We studied a family with hereditary sensory motor neuropathy and deafness accompanying a missense mutation in the MPZ gene. Pathological examination of the cochlea in one of the family members revealed marked loss of auditory ganglion cells and central and peripheral auditory nerve fibres within the cochlea. The inner hair cells were of normal number with preserved morphology. The outer hair cells were normal in number except for a 30% reduction in just the apical turn. Examination of the sural nerve and the auditory nerve adjacent to the brainstem showed marked loss of fibres with evidence of incomplete remyelination of some of the remaining fibres. Studies of auditory function in surviving family members using electrophysiological and psychoacoustic methods provided evidence that the hearing deficits in this form of auditory neuropathy were probably related to a decrease of auditory nerve input accompanying axonal disease. Altered synchrony of discharge of the remaining fibres was a possible additional contributing factor.

Rationale: Exposure to ozone causes a decrease in spirometric lung function and an increase in airway inflammation in healthy young adults at concentrations as low as 0.08 ppm, close to the National Ambient Air Quality Standard for ground level ozone. Objectives: To test whether airway effects occur below the current ozone standard and if they are more pronounced in potentially susceptible individuals, such as those deficient in the antioxidant gene glutathione S-transferase mu 1 (GSTM1). Methods: Pulmonary function and subjective symptoms were measured in 59 healthy young adults (19-35 yr) immediately before and after exposure to 0.0 (clean air, CA) and 0.06 ppm ozone for 6.6 hours in a chamber while undergoing intermittent moderate exercise. The polymorphonuclear neutrophil (PMN) influx was measured in 24 subjects 16 to 18 hours postexposure. Measurements and Main Results: Subjects experienced a significantly greater (P 5 0.008) change in FEV 1 (6 SE) immediately after exposure to 0.06 ppm ozone compared with CA (21.71 6 0.50% vs. 20.002 6 0.46%). The decrement in FVC was also greater (P 5 0.02) after ozone versus CA (22.32 6 0.41% vs. 21.13 6 0.34%). Similarly, changes in %PMN were greater after ozone (54.0 6 4.6%) than CA (38.3 6 3.7%) exposure (P , 0.001). Symptom scores were not different between ozone versus CA. There were no significant differences in changes in FEV 1 , FVC, and %PMN between subjects with GSTM1-positive and GSTM1-null genotypes. Conclusions: Exposure of healthy young adults to 0.06 ppm ozone for 6.6 hours causes a significant decrement of FEV 1 and an increase in neutrophilic inflammation in the airways. GSTM1 genotype alone appears to have no significant role in modifying the effects.

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We measured detailed regional deposition patterns of inhaled particles in healthy adult male (n = 11; 25 +/- 4 yr of age) and female (n = 11; 25 +/- 3 yr of age) subjects by means of a serial bolus aerosol delivery technique for monodisperse fine [particle diameter (Dp) = 1 micron] and coarse aerosols (Dp = 3 and 5 micron). The bolus aerosol (40 ml half-width) was delivered to a specific volumetric depth (Vp) of the lung ranging from 100 to 500 ml with a 50-ml increment, and local deposition fraction (LDF) was assessed for each of the 10 local volumetric regions. In all subjects, the deposition distribution pattern was very uneven with respect to Vp, showing characteristic unimodal curves with respect to particle size and flow rate. However, the unevenness was more pronounced in women. LDF tended to be greater in all regions of the lung in women than in men for Dp = 1 micron. For Dp = 3 and 5 micron, LDF showed a marked enhancement in the shallow region of Vp 200 ml. Total lung deposition was comparable between men and women for fine particles but was consistently greater in women than men for coarse particles regardless of flow rates used: the difference ranged from 9 to 31% and was greater with higher flow rates (P < 0.05). The results indicate that 1) particle deposition characteristics differ between healthy men and women under controlled breathing conditions and 2) deposition in women is greater than that in men.

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