Publications

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.

The objective of this study was to identify risk factors for work disability among persons with carpal tunnel syndrome (CTS). The study was designed to analyze data from the Occupational Health Supplement of the National Health Interview Survey, a nationwide, population-based survey. Subjects included 544 survey respondents with self-report of CTS and 32,688 survey respondents without CTS, all aged 18-64 years, and with a history of labor force participation. Measurements were as follows: Dependent variables were work disability, defined either as cessation of employment without attribution of cause or, alternatively, as cessation of employment or job change specifically attributed to CTS by the survey respondent. Independent variables were ergonomic risk of work disability, defined by minutes of workplace repetitive hand and wrist bending for the most recent job held. This measure was derived from responses categorized by an occupation and industry matrix independent of CTS status. Socio-demographic and health status risk factors for work disability were based on the respondent report. The main results were as follows: Among 544 persons with CTS, 58 (11%, CI 8-13%) reported work disability specifically attributed to CTS, representing an estimated national prevalence of 240,578 persons with this limitation. Workplace ergonomic risk, measured as repetitive hand or wrist bending in the occupation and industry of last employment, was a significant factor predictive of CTS-attributed work disability (per 120 min of daily exposure, OR 1.7, CI 1.1-2.6), even after taking into account socio-demographic factors and health status. The conclusions were that work disability among persons with CTS is common. For those with CTS, working conditions characterized by repetitive bending of the hand or wrist may increase the risk of work disability associated with this condition.

To examine whether diffuse pleural thickening (DPT) causes impairment of pulmonary function independent of other manifestations of asbestos-related disease, we studied individuals selected from 1,150 men with occupational asbestos exposure who had undergone pulmonary function testing and computed tomographic (CT) scanning. The CT scans revealed 84 subjects with DPT as defined for CT. Of these 84 subjects, 53 eligible study cases were matched by age with a referent group without DPT from the same exposed group. No difference was demonstrated between cases and referents in smoking history, length of exposure, latency, or the proportion with either interstitial fibrosis or pleural plaques. Individuals with DPT demonstrated significantly reduced forced vital capacity (FVC) (p = 0.002) and diffusing capacity for carbon monoxide (DLCO) (p = 0.002) as compared with the referents. No difference was found in the two groups' FEV1 to FVC ratio (FEV1/FVC). Individuals with DPT and either interstitial fibrosis or pleural plaques showed a significantly lower FVC than did those with fibrosis or pleural plaques alone. Individuals with DPT and rounded atelectasis had similar pulmonary function to those with DPT and no rounded atelectasis. Subjects with DPT had a more frequent history of coronary bypass surgery than referents (19% versus 2%; p = 0.008). We conclude that subjects with DPT have restrictive pulmonary function and reduced diffusing capacity independent of other manifestations of asbestos-related disease.

The aim of this study was to determine the dose-response relationship between cigarette smoke exposure and pulmonary cell and cytokine concentrations in bronchoalveolar lavage (BAL). BAL cells and BAL supernatant concentrations of tumour necrosis factor-alpha (TNF alpha), interleukin (IL)-1 beta, IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1 from 14 healthy smokers and 16 healthy nonsmokers were quantified. Statistically greater concentrations of neutrophils, macrophages, IL-1 beta, IL-6, IL-8 and MCP-1 were observed among smokers compared with nonsmokers (p < or = 0.0007 in all cases). Cigarette smoking, categorized ordinally as: less than one pack, one pack, or greater than one pack per day, was predictive of BAL macrophages (p < 0.0001), neutrophils (p = 0.015), IL-1 beta (p < 0.001) and IL-8 (p = 0.02). We conclude that concentrations of macrophages, neutrophils, IL-1 beta and IL-8 are elevated in the pulmonary microenvironment of smokers in a cigarette dose-dependent manner. Based on the present findings, we would caution against simple analyses that treat current smokers as a homogeneous group and which do not account for smoking intensity.