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Allergology International (1998) 47: 177-
Review Article
A link between allergic rhinitis and otitis media
with effusion
Masashi Suzuki and Goro Mogi
Department of Otolaryngology, Oita Medical University, Oita, Japan
ABSTRACT
The role of allergy, particularly allergic rhinitis (AR), in otitis media with effusion (OME) is discussed. Because both OME and AR are common in young children, these disorders are occasionally seen in the same patient. Many clinical and experimental reports have discounted the allergies as a cause of middle ear effu- sion (MEE) because type I allergic reactions in the nose cause eustachian tube dysfunction but do not induce MEE, because the associated tubal dysfunction has a short duration. It has been shown that allergy-induced tubal dysfunction significantly disturbs the clearance of MEE. Since clinical and experimental studies have demonstrated the efficacy of allergy treatment in patients or animals having both diseases, combination treatment for allergy and OME in patients with both diseases should be initiated.
Key words: allergic rhinitis, nasal allergy, otitis media with effusion, pathogenesis, Type I allergy.
INTRODUCTION
The causes and pathogenesis of otitis media with effusion (OME) are considered to be multifactorial, involving infec- tion of the tubotympanum, eustachian tube dysfunction, and allergy. Allergic rhinitis (AR) is a typical immuno- globulin E (lgE)-mediated allergic disorder. The role of allergy, particularly of IgE-mediated immune reactions, in OME has been debated. Although many recent laboratory and experimental studies have discounted an allergic
Correspondence: G. Mogi, MD. Department of Otolaryngology,
Oita Medical University, 1-1 Idaigaoka, Hasama-machi Oita
879-55, Japan. E-mail: gmogi@oita-med.ac.jp
Received 7 March 1998. Accepted for publication 20 April
reaction as a cause of OME, the continuity of the mucous membrane between the nose and tympanic cavity via the eustachian tube, suggests that the middle ear mucosa may respond functionally as a sensitized tissue in patients with respiratory allergy. In this paper, we review the evidence of IgE-mediated allergic reactions in the etiopathogenesis of OME in order to examine the role of allergy in OME.
INCIDENCE OF ALLERGY IN OTITIS MEDIA
WITH EFFUSION
A number of studies have reported a high incidence of allergy in patients with OME. Jordan reported that allergy
was associated with OME in 91 of 123 patients (74%).
Leckstested 82 children with OME using skin scratch tests
with common environmental, inhalant, pollen, and mold
allergens and found a positive reaction in 72 (88%)
potients.? Draper found OME in 270 of 520 (52%) chil-
dren with allergic rhinitis.:' Since the discovery of IgE in
1966,4 more specific allergy tests have been developed.
Bernstein and Reisman, using an objective definition of
OME, examined 200 consecutive OME patients for evi-
dence of allergy.s They reported that 46 of the patients
(23%) were allergic. Hurst defined allergy using the
radioallergosorbent test (RAST), serum IgE levels, and skin
tests, and found that allergies were present in 97% of the
patients with non-acute OME.6 The results indicated that
allergy and OME were correlated clinically in 89% of
patients. Fig. 1 shows the incidence of OME in patients with AR from different age groups who were examined at
our institution between 1982 and 1996. Diagnosis of
allergic rhinitis was made based on the clinical symptoms, results of skin tests, eosinophils in nasal secretion, nasal provocation tests, RAST, and serum IgE levels. Otitis media with effusion was diagnosed by the presence of effusion in the tympanic cavity as determined by paracen-
] 78 M SUZUKI AND G MOGI
Fig. 2 Ratios of complications of nasal allergy (NA) in otitis media with effusion (OM E) and of OME in NA.
the middle ear mucosa. King studied 72 ears of 56 chil- dren and found that seven of 39 ears containing mucous secretion showed 5-10% eosinophils, while no child with serous effusion had eosinophil intlltrotion." Ivstam repor- ted smears from 33 case patients with secretory catarrh, and 13 of these had very small numbers of eosinophils.? Jordan reported 123 patients with MEE; 91 (74%) were diagnosed as allergic based on the presence of eosine- phi Is in nasal smears, positive skin tests, and response to allergy therapy.^1 However, he also found that direct smears of the effusion only showed occasional eosino- phils, scattered leukocytes, and no bacteria. Other studies also failed to find eosinophils in MEE.1O,11 Recent studies by Lim and Birck^12 Bernstein and Reismon.f and Spila and Karma^13 found no significant numbers of eosinophils in MEE or middle ear mucosa from patients with OME. Thus, a number of investigators have discounted MEE as an allergy-related fluid. More recently, however, Hurst? and Hurst and Venge 14 examined eosinophil cationic pro- tein (ECP) in MEE and middle ear mucosa from 89 patients with OME and found elevated ECP in 87.5% of MEE samples. Hurst suggested that OME is a sign of allergic inflammation in the middle ear.^6 Since the discovery of IgE,4 many investigators have studied total IgE and specific IgE antibodies in MEE, comparing them with values in corresponding sera.
Although Phillips et 0/. reported increased total IgE and
IgE-bearing cells in all MEE samples (n = 26) collected from patients with OME,15 suggesting that MEE is an allergy-related fluid, a majority of studies found that MEE did not contain total or antigen-specific IgE anti- body concentrations exceeding those in matched serum samples, thus excluding MEE as a product of allergic reactions. 5, 16- There are few immunocompetent cells in the normal
middle ear mucoso.F Mast cells are the exception. There
are significant numbers of mast cells in the tympanic orifice of the eustachian tube and in other parts of the middle ear in rats and in adult, neonatal, and developing guinea pigs.^2 3,24^ The evidence suggests that the middle ear acts as an allergic shock organ. Miglets induced OME in monkeys passively sensitized (with human anti- ragweed IgE antibodies) by daily delivery of ragweed pollen to the middle ear mucosa via an eustachian tube cotheter." Miglets found that the constituents of the provoked MEE were consistent with an allergic origin.
However, a replicating study by Doyle et 0/. failed to dis-
cover any MEE, even though they confirmed that pollen was present in the middle ear rnucosc.i" Doyle et 0/.
Control n=
OME6%
OME+NA 1.9%
NA
n=
OME36%
OME
n=
NA42%
150
II) Q) II) o 100 u 0 Z (^) 31.4% 50
o 0-
Fig. 1 Numbers of patients with otitis media with effusion (OME; .) among patients with allergic rhinitis (0). Patients were managed in the Department of Otolaryngology, Oita Medical University between 1982 and 1996.
Because eosinophil infiltration is a phenomenon charac- teristic of allergic reactions, many investigators have examined eosinophils in middle ear effusion (MEE) and in
EOSINOPHILS AND IGE IN MIDDLE EAR
EFFUSION AND MIDDLE EAR MUCOSA
tesis. Because OME and AR are both common among children, we determined the ratios at which both occurred
in three age-matched groups (mean age, 6 years; range
6-8). As shown in Fig. 2, the ratio of AR complications in
222 children with OME was 42%, whereas that of OME in
259 children with AR was 36%.7 These ratios were signifi-
cantly higher than those seen in the control group. Thus, findings of previous and recent studies indicate that the frequency of allergy in young patients with OME is high.
180 M SUZUKI AND G MOGI
Nasal global improvement ratings
Aggravated Unchanged Slight Moderate Marked improvement improvement improvement
Fig. 3 Correlation of global improvement ratings (GIR) between nasal and ear symptoms in a patient group treated for
both OME and AR. r = 0.43; P < 0.05.
0, (^) Marked .!:: (^) • • •• "§ improvement CQ) (^) improvementModerate • • E Q) ••
Slight^ • (^0) Q. (^) improvement (^) • •• •• .§ (^) Unchanged 0 •^ ••• •• ....0 (^0) Aggravated m • •
w^ C
who received s-CMC only. Azelastine hydrochloride, an anti-allergy medicine, was developed for the treatment of AR, asthma, and atopic dermatitis.37 S-carboxymethyl cys- teine has been shown to accelerate the clearance of MEE.
As shown in Fig. 3, global improvement ratings (GIR) bet-
ween nasal and ear symptoms in group A were significantly correlated. However, the correlation was not significant in group B.
In order to confirm the efficacy of Al in OME associ-
ated with AR, we recently performed experiments in an animal model. Allergic rhinitis and OME were induced in the same guinea pigs simultaneously using the method
reported previouslv" A total of 51 guinea pigs passively
sensitized with guinea pig IgE antibodies against DNP- ascaris, had immunocomplex injected into the tympanic cavity. Otitis media with effusion developed within a few days and subsided approximately 10 days after instillation of the immunocomplex. Thirteen animals received no
treatment (group A), 13 were given 1 mg/kg of Al (group
B), and 13 were given 2 mg/kg of Al (group C). Azelas-
A total of 53 patients diagnosed with OME accompanied by perennial AR were enrolled in a clinical study conducted by Kawauchi et al.^36 The patients were randomly allocated
into two groups: group A, consisting of 30 patients who
received azelastine hydrochloride (Al) and s-carboxymethyl
cysteine (s-CMC), and group B, consisting of 23 patients
and functional dysfunctions of the tube evoked by nasal allergic reactions were transient, culminating in no MEE. These studies suggest that type I allergic reactions of the nose are not an etiologic factorfor OME. In order to investigate the influence of nasal allergic
reactions on the clearance of MEE, Mogi et a/. gener-
ated an animal model of simultaneous AR and OME in the guinea pigs by passive sensitization with IgE anti- bodies (for AR), and inoculation of immunocomplexes into the tympanic cavity (for OME).34 After inoculation with the immunocomplexes, intranasal antigen chal- lenges were performed. The disappearance of MEE appeared to be delayed in animals with induced nasal allergic reactions; however, MEE was not found in ears that had not been inoculated with the immuno- complexes. The results of this study indicate that IgE- mediated allergic reactions in the nose, nasopharynx, and eustachian tube are indicative of a chronic disease state and do not cause OME. This finding is consistent with the results of an epidemiological study by Pukander and Karma of 753 infants with acute otitis media.^35 They reported a significantly longer persistence of MEE in infants with a history of allergy compared with those in a nonallergic control group. Mogi et al. recom- mended that allergy treatment be combined with OME treatment in patients with both AR and OME.
EFFECT OF ANTIALLERGIC DRUGS ON OTITIS
MEDIA WITH EFFUSION IN ASSOCIATION WITH
ALLERGIC RHINITIS
Group A
Group B
Group C
Group D 3/12 (25.0%)
Fig. 4 The presence of middle ear effusion (MEE; ~) on the eleventh day after immunocom- plex instillation into the tympanic cavity of guinea pigs. OME, otitis media with effusion; AR, allergic rhinitis; Al, azelastine hydrochloride.
tine hydrochloride was administered by gastric intubation from the 3rd to 10th day after immunocomplex injection. As a control, the 12 remaining guinea pigs were given saline drops nasally instead of ONP-ovalbumin and did
not receive AZ (group 0). All animals were killed on the
11th day after immunocomplex instillation into the tym- panic cavity and the degree of MEE stagnation was deter- mined. Fig. 4 shows the incidence of MEE in each group. In group A, 92.3% of guinea pigs had MEE, while the inci- dence of MEE was significantly lower (30.8%) in group C animals, compared with that of both group A and B ani- mals (69.2%). These findings suggest that administration of AZ significantly accelerates the clearance of MEE. In order to see whether AZ (2 mg/kg) inhibits MEE pro- duction, 14 non-sensitized, normal guinea pigs were randomly assigned to one of two groups (seven each, groups E and F). Group E animals received 2 mg/kg of AZ for 5 consecutive days before immunocomplex instil- lation into the tympanic cavity and for the 3rd day after instillation. Group F animals, in which OME was induced by immunocomplex instillation, served as non-treatment controls. Group E and F animals were killed on the 4th day after immunocomplex instillation because the MEE stagnation peaks on that day. All group E and F animals were found to have MEE, which suggests that AZ does not alleviate experimental OME. Because allergy-induced tubal dysfunction disturbs the clearance of MEE and because the control of nasal aller- gic inflammation may improve the eustachian tube dysfunction induced by allergic reaction, combined treat- ment of allergy and OME in patients with both diseases should be indicated.
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