Distortion-product otoacoustic emissions: a useful test for monitoring ototoxicity induced by pegylated interferon and ribavirin treatment in patients with chronic hepatitis C.

Pegylated-interferon (peg-IFN) and ribavirin combination therapy for the treatment of hepatitis C virus (HCV) infection is well known to be associated with significant adverse effects. Several studies have investigated a possible auditory pathway involvement during IFN therapy, but a method to monitor the potential auditory involvement during treatment has not yet been described. The aim of this study is to evaluate possible modifications of the outer hair cell (OHC) function in HCV patients receiving peg-IFN and ribavirin combination therapy. Thirteen adult HCV patients (8 F/5 M, mean age 52∓12 years) treated with peg-IFN and ribavirin combination therapy underwent Pure Tone Audiogram and Distortion Product Otoacoustic Emission (DPOAE) tests. We compared mean auditory thresholds (PTA) and mean DPOAE amplitude before, at month 3 during, and at the end of treatment (T0, T3, and Tend, respectively), and 3 months after treatment discontinuation (Tfu). No significant differences were found in hearing levels at the different time points analyzed. During treatment, three patients developed tinnitus, which in 2 cases resolved spontaneously after the end of therapy. Compared to T0 (19.5±0.83), a statistically significant DPOAE increase at T3 (30±1,26) and Tend (28.6±2.16) was found (p<0.05 at both time points), while DPOAEs returned to pre-treatment levels at Tfu (19.3±1.3). In our group, none of the patients reported a permanent auditory impairment, excluding one patient with persistent tinnitus. Peg-IFN could produce an increase of motility of the OHCs by means of intracellular pathways. DPOAE test could be considered a new method for monitoring ototoxicity induced by IFN. On the basis of recent literature and our audiological results, physicians should be aware of the possible ototoxic effects of peg-IFN, requiring appropriate surveillance, and the patient should be informed of the potential side effects of IFN therapy on the auditory pathway.

Obstructive sleep apnea syndrome: from phenotype to genetic basis.

Obstructive sleep apnea syndrome (OSAS) is a complex chronic clinical syndrome, characterized by snoring, periodic apnea, hypoxemia during sleep, and daytime hypersomnolence. It affects 4-5% of the general population. Racial studies and chromosomal mapping, familial studies and twin studies have provided evidence for the possible link between the OSAS and genetic factors and also most of the risk factors involved in the pathogenesis of OSAS are largely genetically determined. A percentage of 35-40% of its variance can be attributed to genetic factors. It is likely that genetic factors associated with craniofacial structure, body fat distribution and neural control of the upper airway muscles interact to produce the OSAS phenotype. Although the role of specific genes that influence the development of OSAS has not yet been identified, current researches, especially in animal model, suggest that several genetic systems may be important. In this chapter, we will first define the OSAS phenotype, the pathogenesis and the risk factors involved in the OSAS that may be inherited, then, we will review the current progress in the genetics of OSAS and suggest a few future perspectives in the development of therapeutic agents for this complex disease entity.

Air- and bone-conducted vestibular evoked myogenic potentials (VEMPs) in otosclerosis: recordings before and after stapes surgery.

Aim of the study was to investigate, in a randomized prospective trial, air-conducted vestibular evoked myogenic potentials (AC-VEMPs) and bone-conducted vestibular evoked myogenic potentials (BC-VEMPs) before and after successful stapedotomy. Enrolled in the study were 41 consecutive patients (32 female, 9 male; mean age 36 years) (42 ears) with otosclerosis. Audiological evaluations and diagnosis of otosclerosis were made according to the guidelines of the Committee on Hearing and Equilibrium. Successful stapedotomy was carried out in all otosclerotic ears. Air- and bone-conducted 4-frequency pure tone average (4-PTA), air-bone gap (ABG), AC- and BC-VEMPs were evaluated pre- and post-operatively. As far as concerns results, pre-operatively, AC- and BC-VEMPs could be recorded in 9 (21.4%) and 16 (38.1%) otosclerotic ears, respectively. Lower ABG was detected in patients with AC-VEMPs in comparison to those in whom air-conducted potentials (p = 0.032) could not be elicited. At 12-month post-operative follow-up, AC-VEMPs were present in 11 (26.2%) ears, while BC-VEMPs could be elicited in 15 (35.7%) cases. Reduced bone-conduction 4-PTA was observed in patients with BC-VEMPs in comparison to those without recordable bone-conducted potentials pre- and post-operatively (p = 0.003 and p = 0.005, respectively). A significantly (p = 0.022) lower air-conducted 4-PTA was measured post-stapedotomy in patients with BC-VEMPs in comparison to those without elicitable bone-conducted potentials. In conclusion, VEMPs reduced elicitability, in otosclerosis, is likely due to conductive hearing loss and inner ear impairment.