral infections. Uhari etal. [56], in a case–control study, found an association between respiratory syncytial virus infection in children and a higher risk of developing AOM.

Craniofacial malformations (Pierre Robin sequence, Treacher Collins syndrome, Crouzon’s disease and, especially, cleft palate) are also associated with a higher risk of OM due to a malfunctioning ET [57]. According to Bluestone (1997), virtually all children with cleft palates have chronic effusion in the middle ear, which persists even after surgical reconstitution of the palate. Histopathological studies have shown that tubal dysfunction in these cases is due to functional dysfunction rather than an anatomical obstruction. Abnormalities in the constitution of the tubal cartilage, erratic insertion of the palate tensor muscle into

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the lateral layer of the Eustachian Tube, and deciency in the amount of elastin can all compromise the tubal opening mechanism.

Children with Down syndrome are also at a risk of OM.In these situations, it seems that a decrease in the total length of the Eustachian tube when compared to those of normal individuals would facilitate the access of germs to the middle ear [57].

Ciliary diseases (Kartagener’s syndrome) or diseases that affect the natural composition of the mucus (mucoviscidosis) can cause accumulation and stasis, and subsequent contamination of secretions, also predisposing to OM.O’Reilly etal. [58] studied 129 pediatric patients undergoing myringotomy for ventilation tubes. Among them, 50% had pepsin A in their middle ear uid. This suggests that extraesophageal reux may play a role in the complex process of the OM pathophysiology.

The social factors that may increase the risk of developing OM are low socioeconomic status, secondhand tobacco smoking, and the use of a pacier. Conversely, breastfeeding is considered a protection factor, as it provides adequate nourishment and transmits acquired immunity from the mother [6].

A meta-analysis by Zhang etal. [59] evaluated the risk factors for recurrent OM and COM: Allergy or atopy (may be associated with Eustachian tube disfunction); upper respiratory tract infection; snoring (possibly related to adenoid hypertrophy); and previous history of recurrent OM or chronic OM.Schilder also listed social factors such as malnutrition, contaminated water, poor hygiene, overcrowding, human immunodeciency virus (HIV) infection, tuberculosis, malaria and poor access to healthcare, which seem to increase the risk of chronicity and complications of OM in children [6]. Conversely, sex, breastfeeding, and the number of siblings did not result in increased risks of developing OM or chronic OM.

In adults, OM tends to affect people who have allergies [60], recurrent infections of the upper airways [60], nasopharyngeal tumors [61], and tobacco dependence [62]. Finkelstein et al. [63], in a study carried out in Israel, found a considerable number of adults with OME, which was mostly associated with the presence of recurrent sinus infections. Head and neck tumors, located especially at the nasopharynx, should be actively searched for in adult patients with OME, especially ones with unilateral disease [64]. Besides, patients with head and neck tumors treated with radiotherapy may develop temporary Eustachian tube dysfunction [65].

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2 Otitis Media: Basic Concepts andFundamentals

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Otitis Media andHuman Efforts toDeal

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withIt Through Time

MarcosV.Goycoolea andMarioCastro

Introduction

The study of diseases with a historical perspective strengthens scientic knowledge. When reviewing the prevalence, clinical manifestations, and complications of specic diseases through the centuries, the clever way in which physicians approached problems in spite of the scant knowledge available at a particular time often amazes us. While evaluating the different treatments used over the years, it is interesting to learn about them and the procedures involved, which, at times, were rediscovered and described as new. Some rediscoveries that were once considered a contribution, soon thereafter were discredited. Therefore, it is important to review the history in order to understand the present clinical approaches and why and how some treatments have failed and why they have been discarded. In addition, the study of signicant changes in approaches and treatments over time has shown us that, what at one moment seems to be the nal truth is eventually surpassed by new information, and the mistake of being strict and dogmatic in the approach to multifactorial diseases repeats itself in history, over and over again. This is the case of otitis media, which is a multifactorial, multifaceted disease that manifests in the middle ear, mastoid, and auditory (Eustachian) tube. It is the result of prevailing aggression against the body’s defense system, the degree of which depends on the balance between these two opposing forces: the disease against the immunological defense system.

M. V. Goycoolea (*) Department of Otolaryngology, Clínica Universidad de Los Andes, Santiago, Chile

M. Castro Chilean National Museum of Natural History, Santiago, Chile

Department of Morphology, Faculty of Medicine, Clínica Alemana-Universidad del Desarrollo, Santiago, Chile

Early Descriptions

The earliest written reports of otitis media and its complications can be traced to the Egyptians and Assyrians [1]. In the Ebers Papyrus (dating to the New Kingdom, circa 1550BC), it is suggested that “For an ear that is suppurating, olive oil, frankincense and sea salt syringed into the ear” [2, 3]. In the Brugsch Papyrus (written “shortly” after), otitis is characterized as “re in the heart of the ear” and the use of verdigris (copper sulfate) paste is recommended for its treatment [4]. In India’s oldest available medical works, the Vedas (circa between 1500 and 500BC), purulent discharge of the ear is described and, as in other cultures, ointments and powders are prescribed [5].

Hippocrates (460–370BC) was well aware of otitis media and its consequences: “Children suffer from ear discharge, adults from deafness.” Likewise, he was also aware of brain abscesses but not as caused by otitis media [6]. In fact, it was not until 1736 that Morgagni demonstrated that some brain abscesses were, in many cases, secondary to middle ear infection [7]. The Babylonian Talmud (352–427 AD) also refers to this subject [4, 5, 8].

The earliest Chinese written records of middle ear disease date to the Warring States period, 475–221BC.In the Inner Cannon of Huangdi, two conditions analogous to complications of mastoiditis and cholesteatoma are described [9]. Likewise, in tractate Avodah Zarah (in the Talmud on page

28) when Rabbi Abahu suffered from earache, Rabbi Jochanan prescribed the following: “Otitis is to be treated by roasting upon embers the kidney of a goat collecting the juice and instilling it into the ear in a lukewarm state, not cold and not hot” [4, 5]. Paul of Aegina (625–690AD), the great Byzantine Greek physician, recommended that: “Watery discharges of the ears may be dried up by applying to them wool with alum, or wine and honey” [4]. On the other hand, ancient Japanese texts also referred to otitis media. A text dating to about 982AD, refers to “Te-ro,” the chronic form of suppurative otitis media, whereas in the book Sen-kin-po (1315AD), chronic otitis media with nasal polyposis is mentioned [5].

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M. V. Goycoolea and M. Castro

Paleopathological Evidence ofOtitis Media

The antiquity of infectious middle ear disease and its complications has been documented through different methodological approaches in several regions of the world. In 1909, Derry [10] reported two cases of mastoid infection in Egyptian skulls of the Predynastic/Early Dynastic and Coptic periods, whereas Elliot-Smith and Wood-Jones [11] described a perforation of the suprameatal triangle caused by a mastoid abscess in an Egyptian adult female skull of the New Empire period. In addition, in the Middle East, a probable case of chronic middle ear disease was reported in an early modern Homo sapiens skull found at Qafzeh, Israel. In this specimen, the extremity of the manubrium of the malleus and the long crus of the incus showed erosion, possibly because of chronic otitis media [12]. In 1973, Ziv etal. [13] reported an unusual bony mass obstruction of the right jugular bulb in a 2000-year-old temporal bone of an adult male found near Jerusalem. According to the authors, the most probable cause of the bony formation was thrombophlebitis of the internal jugular vein in the area of the jugular formation followed by calcication and ossication of the thrombus, all of which occurred as a complication of acute otitis media. Recently, Floreanova et al. [14] have examined the promontory of the tympanic cavity to check for either the presence or absence of bone remodeling in 229 individuals from 6 prehistoric and historic populations of the southern Levant (14,900 cal BP–1917 AD). They concluded that otitis media was highly prevalent in protohistoric populations (80%), followed by prehistoric populations (60.6%), and, nally, historic groups (50.4%). Furthermore, they attribute these uctuations to lifestyle and climatic conditions.

In 1974, Lynn and Benitez [15] described perforated tympanic membranes in a 2600-year-old Egyptian male mummy, which they attribute to the sequelae of otitis media; later histological studies have conrmed this diagnosis [15, 16]. Additionally, Horne etal. [17] examined decalcied histological sections of a 4000-year-old Egyptian mummy’s head and found sclerotic changes within the mastoid process, suggesting that the individual suffered from acute and probably chronic otitis media. At Dinkha Tepe, Iran (1300–300BC), Rathbun and Mallin [18] found that 40% of the temporal bones studied had evidence of otitis media and mastoiditis.

In North America, Gregg etal. [19] carried out a comprehensive longitudinal radiological study of mastoid development in prehistoric Native Americans from the South Dakota area and found altered mastoids in 44% of Arikara burials and in 51.8% of Middle Plains Woodland people (Sioux and others). Additionally, Titche etal. [20] evaluated the prevalence of mastoid infection in ancient populations (Late Mogollon Pueblo) from Arizona (950–1450 AD) and reported that 17.3% of the skulls examined had decreased

pneumatization (a reection of having had otitis media during childhood). Gregg and Steele [21] studied the effects of otitis media on the human mastoid process by comparing present-day and four pre-Columbian populations from North America. Based on pneumatization patterns, they suggested that otitis media and its complications were more common and virulent in Native Americans who lived in the interval after contact with Europeans. In a more recent study (2018), Ochi et al. [22] have assessed mastoid development in Puebloan groups (850–1300AD) using computed tomography (CT) scanning and found that 25% of the individuals examined showed arrested mastoid pneumatization. Homoe etal. [23] examined pneumatization in ancient Greenlandic Inuit temporal bones and found low frequencies of decreased pneumatization in the crania from the pre-European colonization period (before 1721AD).

Studies in South America have also reported a high prevalence of decreased pneumatization in prehistoric and historic populations. Goycoolea etal. [24] estimated a 53.7% occurrence of infectious middle ear disease in prehistoric coastal groups (400–1450 AD) and a 47.9% in highland groups (400–1000AD) from northern Chile. Besides, the skulls of historic (1500–1800AD) coastal populations from southern Chile evaluated by Castro etal. [25] also showed a high prevalence of decreased pneumatization.

Among populations of European ancestry, Bruitjes [26] examined the auditory ossicles of 89 individuals from a leper cemetery in Chichester, England, dating from the twelfth century to about the mid-seventeenth century, and found erosive changes attributable to middle ear disease in 51% of them. Flohr etal. [27] used light microscopy and backscattered electron imaging to examine mastoid hypocellularity in 151 temporal bones from 99 individuals from an early medieval cemetery from Germany and found that 33.8% showed some type of mastoid alteration most probably due to middle ear infection. Krenz-Niedbala and Lukasik [28] examined 169 ear ossicles of children from an early medieval urban site (1000–1400AD) and a postmedieval (1400–1700AD) rural site located in Poland and found that 33.9% of them showed pathological changes, with a signicantly higher frequency of altered bones at the early urban site. Likewise, the majority of the mastoid processes of children with pathological ear ossicles showed decreased pneumatization.

Recently (2021), Olivé-Busom etal. [29] have reported evidence of middle ear disease in an Islamic adolescent skull (10–15 years) from Castellón, Spain, dating to the Middle Ages (between the tenth and sixteenth centuries). The right temporal bone presents a perforation with relative smooth margins located superior to the mastoid process as well as abnormal pneumatization. According to the authors, the individual suffered from acute otitis media, which resulted in mastoiditis, and possibly received medical treatment for this condition [29].

3 Otitis Media andHuman Eorts toDeal withIt Through Time

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There are sparse reports of complications of suppurative otitis media in ancient populations both in the clinical and anthropological literature. Singer [30] described a probable case of cholesteatoma in a skull from Boskop, South Africa (Late Stone Age), which eroded through the roof of the antrum and then produced a subdural abscess. Armentano etal. [31] described a unilateral cholesteatoma in a prehistoric skeleton found at La Cova des Pas (800–900BC) on the island of Minorca, in the western Mediterranean Sea. Mays and Holst [32] documented the existence of cholesteatoma in a skull from Lincolnshire, England (late fth to sixth centuries). Based on gross examination, low-power microscopy, and radiology, they suggest middle ear cholesteatoma because of chronic otitis media. Goycoolea etal. [24] described a case of mastoiditis with a temporal bone stula in a prehistoric skull from the highlands of northern Chile (400–1000AD).

This case is described in Figs.3.1, 3.2, and 3.3. The skull had a visible stula above the entrance of the external ear canal and CT scans conrmed the stula and showed signs of mastoiditis. It is of interest to mention that in this study, the data provided by the CT images were used to generate threedimensional (3D) reconstructions with the specic characteristics of this individual skull [24]. On the other hand, facial reconstruction techniques were used to reconstruct the face of this individual [33, 34] to study how it looked.

In short, these reports from different times and different geographic locations conrm the high prevalence of this disease worldwide over the centuries. Moreover, Bluestone and Swarts [35] suggested that otitis media is primarily a human condition, which results from two evolutionary adaptations: being born too soon due to the development of a large fetal brain and the loss of facial prognathism due to speech.

Fig. 3.1 (a) An ancient skull with a temporal bone stula. (b) A model of the skull after 3D reconstruction. (c) 3D reconstruction of the skull with mastoiditis and abscess. (From: Goycoolea MV, Castro M, Galvez M, Montoya C, Fuentes J, Silva-Pinto V.Otitis media and mastoiditis in

temporal bones of prehistoric Chilean populations. A paleopathological and paleoepidemiological study. Acta Otolaryngol. 2019;139:340–344 [24])

ab cd

Fig. 3.2 Facial reconstruction of the skull with a temporal bone stula. (a) 3D skull reconstruction from CT images. (b) Fiducial positioning for face reconstruction using forensic anthropological techniques. (c) Face reconstruction (transparency) allowing see-through. (d) Face reconstruction using forensic anthropological techniques [34]. (From:

Goycoolea MV, Castro M, Galvez M, Montoya C, Fuentes J, SilvaPinto V.Otitis media and mastoiditis in temporal bones of prehistoric Chilean populations. A paleopathological and paleoepidemiological study. Acta Otolaryngol. 2019;139:340–344 [24])

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