To determine the respiratory effects on health care workers of occupational exposure to aerosolized pentamidine (AP) used for the prophylaxis of Pneumocystis carinii pneumonia, we designed a clinical prospective study using subjects as their own controls. Sixteen health care workers whose job duties included administration of AP at one or more of nine San Francisco Bay Area medical centers participated in the study. Pentamidine concentrations ranged in breathing zone samples from < 0.03 to 62.2 micrograms/m3. Pentamidine was not detected in the urine of any of the subjects. There were no significant increases in symptoms on days when AP was administered. Cross-workshift spirometry on days when AP was administered showed a statistically significant mean decrease (0.14 liter) in forced expiratory volume in 1 second. There was no statistically significant difference in mean diurnal variation of peak expiratory flow rate on days when AP was administered. Methacholine inhalation challenge testing did not show a statistically significant mean change in airway responsiveness across the workweek. The ambient concentrations of pentamidine that we measured document that detectable occupational exposure to AP can occur in poorly ventilated treatment rooms. The cross-workshift decrement in forced expiratory volume in 1 second that we observed in association with AP administration supports the respiratory tract irritant potential of inhaled pentamidine. We recommend that steps be taken to minimize health care worker exposure to AP.

Metal fume concentrations inside the welding helmet and in the personal breathing zone in 23 experimental welding exposures were studied to explore whether welding helmet use substantially attenuates exposure to airborne metal fume. Observations produced a mean ratio of inside to outside metal fume concentrations of 0.9 +/- S.D. 0.2 with a highly variable effect. Iron fume concentration was inversely correlated with this ratio, representing greater helmet-associated attenuation with heavier exposure (r = -0.70, p < 0.001). In contrast to previous reports, these data suggest that welding helmet use provides marginal and highly variable reductions in fume exposure and cannot substitute for standard respiratory protection.

We assessed fatal drug overdose and poisoning case surveillance by a regional poison control center, comparing it with medical examiner determinations of death by poisoning over the same 2-year period and from the same catchment area. We studied 358 fatal cases of poisoning or drug overdose reported by a medical examiner and 10 fatal cases of poisoning or drug overdose reported by a poison control center, analyzing demographics and other case-associated factors with with possible successful poison control center case surveillance. Of the medical examiner cases, 245 (68%) were prehospital deaths. Of the remaining 113 emergency department or hospital cases, only 5 (4.4%) were also reported to the poison control center. Compared with cases involving illicit drugs, other narcotics, and sedative drugs, those that involved other prescription drugs (relative odds, 30.6; 95% confidence interval, 2.7 to 351) and over-the-counter products and other substances (odds ratio, 18.9; 95% confidence interval, 1.4 to 257) were significantly more likely to be reported to the poison control center. Most fatal cases of poisoning and drug overdose are not detected through poison control center surveillance. For prevention and treatment, health planners and policy makers should recognize the implications of case underreporting.

Poison control centers in the United States are threatened with closure, and attempts at a cost-benefit analysis of these services have been indeterminate. The purpose of this study was to compare the operating costs of a regional poison control center resulting from public use of its telephone hotline services with those of hypothetical alternative sources of advice and care. We conducted a follow-up telephone survey among 589 public callers to the San Francisco Bay Area Regional Poison Control Center who had been managed at home without medical referral after an unintentional poisoning. All survey respondents were asked what alternative action they would have taken had the poison control center not been available to assist them by telephone consultation. We then surveyed emergency departments and physicians' offices cited as alternatives by the callers to determine their response and charges for evaluating a suspected poisoning case. A total of 464 (79%) of the callers surveyed would have sought assistance from their local emergency health care system had the poison control center not been available. We conservatively estimated that the total charges for such evaluations would be +71,900. Comparatively, the total actual operating cost of services provided by the poison control center for all 589 poisoning cases was +13,547. Most of the study subjects (429 [73%]) had private insurance coverage. Direct public access to these services probably reduces the use of emergency health care resources, thus lowering health care costs.

BACKGROUND

Metal fume fever is a flu-like illness caused by zinc oxide fume inhalation and mediated by unknown mechanisms. It is one of a group of work-related febrile inhalational syndromes. We studied bronchoalveolar lavage (BAL) obtained from cigarette smoking and nonsmoking human volunteers after controlled exposure to purified zinc oxide fume to explore the possible roles of proinflammatory cytokines in this condition.

METHODS

We studied 14 volunteers after inhalation exposure to purified zinc oxide fume and after sham exposure to air. The mean cumulative exposure was 537 +/- 232 mg min per cubic meter elemental zinc. Twenty hours after exposure we performed BAL. We analyzed BAL cells and studied BAL supernatant for cytokines including tumor necrosis factor-alpha (TNF alpha), interleukin(IL)-8, and IL-1 by enzyme-linked immunosorbant assay (ELISA).

RESULTS

Polymorphonuclear leukocytes (PMNs) were significantly increased in the BAL fluid obtained post-exposure compared to sham (mean difference = 41.3 +/- 16.8 x 10(3) per mL; p < 0.05). Cumulative zinc exposure positively correlated with exposure-sham differences in BAL supernatant concentrations of both TNF (r2 = 0.58; p = .002) and IL-8 (r2 = 0.44, p = 0.01). Exposure-sham concentration differences in BAL supernatant IL-8 and BAL PMNs were also positively correlated (r2 = 0.60; p < 0.001). Cigarette smoking was not associated with exposure-sham differences in BAL TNF or IL-8, but did demonstrate a packs-per-day dependent increase in BAL supernatant IL-1 (t = 2.3, p = 0.04) post-exposure compared to sham, after taking into account the zinc exposure response.

CONCLUSIONS

Purified zinc oxide fume inhalation causes an exposure-dependent increase in proinflammatory cytokines and PMNs in the lung. This supports a role for cytokine networking in mediating metal fume fever.

Although chlorine gas is a common irritant exposure, little is known about airway responses to chlorine inhalation among persons with baseline airway hyperreactivity. We wished to determine whether such persons manifest an exaggerated response to chlorine compared with normal subjects. We studied 10 subjects, five with and five without airway hyperresponsiveness (HR) after exposure to 1.0 ppm chlorine and five persons, all with HR, to 0.4 ppm chlorine. After 1.0 ppm inhalation, there was a significant (p < 0.05) fall (mean +/- SE) in FEV1 immediately following exposure among normal (-180 +/- 37 mL) and HR subjects (-520 +/- 171 mL). The fall was greater among the HR compared with the normal subjects (p = 0.04). Specific airway resistance (Sraw) increased to a greater degree among the HR group compared with normal subjects (p = 0.04). Among all subjects (n = 10), the proportional change in FEV1 after 1.0 ppm chlorine correlated with baseline reactivity (Spearman rank correlation r = 0.64, p < 0.05). At 24-h follow-up, there were no significant chlorine-related pulmonary function deficits. After 0.4 ppm chlorine inhalation, there was no significant pulmonary function effect. These data indicated that persons with hyperreactive airways manifest an exaggerated airway response to chlorine at 1.0 ppm. This suggests that when large numbers of persons are exposed to chlorine, a susceptible subpopulation may acutely respond with a greater decrement in pulmonary function.

STUDY OBJECTIVE

Identify risk factors for work disability among adults with asthma treated by pulmonary and allergy specialists.

DESIGN

Cross-sectional survey, including retrospective work history data.

PARTICIPANTS

Sixty-eight pulmonary and 16 allergy internal medicine subspecialists maintaining a registry of patient visits for asthma; 698 registered patients aged 18 to 50 years, of whom 601 (86%) were studied.

MEASURES

Computer-assisted, telephone-administered structured interview assessing asthma severity, perceived general health status, asthma quality of life, demographics, and work history. Complete work disability defined as total work cessation attributed to asthma; partial work disability defined as change in job, duties, or reduction in work hours attributed to asthma.

RESULTS

Complete cessation of work due to asthma was reported by 40 (7%; 95% confidence interval [CI], 5 to 9%) and partial work disability by 53 (10%; 95% CI, 7 to 12%) of 550 subjects with a history of labor force participation. Severity of asthma score predicted both complete disability (odds ratio [OR], 7.9; 95% CI, 4.2 to 15 per 10-point increment) and partial disability (OR 2.6; 95% CI, 1.6 to 4.2). Taking illness severity into account, job conditions, occupation, and work exertion carried a combined disability OR of 3.9 (95% CI, 1.7 to 8.6).

CONCLUSIONS

Work disability is common among adults with asthma receiving specialist care. Severity of disease is a powerful predictor, but not the sole predictor of disability in this group. Working conditions, including job-related exposures, are associated with added disability risk even after taking illness severity into account.

BACKGROUND

Pennyroyal is a widely available herb that has long been used as an abortifacient despite its potentially lethal hepatotoxic effects. However, quantitative data for pennyroyal constituents and their metabolites in humans have not been previously reported.

OBJECTIVES

To quantify pennyroyal metabolites in human overdose, to correlate these findings with clinical variables, and to place these findings in the context of previously reported cases of pennyroyal toxicity.

DESIGN

Clinical case series of pennyroyal ingestions; quantification of pennyroyal metabolites by gas chromatography and mass spectrometry; qualitative detection of protein-bound adducts of the metabolites of pennyroyal constituents in human liver by Western blot assay; and review of the literature based on a search of MEDLINE, Index Medicus, and the reference citations of all available publications.

RESULTS

We report four cases of pennyroyal ingestion. One patient died, one received N-acetylcysteine, and two ingested minimally toxic amounts of pennyroyal and were not treated with N-acetylcysteine. In the fatal case, postmortem examination of a serum sample, which had been obtained 72 hours after the acute ingestion, identified 18 ng of pulegone per mL and 1 ng of menthofuran per mL. In a serum sample from the patient treated with N-acetylcysteine, which had been obtained 10 hours after ingestion, the menthofuran level was 40 ng/mL. Review of 18 previous case reports of pennyroyal ingestion documented moderate to severe toxicity in patients who had been exposed to at least 10 mL of pennyroyal oil.

CONCLUSION

Pennyroyal continues to be an herbal toxin of public health importance. Data on human metabolites may provide new insights into the toxic mechanisms and treatment of pennyroyal poisoning, including the potential role of N-acetylcysteine. Better understanding of the toxicity of pennyroyal may also lead to stricter control of and more restricted access to the herb.