The audiometric profile of middle ear cholesteatoma stages: implications for clinical practice

Introduction

Chronic suppurative otitis media (CSOM) is one of the most common inflammatory conditions of the ear, affecting approximately 20 million people worldwide, and about a quarter of CSOM cases are associated with cholesteatoma (1). Hearing loss is one of the most common presenting complaints in patients who have CSOM with cholesteatoma. The presence of hearing loss in those patients hinders communication and interactions with their surroundings, thus decreasing the quality of life (2,3).

Pure tone audiometry (PTA) is a widely available and non-invasive diagnostic tool that can play a significant role in the early identification of this condition. It is an objective way to assess hearing and is routinely recommended to evaluate hearing in patients with CSOM (2-4). Previous studies have evaluated treatment or hearing outcomes using the European Academy of Otology and Neurotology/Japanese Otological Society (EAONO/JOS) classification (5,6), but none compared the PTA results across the different stages of cholesteatoma. While previous studies have investigated audiometry results in patients with CSOM and ossicular discontinuity (7), this condition only occurs once cholesteatoma has progressed sufficiently to erode the ossicles. Further investigation is needed to evaluate audiometry results in patients with cholesteatoma prior to the onset of ossicular discontinuity, in order to identify any hearing deterioration at earlier stages.

This study aims to investigate the PTA results across different stages of middle ear cholesteatoma. Additionally, the study seeks to further explore the clinical utility of PTA in the diagnosis, early detection, prevention of complications, preoperative planning, and appropriate indication of further diagnostic testing for patients with suspicion of middle ear cholesteatoma.

Methods

The study is reported according to the STROBE reporting guidelines (available at https://www.theajo.com/article/view/10.21037/ajo-25-37/rc).

The data in this cross-sectional study were obtained from secondary data from medical record. All measurements were taken using calibrated instruments and standardized procedures to reduce measurement bias. This study was conducted in the otolaryngology outpatient clinic, Prof. Ngoerah Hospital Bali. Patients were consecutively recruited between August and November 2024.

Patients

Patients included in this study were those diagnosed with CSOM and had a confirmed diagnosis of cholesteatoma through histopathological study. Patients under 18 years of age, those with congenital cholesteatoma, and those with other types of preexisting middle ear pathologies (such as otosclerosis, presbycusis, other cause of sensorineural hearing loss) were excluded. Patients with stage IV cholesteatoma were not included because of the small number of cases and could not undergo audiometric evaluation due to intracranial complications. Age, gender, audiometry results, otoscopy examination, and ossicular status were all documented.

An a priori power analysis was performed to determine the required sample size, using a significance level of 0.05 and 80% power. All eligible patients consecutively seen at the outpatient clinic during the study period were included, with a minimum of 18 patients in each cholesteatoma stage group. Patient recruitment followed convenience sampling, which is acknowledged as a limitation but also reflects real-world clinical practice. The trial was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Ethics Committee of the Faculty of Medicine, Udayana University/Prof. Ngoerah General Hospital, Denpasar, Bali, Indonesia (approval No. 2358/UN14.2.2.VII.14/LT/2024) and informed consent was taken from all individual participants.

PTA

The audiometric evaluation was carried out inside a cabin according to the standardized International Organization for Standardization (ISO) procedures with no more than 40 dB AC noise. PTA was assessed using an audiometer (GSI Audiostar Pro Clinical Audiometer, Grason-Stadler Inc., Minnesota, USA). Audiometric thresholds were analysed as continuous variables and categorized into air conduction (AC), bone conduction (BC), and air bone gap (ABG). The recordings for each patient were obtained preoperatively.

The stage of cholesteatoma

Patients included in this study had a confirmed diagnosis of cholesteatoma through histopathological study and cholesteatoma stage was assessed using the EAONO/JOS classification (8) based on surgical findings. The primary sites of cholesteatoma in the middle ear were further differentiated using the Supratubal recess, Tympanic cavity, Attic, and Mastoid (STAM) system, as proposed by the EAONO/JOS consensus.

Statistical analysis

Only participants with complete data for all model variables were included in the analyses. Data were analysed using IBM SPSS statistical software package for Windows, version 25.0. The statistical tests used in the analysis included descriptive statistics, such as frequencies and percentages for qualitative variables and mean and standard deviations for quantitative variables. Statistical analysis to compare means was carried out using one-way analysis of variance (ANOVA) and continued with post hoc analysis. The non-normally distributed data were analysed using Kruskal Wallis and Mann-Whitney test. A P value of <0.05 was considered significant. To analyse interactions with covariates, ANCOVA test was included. In addition, the cut-off value of PTA result, sensitivity, and specificity were defined using the receiver operating characteristic (ROC) curve. The closer the area under the curve (AUC) is to 1.0, the greater the use of PTA in predicting the presence of early-stage cholesteatoma.

Results

A total of 54 patients were included in this study, with 18 patients for each group of cholesteatoma (stages I, II, and III). The age of patients in this study ranged from 18–58 years with a mean of 30.69±12.22 years. The gender distribution was nearly equal, with 51.9% (n=28) males and 48.1% (n=26) females. The mean AC, BC, and ABG PTA results progressively increased across stages I, II, and III of cholesteatoma. Most patients experienced conductive hearing loss, observed in 66.7% (n=36) patients, but mixed hearing loss was observed in approximately half of patients with stage III cholesteatoma. Overall, subtotal perforations were the most prevalent, occurring in 40.7% (n=22), followed by central perforations in 25.9% (n=14) and total perforations in 24.1% (n=13). In stage I cholesteatoma, the majority of patients (77.8%, n=14) had an intact ossicular chain. Ossicular discontinuity was observed in 83.3% (n=15) of stage II patients and 88.9% (n=16) of stage III patients. The characteristics of the study population are summarized in Table 1. There were no missing data for any of the variables included in the analyses.

The AC and ABG results were normally distributed, and one-way ANOVA tests showed significant differences across cholesteatoma stages for both AC and ABG PTA (F 2,51 =13.5, P<0.001 and F 2,51 =6.15, P=0.040, respectively). Stage I cholesteatoma had significantly lower AC PTA results compared to stage II [mean =23.9; 95% confidence interval (CI): 12.22–35.76; P<0.001] and stage III (mean =28.2; 95% CI: 16.47–40.00; P<0.001). The ABG PTA also differed significantly between stage I and stage II (mean =−10.6; 95% CI: 1.68–19.64; P=0.021) as well as stage III (mean =−15.3; 95% CI: 6.31–24.28; P=0.001). Additionally, there were significant differences in BC PTA results between the stages of cholesteatoma (median =11.2, P=0.040), with stage I cholesteatoma showing differences compared to stage II (median =−15.3, P=0.01) and stage III (median =−15.0, P=0.13). There were no differences in PTA results between stage II and stage III cholesteatoma.

Age, types of tympanic membrane perforation, and ossicular involvement were analysed as covariates using factorial analysis of covariance (ANCOVA). Partial eta squared (ηp²) was used as a measure of effect size, with 0.01 considered small, 0.06 medium, and ≥0.14 large. All audiometric parameters (AC, BC, and PTA) had ηp² of ≥0.14, indicating large effect sizes. For AC PTA, the effect of cholesteatoma stage remained significant (F 2,26 =4.8, P=0.016, ηp² =0.30). Stage I cholesteatoma showed significantly better hearing thresholds compared to stage II (mean difference =16.9 dB, 95% CI: 1.79–32.06; P=0.030) and III (mean difference =23.8 dB; 95% CI: 8.87–38.76; P=0.003). A ranked ANCOVA was used for the BC PTA results, which also differed significantly across stages (F 2,26 =4.7, P=0.018, ηp² =0.3). In this case, stage I BC PTA differed from stage III only (mean =12.8; 95% CI: 2.71–22.85; P=0.015). Finally, the ABG results were significant (F 2,26 =2.7, P=0.035, ηp² =0.2), with stage I having better results than stage II (mean =11.9; 95% CI: 2.60–21.24; P=0.014) and III (mean =12.6; 95% CI: 3.380–21.79; P=0.009). The mean PTA results across cholesteatoma stages are presented in Table 2, while the differences between stages are detailed in Table 3.

The ROC curve analysis (Figure 1) identified an optimal cut-off value of 56.250 for AC PTA, yielding a sensitivity of 94% (95% CI: 72.71–99.86%), specificity of 70% (95% CI: 51.89–83.65%), and an AUC of 0.88 (95% CI: 0.78–0.97). Additionally, the cut-off for ABG PTA was identified as 38.7, with a sensitivity of 94% (95% CI: 72.71–99.86%), specificity of 59% (95% CI: 40.76–74.49%), and an AUC of 0.77 (95% CI: 0.64–0.89).

Figure 1 ROC curves for AC and ABG pure tone audiometry results in distinguishing early stage cholesteatoma. ABG, air bone gap; AC, air conduction; AUC, area under the curve; ROC, receiver operating characteristic.

Discussion

The patient’s characteristics in this study were similar to a previous study conducted in Morocco (9), with similar gender distribution and a mean age of 30 years. The predominant type of hearing loss found in this study was conductive hearing loss with an increasing incidence of mixed type hearing loss as the stage of cholesteatoma progressed. Conductive hearing loss is the most common type of hearing loss observed in patients with CSOM (10). The presence of extracranial complications in stage III cholesteatoma reflects the extensive spread of the disease, which may affect the cochlea and result in mixed hearing loss (3). Cholesteatoma eroding the ossicular chain leads to worse ABG results (7), although the presence of cholesteatoma mass can sometimes act as a conductor, transmitting sound waves to the cochlea and resulting in better hearing (4).

PTA results in CSOM can be influenced by various factors, such as tympanic membrane perforations, the presence of cholesteatoma, and ossicular discontinuity (11). In our study, PTA results differed significantly across cholesteatoma stages for AC (P=0.016), bone conduction (P=0.018), and air bone gap (P=0.035). Hearing loss severity increased as cholesteatoma stage progressed. This association persisted even after adjusting for types of tympanic membrane perforation, ossicles involved, and age, suggesting these covariates did not significantly influence the differences in PTA results (P>0.05).

Previous studies have shown that 60% of ears with tympanic membrane perforation are missed by audiometric hearing screening, and that the degree of hearing loss cannot be predicted solely by examining the tympanic membrane condition, as middle ear pathology is a more important indicator (11). Another study reported that preoperative audiometry is correlated with the size, rather than the location, of tympanic membrane perforation (12). This finding has to be further investigated and future studies should consider the size of the perforation as a variable.

The between-group differences of AC and ABG results showed a significant difference in stage I cholestatoma when compared to stages II and III, but no significant difference was found between stages II and III. This pattern of hearing decline may be explained by ossicular status: according to the STAM classification (8), stage I cholesteatoma is limited to one site and has likely not spread enough to erode the ossicular chain. In contrast, ossicular discontinuity is more common in stages II and III due to extensive cholesteatoma invasion, causing a more pronounced drop in hearing. The difference between stages I and II BC result was not significant (P=0.164), as the bone conduction pathway was still intact, directly transmitting sound vibration to the cochlea in the inner ear (10). However, BC in stage III was significantly worse when compared to stage I (P=0.014), likely due to inner ear involvement.

There appears to be a distinction between early (stage I) cholesteatoma and later stages. ROC curve analysis identified AC threshold of 56 dB hearing level (HL) and ABG 38 dB HL as potential cut-offs to distinguish stage I cholesteatoma from later stages, with 94% sensitivity but limited specificity (70% and 59%, respectively). High sensitivity is desirable for early detection of potential disease and the AUC of 0.88 for AC and 0.77 for ABG indicate good discrimination. Patients with AC ≤56 dB or ABG ≤38 dB may be more likely to have stage I cholesteatoma, and early surgical intervention with targeted computed tomography (CT) imaging may be considered. Those with poorer PTA results may be more likely to have advanced disease, for whom comprehensive imaging, including CT and possibly magnetic resonance imaging (MRI), along with surgical planning are recommended. While audiometry is usually performed to document baseline hearing in patients with CSOM, our findings indicate that simple audiometric parameters, when interpreted together with clinical and otoscopic findings, could assist clinicians in identifying early-stage cholesteatoma among patients with confirmed CSOM with cholesteatoma. This approach may support prioritisation for early surgery, tailoring of imaging requests, and avoidance of unnecessary or delayed intervention, particularly in resource-limited settings.

This study has some limitations, including the absence of eustachian tube function assessment due to incomplete data, despite its known influence on otitis media and audiometry results (2,3). Future research should incorporate this factor, along with larger sample sizes, and consider additional variables such as tympanic membrane perforation size and detailed spread patterns of cholesteatoma to enhance diagnostic accuracy and disease staging.

Conclusions

Audiometric thresholds (AC and ABG) show significant association with cholesteatoma stage and may help indicate disease progression in patients with known CSOM. Hearing thresholds plateau after stage II, suggesting most functional loss occurs early in disease progression. Based on our findings, we recommend that in patients with confirmed CSOM with cholesteatoma, PTA results showing AC ≤56 dB or ABG ≤38 dB should prompt consideration of early-stage cholesteatoma. This could guide tailored imaging requests, earlier surgical intervention, and avoid unnecessary or delayed treatment, particularly in resource-limited settings. Further studies are needed to validate their role in the early detection or screening of cholesteatoma.

Acknowledgments

The authors express their sincere gratitude to the faculty and staff of the Otorhinolaryngology-Head and Neck Surgery Department, Udayana University, for their valuable support and assistance.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://www.theajo.com/article/view/10.21037/ajo-25-37/rc

Data Sharing Statement: Available at https://www.theajo.com/article/view/10.21037/ajo-25-37/dss

Peer Review File: Available at https://www.theajo.com/article/view/10.21037/ajo-25-37/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://www.theajo.com/article/view/10.21037/ajo-25-37/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The trial was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Ethics Committee of the Faculty of Medicine, Udayana University/Prof. Ngoerah General Hospital, Denpasar, Bali, Indonesia (approval No. 2358/UN14.2.2.VII.14/LT/2024) and informed consent was taken from all individual participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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