Otitis media and eustachian tube dysfunction:

Connection to allergic rhinitis

Philip Fireman, MD Pittsburgh, Pa.

Otitis media and otitis media with effusion are among the most common childhood illnesses and
con#ibute a great deal to health care costs. The cause of otitis media is multifactorial. Eustachian tube
dysfunction, bacterial or viral infection of the middle ear, and nasal inflammation resulting from allergic
rhinitis or upper respiratory infection are acknowledged contributing factors. Data from epidemiology
studies indicate that 25% to 40% of upper respiratory infections in children younger than 3 years are
accompanied by an episode of otitis media; 40% to 50% of children older than 3 years with chronic otitis
media have confirmed allergic rhinitis. Studies of the pathogenesis of otitis media have identified
interactions among infection, allergic reactions, and eustachian tube dysfunction. Nasal inflammation due
to allergen challenge results in classic signs and symptoms of allergic rhinitis and eustachian tube
dysfunction. Eustachian tube dysfunction leads to increased negative pressure in the middle ear and
improper ventilation. Both viral upper respiratory infection and nasal allergic reaction provoke nasal
inflammation, eustachian tube dysfunction, and enhanced nasal protein transudation and secretion,
which is likely to be sustained and modulated by inflammatory mediators and cytokines. In a study of
experimental infection with influenza A virus, histamine release increased from peripheral blood basophils
of patients with allergic rhinitis. These data support an interaction between viral infection and nasal
allergy in enhancing certain pathophysiologic responses. Viral upper respiratory infections may promote
secondary bacterial infections by altering bacterial adherence, modulating host immune and inflammatory
responses, and impairing eustachian tube function. In acute otitis media, bacteria are cultured from
approximately 70% of middle ear effusions, with Streptococcus pneumoniae being the most common
organism. Initial management of otitis media consists of appropriate antimicrobial therapy. In the
presence of allergic rhinitis, antiallergic therapies may be used to augment symptom resolution and
therapeutic response. Surgical insertion of tympanostomy or ventilation tubes to promote drainage of
unresolved effusions has become common. Further delineation of the pathogenesis of otitis media and
otitis media with effusion will guide appropriate medical management and may decrease the need and
frequency of surgical procedures. (J Allergy Clin Immunol 1997;99:$787-97.)
Key words: Otitis media, otitis media with effusion, eustachian tube dysfunction~obstruction, allergic
rhinitis, upper respiratory infection

Otitis media (OM) and the resultant otitis media with

effusion (OME) are the most common childhood ill-
n e s s e s requiring physician care. The direct and indirect
health care costs associated with OM are enormous.
Despite advances in the past 20 years in the understand-
ing of the pathogenesis and pathophysiologic process,
the incidence of OM has not decreased. In fact, there is
the clinical impression that despite more aggressive
antimicrobial therapy and other treatment options, OM
is recognized more frequently than it was before. There
also continue to be questions among clinicians as to the
various medical and surgical approaches used in the care
of patients with OM and OME. The role of infection in
the pathogenesis of OM is not disputed, but the possi-
bility that allergy contributes to OM has been debated
for years? If a casual relation between allergy and
From the Departmentof Pediatrics, Universityof PittsburghSchoolof
Medicine,Children'sHospital of Pittsburgh.
Reprint requests: Dr. Philip Fireman, Professor of Pediatrics and
Medicine, Children'sHospital of Pittsburgh, 3705 Fifth Ave., Pitts-
burgh, PA 15213.
Copyright © 1997by Mosby-YearBook, lnc.
0091-6749/97$5.00 + 0 1/0/79126
Abbreviations used
OM: Otitis media
OME: Otitis media with effusion
TVP: Tensor veil palatini
URI: Upper respiratory infection
middle ear disease were to be established, one would
anticipate that antiallergy therapy would reduce the
morbidity and health care costs associated with OM.
CLASSIFICATION OF OTITIS MEDIA
OM is characterized by acute or chronic inflammation
of the middle ear. 2 Although it can occur at any age, OM
occurs most commonly among infants and children
younger than 4 years. The clinical presentation and
course of OM can vary. Clinical classifications of OM are
presented in Table I.
Acute OM is typically preceded or associated with an
upper respiratory tract infection (URI) and a concurrent
or subsequent suppurative process in the middle ear. In
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S788 Fireman
TABLE I. Clinical classifications of otitis media
Acute otitis media
Recurrent acute otitis media
Otitis media with effusion
Chronic otitis media with effusion
approximately 50% of cases recognized and appropri-
ately managed with antibiotics, the acute process re-
solves in less than 3 to 4 weeks. 3 Some children may
experience repeated episodes of acute symptoms and are
considered to have recurrent acute OM. When the acute
process occurs more than six times, the child is consid-
ered otitis prone. Often, the acute middle ear inflamma-
tion manifests as or evolves into an effusion (OME).
Although frequently recognized as a sequela of acute
OM, OME also may be recognized as an occult condi-
tion associated with a subclinical or protracted inflam-
mation of the middle ear. When the duration exceeds 12
weeks without resolution, the process is called chronic
OME.
During the past 50 years, the use of descriptive terms
such as serous otitis media, secretory otitis media, mucoid
otitis, glue ear, and suppurative and nonsuppurative otitis
media have caused much confusion. The nature and
characteristics of a middle ear effusion cannot be deter-
mined by visual inspection of the tympanic membrane.
To define the physical or microbial nature of the effu-
sion, diagnostic tympanocentesis is needed. Because
tympanocentesis is not currently recommended at the
time of initial diagnosis, the generic terms OM or OME
are preferred (see Table I). The use of other terms is to
be discouraged because they are not helpful in under-
standing or managing OM.
EPIDEMIOLOGY OF OTITIS MEDIA
OM is multifactorial. A list of epidemiologic factors
that increase risk for the disease is presented in Table II.
Boys are affected more than girls. Native American,
Eskimo, and some Polynesian peoples have a higher
incidence than white children. 4 Whether there are more
cases of OM among white children than black children is
being debated. 5 Children whose parents or siblings had a
history of chronic OM have a higher incidence of OM
than do those with no family history of the disease. 6
Breast feeding is associated with lower risk for acute or
recurrent OM during the first year of life compared with
bottle feeding. 7 Parental cigarette smoking, especially by
the mother, poses higher risk for acute OM during the
first year of life. s Studies by Rockley in the British
Commonwealth suggest a genetic predisposition to
OME. 9 The studies also indicate an effect related to
socioeconomics, family size, and cigarette smoking in the
family. 9
Sensitization to aeroallergens also has been consid-
ered a risk factor, especially in children with OME or
chronic OME necessitating surgical intervention. I°
However, several large Scandinavian and U.S. studies of
J ALLERGY CLIN IMMUNOL
FEBRUARY 1997
TABLE II. Risk factors for otitis media
Viral upper respiratory infection Male sex
Allergic rhinitis Immunologic deficiency
Eustachian tube dysfunction Cilia dysfunction
Cigarette smoking (passive) Cleft palate disease
Bottle fed, not breast fed Genetic predisposition (?)
acute OM during the first 3 years of life showed no
association with allergic disease and suggested that
allergy is not a risk factor for acute OM among this age
group. 11 Some authors suggest that the increased winter
seasonality of OM refutes an association with pollen-
provoked seasonal allergic rhinitis. However, this would
not refute an association of OM with dust-mite-pro-
voked perennial allergic rhinitis. Studies among children
with chronic OME referred to otolaryngologists and
examined for allergy before surgical placement of ven-
tilation tubes indicated that 40% to 50% of children
have allergic rhinitis confirmed with positive results of
allergy skin tests or increased serum IgE antibodies to
specific allergens. 12 Many of these children are older
than 3 years. If the expression of allergic rhinitis in the 3-
to 6-year-old pediatric population is estimated to be
approximately 10% to 15%, there is a three- to fourfold
greater expression of allergic rhinitis among children
with chronic OME than among the general pediatric
population.
An association of OM with food allergy based on clinical
improvement after avoidance of certain foods, especially
milk, has been proposed in several anecdotal and poorly
designed surveys?3 A definitive association of OM with
food allergy requires better designed studies before food
allergy can be considered a risk factor for OM.
The best-defined risk factor for acute OM is a preced-
ing viral URI. A prospective telephone epidemiologic
survey by Wald et al. showed that 25% to 40% of URIs
among children from birth to 3 years old were accom-
panied by an episode of OMfl 4 The survey also showed
that OM was more frequently associated with a URI
among children ] year old or younger than among 2- or
3-year-old children. The investigators reported that U R I
and acute OM were much more frequent among chil-
dren who attended day-care programs with other chil-
dren than those cared for in small groups or alone by a
caregiver in the home. This study may be criticized
because not all of these episodes of OM were confirmed
by an examination of the patients and no viral cultures or
laboratory studies were performed. Several other spe-
cific diseases have been associated with an increased
expression of U R I and OM. These illnesses include
Downs syndrome, ciliary dysfunction syndromes, and
immune deficiency syndromes, including isolated IgA
deficiency and agammaglobulinemiaJ 5-17
In a number of epidemiologic studies, almost 50% of
children surveyed had at least one episode of acute OM
by the time they were 1 year oldJ 8 By the time they were
3 years old, two thirds of children surveyed had at least
J ALLERGY CLIN IMMUNOL
VOLUME 99, NUMBER 2
one otitis event. Three or more episodes of OM occur
among 10% of children by the time they are 1 year old
and among 33% by the time they are 3 years old. Toos et
al. reported a point prevalence of OME of 13% during
the first 2 years of l i f e . 19 Among 4- to 6-year-old
children, point prevalence decreased to 7%, and among
children 8 to 10 years old, it decreased to 2% to 4%.
Surveys that incorporated results of tympanometry con-
ducted in several day-care and school settings indicated
that OME (supposedly asymptomatic) is relatively fre-
quent, especially in the winter, z° Serial evaluations indi-
cated that many effusions resolve spontaneously without
therapy and that the effusion may shift from one ear to
another and may persist for as long as 6 months without
overt symptoms. Children with persistent OME or re-
current acute OM frequently manifest a conductive
hearing loss with potential for defects in speech and
language development, zl
PATHOPHYSIOLOGY OF OTITIS MEDIA
Structure and Function
OM is a disease of the upper respiratory tract. As
such, it is frequently described as a complication of
rhinitis. Ventilation of the middle ear is accomplished
via the eustachian tube from the posterior nasopharynx.
Understanding and diagnosis of this disease require
familiarity with the anatomy and function of the upper
airway, which is made up of the nasal cavity, nasophar-
ynx, eustachian tube, middle ear, and mastoid cells (Fig.
1). The eustachian tube provides an anatomic commu-
nication between the nasopharynx and the middle ear
and is in a unique position to cause changes in the
middle ear secondary to reactions in the nose. In relation
to the middle ear and the nasopharynx, the eustachian
tube may be considered analogous in part to the bron-
chial tree in relation to the lung and nasopharynx. Like
mucosa elsewhere in the respiratory tract, the mucosal
lining of the eustachian tube contains mucus-producing
cells, ciliated cells, plasma cells, and mast ceUs.z2 Unlike
the bronchial tree, the eustachian tube is usually col-
lapsed and thus is closed to the nasopharynx and its
contents. Active opening of the eustachian tube is
accomplished by contraction of the tensor veli palatini
(TVP) muscle during swallowing, yawning, crying, or
sneezing (Fig. 2). In this regard the eustachian tube, like
the bronchial airway, serves several functions, including
protection from nasopharyngeal secretions, drainage
into the nasopharynx of secretions produced within the
middle ear, and ventilation of the middle ear to equili-
brate air pressure with atmospheric pressure and to
replenish oxygen that has been absorbed.
In normal tubal function, intermittent opening of
the eustachian tube maintains near-ambient pressure
in the middle ear cavity. It is believed that when active
swallowing is inadequate to overcome tubal resis-
tance, the tube remains persistently collapsed, result-
ing in progressively negative middle ear pressure. This
type of ventilation appears to be common among
children; moderate to high negative middle ear pres-
Fireman $789
sures have been identified by means of tympanometry
among many children who are apparently healthy.
However, periodically or persistently high negative
pressure is often pathologic and has been associated
with abnormal function of the eustachian tube. Per-
sistently high negative middle ear pressure with severe
retraction of the tympanic membrane is called atelec-
tasis of the tympanic membrane and results in acute
OM. If effective ventilation does not occur because of
persistent eustachian tube obstruction, transudation
of sterile middle ear effusion into the tympanum can
result as a consequence of the constant absorption of
oxygen by the middle ear epithelium. Because tubal
opening is possible in a middle ear with an effusion,
aspiration of nasopbaryngeal secretions might occur,
producing the clinical condition in which persistent
effusion and recurrent acute OM occur together. Thus
abnormal eustachian tube function may predispose
the middle ear to atelectasis, infection, or effusion. 23
Eustachian tube obstruction
Two types of eustachian tube obstruction, mechanical
or functional, can cause acute or chronic OME. Table
III lists common conditions associated with eustachian
tube obstruction.
Intrinsic mechanical obstruction may result from the
inflammation of infection or allergy; extrinsic obstruc-
tion may result from enlarged adenoids or nasopharyn-
geal tumors. In experiments, allergic rhinitis provoked in
patients with a history of allergy has been associated with
the development of eustachian tube obstruction, z4 This
obstruction, related to edema and inflammation of the
posterior nasopharynx, can be both extrinsic and intrin-
sic. Persistent collapse of the eustachian tube during
swallowing may result in functional obstruction, which
appears to be related to increased tubal compliance or
inefficient active opening by the TVP muscle. Functional
eustachian tube obstruction is common among infants
and younger children, because the amount and stiffness
of the cartilage support of the eustachian tube are less
than among older children and adults. There also appear
to be marked age differences in angulation of the
craniofacial base, which renders the TVP muscle less
efficient before than after puberty. The high incidence of
OME among infants and children with cleft palate is
related to functional obstruction of the eustachian
tubeY
PATHOGENESIS OF OTITIS MEDIA
The development of rational strategies for treatment
and prevention of OM depends On an understanding of
pathogenesis. In that regard, the cause of OM is multi-
factorial. Eustachian tube dysfunction, bacterial or viral
infection of the middle ear, and nasal inflammation
resulting from allergic rhinitis or viral URIs are contrib-
uting factors. However, results of investigations of
pathogenic mechanisms involving each of these individ-
ual factors in isolation are not consistent with the results
of epidemiologic studies, which suggest that the patho-
$790 Fireman J ALLERGYCLLNLMMUNOL
FEBRUARY 1997

Mastoid
Nasopharynx I

I
\ I

Palate Eustachian

EustachianTube
(closed)

Mastoid
Antrum

(tympanic /

I Tensor
V
Palatini Muscle
e l
(at rest)
B

EustachianTube

\\ I / \ ~ Tympanic

FIG. 1. A, The upper respiratory tract. The insert shows the eustachian tube as an airway that provides
anatomic communication between the nasopharynx and the middle ear. B, Enlargement of the insert from A
shows the role of the eustachian tube in ventilation of the middle ear. Tubal function is governed, i n part, by
the tensor veil palatini (TVP) muscle. With the muscle at rest, the tube is almost always closed. C, The tube
opens when the TVP muscle contracts during swallowing, yawning, crying, or sneezing. Obstruction of the
tube plays a central role in the pathogenesis of otitis media (From Atlas of Allergies. 2nd ed. P. Fireman and
R. Slavin, editors, St. Louis, Mosby-Year Book, 1996.)

tors. 26
genesis of OM involves interactions among these fac-
Allergy and otitis media with effusion
The involvement of IgE-mediated allergic reactions in
the pathogenesis of chronic O M E has been suggested by
clinical observations of a high prevalence of chronic
O M E among patients with allergies; however, these
studies were retrospective and lacked appropriate con-
trois and experimental design. The role of allergy in
OME may involve one or more of the following mech-
anisms: (1) middle ear mucosa as a target organ; (2)
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VOLUME 99, NUMBER 2

TABLE II1. Types o f eustachian t u b e o b s t r u c t i o n

\\ Ven.,a.o. y
Mechanical obstruction Functional obstruction (presurnregulating)

Intrinsic Poor tensor veli palatini muscle

Infectious inflammation function
Allergic inflammation Increased tubal compliance
Extrinsic (peritubular)
Adenoidal hypertrophy
Nasopharyngeal tumor

inflammatory swelling of the eustachian tube with result-

ant obstruction; (3) inflammatory obstruction of the
nose and nasopharynx; or (4) reflux, insulflation, or
aspiration of bacteria-laden allergic nasopharyngeal se-
cretions into the middle ear cavity. The latter three
mechanisms are associated with abnormal function of
the eustachian tube.
Experiments conducted with sensitized monkeys indi-
cated that the middle ear mucosa is capable of sustaining
an allergic reaction; however, the extent and duration of
inflammation were limited, and OME was not ob-
served. 27 Although histamine and other mediators of
inflammation are present in middle ear effusions, there
Y B

is minimal evidence that the middle ear mucosa func-

tions as the allergic "shock organ" through the action of Protection ~"
IgE antibody and allergen reactions? °. 12
Intranasal relevant allergen challenge performed on
human adults with allergic rhinitis and on sensitized
monkeys caused classic signs and symptoms of allergic
rhinitis as well as eustachian tube dysfunction. Challenge
tests on patients with allergic rhinitis with irrelevant
allergens or on persons without allergies or rhinitis with
allergens did not provoke these responses, e4-2s-3J These
signs and symptoms were reproduced by means of
intranasal challenges with mediators of inflammation
released or synthesized during an allergic reaction) 2-34
FIG. 2. Function of the eustachian tube as related to the middle
Two response domains were documented with statisti- ear. A, Ventilation of the middle ear regulates and equilibrates
cally significant relationships established between sneez- middle-ear pressure with atmospheric pressure. B, The tube
ing and secretion production and between nasal conges- allows drainage and clearance of middle ear secretions and C
tion and eustachian tube dysfunction) 5 However, none protects the middle ear from nasopharyngeal secretions. These
functions are analogous to those of the bronchial tree. Like other
of these studies resulted in the prerequisite events for
respiratory tract mucosa, the lining of the eustachian tubes
OM by hydrops ex vacuo (sustained middle ear under- contains mast cells, lymphocytes, macrophages, and plasma
pressures). Additional studies have documented eusta- cells. (From Atlas of Allergy. 2nd ed. P. Fireman and R. Slavin,
chian tube dysfunction and middle ear underpressures in editors. St. Louis, Mosby, 1996.)
patients with allergic rhinitis during natural allergen
exposure, but the development of OM was rare?"- ~7
The following sequence of events is postulated to due to poor muscular opening are at greatest risk for
occur in patients who have respiratory allergy and OM. sufficient mechanical obstruction to give rise to middle
A basic eustachian tube dysfunction most likely is ear disease. Many children, as part of normal develop-
present in certain infants and children whose tubal ment, have difficulty actively opening their eustachian
function becomes compromised in the presence of upper tubes and are the population at most risk for OME,
respiratory tract allergy, similar to or in association with especially in association with respiratory allergy or URI.
eustachian tube obstruction caused by URI. Upper
Infection and otitis m e d i a w i t h effusion
respiratory tract allergy may cause some intrinsic and
extrinsic mechanical obstruction in patients who have In contrast to an allergic cause, convincing data exist
normal eustachian tube function, but their normal active with respect to a viral cause of OM. Viral URIs are the
opening mechanism (TVP muscle pull) overcomes the most common infections among human beings. They
obstruction. Patients who have functional obstruction occur between two and four times per year among adults
$792 Fireman
TABLE IV, Potential viral pathogenic mechanisms
for otitis media
Enhances IgE hypersensitivity
Alters mucociliary function
Promotes colonization of pathogenic bacteria
Alters neutrophil function
and much more frequently among children. 38 The pri-
mary etiologic agents identified during viral URIs in-
clude rhinovirus, adenovirus, influenza virus, parainflu-
enza virus, coxsackievirus, and respiratory syncytiai
virus, among others. 39 For OM, approximately 50% of
new episodes are diagnosed immediately after or during
a viral U R I . 4°-42 A causal relation between the two
disease entities is supported by the results of studies in
which OM resulted from adenovirus and influenza virus
infections in chinchillas.43,44 In studies involving adult
volunteers, my research group reported OM to be a
complication of experimental infections with rhinovirus
39 and influenza A virus among approximately 3% and
20% of the subjects, respectively?s, 46 A lower incidence
of acute OM was reported for infants and children
immunized with an influenza virus vaccine compared
with controls who did not receive immunizations during
a seasonal influenza epidemic. 47 The potential mecha-
nisms by which viral URIs are translated into an otologic
complication are listed in Table IV.
An in situ infection of the middle ear mucosa by
viruses has been suggested. Experiments with chinchillas
showed that the middle ear mucosa can be infected with
influenza virus and adenovirus after direct chal-
lenge.43, 44 Although cultures of middle ear effusions
from children with persistent and acute OM have recov-
ered viruses in relatively few instances, 4851 indirect
assays of effusions for viral proteins or nucleic acid
sequences have documented these chemicals in rela-
tively high frequencies. 5244 However, a role for acute
viral infection of the middle ear mucosa is ditficult to
reconcile with middle ear effusion bacterial recovery
rates of 70% for acute OM and 30% to 50% for
persistent O M Y . 56 As with viruses, these rates increase
when a diagnostic polymerase chain reaction assay is
used. 57 These observations and epidemiologic data that
indicate many episodes of OM are preceded by or
associated with a clinical illness typical of a viral U R I
have led investigators to suggest that viral URIs interact
with bacterial infections in promoting OM. Viral effects
that can promote bacterial infection include altered
bacterial adherence, 58-6° modulation of the host immune
and inflammatory response, 61, 62, 63 and impaired eusta-
chian tube function. 64, 65
Viruses that cause U R I s alter respiratory epithelial
receptors and have a differential effect on bacterial
adherence and the bacterial flora of the nasopharynx.
These changes may promote the development of a
secondary bacterial infection of the middle ear. Rhi-
novirus infections alter the immune response of the
J ALLERGY CLIN IMMUNOL
FEBRUARY 1997
TABLE V. Bacteria cultured from middle ear
effusions obtained by tympanocentesis for acute
otitis media
Bacterium Percentage of aspirates
Streptococcus pneumoniae 30
Haemophilus influenzae 20
Moraxella catarrhalis 15
Streptococcus (group A) 3
Staphylococcus aureus 2
No growth 30
host.61.63 Influenza virus infection suppresses poly-
morphonuclear chemotactic activity66-6s and perhaps
phagocytic activity.69, 7o Giebink et al. reported de-
pressed polymorphonuclear function among chinchil-
las infected with influenza A virus 71 and impaired
polymorphonuclear chemotactic bactericidal and che-
moluminescent activity among 15% to 23% of chil-
dren with persistent OM. 72 These effects can compro-
mise host defenses and increase susceptibility to a
secondary bacterial function.
The microbiologic features of middle ear effusions
are similar to those of sinus aspirates of children with
acute sinusitis, ss, 56 As shown in Table V, Streptococ-
cus pneumoniae organisms have been cultured from
approximately 30% of aspirates. This pathogen is
clearly the most common infectious agent among all
age groups. Penicillin-resistant S. pneumoniae has
been recognized. 73 Haemophilus influenzae organisms,
nontypable, have been found in approximately 20% of
the ear effusions. About 30% of the H. influenzae
organisms are [3-1actamase producing, and the per-
centage of this amoxicillin-resistant organism has
gradually increased over the last several years. In the
past, the incidence of Moraxella catarrhalis has been
about 15%, but it is now 20% or higher in some
localities; approximately 75% of M. catarrhalis strains
produce 13-1actamase. The presence of these amoxicil-
lin-resistant, 13-1actamase-producing organisms asso-
ciated with O M E among 15% to 20% of children with
ear disease and the emergence of penicillin-resistant
S. pneumonia has had an important impact on the
choice of antibiotics for therapy. The frequency of
group A 13-hemolytic streptococcus in aspirates is 3%
and of Staphylococcus aureus in aspirates is less than
2%.
It once was assumed incorrectly that chronic middle
ear effusions were sterile, especially after apparently
adequate antimicrobial therapy. In several studies, 55, 74
approximately 50% of chronic, persistent middle ear
effusions had positive cultures for bacteria with micro-
biologic features similar to those in acute OM. An
inadequate host defense can contribute to recurrent
respiratory infections and to OME. The most common
of these unusual problems is IgA deficiency, but other
immunoglobulin or cellular immunodeficiencies and the
immotile cilia syndrome cannot be overlooked.
J ALLERGY CLIN IMMUNOL
VOLUME 99, NUMBER 2
The role of nasal obstruction and nasal
inflammation
Nasal obstruction from infection, allergy, or both may
be involved in the pathogenesis of OME. Swallowing
when the nose is obstructed by inflammation or obstruc-
tive adenoids closes the nasopharyngeal chamber. Dur-
ing swallowing an initial positive nasopharyngeal air
pressure is followed by a negative pressure phase within
the closed system. There are two possible effects of these
pressures on a pliant tube. First, with positive nasopha-
ryngeal pressure, secretions might be insufltated in the
middle ear, especially when the middle ear has a high
negative pressure. Second, with negative nasopharyngeal
pressures, such a tube can be prevented from opening
and can become further obstructed. This is called the
Toynbeephenomenon.
Both viral URI and nasal allergic reactions provoke
nasal inflammation, eustachian tube dysfunction, and
enhanced transudation of nasal protein and secretion in
association with the release of a variety of bioactive
substances. 75-77The provoked nasal and tubal effects are
likely initiated, sustained, and modulated by inflamma-
tory mediators, cytokines, and proteins. Indeed, my
colleagues and I have reproduced these effects by means
of provocative challenges with histamine. We showed
that some of the responses were augmented in persons
with allergic rhinitis? 2-34 Other investigators reported
that patients with allergic rhinitis and rhinovirus URI
had enhanced lower airway responsiveness and basophil
histamine release to ragweed challenge? ~ These data
suggest that patients with allergic rhinitis may be physi-
ologically hyperresponsive to various mediators of in-
flammation elaborated during a viral URI and that this
can be potentiated by the priming of a preceding allergy
season or URI.
To test this hypothesis, my research group experimen-
tally infected persons with allergic rhinitis and persons
with nonallergic rhinitis with rhinovirus 39 and moni-
tored the development of nasal and otologic signs,
symptoms, and pathophysiologic features. TM The results
did not support a physiologic hyperresponsiveness
among persons with allergic rhinitis, but in vitro studies
documented augmented IgE synthesis and increased
basophil histamine release among persons with allergic
rhinitis only. 79 After experimental infection with influ-
enza A virus, persons with allergic rhinitis manifest
enhanced release of histamine from peripheral blood
basophils/° Other studies evaluated the hypothesis that
viral URIs can prime the nasal response to specific and
nonspeciflc stimuli. In one study, paired histamine and
cold air challenges were performed before infection with
rhinovirus 39 and after acute symptoms subsided. The
results showed greater provoked sneezing and secretions
to these stimuli for the sessions conducted after virus
infection for both subjects with allergic rhinitis and those
with nonallergic rhinitis/~ Similar results were docu-
mented for histamine challenges conducted before and
after infection with influenza A virus/2 These observa-
tions showed that a preexisting viral infection may prime
Fireman $793
certain responses of the nose in both persons with
allergic rhinitis and those with nonallergic rhinitis to
challenges with a mediator of inflammation (histamine)
and a stimulus (cold air) that cause the release of
mediators of inflammation, s3 These data support the
hypothesized interaction between viral infection and
nasal allergy in enhancing certain responses. Such an
interaction may explain the mechanism by which allergic
rhinitis acts as a risk factor for OM and thereby define a
target population for therapeutic interventions focused
on risk reduction.
Eustachian tube dysfunction
A role for eustachian tube dysfunction in the patho-
genesis of OM during a viral URI is supported by the
results of a variety of clinical and experimental studies.
Studies showed tubal dysfunction among children and
adults with natural viral U R I , 84"86 among adults with
experimental viral respiratory infections, 65, 87 and among
animals infected with influenza virus. 44,88 URIs have
been shown to result in the local release of mediators of
inflammation, 46 which provoke tubal dysfunction when
applied to the nasal mucosa. 34 In a study with chinchil-
las, damage to the eustachian tube mucosa was evident
after nasal infection with influenza, s9 In experiments
with ferrets, influenza infection resulted in peritubal
mucosal swelling and middle ear underpressures. 8s Sus-
tained tubal dysfunction resulted in middle ear under-
pressures and OM sterile for pathogens. 89 Intermittent
tubal opening during middle ear underpressures can
promote bacterial or viral infection of the middle ear by
aspiration of nasopharyngeal secretions that contain
pathogens. 9°
DIAGNOSIS OF OTITIS MEDIA
Signs and symptoms
The earliest signs of acute OM are ear pain and
discomfort, which may be difficult to discern in a child
who is nonverbal. The child may be irritable and pull on
the affected ear. There may be an associated conductive
hearing deficit, which, if not recognized or neglected for
prolonged period of time, may predispose the child to
speech difficulties.
Most children with OM have associated rhinitis. It is
important to decide whether the rhinitis is infectious or
allergic. Differentiation between infection and perennial
allergic rhinitis can be difficult. Symptoms of URI, such
as fever and malaise with profuse active rhinorrhea,
suggest infection. The presence of a similar acute illness
in immediate family members or contacts also indicates
infection. Purulent rhinorrhea or pharyngitis suggests
infection. Recurrent OM in association with recurrent
URIs with recurrent sinusitis or pneumonia suggests an
undue susceptibility to infection and raises the possibility
of an immune deficiency syndrome. For these patients,
the initial laboratory tests include quantitation of serum
IgG, IgA, and IgM, and a complete blood count includ-
ing total leukocyte and leukocyte differential count to
ascertain absolute lymphocyte count. A delayed skin test
$794 Fireman
~ a n ~ "~
FIG. 3. Diagram of proposed interactions among infection, eusta-
chian tube obstruction, allergy, and host defense defects in
pathogenesis of otitis media with effusion.
with Candida, mumps, or tetanus can be performed to
assess cell-mediated immunity. The need for additional
immunologic laboratory tests to assess specific func-
tional serum antibodies, serum IG subclasses, T and B
lymphocytes, and complement function depends on the
other signs and symptoms of recurrent infection.
Prolonged perennial or recurrent seasonal rhinitis
with itching and sneezing suggests an allergy, as does
bilateral red, itchy, swollen, nonpurulent inflammation
of the eyes, all of which are manifestations of allergic
rhinoconjunctivitis. A family history of allergy and other
allergic conditions associated with allergic rhinitis, such
as atopic dermatitis and allergic asthma, should be
determined if the patient has one of these conditions.
Seasonal allergic rhinitis occurs episodically, typically in
temperate climates during the tree, grass, and weed
pollen seasons, whereas perennial allergic rhinitis evokes
symptoms all year. Pollens or fungi can be perennial
allergens in tropical climates. Indoor perennial allergens
in the home, especially in the bedroom, or in the
workplace include house dust, dust mites, cockroaches,
storage mold spores, pet, or occupational allergens.
Allergy testing is suggested to confirm the specific cause.
Skin prick testing is preferred to serologic anti-IgE
antibody tests for the detection of IgE antibodies to
specific allergens because of increased sensitivity and
lower cost of skin tests. Total serum IgE levels are not
usually helpful in the evaluation of allergic rhinitis
because only one third of patients with allergic rhinitis
have elevated total serum IgE. In addition, total serum
IgE does not assist in defining allergies to specific
allergens.
Even if eustachian tube obstruction is minimal, pa-
tients with allergic rhinitis may have symptoms of eusta-
chian tube dysfunction, such as popping and snapping
sounds in the ear. These symptoms may be aggravated
during airplane travel. Many of these patients experi-
ence these symptoms and continue to have more prob-
lems, such as hearing loss, ear discomfort, tinnitus, and
J ALLERGY CLIN IMMUNOL
FEBRUARY 1997
rarely vertigo, during the worst periods of their allergic
rhinitis. These symptoms may not be manifested by a
nonverbal child.
Diagnostic techniques
Pneumatic otoscopy. Recognition of OME during a
physical examination necessitates pneumatic otoscopy.
It is necessary to obtain a good pneumatic seal during an
otoscopic examination to ascertain motility of the tym-
panic membrane by means of gentle application of air
pressure with a handheld bulb. Loss of normal move-
ment of the eardrum during this procedure indicates loss
of compliance of the eardrum due to middle ear effusion
behind the drum or increased stiffness due to scarring or
thickening of an inflamed eardrum.
Otoscopic inspection involves visualization of the tym-
panic membrane. Frequently cerumen may have to be
removed from the external ear canal for adequate
examination. A normal tympanic membrane is thin,
translucent, neutrally positioned, and mobile. The bony
ossicles, particularly the malleus, are generally visible
through the tympanic membrane. A bulging eardrum
indicates the presence of excessive middle ear fluid and
documents effusion. The presence of marked erythema
and hyperemia point to a clinical diagnosis of acute OM.
Sometimes the presence of air bubbles and fluid levels
documents OME. The presence of a retracted eardrum
suggests negative pressure and possibly atelectasis within
the middle ear. Acute OM may, by virtue of increased
middle ear pressure, result in acute perforation of the
tympanic membrane. On presentation the canal may be
filled with pus. Careful removal of the pus with a cotton
wick usually reveals an inflamed drum with perforation.
Neglected otitis with recurrent inflammation may result
in cholesteotoma.
Persistence of OME in spite of adequate therapy for
more than 4 to 6 months and the presence of a hearing
deficit are indications for myringotomy and insertion of
ventilation tubes. These facilitate hearing and reduce the
frequency of recurrent otitis.
Tympanometry and audiometry. The use of a tympa-
nometer in the assessment of potential ear disease is a
valuable adjunct in the management of OME. When
otoscopic findings are unclear or otoscopy is difficult to
perform, tympanometry can be useful in examinations of
children older than 6 months. This procedure, which is
used to measure the compliance of the eardrum as well
as middle ear pressure, helps confirm the diagnosis of
OME. The evaluation of a potential conduction hearing
deficit as a complication of this disease is an important
aspect of patient care that must not be ignored. There-
fore, an audiogram is necessary for the management of
recurrent and chronic OME.
TREATMENT OF OTITIS MEDIA
Medical
The initial management of acute OM consists of
choosing appropriate antibiotics. Amoxicillin is the ini-
tial therapy of choice. 91 For recurrence, or if 13-1acta-
J ALLERGY CLIN IMMUNOL
VOLUME 99, NUMBER 2
mase-producing 14. influenzae or 34. catarrhalis is the
suspected pathogen, use of amoxicillin with clavulanic
acid, erythromycin with sulfamethoxasole, or a cephalo-
sporin is suggested. Trimethoprim with sulfamethoxa-
sole is used less often. If penicillin-resistant S. pneu-
moniae is the suspected pathogen, use of a newer
macrolide, such as clarithromycin or azithromycin is
indicated. Decongestants are widely used, but their
efficacy has not been documented in controlled s t u d i e s . 92
If allergic rhinitis is documented in association with
OME, management of the allergic rhinitis includes
antihistamine therapy and avoidance of offending aller-
gens. If these are not effective, intranasal corticosteroids,
intranasal cromolyn, and allergen immunotherapy may
be considered. However, no double-blind, placebo-con-
trolled trials have documented improvement in the
course of OM or OME with the treatment of allergic
rhinitis in children.
After the initiation of appropriate antibiotic and
analgesic therapy for acute or recurrent chronic OM, a
follow-up physical examination is important. This is best
performed 3 to 4 weeks after diagnosis and the start of
antibiotic therapy, when resolution of the effusion and
inflammation can be expected among more than 50% of
patients without symptoms. Of course, patients with
symptoms must be examined sooner to ascertain
whether the selected antibiotic therapy was appropriate
and that no potential complications have developed. The
purpose of the re-examination is to identify patients at
risk for persistent effusion. Ten percent of patients with
acute OM still have OME 12 weeks after diagnosis, even
after appropriate antibiotic therapy. Therefore, OME
may be diagnosed during acute otitis, the residual of
treated otitis, or as an occult finding at physical exami-
nation of a patient without apparent antecedent otitis.
Children with recurrent acute OM may benefit from a
regimen of antibiotic prophylaxis, such as once-daily
amoxicillin during the winter months. The role of corti-
costeroids in the management of chronic OM or recur-
rent OM is promising but requires better definition and
additional studyY3
Surgical
Surgical management of OME includes insertion of
tympanostomy (ventilation) tubes to promote drainage
of persistent unresolved effusions and to improve hear-
ing. 94 With the recognition of the sequelae of chronic
OME, this surgical procedure has become the most
frequently performed operation in the United States.
Many physicians have questioned the increasing popu-
larity of this operation and have cautioned against its
potential abuse. Indications for consultation with an
otolaryngologist to consider insertion of tympanostomy
tubes include the following: (1) appropriate medical
management has not been successful in alleviating
OME; (2) OME was documented as recurrent with three
or more episodes in the preceding 6 months; (3) OME
has persisted for more than 4 to 6 months; or (4)
persistent conductive hearing deficiency was docu-
Fireman S795
mented. Adenoidectomy has been recommended to
relieve extrinsic eustachian tube obstruction caused by
peritubular lymphoid tissue. 95 Both of these surgical
procedures appear to be beneficial to certain patients,
but better documentation of their efficacy needs to be
established and confirmed in controlled, double-blind
studies.
SUMMARY
OM is a multifactorial illness that affects many chil-
dren as an acute or chronic and recurrent disease. The
roles of infection, eustachian tube obstruction, allergy,
and host defense defects have been delineated and are
diagramed in Fig. 3. Infection and eustachian tube
obstruction are the principle contributing factors in
acute OM; however, the role of allergy in a child with
chronic or recurrent OM should not be ignored. As
many as 50% of children older than 3 years with chronic
OM have confirmed allergic rhinitis, and nasal provoca-
tion testing with histamine results in eustachian tube
dysfunction in persons with allergic rhinitis. It is antici-
pated that better definition of the pathogenesis of OME
will provide the basis for more appropriate medical
management, which will reduce the need for and fre-
quency of insertion of myringotomy tubes and other
surgical procedures. This may also reduce the health
care costs and increase the well-being of these children.
The author appreciates and thanks Carol Wagner for her
secretarial assistance in the preparation of this publication.
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