Changes in the inner ear structures in cystic fibrosis patients

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Abstract

Objective

Although prolonged use of antibiotics is very common in cystic fibrosis (CF) patients, no studies have assessed the changes in both cochlear and peripheral vestibular systems in this population.

Methods

We used human temporal bones to analyze the density of vestibular dark, transitional, and hair cells in specimens from CF patients who were exposed to several types of antibiotics, as compared with specimens from an age-matched control group with no history of ear disease or antibiotic use. Additionally, we analyzed the changes in the elements of the cochlea (hair cells, spiral ganglion neurons, and the area of the stria vascularis). Data was gathered using differential interference contrast microscopy and light microscopy.

Results

In the CF group, 83% of patients were exposed to some ototoxic drugs, such as aminoglycosides. As compared with the control group, the density of both type I and type II vestibular hair cells was significantly lower in all structures analyzed; the number of dark cells was significantly lower in the lateral and posterior semicircular canals. We noted a trend toward a lower number of both inner and outer cochlear hair cells at all turns of the cochlea. The number of spiral ganglion neurons in Rosenthal's canal at the apical turn of the cochlea was significantly lower; furthermore, the area of the stria vascularis at the apical turn of the cochlea was significantly smaller.

Conclusions

Deterioration of cochlear and vestibular structures in CF patients might be related to their exposure to ototoxic antibiotics. Well-designed case-control studies are necessary to rule out the effect of CF itself.

Introduction

Cystic fibrosis (CF), an autosomal recessive hereditary disease, is common among the white population. It primarily affects exocrine gland function and the viscosity of mucous secretion. Overall, the median survival time for CF patients is around 30 years, but children born in the United States in 1990 are projected to live longer than 40 years [1]. In 1989, the CF transmembrane conductance regulator (CFTR) gene was identified in the long arm of chromosome 7; its mutations can result in abnormal chloride ion transport [1], [2], [3].

CF patients are often repeatedly treated with a long-term course of antibiotics. Given the known accumulation of toxic antibiotics in other organs after prolonged antibiotic treatment, it is likely that the perilymph of the inner ear (including the cochlea and vestibule) is also affected [4]. Yet, in CF patients, an untreated infection due to Pseudomonas aeruginosa can result in progressive lung damage (bronchiectasis), respiratory failure, and death [4], [5].

Despite the higher incidence of respiratory infections in CF patients, their incidence of otitis media in this population remains under debate; in fact, studies published in this regard show conflicting data [1], [6], [7]. Although hearing impairment is easily recognizable in these patients, the vestibular symptoms due to damage in the vestibular system are insidious and include vague dizziness, vertigo, or a light-headed sensation, constituting a diagnostic challenge to both pediatricians and otolaryngologists [5]. Only a few studies have included histologic evaluation of the vestibular end organs in patients exposed to ototoxic antibiotics [8], [9].

To the best of our knowledge, ours is the first study to analyze the changes in both inner ear structures (cochlea and vestibule) of CF patients exposed to a several types of antibiotics, as compared with a control group of patients with no history of ear disease or antibiotic use, looking for initial changes that may indicate clinical features of the patients.

Section snippets

Materials and methods

From our archived human temporal bone collection at the University of Minnesota, we selected specimens for this study from deceased donors with a clinical diagnosis of CF by positive sweat test (sweat chloride value above 60 mEq/L [1], [10]). Excluded were specimens from donors who had tumors affecting the ear; who had leukemia; who underwent irradiation of the head and neck, chemotherapy, or any otologic surgery; who had clinical otosclerosis or a systemic autoimmune disease; or whose temporal

Results

Of the 12 specimens in the CF group, one (8.33%) had signs of effusion in the middle ear. Of those 12 specimens, 10 (83.33%) were from donors who were exposed to one or more aminoglycosides (e.g. gentamicin, tobramycin); however, information regarding the length of use for those antibiotics was not available in the medical charts. In addition, 8 (66.67%) of the 12 specimens in the CF group was from a donor who had a positive culture for P. aeruginosa in the sputum. Of the 6 donors in that group

Discussion

P. aeruginosa is among the most common organisms causing bacterial infections in CF patients. The antibiotic therapy in these patients usually include more than one class of drugs. Antipseudomonal beta-lactam penicillin or quinolones, in conjunction with aminoglycosides are usually necessary to treat these patients. But because of their narrow therapeutic window, those antibiotics can have a toxic effect on the kidney and on the inner ear structures. A clinical study with 23 CF patients (median

Conclusion

In our study, we found histopathologic changes due to exposure to ototoxic antibiotics—especially aminoglycosides—in both vestibular and cochlear structures of human temporal bone specimens from deceased donors with CF. We believe that deterioration of those structures might be responsible for the clinical symptoms of dizziness and/or vertigo as well as hearing loss. Our results reinforce the necessity of rational use of antibiotics that follow strict treatment guidelines and protocols; plus,

Financial disclosure

The authors have no financial relationships relevant to this article to disclosure.

Conflict of interest

None.

Clinical trial registration

None.

Acknowledgements

This project was funded by the National Institute of Health's National Institute on Deafness and Other Communication Disorders (NIDCD), grant number U24 DC01 1968-01; the International Hearing Foundation; the Starkey Hearing Foundation; and the Lions 5M International.

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