Attenuated response to repeated daily ozone exposures in asthmatic subjects.

The development of attenuated response ("tolerance") to daily ozone (O3) exposures in the laboratory is well established in healthy adult volunteers. However, the capability of asthmatics to develop tolerance during multiday ozone exposures is unclear. We exposed 10 adult volunteers with mild asthma to 0.4 ppm O3 in filtered air for 3 h/d on 5 consecutive d. Two similar filtered-air exposures during the preceding week served as controls. Follow-up O3 exposures were performed 4 and 7 d after the most recent consecutive exposure. All exposures were performed in an environmental chamber at 31 degrees C and 35% relative humidity. The subjects performed moderate exercise (mean ventilation rate of 32 l/min) for 15 min of each half-hour. Responses were measured with spirometry and symptom evaluations before and after each exposure, and a bronchial reactivity test (methacholine challenge) was conducted after each exposure. All response measurements showed clinically and statistically significant day-to-day variation. Symptom and forced-expiratory-volume-in-1-s responses were similarly large on the 1st and 2nd O3 exposure days, after which they diminished progressively, approaching filtered air response levels by the 5th consecutive O3 day. This tolerance was partially lost 4 and 7 d later. Bronchial reactivity peaked after the first O3 exposure and remained somewhat elevated after all subsequent O3 exposures, relative to its control level following filtered-air exposures. Individual responses varied widely; more severe initial responses to O3 predicted less rapid attenuation. We concluded that asthmatics can develop tolerance to frequent high-level O3 exposures in much the same manner as normal subjects, although the process may be slower and less fully effective in asthmatics.

Human nasal epithelium: characterization and effects of in vitro exposure to sulfur dioxide.

Human nasal turbinate tissue from surgical specimens was dissected free of connective tissue, and primary epithelial cultures were established by explant techniques. Transmission electron microscopy revealed that cultured cells retained homogeneous cytoplasmic granules, tonofilaments, and desmosomes and formed a homogeneous monolayer. The epithelial cells stained positively with cytokeratin antibodies AE1, AE3, and 35BH11 but failed to stain with two other cytokeratin antibodies, AE2 and 34BE12. Staining was also positive with anti-desmoplakin I and II but negative with antivimentin (43BE8), anti-desmin, and anti-human factor VIII antibodies. Cultured cells were exposed to filtered air or sulfur dioxide at 1-5 ppm for 30-60 min. Although there was no increase in cell lysis as measured by chromium-51 release, SO2 exposure significantly inhibited [3H]leucine incorporation compared to air exposure. This effect was dependent on both SO2 concentration and exposure duration. Control experiments revealed that these SO2 effects were not caused by the [H+] load produced by SO2 exposure. Electron microscopy of cells exposed to air or SO2 did not show any significant morphological differences.

Pulmonary effects of sulfur dioxide exposure and ipratropium bromide pretreatment in adults with nonallergic asthma.

In this study we examined the potential short-term effect of sulfur dioxide (SO2) on total respiratory resistance and forced expiratory volume in patients with nonallergic asthma. A group of nine adult subjects with nonallergic asthma, 55 years of age or older, were exposed to SO2 at 0, 0.5, and 1.0 ppm for 20 minutes at rest followed by 10 minutes during light-moderate exercise. The measures of pulmonary function assessed were FEV1, specific total respiratory resistance (SRT), and maximal expiratory flow rates at 50% (Vmax50) and 75% (Vmax75) of expired vital capacity. Measurements were made before exposure to SO2 (baseline), postresting exposure, postexercising exposure, and at 30 minutes thereafter (recovery). Repeat measure analysis of variance revealed a statistically significant dose-response effect of SO2 inhalation on FEV1 (p = 0.008), SRT (p = 0.033), Vmax50 (p = 0.017), and Vmax75 (p = 0.048). Eight subjects had repeat exposure to SO2 at 1.0 ppm after treatment with either placebo or ipratropium bromide, 60 micrograms by metered-dose inhaler. Inpratropium bromide treatment, compared to placebo treatment, resulted in a statistically significant improvement in all baseline measures of pulmonary function: FEV1 (p = 0.017), SRT (p = 0.027), Vmax50 (p = 0.018), and Vmax75 (p = 0.035). However, this drug did not significantly alter the proportionate change in pulmonary function caused by SO2 inhalation in these subjects. These findings indicate that adults with nonallergic asthma are sensitive to short-term low-level SO2 exposure and that treatment with 60 micrograms of ipratropium bromide causes significant bronchodilation but does not protect, completely, these patients from the effect of SO2 inhalation.

Therapeutic range cromolyn dose-response inhibition and complete obliteration of SO2-induced bronchoconstriction in atopic adolescents.

Eight atopic adolescent subjects with exercise-induced bronchospasm were studied to determine whether cromolyn sodium could inhibit or block sulfur dioxide (SO2)-induced bronchoconstriction. Cromolyn or placebo were administered by turboinhaler 20 minutes before 10 minutes of SO2 exposure at 1.0 ppm during continuous moderate exercise on a treadmill. The exercise level that was chosen did not in itself produce bronchoconstriction. The cromolyn doses were 0 (placebo), 20, 40, and 60 mg. Pulmonary functions (FEV1, and total respiratory resistance) were measured before and after drug administration and after exposure. SO2 exposure after placebo produced significant bronchoconstriction. Pretreatment with 20 mg of cromolyn did not change the SO2 response, 40 mg significantly inhibited the response, and 60 mg completely abolished the pulmonary function changes. These results demonstrate for the first time a dose-response inhibition of SO2-induced bronchoconstriction in atopic subjects within a clinically acceptable dosage range and complete obliteration of SO2 sensitivity in this group with 60 mg of cromolyn pretreatment.