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Eur Arch OtorhinolaryngolDOI 10.1007/s00405-014-3006-6

REvIEw ARtIclE

Association between atopy, mastoid pneumatization and tympanometric findings

Mustafa Kaymakçı · Bahar Yanık · Fuat Erel · Nuray Bayar Muluk · Cemal Cingi

Received: 12 November 2013 / Accepted: 7 March 2014 © Springer-verlag Berlin Heidelberg 2014

abnormal tympanograms was significantly higher in the atopic group than in the control group. Moreover, the pres-ence of atopy was found to be associated with an almost 4.5-fold increased risk of having an abnormal tympano-gram. Individuals with abnormal tympanograms (type BB or cc) demonstrated significantly lower right and left mas-toid volumes than did individuals with normal type A tym-panograms. Atopic individuals demonstrated significantly lower right and left mastoid volumes than did subjects in the control group. this study suggests a direct associa-tion between atopy and mastoid cell volumes. It was found that the mastoid cell systems of atopic individuals are less pneumatized, and tympanometric measurements are worse in atopic subjects. therefore, the authors suggest that when a medical or surgical treatment is planned for ear disease in atopic individuals, atopy is an important factor that should be taken into consideration.

Keywords tympanometric test · Mastoid pneumatization · Mastoid volume · Skin prick test · 3D temporal computed tomography · Atopy

Introduction

the mastoid air cell system is one of the most complex aeration systems in the human body. there are two main theories regarding the development of the mastoid air sys-tem: genetic and environmental. Darmant’s genetic or hereditary theory proposes that genetically determined fac-tors regulate the extent of mastoid pneumatization and that individuals with low mastoid aeration are thus more prone to the development of middle ear infections, such as acute or chronic otitis [1, 2]. the environmental theory, on the other hand, is based on wittmaack’s “endodermal theory”,

Abstract the purpose of this study was to reveal whether the presence of atopy plays any unfavorable role in the development of a healthy middle ear as evaluated by tym-panometry or in the degree of mastoid pneumatization as measured by mastoid volume. 33 atopic patients with posi-tive skin prick test results (atopic group) and 30 healthy subjects (control group) were included in this study. tym-panometric tests were performed in all participants, and the results were classified as type A to c. Mastoid cell volumes were measured by three-dimensional tempo-ral computed tomography. Both the right and left mas-toid volumes were significantly lower in the atopic group than in the control group. tympanogram types among all participants showed that the number of individuals with

M. Kaymakçı ENt Department, Faculty of Medicine, Balıkesir University, Balıkesir, turkey

B. Yanık Radiology Department, Faculty of Medicine, Balikesir University, Balıkesir, turkey

F. Erel Department of Allergy, Faculty of Medicine, Balikesir University, Balıkesir, turkey

N. Bayar Muluk ENt Department, Faculty of Medicine, Kırıkkale University, Kirikkale, turkey

N. Bayar Muluk (*) Birlik Mahallesi, Zirvekent 2. Etap Sitesi, c-3 blok, No: 62/43, Çankaya, 06610 Ankara, turkeye-mail: nbayarmuluk@yahoo.com; nurayb@hotmail.com

c. cingi ENt Department, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, turkey

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which suggests that healthy mastoid cell development and normal mastoid pneumatization are only possible in the presence of a healthy middle ear mucosa; hence, inflamma-tion of the middle ear mucosa or a disruption in the venti-lation function of the Eustachian tube may result in insuf-ficient development of mastoid cell [3, 4]. various studies have demonstrated that the physiology of the middle ear can be impaired in association with Eustachian dysfunction in allergic individuals, and that the amounts of inflamma-tory mediators specific for allergic reactions are increased in the inner ear fluid [5, 6].

there is an ongoing debate about the relationship of allergy with otitis media (OM), although a number of studies strongly support the idea that allergy is a risk fac-tor for OM development. Based on insufficient evidence of therapeutic efficacy or a causal relationship between allergy and OM with effusion (OME), the 2004 clinical practice guidelines on OM concluded that no recom-mendations could be made for “allergy management” as a treatment for OME [7]. However, it was reported a 52.2 % incidence of chronic secretory OM (SOM, also called OME) in patients with low-pneumatized ears in contrast to an incidence of 20 % in well-pneumatized ears [8].

No studies to date have investigated the association between atopy and mastoid cell development. the pur-pose of this study was to determine whether the presence of atopy plays an unfavorable role in the development of a healthy middle ear, as evaluated by tympanometry, or in the degree of mastoid pneumatization, as measured by mastoid volume. the hypothesis that atopic individuals are more prone to OM was tested by comparing the three-dimen-sional (3D) mastoid cell volumes of atopic and nonatopic individuals.

Materials and methods

this prospective study was conducted at the ENt and Allergy clinics of Balikesir University Faculty of Medicine

between August 2012 and March 2013 following approval from the local ethics committee.

Subjects

A total of 63 adult patients admitted to the ENt and Allergy clinics of Balikesir University Faculty of Medi-cine with a suspicion of allergy were included in the study. According to skin prick test results, 33 patients (13 male, 20 female) had positive results (atopic group), and 30 sub-jects (12 male, 18 female) did not have positive results (control group). the mean age of the atopic group was 32.1 (range 19–51) years, whereas the mean age of the control group was 30.2 (range 17–50) years.

Otoscopic examinations were performed on all partici-pants, and the condition of their tympanic membranes and the presence of OME were recorded. Nasal endoscopic examinations were also performed to identify any sinona-sal pathologies. Participants with perforated tympanic membranes, advanced degrees of septum deviation, acute sinusitis, excessive serous rhinorrhea, nasal polyposis, mucociliary dyskinesia, a previous history of middle ear surgery, adenoidectomy and/or ventilation tube insertion, Ménière’s disease, otosclerosis, or a history of radiotherapy to the head and neck region were excluded from the study. Informed consent was obtained from each participant.

when conducting this study, none of the subjects in the atopy and control groups were known as having allergy and/or atopy. Additionally, none of the subjects in the study and control group was using allergic treatments (immuno-therapy, nasal cortisone, etc.).

One limitation of this study was that the extent of mas-toid cell development in atopic individuals receiving regu-lar antiallergy therapy in the prepubertal period could nei-ther be investigated nor identified.

Skin prick test

A skin prick test that involved the 25 most common regional environmental antigens (Allergopharma extracts;

Table 1 Antigens and mixes used in prick tests

a All mixes and antigens written in the table were used

Mixesa

trees I trees I Betula verrucosa, Platanus orientalis

trees II trees II Populus alba, Salix caprea

Other trees Pinus silvestris, Olea europatea

weeds weeds Artemisia vulgaris, Plantago

Grasses-cereals Grasses-cereals Cynodon dactylon, Triticum sativum, Phleum pratense

Moulds I Moulds I Alternaria tenius, Cladosporium herbarum

Moulds II Moulds II Aspergillus fumigatus

Mites Dermatophagoides faringae, Dermatophagoides pteronyssinus

Epithelia Dog epithelia, Cat epithelia, cockroach

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Allergopharma, Reinbek, Germany) was applied to each par-ticipant (table 1). Histamine and saline solutions were used as positive and negative controls, respectively. the resulting “wheal and flare” reactions were evaluated 10 min after the application. Each reaction wider than 3 mm in diameter was regarded as a positive result. Each participant who developed at least one positive reaction against an antigen was evalu-ated as an atopic individual; collectively among these indi-viduals, patients with normal physical examination findings constituted the atopic study group (Group 1). In contrast, individuals who did not develop a positive reaction against any antigen were evaluated as nonatopic individuals; among these, individuals with normal physical examination findings constituted the control group (Group 2).

tympanometric test

All individuals in Groups 1 and 2 were further evaluated by tympanometry, and their tympanograms were obtained. Data obtained from evaluation of the patients’ tympanograms were categorized into three groups: type A (+99 to −99 mmH2O), type c (≥100 mmH2O), or type B (flat curve without peak identification). tympanometric exam was performed once for each of the subjects; and were not performed before.

Measurement of mastoid cell volumes

the mastoid cell volumes of all participants (a total of 63 individuals among Groups 1 and 2) were measured at the radiology clinic by 3D temporal computed tomography

(ct) using a 64-slice ct scanner (Aquilion 64; toshiba, tokyo, Japan) in the supine position. continuous nono-verlapping sections of temporal ct scans were used with acquisition parameters of 1.0-mm slice thickness, 100–120 kv, and 100–200 mA s (according to age). the imaging data were stored as Digital Imaging and communication in Medicine (DIcOM) files. three-dimensional images were reconstructed using previously scanned ct DIcOM data on a workstation (Aquarious iNtuition, version 4.6; toshiba Medical Systems). when performing reconstruction using a surface-rendering algorithm, the selection of the window thresholds was −1,024 to −350 Hounsfield units (HU). the volumes of mastoid air cells were automatically calcu-lated in the 3D reconstruction.

Statistical analyses

Statistical analyses were performed using the SPSS soft-ware version 18. the Mann–whitney U test, chi-square test, and Spearman’s correlation rho efficient test were used for analyses. A p value of <0.05 was considered to demon-strate a statistically significant result.

Results

Sex distribution, mastoid volumes, and tympanogram data of Groups 1 and 2 are shown in table 2. the difference in the sex distribution of the groups was not statistically sig-nificant (chi-square test, p > 0.05).

Table 2 Sex distribution, mastoid volumes, and tympanogram data of Groups 1 and 2

IQR interquartile range

* p value by Mann–whitney U test¶ p value by chi-square test

Subjects Mastoid volume (cm3) (median, IQR) pOverall

Atopic group (Group 1-study) (n = 33) Nonatopic group (Group 2-control) (n = 30)

n Right left n Right left

Male 13 6.34 (7.47) 6.63 (6.56) 12 9.03 (3.13) 8.71 (2.03)

Female 20 4.93 (7.25) 5.31 (3.59) 18 9.10 (3.89) 8.48 (3.30)

pMale–female* 0.883 0.912 0.385 0.735

Overall 33 5.20 (5.59) 6.01 (4.77) 30 9.10 (3.09) 8.62 (2.96) pOverall-right < 0.001*

pOverall-right < 0.001*

tympanogram types tympanogram types pOverall

Subjects n Normal (AA) Abnormal (BB or cc) n Normal (AA) Abnormal (BB or cc)

Male 13 10 (30.3 %) 3 (9.1 %) 12 11 (36.6 %) 1 (3.3 %)

Female 20 13 (39.4 %) 7 (21.2 %) 18 17 (56.6 %) 1 (3.3 %)

pMale–female 0.701 1.000

Overall 33 23 (69.7 %) 10 (30.3 %) 30 28 (93.4 %) 2 (6.6 %) pOverall = 0.024¶

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Mastoid volume

In Groups 1 and 2 separately, the difference between the right and left mastoid volumes of the male and female participants were analyzed with the Mann–whitney U test; there was no significant difference (p > 0.05). How-ever, when the differences between the overall participants in Groups 1 and 2 were compared, both the right and left mastoid volumes were significantly lower in Group 1 than in Group 2 (Mann–whitney U test, p < 0.001 for both the right and left mastoid volumes) (Fig. 1). In Group 1, the right mastoid volume was 5.20 cm3 and the left mastoid volume was 6.01 cm3; in Group 2, these values were 9.10 and 8.62 cm3, respectively. Moreover, both the right and left mastoid volumes demonstrated very strong correlations among all study participants (r = 0.907, p < 0.001) as well as within Group 1 (r = 0.843 and p < 0.001) and Group 2 (r = 0.879 and p < 0.001; Spearman’s rho).

tympanogram results

Abnormal tympanogram types (BB or cc) were obtained from 10 (30.3 %) patients in Group 1 (3 male, 7 female) and 2 (6.6 %) subjects in Group 2 (1 male, 1 female). In Groups 1 and 2 separately, the differences between tym-panogram types (normal, AA; abnormal, BB or cc) of the male and female participants were analyzed with the chi-square test, and no significant differences were found (p > 0.05). tympanogram data were non-differently distrib-uted between the male and female participants.

However, when the differences among tympano-gram types of the overall subjects in Groups 1 and 2 were compared, the number of individuals with abnormal

tympanograms was significantly higher in Group 1 than in Group 2 (chi-square test, p = 0.024) (Fig. 2). Moreover, the presence of atopy was found to be associated with an almost 4.5-fold increased risk of having an abnormal tym-panogram (chi-square test; relative risk, 4.545; 95 % confi-dence interval, 1.082–19.097).

For all participants in Groups 1 and 2 (n = 63), the tympanogram types and mastoid volumes (right and left separately) are shown in Fig. 3. Individuals with abnormal

Fig. 1 comparison of the right and left mastoid volumes between the atopic study group and the control group. Both the right and left mas-toid volumes were significantly lower in the atopic study group than

the control group (Mann–whitney U test, p < 0.001 for both the right and left mastoid volumes)

Fig. 2 tympanogram results of the Groups 1 and 2. the number of individuals with abnormal type BB or cc tympanograms was signifi-cantly higher in the atopic group (G1) than the control group (G2) (chi-square test, p = 0.024)

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tympanograms (type BB or cc) demonstrated signifi-cantly lower right and left mastoid volumes than individu-als with normal type A tympanograms (Mann–whitney U test; p < 0.001 for both right and left mastoid volumes) (Fig. 3).

Among all participants in Groups 1 and 2 (n = 63), the difference between each of the right and left mastoid vol-umes of the males and females was analyzed separately in individuals with abnormal and normal tympanograms using the Mann–whitney U test. the results showed that sex did not affect mastoid volumes in individuals with either abnor-mal or normal tympanograms. For individuals with normal (type A) tympanograms; p = 0.275 for right mastoid vol-umes and p = 0.931 for left mastoid volumes. For individu-als with abnormal (type B or c) tympanograms; p = 0.671 for right mastoid volumes and p = 0.739 for left mastoid volumes.

Moreover, irrespective of having either normal or abnor-mal tympanograms, individuals in Group 1 demonstrated significantly lower right and left mastoid volumes than did individuals in Group 2 (Mann–whitney U test; for individ-uals with normal type A tympanograms, p = 0.032 for right mastoid volumes and p = 0.006 for left mastoid volumes; for individuals with abnormal type B or c tympanograms, p = 0.031 for right mastoid volumes and p = 0.053 for left mastoid volumes).

No correlations were found between the number of allergens giving positive results or the severity of allergic

reactions and the degree of pneumatization according to Spearman’s correlation rho efficient test.

Discussion

the mastoid air cell system is an important regulator of middle ear physiology. It is clear that previous middle ear infections may result in low mastoid cell volumes. In addi-tion, individuals with low mastoid cell volumes are more prone to middle ear infections, although there is an ongoing debate about whether infection is the cause or the result of these low volumes. the first study of the size of mastoid cells was performed by Diamant [1, 2], who found through planimetric measurements that the mean mastoid area in healthy subjects was 12.07 cm2. More complex measure-ment techniques were subsequently developed. However, measurement of the volume of mastoid air cells is not easy due to their irregular and interconnected structure. Although the water-weight method, pressure transducer method, planimetric method, and 2D ct measurement techniques have been employed to measure the volume of mastoid cells, 3D ct reportedly provides the most defini-tive results.

the first mastoid air cell that can be recognized is the antrum, which develops during weeks 21–22 of gesta-tion. At birth, the middle ear cavity is a groove filled with mesenchymal tissue. later, this mesenchymal tissue is

Fig. 3 tympanogram types and mastoid volumes (right and left sepa-rately) in all subjects in Groups 1 and 2. Individuals with abnormal type BB or cc tympanograms demonstrated significantly lower right

and left mastoid volumes than did individuals with normal type AA tympanograms (Mann–whitney U test, p < 0.001 for both right and left mastoid volumes)

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swiftly absorbed, and mastoid cell development continues until puberty [9]. Mastoid cell development is the combi-nation of two processes: epithelial growth from the Eus-tachian tube into the middle ear with disappearance of the space-occupying mesenchyme, and preformation of the bone space around the mastoid antrum [10–12]. this pro-cess progresses beginning at birth under the influence of several factors, such as the presence of chronic or recur-rent OM, aural atresia, congenital cholesteatoma, patu-lous Eustachian tube, middle ear barotrauma, otosclerosis, Ménière’s disease, race, and sex [13–15].

In the present study, the effect of atopy on middle ear development was investigated by measuring the volumes of the mastoid air cells. the objectively obtained data clearly indicate that atopy is also an important factor that affects the development of mastoid air cells. In Group 2, the median right mastoid cell volume was 9.03 cm3 in male subjects and 9.10 cm3 in female subjects. Similarly in Group 2, the median left mastoid cell volume was 8.71 cm3 in male subjects and 8.48 cm3 in female subjects. the right and left mastoid volumes were not significantly different between male and female individuals within each group. However, both males and females with atopy demonstrated significantly lower mastoid cell volumes. In Group 1, the median right mastoid cell volume was 6.34 cm3 in male patients and 4.93 cm3 in female patients. the median left mastoid volumes were also significantly lower in Group 1, being 6.63 cm3 in male patients and 5.31 cm3 in female patients.

Both the right and left mastoid volumes were signifi-cantly lower in Group 1 than in Group 2. the tympanogram types of the overall participants showed that the number of individuals with abnormal tympanograms was significantly higher in Group 1 than Group 2. Moreover, the presence of atopy was associated with an almost 4.5-fold increased risk of having an abnormal tympanogram. Individuals with abnormal tympanograms (type BB or cc) demonstrated significantly lower right and left mastoid volumes than did individuals with normal type A tympanograms. Atopic individuals (Group 1) demonstrated significantly lower right and left mastoid volumes than subjects in the control group (Group 2).

the health of the mastoid air cell system is important in the regulation of the middle ear gas balance. Individu-als with insufficient mastoid air cell development are more prone to develop otitis. Moreover, the outcomes of sur-gery in individuals with inadequately pneumatized ears are worse than in individuals with sufficiently pneumatized ears [8]. the decrease in mastoid cell volumes due to recur-rent otitis exacerbations in atopic individuals is not an indi-rect effect depending solely on Eustachian dysfunction. In fact, levels of allergy-specific inflammatory mediators are higher in the inner ear fluids of allergic individuals [16, 17].

Histologically, the mucosa of the mastoid cavity is simi-lar to that of the nose and lungs and possesses an appropri-ate architecture for gas effusion and diffusion. compared with the other regions of the middle ear, mastoid air cells are paved with a highly vascularized cuboidal epithelium, and the contact between blood vessels and the basement membrane of the mucosa is closer. these are the character-istic features of respiratory epithelium performing the func-tion of gas exchange [8, 18]. Previous studies demonstrated that middle ear inflammation reduces the normal pneumati-zation process and causes mastoid hypocellularity [19].

this study clearly showed that the mastoid air cell vol-ume is decreased in individuals with atopy. this supports the view that the tendency to develop otitis is greater in atopic individuals. However, some authors have consid-ered that studies emphasizing the importance of atopy are poorly designed and inadequate, and these authors do not recommend that atopy be considered in the etiology and treatment of otitis. their criticisms are based mainly upon the considerations that the diagnosis of atopy is usually made based on different and often poorly defined criteria, that presentational bias by the authors artificially increases the frequency of allergy in patients with OM, and that studies reporting favorable responses to antiallergy thera-pies were conducted in neither blinded nor a placebo-con-trolled manner and fail to account for the natural history of OM, which includes variable time courses for resolu-tion without therapy [20, 21]. In contrast, there are also some strong suggestions in the literature that allergy is a predisposing factor in otitis and that it should be consid-ered during treatment decision-making. Alles et al. [22] investigated the presence of allergy in children with a his-tory of chronic OM or chronic recurring OM and obtained positive skin test results for one or more allergens in 57 % of the subjects. Similarly, Martinez et al. [23] compared the otoscopic, tympanometric, and acoustic reflexes in atopic and nonatopic school-aged children and concluded that the higher prevalence of OM in atopic children and the statistically significant differences in audiometric and tympanometric measurements among atopic and nonatopic subjects with OM were indicative of an important role played by allergic reactions in the development and recur-rence of OM [23]. therefore, it seems reasonable to sug-gest that aggressive treatment of allergic rhinitis should be performed if significant allergic rhinitis is diagnosed in an individual with OM [7].

One interesting finding of this study was that the mas-toid cell volumes were lower in atopic individuals without a history of OM and with normal tympanic membranes at physical examination than in nonatopic individuals. Simi-larly, tympanometric measurements in this study revealed that atopic individuals demonstrated worse middle ear pres-sure levels than did nonatopic control subjects. the authors

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believe that these atopic individuals underwent mild epi-sodes of inflammation in the middle ear, particularly in prepuberty, which did not lead to any sequelae in the tym-panic membrane and gave rise only to a few mild subjec-tive symptoms that even the patients themselves could not recall. It is widely known that mastoid pneumatization is inhibited during infancy when there is stimulation due to inflammation, such as in cases of OM [24]. the degree of pneumatization of the mastoid air cells may therefore be used as an indicator of a history of chronic inflammation of the middle ear [25, 26].

One limitation of this study was that the extent of mas-toid cell development in atopic individuals receiving regu-lar antiallergy therapy in the prepubertal period could nei-ther be investigated nor identified. Future efforts aiming to address whether mastoid air cell development benefits from regular antiallergy therapy in the prepubertal period might constitute a new guideline for the treatment of OM in atopic individuals.

this study suggests a direct association between atopy and mastoid cell volumes. It was found that the mastoid cell systems of atopic individuals are less pneumatized and that the tympanometric measurements are worse in atopic subjects. therefore, we suggest that when medical or surgi-cal treatment is planned for ear disease in atopic individu-als, atopy is an important factor that should be taken into consideration.

Acknowledgments Except data collection, preparation of this paper including design and planning was supported by continuous Educa-tion and Scientific Research Association.

Conflict of interest the authors declare that there is no conflict of interest.

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