Several sources have suggested an association between chronic sensory hearing impairment and chronic otitis media (COM). However, to our knowledge, no studies have evaluated the risk of sudden sensorineural hearing loss (SSNHL) in patients with COM (COM-positive).
To examine the risk of developing SSNHL in COM-positive patients.
Design, Setting, and Participants
This was a retrospective cohort study; we compared 10 248 patients with newly diagnosed COM from January 1, 2001, through December 31, 2008, with 30 744 age- and sex-matched controls using data from Taiwan’s National Health Insurance Research Database.
We followed each patient and evaluated the incidence of SSNHL.
Main Outcomes and Measures
The incidence of SSNHL at the end of 2011.
The incidence of SSNHL was 3 times higher in the COM-positive cohort than in the COM-negative cohort (14.47 vs 4.83 per 10 000 person-years). Cox proportional hazard regressions showed that the adjusted hazard ratio (AHR) was 3.02 (95% CI, 2.30-3.98). A stratified analysis showed that the highest risk of developing SSNHL was in the first follow-up year (incidence rate ratio [IRR], 3.87; 95% CI, 1.93-7.79). Thereafter, the risk declined during years 1 to 5 and then peaked (IRR, 3.01; 95% CI, 1.89-4.79). Patients who needed surgery had a higher incidence of SSNHL (AHR, 2.69; 95% CI, 1.62-4.48) compared with patients who needed only medication and observation.
Conclusions and Relevance
Chronic otitis media was significantly associated with a higher risk of developing SSNHL.
Several disparate sources,1-5 including histopathological and audiological studies, have suggested an association between chronic otitis media (COM) and chronic sensory hearing impairment. It is plausible that COM-mediated cochlear disease is related to chronic sensory hearing impairment.1-5 For example, Cureoglu et al5 discovered a significant loss of outer and inner hair cells in the basal turn of the cochlea in the temporal bones of patients with COM (hereinafter, COM-positive) compared with the control group (COM-negative). Papp et al3 discovered that bone conduction threshold averages were significantly higher in 121 patients with unilateral chronic suppurative otitis media. The pathogenesis of chronic sensory hearing impairment may be related to inflammatory noxious substances that cross the round window membrane, which leads to serous labyrinthitis, or to fluid in the middle ear that impedes oxygen transport to the inner ear, or an adverse effect of ototoxic drugs.6
To our knowledge, there are, in the English literature, no case series or cohort studies on the risk of sudden sensorineural hearing loss (SSNHL) in patients with COM. When the symptoms of SSNHL appear, they might be startling and unsettling for the patient with COM and also for the physician.
There are possibly some similar underlying mechanisms for both SSNHL and chronic hearing impairment. The results of the studies cited1-5 inspired us to study COM as a risk factor of SSNHL. We wanted to test the hypothesis that there is a discernable link between chronic hearing impairment and COM-mediated cochlear disease; thus, we chose to examine the association between COM and SSNHL.
To identify the effect of COM on the risk of developing SSNHL, we did a population-based cohort study using Taiwan’s National Health Insurance Research Database (NHIRD). We also examined the relationship between the severity of COM and the risk of developing SSNHL.
Taiwan’s National Health Insurance (NHI) program, a universal and mandatory single-payer system, was launched on March 1, 1995. More than 98% of Taiwan’s 22.96 million legal residents (citizens and noncitizens) are enrolled in this program. The NHIRD is an administrative compilation of patient demographic and clinical data and of monetary claims made by health care providers and paid for by the NHI program. For this study, we used the Longitudinal Health Insurance Database (LHID) 2012, which contains all claims data from 1996 to 2011 of 1 million randomly selected NHI beneficiaries. The database contains encrypted patient identification numbers, the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes of diagnoses, inpatient claims, ambulatory care claims, procedures and prescriptions, dates of admission and discharge, and patient registration data, which include basic sociodemographic information: sex, date of birth, area of residence, date of NHI registration, and date of termination of NHI coverage.
There were 2 cohorts in this retrospective cohort study: (1) a COM-positive cohort (patients with COM) and (2) a COM-negative cohort (patients without COM, a matched control [comparison] cohort). COM (ICD-9-CM codes 381.1-381.3; 382.1-382.3) and SSNHL (ICD-9-CM code 388.2) were defined if patients had a minimum of 3 outpatient service claims or any single hospitalization with a corresponding diagnosis made by a secondary or tertiary referral hospital. Patients with a diagnosis of labyrinthitis (ICD-9-CM code 386.3) or meningitis (ICD-9-CM code 320-322) were excluded. The COM-positive cohort was composed of patients who were newly diagnosed from January 1, 2001, to December 31, 2008, as having COM. The COM-negative control cohort included randomly selected patients without SSNHL-related medical claims but propensity-score matched to the study cohort for the baseline covariates of age, sex, comorbidities, area of residence, and monthly income.7 We defined the index date as the first occurrence of COM for patients in the COM-positive cohort. Matching the year of the index date to the COM-positive cohort, we further defined the index date for the COM-negative cohort. Comorbid major diseases that existed before the index date were diabetes mellitus (DM) (ICD-9-CM code 250), hypertension (HTN) (ICD-9-CM codes 401-405), chronic kidney disease (CKD) (ICD-9-CM code 585), and hypercholesterolemia (HCh) (ICD-9-CM codes 272.0). The comorbidities were identified using a diagnosis made during admission or by a specialist during the patient’s hospital visit. The routine peer review system of the Taiwan Health Insurance Bureau looks over the diagnoses made in every referral hospital to ensure that diagnostic methods are standardized. To investigate the association between the occurrence of SSNHL and the pathological progress of COM, only patients with newly diagnosed COM from January 1, 2001, to December 31, 2008, were included. The claims data from 1996 to 2000 were used to confirm that none of the enrolled patients had ever been diagnosed as having COM or SSNHL before 2001. The cohort in this study consists of patients who have been evaluated in terms of the incidence of SSNHL that developed 3 months beyond the index date through the end of 2011 or until the death of the patients. The institutional review board of Chi Mei Medical Center approved this study.
All statistical analyses were performed using SAS software (version 9.2 for Windows; SAS Institute Inc). Differences in sociodemographic characteristics and comorbidities between the COM-positive cohort and COM-negative control cohort were compared using Pearson χ2 tests. We calculated the incidence rate using the following formula: number of SSNHL incidents detected during the follow-up period divided by the total number of person-years for each cohort group; both were classified by sex, age, and years of follow-up. Poisson regression was used to estimate the incidence rate ratio (IRR) of developing SSNHL between the COM-positive and COM-negative cohorts. We used Cox proportional hazard models to assess the risks for developing SSNHL with comorbid DM, HTN, CKD, and HCh. To calculate the total incidence rates of SSNHL in the 2 cohort groups, we used Cox proportional hazard regression analyses and Kaplan-Meier analyses. The differences in the cumulative incidence rates between the 2 cohorts were analyzed using a log-rank test. Each dichotomous variable in the model was tested for proportionality using investigative, diagnostic log-log survival plots. In this study, the follow-up period was time to event (event = SSNHL), time to death, or time to the end of follow-up. When the first event occurred, the end point was the date of the first event. Therefore, in the present study, an IRR is a hazard ratio (HR) with a very particular set of assumptions: the hazard is both proportional and constant. Significance was set at P < .05 (2-tailed). We used Stata statistical software (version 12; STATA Corp) for power calculations. The Stata command stpower logrank can be used to estimate power for survival data for a sample of at least 10 248 patients, an effect size of 3.0 (expressed as an HR), and an α of .05 with a 2-sided test are set in STATA software. The statistical power was estimated to be more than 99% and would be able to detect any significant difference in 2 cohorts.
Incidence of SSNHL Relative to Patient Characteristics
We enrolled from the NHIRD 10 248 COM-positive patients who, between January 1, 2001, and December 31, 2008, met the eligibility criteria for this study. For the COM-negative cohort, we enrolled 30 744 age- and sex-matched patients (ratio, 1:3) (Table 1). There were no significant baseline differences in the prevalence of DM, CKD, HTN, or HCh, or in the monthly incomes or the areas of residence for the 2 cohorts (Table 1).
Patients with newly diagnosed COM had 3 times the incidence of SSNHL than did COM-negative patients (P < .01) (Figure). When the follow-up period was over, the SSNHL IRR of the COM-positive cohort was generally significantly (P < .01 for all age groups) higher than that of the COM-negative control cohort. In the COM-positive cohort, patients who were 50 to 64 years old had the highest incidence (19.43 per 10 000 person-years) of SSNHL, and patients who were 35 to 49 years old had the highest IRR, 4.28 (95% CI, 2.48-7.39) (Table 2).
SSNHL and Its Associated Comorbidities
Considering all the stratified analyses we did that are listed with their matched variables, the COM-positive cohort was associated with a higher risk of SSNHL. Because of the differential effect of COM stratified for some of these matching variables, the matching had to be retained in the analyses.
We used a multivariate Cox proportional hazards regression analysis to show that there was an adjusted HR (AHR) for SSNHL of 3.02 (95% CI, 2.30-3.98) for COM (Table 3). In general, the HR increased with age. Sex, however, was not a significant risk for SSNHL. Table 3 indicates that none of the comorbid diseases (DM, HTN, CKD, and HCh) were overall risk factors for SSNHL.
Furthermore, we calculated the IRR for each comorbidity between the COM-positive and COM-negative control cohorts to examine the effects of the comorbidities (Table 2). In the comorbid HTN and HCh subgroups, the incidence of ISSNHL between the COM-positive and COM-negative control cohorts was significantly different (IRR, 1.91; 95% CI, 1.06-3.42 vs 2.91; 95% CI, 1.02-8.29), respectively. Nevertheless, both HTN and HCh created an attenuation effect for the IRR value of COM-positive to COM-negative control cohorts, that is, the IRR measured for the overall study was 3.00, but the IRR measured for the HTN comorbidity subgroup was only 1.91, and that for the HCh comorbidity subgroup was 2.91.
Requirements for Surgical Treatment Relative to the Risk of Developing SSNHL
We also evaluated the association between the requirement for surgical treatment, either tympanoplasty and mastoidectomy, and the risk of SSNHL (Table 4). Patients who required surgical treatment had a higher incidence of SSNHL (AHR, 2.69; 95% CI, 1.62-4.48) than did patients who required only medication and observation, after sex, age, comorbidities, area of residence, and monthly income had been adjusted for. There were 672 patients in the COM-positive cohort who needed surgery. Before surgery, 9 of them developed SSNHL. Another 10 patients developed SSNHL within an average of 3.12 years after COM surgery (range, 0.96-5.58 years). There was almost no association between the occurrence of SSNHL and the surgical treatments in our studied cohorts.
Higher Risk of SSNHL in Patients With COM
We found that the patients with newly diagnosed COM had a greater chance of developing SSNHL than did the COM-negative controls. This is, to the best of our knowledge, the first nationwide, retrospective cohort study that examines the risk of SSNHL in COM-positive patients.
It is noteworthy that 17.82% of the COM-positive patients who later developed SSNHL did so within the first year after the COM diagnosis, 24.75% with 1 to 2 years after, 22.77% within 3 to 4 years after, and 34.65% more than 5 years after. Nearly 70% of the COM-positive patients who later developed SSNHL did so within 4 years after the COM diagnosis. The age group with the largest number of patients who developed SSNHL was the 50- to 64-year-old group (n = 32), and the group with the second largest number was the 35- to 49-year-old group (n = 31). A timely effort to detect SSNHL is recommended, especially within 4 years after the initial COM diagnosis.
Other studies8,9 have reported that the incidence of SSNHL in men is higher than in women. However, sex was not a significant factor in the present study.
Lifestyle-related risk factors for developing SSNHL might come from income differences. Environmental factors that also lead to hearing loss may stem from differences in areas of residence of the COM-positive and COM-negative patients.10 To treat these possible confounding factors, monthly income and area of residence of the patients were matched in the present study.
Comorbid DM,11 HTN,12 CKD,13 and HCh14 are the well-known risk factors for SSNHL. We matched these potential confounding factors between the COM and the control cohorts to treat these comorbidities as potential confounding factors. In the present study, a subgroup analysis confirmed (1) that comorbid DM and CKD were not significantly associated with the effect of COM on the occurrence of SSNHL, and (2) that the IRR between COM-positive and COM-negative patients in the subgroups of comorbid HTN and HCh were lower than in the overall studied cohort. None of the potential confounders (DM, HTN, CKD, and HCh) were risk factors for SSNHL in the patients in either cohort with comorbidities, after additional multivariate Cox proportional hazards regression analyses of both cohorts had been performed. In the present study, we concluded that the comorbidities of DM, HTN, CKD, and HCh did not contribute to the underlying mechanism of the effect of COM on the occurrence of SSNHL.
SSNHL and Factors That Indicate the Severity of COM
Assuming that to some extent the indication for surgical treatment reflected the severity of COM, we decided to compare the severity of COM based on the requirements for the surgical interventions of tympanoplasty and mastoidectomy. Although surgical intervention for COM is usually performed in the absence of any acute infection, the need for surgical intervention might be a secondary marker for an intractable middle ear infection and clinically significant hearing changes, which is the primary risk for SSNHL in COM-positive patients.
We found that there was a higher risk of developing SSNHL in COM-positive patients, which was indicated by a need for surgical intervention.
Underlying Mechanism of SSNHL in COM-Positive Patients
Diagnoses of certain types of chronic infection have been significantly associated with subsequent SSNHL.15,16 However, the mechanism underlying the association between COM and subsequent SSNHL remains unclear. The risk factors for chronic sensorineural hearing loss are middle ear infections, which are also important in the development and progression of labyrinthitis. The findings from temporal bone studies on SSNHL4,5 include a significant loss of outer and inner hair cells, serofibrinous precipitates and inflammatory cells in the scala tympani in the basal turn and cochlear aqueduct, and a clinically significant decrease in the area of the stria vascularis and spiral ligament in the basal turn of the cochlea. One study17 on the temporal bone histopathologic characteristics in the ears of patients with SSNHL reported that 15 patients who did not recover from their sudden deafness had lost hair cells and supporting cells of the organ of Corti (13 ears); the tectorial membrane, supporting cells, and stria vascularis (1 ear); and cochlear neurons (1 ear). Hence, the authors17 hypothesized that pathological activation of cellular stress pathways involving nuclear factor (NF)-κB within the cochlea led to the development of SSNHL. We hypothesized that COM, as a source of systemic inflammation,18 activates monocytes entering the inner ear from the systemic circulation as a consequence of a chronic antigen challenge or serves as a triggering stimulus that causes pathological activation of NF-κB and aberrant cellular stress pathways within the cochlea, which, in turn, causes SSNHL.17,18 Except for the common finding of a loss of inner hair cells, disparate pathological findings between COM and SSNHL remained and did not strongly support the theory of direct infection of the cochlea as the pathogenesis of SSNHL. It is possible that the development of SSNHL in COM-positive patients is caused by the chronic inflammation associated with the dysregulation of NF-κB. An immune response in the cochlea may remain long after the original infection is abolished19 and accelerate the rate of cell death.20 However, the findings of the present study cannot be considered the general pathologic course of SSNHL because of the clinically high reversibility of SSNHL. Other possible mechanisms for the development of SSNHL should be considered; for example, an underlying vascular mechanism. The inner ear has high metabolic requirements, but it lacks a collateral blood supply; thus, it is comparably more sensitive to transient ischemia. Others11,12,14,21,22 have proposed that impaired cochlear blood perfusion and microvascular damage are important etiopathogenetic events in the development of SSNHL, and mounting evidence23,24 indicates that the development of atherosclerosis is associated with inflammation. We hypothesize that the chronic inflammation in patients with COM is important in microangiopathy and transient ischemia of the cochlea. However, further study to demonstrate the cochlear pathologic characteristics of patients with COM who developed SSNHL is needed.
Strengths and Limitations
The major strength of the present study is its large study population. The large nationwide insurance claims data set allowed us to look, with a low selection bias, at the risk factors that can lead to SSNHL. Our statistical power and the precision of our risk appraisal is also increased by the size of the study population.25
The study has some limitations. First, the NHIRD did not indicate which ear was affected by COM; all we could conclude is that the chance of a patient with COM in 1 ear developing SSNHL is significant. Having 1 normal ear can only dilute the effect of COM on the risk of SSNHL. Second, the NHIRD did not have information on the severity of SSNHL or its associated risk factors. This information includes the patient’s history of smoking and exposure to environmental and occupational noise. The inability to access these factors might have caused some bias. Third, we hypothesized that because COM-positive patients tend to visit physicians frequently, they are likely to have their hearing changes detected. However, this limitation is a weak one for our study because we used the Taiwan NHIRD. Patients in Taiwan have easy access to necessary medical attention; thus, COM-negative patients are likely to have their SSNHL diagnosed. For the COM, it is possible that patients in the control cohort may not have been diagnosed as having COM if they did not visit physicians. This means that patients in the control cohort may also have had COM that was not diagnosed. However, this possibility may bias the results only to the null. Finally, laboratory test results are not included in the NHIRD claims data.
Theoretically, anti-inflammatory agents and medications that increase microcirculation may benefit COM-positive patients with a risk of SSNHL, especially those older than 35 years and those who require surgical intervention. The findings of this study can also be a valuable reference for preoperative consultations for COM-positive patients.
This study showed that COM-positive Taiwanese patients had a higher risk of developing SSNHL than did the matched COM-negative control patients. The risk of developing SSNHL was significantly higher for COM-positive patients who required surgical intervention. This observation may, for high-risk patients, encourage early detection and timely treatment. Additional research using large samples would be helpful in exploring any protective effect rising from anti-thrombotic and anti-inflammatory drugs on hearing.
Corresponding Author: Yung-Song Lin, MD, Department of Otolaryngology, Chi Mei Medical Center, 901 Zhonghua Rd, Yongkang District, Tainan City 710, Taiwan (email@example.com).
Submitted for Publication: September 15, 2014; final revision received December 11, 2014; accepted January 18, 2015.
Published Online: March 5, 2015. doi:10.1001/jamaoto.2015.102.
Author Contributions: Dr Lin had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Yen, Weng, Y. S. Lin.
Acquisition, analysis, or interpretation of data: Yen, C. Lin, Y. S. Lin.
Drafting of the manuscript: Yen, Weng, Y. S. Lin.
Critical revision of the manuscript for important intellectual content: Yen, C. Lin, Y. S. Lin.
Statistical analysis: Yen, Weng, Y. S. Lin.
Administrative, technical, or material support: C. Lin.
Study supervision: Yen, Y. S. Lin.
Conflict of Interest Disclosure: None reported.
Funding/Support: This study was supported by the Chi Mei Medical Center Research Fund.
Role of the Funder/Sponsor: The Chi Mei Medical Center Research Fund had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Y. Bone conduction impairment in uncomplicated chronic suppurative otitis media. Am J Otolaryngol
. 1998;19(3):149-153.PubMedGoogle ScholarCrossref
S. Does chronic otitis media cause sensorineural hearing loss? J Otolaryngol
. 1998;27(1):17-20.PubMedGoogle Scholar
I. Sensorineural hearing loss in chronic otitis media. Otol Neurotol
. 2003;24(2):141-144.PubMedGoogle ScholarCrossref
et al. Cochlear pathology in human temporal bones with otitis media. Acta Otolaryngol
. 2010;130(4):472-476.PubMedGoogle ScholarCrossref
BR. Cochlear changes in chronic otitis media. Laryngoscope
. 2004;114(4):622-626.PubMedGoogle ScholarCrossref
G. Inner ear hearing loss in acute and chronic otitis media. Adv Otorhinolaryngol
. 1981;27:138-143.PubMedGoogle Scholar
DB. Estimating causal effects from large data sets using propensity scores. Ann Intern Med
. 1997;127(8, pt 2):757-763.PubMedGoogle ScholarCrossref
CW. Risk of developing sudden sensorineural hearing loss in diabetic patients: a population-based cohort study. Otol Neurotol
. 2012;33(9):1482-1488.PubMedGoogle ScholarCrossref
TM. Sudden sensorineural hearing loss is correlated with an increased risk of acute myocardial infarction: a population-based cohort study. Laryngoscope
. 2013;123(9):2254-2258.PubMedGoogle ScholarCrossref
SF. Increased risk of getting sudden sensorineural hearing loss in patients with chronic kidney disease: a population-based cohort study. Laryngoscope
. 2013;123(3):767-773.PubMedGoogle ScholarCrossref
YS. Hypercholesterolemia is correlated with an increased risk of idiopathic sudden sensorineural hearing loss: a historical prospective cohort study. Ear Hear
. 2014;35(2):256-261.PubMedGoogle ScholarCrossref
D. Sudden sensorineural hearing loss associated with chronic periodontitis: a population-based study. Otol Neurotol
. 2013;34(8):1380-1384.PubMedGoogle ScholarCrossref
A. Sudden sensorineural hearing loss: subclinical viral and toxoplasmosis infections as aetiology and how they alter the clinical course. ORL J Otorhinolaryngol Relat Spec
. 2011;73(2):110-115.PubMedGoogle ScholarCrossref
Jr. Pathology and pathophysiology of idiopathic sudden sensorineural hearing loss. Otol Neurotol
. 2005;26(2):151-160.PubMedGoogle ScholarCrossref
B. The effect of chronic otitis media on the immunoreactivity of human inner ear. Eur Arch Otorhinolaryngol
. 2001;258(10):529-532.PubMedGoogle ScholarCrossref
C. The impact of systemic infection on the progression of neurodegenerative disease. Nat Rev Neurosci
. 2003;4(2):103-112.PubMedGoogle ScholarCrossref
et al. Unbalanced oxidative status in idiopathic sudden sensorineural hearing loss. Eur Arch Otorhinolaryngol
. 2012;269(2):449-453.PubMedGoogle ScholarCrossref
M. Vascular risk factors in sudden hearing loss. Thromb Haemost
. 2006;95(3):454-461.PubMedGoogle Scholar
et al. Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries. Arterioscler Thromb Vasc Biol
. 1999;19(10):2355-2363.PubMedGoogle ScholarCrossref
T. Taiwan’s national health insurance system: high value for the dollar. In: Okma
L, ed. Six Countries, Six Reform Models: Their Healthcare Reform, Experience of Israel, the Netherlands, New Zealand, Singapore, Switzerland and Taiwan. Hackensack, NJ: World Scientific; 2009:171-204.