Tuberculosis (TB) remains a major communicable disease requiring prolonged multidrug therapy. Although antitubercular therapy (ATT) is essential for achieving microbiological cure and preventing disease transmission, some drugs used particularly in drug-resistant TB regimens may produce clinically important adverse effects. Ototoxicity is among the most disabling complications associated with injectable aminoglycosides, including amikacin, kanamycin and streptomycin. These agents may accumulate within the inner ear and damage cochlear hair cells, producing bilateral, symmetrical and predominantly sensorineural hearing loss. The impairment usually begins at higher frequencies and may progressively involve speech frequencies with continued exposure. It is often irreversible and may be accompanied by tinnitus, vertigo or impaired balance.^[1,2] The risk of ototoxicity may be influenced by the specific medication, cumulative dose, duration of exposure, increasing age, renal impairment, concurrent use of other ototoxic drugs, previous noise exposure and pre-existing auditory dysfunction. A systematic review by Dillard et al. reported a pooled prevalence of approximately 41% for aminoglycoside-induced hearing loss among patients treated for drug-resistant TB, demonstrating the considerable magnitude of this preventable treatment-related disability.^[3] Wangchuk et al. similarly documented hearing loss in 45.2% of patients undergoing multidrug-resistant TB treatment, highlighting the importance of systematic audiological surveillance.^[4] Pure-tone audiometry is a widely accepted method for detecting and quantifying hearing impairment. Conventional audiometry evaluates frequencies important for speech perception, while extended high-frequency audiometry, where available, may identify cochlear changes before conventional frequencies are affected. Otoscopy and impedance audiometry are also useful for excluding external- and middle-ear disorders that may cause conductive hearing loss. Baseline testing before initiating an ototoxic medicine, followed by periodic monitoring during treatment, enables early recognition of threshold deterioration and facilitates clinical decisions regarding dose modification, drug substitution and auditory rehabilitation.^[2,5] Current WHO recommendations favour effective all-oral regimens for eligible drug-resistant TB patients, thereby reducing exposure to injectable ototoxic medicines; nevertheless, patients with current or previous exposure to such drugs remain at risk.^[1] Hearing impairment can adversely affect communication, employment, social participation, mental health and adherence to treatment. Assessment of its prevalence, severity and associated clinical factors among patients receiving ATT is therefore important for strengthening pharmacovigilance and integrating audiological monitoring into TB services. The present study was undertaken to assess hearing impairment among patients receiving antitubercular therapy and to examine its relationship with treatment and patient-related characteristics.

 

AIM

To assess hearing impairment among patients receiving antitubercular therapy.

 

OBJECTIVES

1. To determine the prevalence, type and severity of hearing impairment among patients receiving antitubercular therapy.
2. To examine the association of hearing impairment with demographic characteristics, comorbidities, treatment regimen, ototoxic-drug exposure and duration of therapy.

Source of Data The study participants were recruited from patients with diagnosed tuberculosis who were receiving antitubercular therapy and attending the designated TB centre, respiratory medicine outpatient department or inpatient services of the study institution during the study period. Treatment records, laboratory reports, prescriptions and audiological findings constituted the principal sources of data. Study Design A hospital-based cross-sectional analytical study was conducted. Study Location The Department of Otorhinolaryngology and Audiology of a tertiary-care teaching hospital. Study Duration The study was conducted over a period of 12 months, Participant recruitment, clinical evaluation, review of treatment records and audiological assessment were completed during this period. Sample Size A total of 120 eligible patients receiving antitubercular therapy were included. Participants were enrolled consecutively until the required sample size was attained. Inclusion Criteria • Patients with microbiologically or clinically diagnosed pulmonary or extrapulmonary TB. • Patients who were currently receiving ATT for drug-sensitive or drug-resistant TB. • Patients aged 18 years or older. • Patients who had received ATT for at least two weeks at the time of assessment. • Patients who provided written informed consent. • Patients who were able to understand and respond reliably during audiological testing. Exclusion Criteria • Patients with documented congenital or hereditary hearing loss. • Patients with active otitis externa, acute otitis media, tympanic-membrane perforation or another condition producing temporary conductive hearing loss. • Patients with a history of major ear surgery, head injury involving the temporal bone or acoustic trauma. • Patients with occupational noise exposure severe enough to represent an alternative primary cause of hearing loss. • Patients receiving chemotherapy or other established ototoxic medicines unrelated to ATT, where their effect could not be separated from ATT exposure. • Patients who were critically ill, uncooperative or unable to complete pure-tone audiometry. • Patients who declined consent. Procedure and Methodology Approval was obtained from the Institutional Ethics Committee before commencing the study. Eligible patients were approached consecutively, informed about the study and enrolled after written informed consent had been obtained. Each participant was interviewed using a predesigned and pretested data-collection form. Information was obtained regarding age, sex, residence, occupation, socioeconomic characteristics, smoking, alcohol consumption, previous noise exposure, history of ear disease, tinnitus, vertigo, subjective hearing difficulty and previous exposure to ototoxic medicines. Clinical information included type and site of TB, drug-susceptibility status, category of treatment, current ATT regimen, individual drugs received, duration of treatment, injectable-drug exposure, cumulative duration of such exposure, previous TB treatment and relevant comorbidities such as diabetes mellitus, hypertension, HIV infection and renal disease. Treatment details were verified from treatment cards, prescriptions and hospital records. Participants were classified according to whether they had received an ototoxic injectable antitubercular drug such as amikacin, kanamycin or streptomycin. Current all-oral and injectable-containing regimens were analysed separately. A general clinical and otorhinolaryngological examination was performed. Otoscopy was undertaken to assess the external auditory canal and tympanic membrane. Tuning-fork tests, including Rinne and Weber tests, were performed as preliminary assessments. Tympanometry was undertaken where indicated to exclude middle-ear pathology. Pure-tone audiometry was conducted by a trained audiologist in a sound-treated room using a calibrated clinical audiometer. Air-conduction thresholds were determined separately for each ear at 250, 500, 1,000, 2,000, 4,000 and 8,000 Hz. Bone-conduction thresholds were measured at 500-4,000 Hz whenever air-conduction thresholds were elevated. Extended high-frequency thresholds above 8,000 Hz were assessed where the equipment permitted. The pure-tone average was calculated using hearing thresholds at 500, 1,000, 2,000 and 4,000 Hz. Hearing impairment was defined as a pure-tone average of 20 dB hearing level or greater in the better-hearing ear. It was classified as sensorineural when air- and bone-conduction thresholds were elevated without a clinically significant air-bone gap, conductive when an air-bone gap was present with relatively preserved bone conduction and mixed when both components occurred. The degree of impairment was categorized as mild, moderate, moderately severe, severe or profound according to the audiological classification adopted by the study institution. Because this was a cross-sectional assessment, an ATT-attributable threshold shift could not be established in participants without pretreatment audiograms. Therefore, the primary outcome was reported as prevalent hearing impairment during ATT, while its possible association with ototoxic exposure was assessed analytically without assuming causation. Sample Processing No separate biological specimen was collected specifically for the study. Recent renal-function reports, including serum creatinine and estimated glomerular filtration rate, were retrieved from the patient records because impaired renal clearance could increase aminoglycoside exposure. When a recent report was unavailable and testing was clinically indicated, a venous blood sample was collected under aseptic precautions, transported to the biochemistry laboratory and analysed according to the institution’s standard operating procedures. Audiological data were recorded directly from the calibrated audiometer and entered into the study form. Data Collection Data were collected using a predesigned, structured and pretested case-record form. The form included: • Sociodemographic characteristics. • TB type, site and drug-resistance status. • Current and previous ATT regimens. • Exposure to individual potentially ototoxic medicines. • Treatment duration and relevant cumulative exposure. • Comorbidities and other risk factors for hearing loss. • Ear-related symptoms and otoscopic findings. • Tympanometry and pure-tone audiometry results. • Type, laterality and severity of hearing impairment. Each completed form was checked for accuracy and completeness. Participants were assigned unique identification numbers, and personally identifiable information was kept confidential. Data were entered into an electronic database and verified before analysis. Statistical Methods Data were analysed using SPSS/R or an equivalent statistical package. Categorical variables were summarized as frequencies and percentages, while continuous variables were expressed as mean with standard deviation or median with interquartile range according to their distribution. The prevalence of hearing impairment was reported with a 95% confidence interval. The association of hearing impairment with categorical predictors was assessed using the chi-square test or Fisher’s exact test. Continuous variables were compared using the independent-samples t test or Mann-Whitney U test, as appropriate. Effect estimates were presented as odds ratios with 95% confidence intervals. Variables that were clinically important or showed a univariable association at p<0.20 were considered for multivariable binary logistic-regression analysis to identify factors independently associated with hearing impairment. Age, sex, ototoxic-drug exposure, treatment duration, previous ATT, renal dysfunction, diabetes and other relevant confounders were considered in the adjusted model. Multicollinearity and model fit were assessed before interpreting the model. All tests were two-tailed, and p<0.05 was considered statistically significant.