Publications

The association between serum beta-carotene or retinol concentration and level of ventilatory function was investigated in a population of asbestos-exposed men with a high rate of current and former cigarette smoking. The study population consisted of 816 subjects enrolled in the pilot component of the Carotene and Retinol Efficacy Trial (CARET), a placebo-controlled trial of supplemental beta-carotene and retinyl palmitate for the chemoprevention of lung cancer. Data available for analysis included baseline questionnaire, spirometry, chest X-ray, food frequency questionnaire, and serum beta-carotene and retinol concentrations. Serum beta-carotene concentration was associated with FEV1 (p < 0.05) and FVC (p < 0.05), with an approximately 100-ml increase over predicted values associated with raising the serum concentration from the 25th to the 75th percentile of the distribution in the study population (absolute difference = 155 ng/ml), even after adjustment for the confounding effects of asbestos exposure and cigarette smoking. Raising the serum retinol concentration from the 25th to the 75th percentile (absolute difference = 211 ng/ml) was associated with an approximately 70 ml increase in FVC (p < 0.05) over the predicted value. These results provide support for the hypothesis that beta-carotene and retinol have a protective effect on loss of ventilatory function.

Organic Dust Toxic Syndrome (ODTS) is a flu-like syndrome that can occur after inhalation of cotton, grain, wood chip dusts, or other organic dusts or aerosols. We investigated whether inflammatory pulmonary responses occur, even after relatively brief, low-level wood chip mulch exposure. Six volunteers were exposed to wood chip mulch dust. Total dust and/or endotoxin levels were measured in five subjects. Pulmonary function and peripheral blood counts were measured before and after exposure in each subject. Bronchoalveolar lavage (BAL) was performed in each subject after exposure, and cell, cytokine, and protein concentrations were measured. Control BAL without previous exposure was also performed on three of the subjects. Three of six subjects had symptoms consistent with ODTS. No clinically relevant or statistically significant changes in pulmonary function tests after exposure were found. Three subjects manifested a marked elevation in neutrophil percentage in their BAL (range, 10 to 57%). When these three subjects underwent control BAL, the postexposure comparison demonstrated an increase in neutrophil levels of 154 +/- 89 x 10(3)/mL (mean +/- standard error; P = 0.22). The mean increase in BAL interleukin-8 levels after exposure, compared with paired control values, was 11.2 +/- SE 2.5 pg/mL (P = 0.047). There was also an increase in BAL interleukin-6 levels that reached borderline significance (6.4 +/- SE 2.0 pg/mL; P = 0.08). Tumor necrosis factor levels were increased in all three subjects' BAL as well (0.4 +/- SE 0.2 pg/mL), but this change was not statistically significant (P = 0.2). Our findings of increased BAL proinflammatory cytokine and neutrophil levels are consistent with the theory that cytokine networking in the lung may mediate ODTS.

STUDY OBJECTIVE

Many persons with asthma self-medicate with widely available and potentially hazardous nonprescription medicines. This study assessed the demographic and clinical covariates of self-treatment with over-the-counter asthma medications (OTCs).

DESIGN AND SETTING

We conducted an analytical investigation using questionnaires and measures of lung function, comparing OTC and prescription medication users. We recruited adults with asthma by public advertisement.

SUBJECTS

We studied 22 exclusive prescription asthma medication users, 15 exclusive OTC users, and 13 other subjects who combined prescription medication use with self-treatment with asthma OTCs. All but one OTC user self-medicated with a nonselective, sympathomimetic metered-dose inhaler.

RESULTS

Taking income, access to care, and self-assessed disease severity into account, male gender was strongly associated with exclusive OTC use alone (odds ratio [OR]=8.9, 95% confidence interval [CI]= 1.3 to 61) and mixed OTC-prescription medication use (OR=9.7, 95% CI=1.1 to 83). The covariates of income, access to care, and self-assessed disease severity provided significant additional explanatory power to the model of exclusive OTC use (model chi2 difference 11.3, 5 df, p<0.05). Pulmonary function was similar among OTC and prescription medication users. However, prescription medication users' self-assessed asthma severity (mild compared to more severe) was associated with postbronchodilator reversibility of FEV1 obstruction (6% vs 18% reversibility, p<0.05) while exclusive OTC users' self-assessed severity showed the reverse pattern (19% vs 8%, p=0.2).

CONCLUSION

Asthma education programs attempting to discourage unregulated bronchodilator use should give consideration to this profile of the "asthmatic-at-risk."

Zinc oxide inhalation causes metal fume fever, a flu-like syndrome common among welders. Proinflammatory pulmonary cytokines play a role in mediating this occupational illness. The goal of this investigation was to characterize early pulmonary cytokine responses after experimental human exposure to inhaled purified zinc oxide fume. We quantified bronchoalveolar lavage (BAL) cytokine concentrations in 15 healthy volunteers 3 hr after inhalation of zinc oxide fume. We compared postexposure cytokine responses with postsham exposure responses in the same 15 subjects. We also compared cytokine responses with those of 14 "late follow-up" subjects previously studied by BAL 20 hr after zinc oxide fume exposure. Zinc oxide exposure was a statistically significant, dose-dependent predictor of increases in BAL TNF (mean exposure-sham difference +/- SE = 9.5 +/- 3.6 pg/mL, P = 0.02), IL-6 (mean exposure-sham difference +/- SE = 5.5 +/- 1.8 pg/mL, P = 0.009), and IL-8 (mean exposure-sham difference +/- SE = 64.1 +/- 23.9 pg/mL, P = 0.02). The TNF response was significantly greater at 3 hr follow-up compared with 20 hr follow-up, after adjusting for smoking status, zinc dose, and BAL macrophages (P = 0.004). Our findings provide evidence for a pulmonary inflammatory response 3 hr after inhalation of zinc oxide fume characterized by dose-dependent increases in BAL proinflammatory cytokine concentrations. These data indicate that TNF plays an important initial role in mediating metal fume fever.

Exposure to air polluted with particles less than 2.5 micron in size is associated epidemiologically with adverse cardiopulmonary health consequences in humans. The goal of this study was to characterize human pulmonary responses to controlled experimental high-dose exposure to fine and ultrafine magnesium oxide particles. We quantified bronchoalveolar lavage (BAL) cell and cytokine concentrations, pulmonary function, and peripheral blood neutrophil concentrations in six healthy volunteers 18 to 20 hr after inhalation of fine and ultrafine magnesium oxide particles produced from a furnace system model. We compared postexposure studies with control studies from the same six subjects. Mean +/- standard deviation (SD) cumulative magnesium dose was 4,138 +/- 2,163 min x mg/m3. By weight, 28% of fume particles were ultrafine (<0.1 micron in diameter) and over 98% of fume particles were fine (<2.5 micron in diameter). There were no significant differences in BAL inflammatory cell concentrations, BAL interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor, pulmonary function, or peripheral blood neutrophil concentrations postexposure compared with control. Our findings suggest that high-dose fine and ultrafine magnesium oxide particle exposure does not produce a measurable pulmonary inflammatory response. These findings are in marked contrast with the well-described pulmonary inflammatory response following zinc oxide particle inhalation. We conclude that fine and ultrafine particle inhalation does not result in toxicity in a generic manner independent of particle composition. Our findings support the concept that particle chemical composition, in addition to particle size, is an important determinant of respiratory effects.

BACKGROUND

There are few data on the use of alternative therapies in adult asthma and their impact on health outcomes.

OBJECTIVE

The objective of this study was to study the prevalence and morbidity of asthma self-treatment with herbs, coffee or black tea, and over-the-counter (OTC) medications containing ephedrine or epinephrine.

METHODS

We carried out a cross-sectional analysis of interview data for 601 adults with asthma recruited from a random sample of pulmonary and allergy specialists. We estimated the 12-month prevalence of reported use of herbal products, coffee or black tea, or OTC products to self-treat asthma and their association with emergency department visits and hospitalization.

RESULTS

Herbal asthma self-treatment was reported by 46 (8%; 95% confidence interval [CI] 6% to 10%); coffee or black tea self-treatment by 36 (6%; 95% CI 4% to 8%), epinephrine or ephedrine OTC use by 36 (6%; 95% CI 4% to 8%), and any of the three practices by 98 subjects (16%; 95% CI 13% to 19%). Adjusting for demographic and illness covariates, herbal use (odds ratio [OR] 2.5; 95% CI 1.1 to 5.6) and coffee or black tea use (OR 3.1; 95% CI 1.2 to 7.8) were associated with asthma hospitalization; OTC use was not (OR 0.8; 95% CI 0.3 to 2.5).

CONCLUSIONS

Even among adults with access to specialty care for asthma, self-treatment with nonprescription products was common and was associated with increased risk of reported hospitalization. This association does not appear to be accounted for by illness severity or other disease covariates. It may reflect delay in utilization of more efficacious treatments.

To study the relationship between physician subspecialty practice type and health measures in patients with adult asthma, we prospectively studied 601 adults with asthma. The subjects were recruited from a random sample of board-certified pulmonary or allergy internal medicine subspecialists practicing in northern California; 539 patients (90%) were restudied after 18 months. Structured telephone interviews were used to elicit demographics, clinical variables, and measures of asthma severity, asthma-specific quality of life, and physical function status. At baseline and follow-up, 283 subjects (53%) reported their principal asthma care provider type as a pulmonary specialist throughout and 150 (28%) as an allergy specialist throughout, 53 (10%) switched provider type during follow-up, and 53 (10%) reported that their principal asthma care physician was from neither subspecialist group. Taking into account illness severity and other demographic and clinical covariates, the group whose principal asthma care came from an allergy subspecialist was more likely than the pulmonary specialist-care group to report possessing a peak expiratory flow rate meter (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.8 to 4.6) and less likely to be receiving high-dose inhaled steroids (OR, 0.3; 95% CI, 0.1 to 0.6). Taking into account demographic and clinical covariates, allergists' care was related to worse subject-reported asthma-specific quality of life (P = 0.02), but not to statistically increased risk of hospitalization, decreased physical function, or an increased number of reported health-related restricted-activity days. We observed subject-reported specialist variation in management and health outcomes among adults with asthma not accounted for by differing disease severity or other clinical and demographic variables.