<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.167063.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Research Article</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Association of chronic otitis media with rhinologic and otologic variations: a high-resolution computed tomography study</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 1 approved with reservations]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Liaqat</surname>
                        <given-names>Nazneen</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <uri content-type="orcid">https://orcid.org/0009-0006-0472-2088</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Qadri</surname>
                        <given-names>Junaid Aziz</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Din</surname>
                        <given-names>Israr Ud</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Ali</surname>
                        <given-names>Zeeshan</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <uri content-type="orcid">https://orcid.org/0009-0007-3028-4947</uri>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Baseer</surname>
                        <given-names>Abdul</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <uri content-type="orcid">https://orcid.org/0009-0001-0763-9216</uri>
                    <xref ref-type="aff" rid="a3">3</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Department of Otorhinolaryngology, Head and Neck Surgery, Khyber Teaching Hospital, MTI, Peshawar, Khyber Pakhtunkhwa, 25000, Pakistan</aff>
                <aff id="a2">
                    <label>2</label>Department of Surgery, Hayatabad Medical Complex, MTI, Peshawar, Khyber Pakhtunkhwa, 25000, Pakistan</aff>
                <aff id="a3">
                    <label>3</label>Department of Radiology, Kabul Medical University, Kabul, 1007, Afghanistan</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:israr_uddin2000@yahoo.com">israr_uddin2000@yahoo.com</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>18</day>
                <month>8</month>
                <year>2025</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2025</year>
            </pub-date>
            <volume>14</volume>
            <elocation-id>793</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>4</day>
                    <month>8</month>
                    <year>2025</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Liaqat N et al.</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/14-793/pdf"/>
            <abstract>
                <sec>
                    <title>Background</title>
                    <p>Unilateral chronic otitis media (COM) offers a unique opportunity to investigate anatomical variations that may predispose one side to disease while sparing the other. This study aimed to compare the anatomical variations between the diseased and healthy sides of the skull of patients with unilateral COM.</p>
                </sec>
                <sec>
                    <title>Methods</title>
                    <p>This within-subject case-control study, conducted at the Department of ENT of Khyber Teaching Hospital, Peshawar, Pakistan, included 100 temporal bones (50 adult patients) with unilateral COM. Utilizing high-resolution computed tomography scans, COM sides (50 temporal bones) were compared with the healthy sides (50 temporal bones) in terms of anatomical variations in the nose, paranasal sinuses, temporal bone, and eustachian tube (ET).</p>
                </sec>
                <sec>
                    <title>Results</title>
                    <p>Among the rhinologic variants, a deviated nasal septum was more frequent on the COM side than on the healthy side (19 vs. 8; p=0.05, OR=2.37), and the angle of septal deviation was significantly larger on the COM side (1.89&#x00b1;2.66 vs 0.46&#x00b1;1.13; p=0.003, Cohen&#x2019;s d=0.44). Concha bullosa was more common on the COM side (18vs 9; p=0.04, OR=3.25). Sinus opacification and turbinate hypertrophy showed no statistically significant difference between the two sides (p&gt;0.05).</p>
                    <p>Among the otologic variants, the mastoid was less pneumatized (4vs 20) and more frequently sclerotic on the COM side (39vs 12; p&lt;0.01, Cram&#x00e9;r&#x2019;s V=0.54). The prevalence and thickness of Korner septa were similar on both sides (p&gt;0.05).</p>
                    <p>ET lengths were comparable between sides, but the ET angle was narrower on the COM side (22.09&#x00b1;1.80 vs 22.90&#x00b1;1.76; p=0.01, Cohen&#x2019;s d=0.34). The tubotympanic angle was wider (148.86&#x00b1;3.57 vs 144.76&#x00b1;2.15&#x00b0;; p&lt;0.001, Cohen&#x2019;s d=0.96), and the pretympanic diameter was smaller on the COM side (3.03&#x00b1;0.77 vs 3.91&#x00b1;0.56, p&lt;0.001, Cohen&#x2019;s d=1.01).</p>
                </sec>
                <sec>
                    <title>Conclusion</title>
                    <p>Significant anatomical differences were observed between the diseased and healthy sides of the skull in patients with unilateral chronic otitis media, particularly in the nasal septum, concha bullosa, mastoid pneumatization, and ET anatomies.</p>
                </sec>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Chronic Otitis Media</kwd>
                <kwd>Anatomical variations</kwd>
                <kwd>HRCT</kwd>
                <kwd>computed tomography</kwd>
            </kwd-group>
            <funding-group>
                <funding-statement>The author(s) declared that no grants were involved in supporting this work.</funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec id="sec5" sec-type="intro">
            <title>Introduction</title>
            <p>Chronic otitis media (COM) is defined as intermittent or persistent inflammation of the middle ear cleft characterized by chronic otorrhea and hearing impairment.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup> Affecting an estimated 65&#x2013;330 million people worldwide and remains a major public health concern, particularly in low- and middle-income countries.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup>
            </p>
            <p>The etiology of COM is multifactorial and includes genetic, environmental, and anatomical factors.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup> Among anatomical factors, the Eustachian tube (ET) has been consistently identified as a key anatomical structure involved in the pathogenesis of COM.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup> ET is responsible for ventilation of the middle ear, drainage, and protection against infections.
                <sup>
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup> Changes in its angulation with respect to the Reid&#x2019;s plane or external auditory canal can disrupt these functions, thus predisposing individuals to recurrent or chronic middle ear infections.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup> Moreover, anatomical changes in the nose and paranasal sinuses, such as a deviated nasal septum, have also been proposed to disrupt aeration of the middle ear cleft and contribute to the pathogenesis of COM.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>,
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup>
            </p>
            <p>COM usually affects both the ears.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup> Unilateral COM, a condition in which only one ear is clinically affected, offers a unique opportunity to investigate anatomical variations that may predispose one side to disease while sparing the other. It has been postulated that the contralateral ear in these cases may reveal early stage pathologies, such as retractions or tympanosclerosis, but have not progressed enough to cause symptoms.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>,
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup>
            </p>
            <p>This study aimed to compare the anatomical features of the temporal bone, ET, and paranasal sinuses between the affected and unaffected sides of patients with unilateral COM. This will provide insights into the anatomical predispositions that may contribute to the pathogenesis of COM.</p>
        </sec>
        <sec id="sec6" sec-type="methods">
            <title>Methods</title>
            <p>This within-subject case-control study was conducted in the Department of ENT at Khyber Teaching Hospital, Peshawar, Pakistan, from August 2024 to December 2024, according to the ethical standards of the Institutional Review Board of Khyber Teaching Hospital, Peshawar, Pakistan (registration no. 495/DME/KMC issued on 18/08/2023). A non-probability convenience sampling method was used. All adult patients (aged &#x2265;18 years) with recurrent or unsettled unilateral otorrhea and hearing loss were screened. Diagnostic bilateral otoscopy and audiological investigations were performed for every patient. The diagnosis of unilateral COM was made in which one ear had a perforated tympanic membrane, while the other ear was intact with no previous history of ear discharge. Patients with a history of trauma, temporal bone or nasal surgery, or any additional anomalies affecting the skull were also excluded. Those who refused to participate were excluded from the study. Fifty patients (100 temporal bones) were included.</p>
            <p>All patients underwent high-resolution computed tomography (HRCT) of the temporal bones with paranasal sinuses, and axial and coronal reconstructions were performed. These scans were assessed for rhinologic variants including the presence and angulation of septal deviation, concha bullosa, turbinate hypertrophy, and opacification of the paranasal sinuses. Otologic variants were also interpreted, including the pattern of mastoid pneumatization, presence and thickness of the Korner septum, and ET measurements (length, angle with respect to Reid&#x2019;s plane, tubotympanic angle, and pretympanic diameter). All scans were interpreted by two radiologists independently, and significant discrepancies were resolved by discussion with a third radiologist. The COM-affected side (case) and healthy side (control) were evaluated for within-subject comparisons.</p>
            <p>The data were analyzed using SPSS v23.0. The distribution of data was determined using the Shapiro-Wilk test. For continuous and categorical variables, means with standard deviations and frequencies with percentages were calculated, respectively. For comparison, McNemar&#x2019;s test was applied for paired categorical variables, whereas paired t-tests were used to compare continuous variables between the COM and healthy sides. Odds ratios (OR) were calculated for the significant dichotomous variables. For the effect sizes, Cohen&#x2019;s d was used for continuous variables to estimate the magnitude of differences. At the same time, Cramer&#x2019;s V was applied to categorical variables to measure the strength of association. Statistical significance was set at P &lt;0.05. The results of this study were selected for a presentation at the 158
                <sup>th</sup> meeting of the American Otological Society.
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>
                </sup>
            </p>
        </sec>
        <sec id="sec7" sec-type="results">
            <title>Results</title>
            <p>A total of 100 temporal bones of 50 patients with a mean age of 37.72 &#x00b1; 10.47 years, comprising 21 females and 29 males, were included in the study. These yielded 50 bones from the COM-affected side serving as cases and contralateral 50 healthy bones as controls. Of the 50 case-temporal bones, 29 were right sided and 21 were left sided.</p>
            <p>

                <bold>Rhinologic variants</bold> (
                <xref ref-type="table" rid="T1">
Table 1</xref>):
                <list list-type="order">
                    <list-item>
                        <label>1.</label>
                        <p>

                            <bold>Deviated Nasal Septum (DNS)</bold>
                        </p>
                        <p>
DNS was more frequent towards the COM side compared to the healthy side (p = 0.05, marginally significant). The OR = 2.37 showed that it was 2.37 times more likely towards the COM side.</p>
                    </list-item>
                    <list-item>
                        <label>2.</label>
                        <p>

                            <bold>Angle of Septal Deviation (ASD)</bold>
                        </p>
                        <p>
The ASD was significantly greater on the COM side compared to the healthy side (1.89 &#x00b1; 2.66 vs. 0.46 &#x00b1; 1.13, p = 0.003). Cohen&#x2019;s d = 0.44, indicated a medium effect size for the difference between the two sides.</p>
                    </list-item>
                    <list-item>
                        <label>3.</label>
                        <p>

                            <bold>Concha Bullosa</bold>
                        </p>
                        <p>
It frequent in the COM side (18 vs. 9, p = 0.04). The OR = 3.25 suggested its presence was strongly associated with the COM side.</p>
                    </list-item>
                    <list-item>
                        <label>4.</label>
                        <p>

                            <bold>Turbinate Hypertrophy</bold>
                        </p>
                        <p>
There significant difference in the frequency of inferior or middle turbinate hypertrophy between the COM and healthy sides (p &gt; 0.05).</p>
                    </list-item>
                    <list-item>
                        <label>5.</label>
                        <p>

                            <bold>Sinus Opacification</bold>
                        </p>
                        <p>
No significant differences were observed between the COM and healthy sides for opacification in the frontal, maxillary, or sphenoid sinuses (p &gt; 0.05).
</p>
                    </list-item>
                </list>
            </p>
            <table-wrap id="T1" orientation="portrait" position="float">
                <label>
Table 1. </label>
                <caption>
                    <title>Comparison of anatomical variants between case and control sides.</title>
                </caption>
                <table content-type="article-table" frame="hsides">
                    <thead>
                        <tr>
                            <th align="left" colspan="2" rowspan="1" valign="top">Anatomical variants</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Cases 
(N=50)</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Controls 
(N=50)</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">
P value</th>
                        </tr>
                    </thead>
                    <tbody>
                        <tr>
                            <td align="left" colspan="1" rowspan="9" valign="top">Rhinologic Variants</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Ipsilateral Deviated nasal septum n (%)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">19 (38)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">8 (16)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>0.05</bold>
                                <xref ref-type="table-fn" rid="tfn1">
                                    <sup>

                                        <bold>a</bold>
                                    </sup>
                                </xref>
                                <break/>

                                <bold>OR=2.37</bold>
</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Angle of septal deviation in degrees (mean&#x00b1;SD)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">1.89&#x00b1;2.66</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">0.46&#x00b1;1.13</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>0.003</bold>
                                <xref ref-type="table-fn" rid="tfn2">
                                    <sup>

                                        <bold>b</bold>
                                    </sup>
                                </xref>
                                <break/>

                                <bold>Cohen&#x2019;s d=0.44</bold>
</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Concha bullosa n (%)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">18 (36)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">9 (18)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>0.04</bold>
                                <xref ref-type="table-fn" rid="tfn1">
                                    <sup>

                                        <bold>a</bold>
                                    </sup>
                                </xref>
                                <break/>

                                <bold>OR=3.25</bold>
</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Inferior turbinate hypertrophy n (%)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">10 (20)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">19 (38)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">0.12
                                <xref ref-type="table-fn" rid="tfn1">
                                    <sup>a</sup>
                                </xref>
                            </td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Middle turbinate hypertrophy n (%)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">14 (28)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">11(22)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">0.58
                                <xref ref-type="table-fn" rid="tfn1">
                                    <sup>

                                        <bold>a</bold>
                                    </sup>
                                </xref>
                            </td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Sinus opacification n (%)</td>
                            <td colspan="1" rowspan="1"/>
                            <td colspan="1" rowspan="1"/>
                            <td colspan="1" rowspan="1"/>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">&#x2003;Frontal</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">6 (12)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">2 (4)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">0.21
                                <xref ref-type="table-fn" rid="tfn1">
                                    <sup>

                                        <bold>a</bold>
                                    </sup>
                                </xref>
                            </td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">&#x2003;Maxillary</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">11 (22)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">11 (22)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">1.00
                                <xref ref-type="table-fn" rid="tfn1">
                                    <sup>

                                        <bold>a</bold>
                                    </sup>
                                </xref>
                            </td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">&#x2003;Sphenoid</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">2 (4)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">2 (4)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">1.00
                                <xref ref-type="table-fn" rid="tfn1">
                                    <sup>

                                        <bold>a</bold>
                                    </sup>
                                </xref>
                            </td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="10" valign="top">Otologic Variants</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Mastoid Pneumatization n (%)</td>
                            <td colspan="1" rowspan="1"/>
                            <td colspan="1" rowspan="1"/>
                            <td align="left" colspan="1" rowspan="4" valign="top">
                                <bold>&lt;0.01</bold>
                                <xref ref-type="table-fn" rid="tfn3">
                                    <sup>

                                        <bold>c</bold>
                                    </sup>
                                </xref>
                                <break/>

                                <bold>Cramer&#x2019;s V=0.54</bold>
</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">&#x2003;Pneumatized</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">4 (8)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">20 (40)</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">&#x2003;Sclerotic</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">39 (78)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">12 (24)</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">&#x2003;Diploic</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">7 (14)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">18 (36)</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Korner septum n (%)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">8 (16)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">10 (20)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">0.68
                                <xref ref-type="table-fn" rid="tfn1">
                                    <sup>

                                        <bold>a</bold>
                                    </sup>
                                </xref>
                            </td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Thickness of Korner septum in mm (mean&#x00b1;SD)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">0.20&#x00b1;0.48</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">0.21&#x00b1;0.43</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">0.92
                                <xref ref-type="table-fn" rid="tfn2">
                                    <sup>

                                        <bold>b</bold>
                                    </sup>
                                </xref>
                            </td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Eustachian tube length in mm (mean&#x00b1;SD)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">36.99&#x00b1;2.12</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">37.07&#x00b1;2.06</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">0.60
                                <xref ref-type="table-fn" rid="tfn2">
                                    <sup>

                                        <bold>b</bold>
                                    </sup>
                                </xref>
                            </td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Eustachian tube angle in degrees (mean&#x00b1;SD)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">28.13&#x00b1;1.35</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">27.97&#x00b1;1.86</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>0.00</bold>
                                <xref ref-type="table-fn" rid="tfn2">
                                    <sup>

                                        <bold>b</bold>
                                    </sup>
                                </xref>
                                <break/>

                                <bold>Cohen&#x2019;s d=0.31</bold>
</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Pretympanic diameter in mm (mean&#x00b1;SD)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">3.03&#x00b1;0.77</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">3.91&#x00b1;0.56</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>0.00</bold>
                                <xref ref-type="table-fn" rid="tfn2">
                                    <sup>

                                        <bold>b</bold>
                                    </sup>
                                </xref>
                                <break/>

                                <bold>Cohen&#x2019;s d=1.01</bold>
</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Tubotympanic angle in degrees (mean&#x00b1;SD)</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">148.86&#x00b1;3.57</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">144.76&#x00b1;2.15</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">
                                <bold>0.00</bold>
                                <xref ref-type="table-fn" rid="tfn2">
                                    <sup>

                                        <bold>b</bold>
                                    </sup>
                                </xref>
                                <break/>

                                <bold>Cohen&#x2019;s d=0.96</bold>
</td>
                        </tr>
                    </tbody>
                </table>
                <table-wrap-foot>
                    <fn-group content-type="footnotes">
                        <fn id="tfn1">
                            <label>
                                <sup>a</sup>
                            </label>
                            <p>McNemar Test.</p>
                        </fn>
                        <fn id="tfn2">
                            <label>
                                <sup>b</sup>
                            </label>
                            <p>Paired Sample T-test, OR-Odds Ratio.</p>
                        </fn>
                        <fn id="tfn3">
                            <label>
                                <sup>c</sup>
                            </label>
                            <p>Chi-square.</p>
                        </fn>
                    </fn-group>
                </table-wrap-foot>
            </table-wrap>
            <p>

                <bold>Otologic variants</bold> (
                <xref ref-type="table" rid="T1">
Table 1</xref>):
                <list list-type="order">
                    <list-item>
                        <label>1.</label>
                        <p>

                            <bold>Mastoid Pneumatization</bold>
                        </p>
                        <p>
Mastoid pneumatization showed a significant difference, with the COM side being less pneumatized (4 vs. 20) and more frequently sclerotic (39 vs. 12) (p &lt; 0.01). Cram&#x00e9;r&#x2019;s V = 0.54, indicated a large effect size and a strong association between mastoid pneumatization and COM.</p>
                    </list-item>
                    <list-item>
                        <label>2.</label>
                        <p>

                            <bold>Korner Septum</bold>
                        </p>
                        <p>
The prevalence and thickness of the Korner Septum The similar between COM and healthy sides, with no statistically significant difference (p &gt; 0.05).</p>
                    </list-item>
                    <list-item>
                        <label>3.</label>
                        <p>

                            <bold>ET Length (ETL)</bold>
                        </p>
                        <p>
ETL was comparable between the COM and healthy sides (p = 0.60).</p>
                    </list-item>
                    <list-item>
                        <label>4.</label>
                        <p>

                            <bold>ET Angle (ETA)</bold>
                        </p>
                        <p>
The ETA with respect to Reid&#x2019;s plane was significantly acute on the COM side compared to the healthy side (28.13&#x00b1;1.35 vs. 27.97&#x00b1;1.86, p=0.00). Cohen&#x2019;s d = 0.31 indicated a small-to-medium effect size (
                            <xref ref-type="fig" rid="f1">
Figure 1</xref>).</p>
                    </list-item>
                    <list-item>
                        <label>5.</label>
                        <p>

                            <bold>Pretympanic Diameter (PTD)</bold>
                        </p>
                        <p>
The PTD was significantly smaller on the COM side compared to the healthy side (3.30 &#x00b1; 0.77 vs. 3.91 &#x00b1; 0.56, p &lt; 0.001). Cohen&#x2019;s d = 1.01 reflected a large effect size (
                            <xref ref-type="fig" rid="f2">
Figure 2</xref>).</p>
                    </list-item>
                    <list-item>
                        <label>6.</label>
                        <p>

                            <bold>Tubotympanic Angle (TTA)</bold>
                        </p>
                        <p>
The TTA was significantly wider on the COM side (148.86 &#x00b1; 3.57 vs. 144.76 &#x00b1; 2.15, p &lt; 0.001). Cohen&#x2019;s d = 0.96, indicating a large effect size (
                            <xref ref-type="fig" rid="f3">
Figure 3</xref>).
</p>
                    </list-item>
                </list>
            </p>
            <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                <label>
Figure 1. </label>
                <caption>
                    <title>Eustachian tube angle with respect to Reid's plane. 1-ETA.
                        <sup>
                            <xref ref-type="bibr" rid="ref9">9</xref>
                        </sup>
                    </title>
                </caption>
                <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/184141/9b872fc5-3bc8-4b8c-aa01-9c27199c4758_figure1.gif"/>
            </fig>
            <fig fig-type="figure" id="f2" orientation="portrait" position="float">
                <label>
Figure 2. </label>
                <caption>
                    <title>Parts of Eustachian tube.</title>
                    <p>Labels: 1-Pharyngeal orifice, 2-Pharyngeal portion, 3-Mid-portion, 4-Pre-isthmus, 5-Isthmus, 6-Post-isthmus, 7-Pretympanic, 8-Tympanic orifice.
                        <sup>
                            <xref ref-type="bibr" rid="ref9">9</xref>
                        </sup>
                    </p>
                </caption>
                <graphic id="gr2" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/184141/9b872fc5-3bc8-4b8c-aa01-9c27199c4758_figure2.gif"/>
            </fig>
            <fig fig-type="figure" id="f3" orientation="portrait" position="float">
                <label>
Figure 3. </label>
                <caption>
                    <title>Tubotympanic angle.</title>
                    <p>1-External auditory canal, 2-Tubotympanic angle, 3-Eustachian tube.
                        <sup>
                            <xref ref-type="bibr" rid="ref9">9</xref>
                        </sup>
                    </p>
                </caption>
                <graphic id="gr3" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/184141/9b872fc5-3bc8-4b8c-aa01-9c27199c4758_figure3.gif"/>
            </fig>
        </sec>
        <sec id="sec8" sec-type="discussion">
            <title>Discussion</title>
            <p>Radiological investigations, particularly HRCT, are used as an adjunct to clinical and audiological assessments in the diagnosis of middle ear diseases and planning surgeries.
                <sup>
                    <xref ref-type="bibr" rid="ref10">10</xref>
                </sup> As COM is a multifactorial disease, otologists need to know the anatomical variants to detect the risk factors and plan treatment accordingly.
                <sup>
                    <xref ref-type="bibr" rid="ref11">11</xref>,
                    <xref ref-type="bibr" rid="ref12">12</xref>
                </sup> By studying unilateral COM, an underexplored manifestation of the disease, this study offers insights into these anatomical structures playing roles in the pathogenesis of COM.</p>
            <p>Among anatomical variations in the nose and paranasal sinuses, DNS, particularly with a greater angle, and concha bullosa were associated with increased COM risk. These nasal pathologies can impede nasal airflow to the ET, thus affecting mastoid cell aeration.
                <sup>
                    <xref ref-type="bibr" rid="ref13">13</xref>,
                    <xref ref-type="bibr" rid="ref14">14</xref>
                </sup> This finding corroborates the findings of Damar et al. and Atila et al., who observed that anatomical alterations in the nose, such as DNS, concha bullosa, and inferior turbinate hypertrophy disrupt nasal airflow, ET pressure, and mastoid aeration, and thus increase the incidence of COM.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>,
                    <xref ref-type="bibr" rid="ref15">15</xref>
                </sup> These nasal pathologies may affect the ipsilateral ear, helping explain why unilateral COM is associated with nasal or sinus abnormalities on the same side. However, contrary to the findings of Atila et al. and Khaksari et al., no association of COM was observed with hypertrophy of turbinates or sinusitis.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>,
                    <xref ref-type="bibr" rid="ref14">14</xref>
                </sup>
            </p>
            <p>The mastoid air cells were less pneumatized and predominantly sclerotic on the COM side, while 24% (n=12) of the contralateral normal temporal bones were also sclerotic. According to Jadia et al., the contralateral temporal bones in unilateral COM exhibit poor pneumatization, ranging from 17.8% in mucosal diseases to 55.9% in squamous diseases.
                <sup>
                    <xref ref-type="bibr" rid="ref16">16</xref>
                </sup> This supports the theory that unilateral COM represents a continuous process with an increased risk of disease development in the contralateral ear.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>,
                    <xref ref-type="bibr" rid="ref16">16</xref>
                </sup>
            </p>
            <p>KS is a bony partition extending from the petrosquamosal fissure to the anterolateral surface of the mastoid process, and is postulated to reduce mastoid aeration. Toros et al. found no significant relationship between KS and temporal bone aeration, whereas Elibol et al. found KS more frequently in patients with COM.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>,
                    <xref ref-type="bibr" rid="ref17">17</xref>
                </sup> By studying purely unilateral COM cases, the authors found no association between COM and KS presence or thickness.</p>
            <p>The genetic theory claims that pneumatization of the temporal bone is genetically determined, rendering poorly pneumatized bones susceptible to COM. ET orientation and angulation can affect mastoid pneumatization.
                <sup>
                    <xref ref-type="bibr" rid="ref18">18</xref>
                </sup> The two commonly studied ET angles are the ETA and TTA. The ETA is defined as the angle between the right plane and the tympanic pharyngeal orifice. The angle between the longitudinal axes of the ET and the bony external auditory canal is called the TTA.
                <sup>
                    <xref ref-type="bibr" rid="ref19">19</xref>
                </sup> Nemade et al. detected ETA 27.56 &#x00b1; 3.62 in healthy ears and 25.41 &#x00b1; 2.57 in diseased ears. They found the TTA to be 148.12 &#x00b1; 3.43 &#x00b0;in diseased ears and 145.14&#x00b0; &#x00b1; 4.34&#x00b0; in healthy ears.
                <sup>
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup> In a nutshell, they found significantly less ETA and significantly less TTA obtuse in patients with COM. In patients with unilateral COM, the authors found a significantly acute ETA, wider TTA, and narrower PTD on the COM side of the skull than on the healthy temporal bones. A narrower ETA may facilitate nasopharyngeal reflux, thereby increasing the risk of infection and inflammation in the middle ear. Additionally, a wider TTA can enhance pathogen entry into the middle ear, contributing to chronic inflammation and infection. A narrower PTD can impede airflow and ventilation of the mastoid. These results highlight the impact of ET anatomical variations on COM pathogenesis, further supporting the theory that specific anatomical features predispose individuals to middle ear infections.</p>
            <p>Despite these significant findings, this study has several limitations. The sample was drawn from a single center. Furthermore, detailed assessments of subtypes were not included, which could have offered a more comprehensive understanding of the COM subtypes and their anatomical correlates. Nevertheless, the authors&#x2019; institution is a major referral center that enhances the representativeness of the study sample. Future multicenter studies should explore a broader population for these anatomical variations and correlate these with COM subtypes.</p>
        </sec>
        <sec id="sec9" sec-type="conclusion">
            <title>Conclusion</title>
            <p>Significant anatomical differences were observed between the diseased and healthy sides of the skull of patients with unilateral COM. Among the rhinologic variants, ipsilateral DNS with a greater angle and concha bullosa were associated with COM. Poor mastoid pneumatization, acute ETA, narrow PTD, and wide TTA were significantly associated with COM. These anatomical factors should be considered during the diagnostic evaluation and treatment planning for COM.</p>
            <p>

                <bold>Preregistered data analysis:</bold> This research was not preregistered.</p>
        </sec>
        <sec id="sec10">
            <title>Ethical approval and consent</title>
            <p>The experimental protocols were approved by the ethical standards of the Institutional Review Board of the Khyber Teaching Hospital. The study was conducted in accordance with the ethical standards of the Institutional Review Board of Khyber Teaching Hospital, Peshawar, Pakistan (registration no. 495/DME/KMC issued on 18/08/2023). Written informed consent was obtained from all participants included in this study.</p>
        </sec>
        <sec id="sec11">
            <title>Abstract presentation</title>
            <p>The abstract of this manuscript was accepted for a poster presentation at the American Otological Society AOS/COSM Spring Meeting, 2025.</p>
        </sec>
        <sec id="sec12">
            <title>Limitations of study</title>
            <p>Despite these significant findings, this study had some limitations. The sample was drawn from a single center. Furthermore, detailed assessments of subtypes were not included, which could have offered a more comprehensive understanding of the COM subtypes and their anatomical correlates.</p>
        </sec>
    </body>
    <back>
        <sec id="sec15">
            <title>Data and software availability</title>
            <p>OSF: Association of chronic otitis media with rhinologic and otologic variations: A high-resolution computed tomography study, 
                <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.17605/OSF.IO/A4HS3">https://doi.org/10.17605/OSF.IO/A4HS3</ext-link>.
                <sup>
                    <xref ref-type="bibr" rid="ref20">20</xref>
                </sup>
            </p>
            <p>This project contains the following underlying data:
                <list list-type="bullet">
                    <list-item>
                        <label>&#x2022;</label>
                        <p>Data file. Untitled1.sav</p>
                    </list-item>
                </list>
            </p>
            <p>Data are available under the terms of the 
                <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">Creative Commons Zero &#x201c;No rights reserved&#x2019; data waiver</ext-link> (CC0 1.0 Public domain dedication).</p>
            <sec id="sec16">
                <title>Reporting guidelines</title>
                <p>STROBE checklist for &#x2018;Association of chronic otitis media with rhinologic and otologic variations: A high-resolution computed tomography study, 
                    <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.17605/OSF.IO/A4HS3">https://doi.org/10.17605/OSF.IO/A4HS3</ext-link>.
                    <sup>
                        <xref ref-type="bibr" rid="ref20">20</xref>
                    </sup>
                </p>
                <p>Data are available under the terms of the 
                    <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">Creative Commons Zero &#x201c;No rights reserved&#x2019; data waiver</ext-link> (CC0 1.0 Public domain dedication).</p>
            </sec>
        </sec>
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    <sub-article article-type="reviewer-report" id="report468254">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.184141.r468254</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Sun</surname>
                        <given-names>Yu</given-names>
                    </name>
                    <xref ref-type="aff" rid="r468254a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <aff id="r468254a1">
                    <label>1</label>Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>9</day>
                <month>4</month>
                <year>2026</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2026 Sun Y</copyright-statement>
                <copyright-year>2026</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport468254" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.167063.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This study uses a within-subject design to investigate the association between unilateral chronic otitis media and anatomical variations of the nasal and otologic regions. The self-controlled design effectively controls for individual differences. However, several revisions are needed.</p>
            <p> </p>
            <p> 1. The study does not specify the disease duration, perforation type, or presence of cholesteatoma/granulation tissue for stratification of unilateral COM subtypes. A baseline characteristics table is recommended.</p>
            <p> </p>
            <p> 2. Confounding factors for middle ear infection, such as nasopharyngeal lesions, adenoid hypertrophy, and gastroesophageal reflux, are not mentioned in the exclusion criteria and should be added.</p>
            <p> </p>
            <p> 3. Technical parameters of CT scanning, including slice thickness, reconstruction thickness, window width, and window level, are not reported and should be supplemented.</p>
            <p> </p>
            <p> 4. Inter-observer reliability (Kappa value / ICC) is not provided and should be included to confirm the reproducibility of the results.</p>
            <p> </p>
            <p> 5. Key measurements (eustachian tube angle, pretympanic diameter) are only described in text; standard HRCT measurement diagrams should be added.</p>
            <p> </p>
            <p> 6. Data on the laterality of the affected side and subgroup analyses by age and sex are not reported and should be supplemented.</p>
            <p> </p>
            <p> 7. The main limitations&#x2014;single-center design, adult-only sample, and no stratification of COM subtypes&#x2014;should be clearly stated in the Discussion section to note the limited generalizability of the conclusions.</p>
            <p> </p>
            <p> 8. The values for eustachian tube angle are inconsistent between the Abstract and the main text and require verification:</p>
            <p> Abstract: ET angle was narrower on the COM side (22.09&#x00b1;1.80 vs 22.90&#x00b1;1.76; p=0.01)</p>
            <p> Results, 4. ET Angle: The ETA was significantly acute on the COM side (28.13&#x00b1;1.35 vs. 27.97&#x00b1;1.86, p=0.00)</p>
            <p> </p>
            <p> I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however, I have a number of small changes to the article, or specific, sometimes more significant revisions.</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Yes</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Partly</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Partly</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Partly</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Partly</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>NA</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
    </sub-article>
</article>
