Objective: To investigate the effects of chronic tobramycin treatment on distortion product otoacoustic emission (DPOAE) latencies and response growth detection thresholds in human subjects to determine the sensitivity of these DPOAE features to ototoxic damage.
Design: Six groups of children in two different age ranges were tested: three groups in the 7 to 14 yr age range, i.e., six children with normal hearing, four cystic fibrosis (CF) patients who received no aminoglycosides, and eight CF patients who received low- to moderate-cumulative doses of tobramycin (< 1250 mg/kg) for respiratory infections; and three groups of five subjects each in the 15 to 23 yr age range, i.e., the healthy group and the CF groups that received low- (< 285 mg/kg) and moderate-(1000 to 2000 mg/kg) cumulative drug dosages. The aggregate drug dosages compiled longitudinally over the past 5 yr were used to group the drug-treated CF patients. All subjects showed normal audiometric profiles (< or = 25 dB HL in the conventional frequency region and age-appropriate thresholds as described by Osterhammel and Osterhammel  in the high-frequency region) and DP-grams (absolute DPOAE and noise amplitudes being consistent with the normative data obtained with the CUBeDIS system at this institution).
Results: Even though the audiometric profiles and DP-grams of all drug-treated CF groups were identical to their healthy counterparts, the DPOAE latencies and growth function thresholds showed significant changes. Whereas low and low-to-moderate doses of tobramycin were related to DPOAE latency prolongations, higher cumulative drug doses of 1000 to 2000 mg/kg produced significant reductions in DPOAE latencies. Response growth detection thresholds at high frequencies showed significant elevations in all CF patient groups treated with tobramycin, regardless of drug dosages, as compared with the control subjects.
Conclusions: DPOAE amplitudes may not reflect the earliest changes produced by chronic aminoglycoside treatment, suggesting that cochlear ototoxicity may be more effectively monitored through the assessment of latencies and response growth detection thresholds. These findings pertain at least to the early stages of ototoxicity development, specifically during chronic tobramycin treatment. In light of the small sample size, however, these outcomes must be considered as tentative.