N-acetyltransferase 1 polymorphism increases cotinine levels in Caucasian children exposed to secondhand smoke: the CCAAPS birth cohort.

Cotinine is a proxy for secondhand smoke (SHS) exposure. Genetic variation along nicotine and cotinine metabolic pathways may alter the internal cotinine dose, leading to misinterpretations of exposure-health outcome associations. Caucasian children with available SHS exposure and hair cotinine data were genotyped for metabolism-related genes. SHS-exposed children had 2.4-fold higher hair cotinine (0.14±0.22 ng mg(-1)) than unexposed children (0.06±0.05 ng mg(-1), P<0.001). SHS-exposed children carrying the NAT1 minor allele had twofold higher hair cotinine (0.18 ng mg(-1) for heterozygotes and 0.17 ng mg(-1) for homozygotes) compared with major allele homozygotes (0.09 ng mg(-1), P=0.0009), even after adjustment for SHS dose. These findings support that NAT1 has a role in the metabolic pathway of nicotine/cotinine and/or their metabolites. The increased cotinine levels observed for those carrying the minor allele may lead to SHS exposure misclassification in studies utilizing cotinine as a biomarker. Additional studies are required to identify functional single-nucleotide polymorphism(s) (SNP(s)) in NAT1 and elucidate the biological consequences of the mutation(s).

Airway obstruction related to diacetyl exposure at microwave popcorn production facilities.

Obstructive lung diseases including bronchiolitis obliterans have been reported among microwave popcorn production employees. Butter flavourings including diacetyl have been associated with these findings. The present study was initiated at four microwave popcorn production plants to determine if exposure to diacetyl was associated with decrements in pulmonary function. Comprehensive diacetyl exposure assessment was undertaken for all job tasks. Spirometry was conducted for 765 full-time employees between 2005 and 2006. Outcomes included decrement in forced expiratory volume in one second (FEV(1)) % predicted, airway obstruction and persistent decline in FEV(1). Inclusion in the high-exposure group (mixers) prior to respirator use was associated with a significantly decreased FEV(1) % pred in non-Asian and Asian males at -6.1 and -11.8% pred, respectively, and an eight-fold increased risk for airway obstruction. Cumulative diacetyl exposure >or=0.8 ppm-yr caused similar results. No significant impact was seen in nonmixers or between current diacetyl exposure and persistent decline in FEV(1). Unprotected exposure as a mixer to butter flavouring including diacetyl resulted in decrements in FEV(1) (% pred) and increased airway obstruction. Control of employee exposure to butter flavouring additives is warranted in regard to both short-term peak and 8-h workday exposure.

Normal spirometric values in healthy Hispanic Americans.

FVC, FEV1, FEV1/FVC, and FEF25-75% were measured in 259 (116 men and 143 women) healthy nonsmoking Hispanic American volunteers from Utah and California. Linear regression equations were created for women greater than or equal to age 20 years and men greater than or equal to age 25 years using height, age, and weight as independent variables and the spirometric indices as dependent variables. Weight was a significant predictor only for female FEV1. The raw data from this study were compared with data from our previous studies in North American Indians and Salt Lake City whites with Middle European ethnic backgrounds. No differences were found for any of the age and height coefficients. The only differences found were in the comparisons of the equation intercepts (bias) for male FVC and FEV1 between data for the Salt Lake City white subjects and both Hispanic American and North American Indian men. These small biases could be explained by technical or sampling biases or they may represent small ethnic differences. Although the differences from our Salt Lake City study are small, we recommend that ethnic-specific equations be used where they are available.

Variability in the classification of radiographs using the 1980 International Labor Organization Classification for Pneumoconioses.

This study describes the extent of agreement in classification of chest radiographs using the International Labor Organization (ILO) classification among six readers from the United States and Canada. A set of 119 radiographs was created and read by three Canadian and three US readers. The two ratings of interest were profusion (scored from 0/- to 3/+) and pleural abnormalities consistent with pneumoconiosis (scored with the ILO system, then collapsed into a yes/no). We used a number of approaches to evaluate interreader agreement on profusion and pleural changes, determining concordance, observed agreement, kappa statistic, and a new measure to approximate sensitivity and specificity. This study found that five of six readers had good fair to good agreement for pleural findings and for profusion as a dichotomous variable (> or = 1/0 vs < or = 0/1) using the kappa statistic, while a sixth reader had poor agreement. We found that concordance, expressed as percent agreement, was higher for normal radiographs than for ones that showed disease, and describe the use of the kappa statistic to control for this finding. This analysis adds to the existing literature with the use of the kappa statistic, and by presenting a new measure for "underreading" and "overreading" tendencies.

Reliability and validity of chest radiograph surveillance programs.

STUDY OBJECTIVES: Due to the lack of consensus in the literature in the use of posteroanterior (PA) vs PA with right and left oblique views as the optimum radiograph surveillance methodology to investigate pleural changes, a study was undertaken to evaluate the reliability, sensitivity, and specificity of these two approaches. DESIGN: Three experienced radiologist B readers used the 1980 International Labor Office classification system for pneumoconiosis to independently read chest radiographs of workers with individual identifiers masked. All radiographs were read first as a PA view only. Unknown to the B readers, each subject's PA was then matched to his or her corresponding right and left oblique views (film triad) and re-read several weeks later. SETTING AND PARTICIPANTS: The respiratory health of 652 workers exposed to refractory ceramic fiber was assessed as part of cross-sectional and longitudinal surveillance programs. MEASUREMENTS AND RESULTS: kappa Statistics for interreader and intrareader reliability between the PA view and film triad methods were calculated. Sensitivity, specificity, and positive predictive value were assessed by comparing the initial cross-sectional study to the longitudinal study. The film triad method had considerably higher interreader reliability (kappa = 0.59) compared to the PA-only method (kappa = 0.44). Results from the initial cross-sectional study were then compared to findings evaluated longitudinally. The film triad again was superior, demonstrating a positive predictive value of 73.7% compared to only 47.8% for the PA method. CONCLUSIONS: It is our recommendation that the film triad method be used in surveillance studies where both parenchymal and pleural changes are anticipated.

Refractory ceramic fibers activate alveolar macrophage eicosanoid and cytokine release.

Refractory ceramic fiber has been developed for industrial processes requiring materials with high thermal and mechanical stability. To evaluate the biological activity of this fiber, rat alveolar macrophages were exposed for < or = 24 h to 0-1,000 micrograms/ml of refractory ceramic fiber, crocidolite asbestos, silica (fibrogenic particles), or titanium dioxide (a nonfibrogenic particle), and eicosanoid, tumor necrosis factor-alpha (TNF), and lactate dehydrogenase release were measured. Particle dimensions were determined by electron microscopy. Radioactivity coeluting with leukotriene B4 (LTB4) and immunoreactive LTB4 and TNF release increased after refractory ceramic fiber and were similar in magnitude after asbestos but less than after silica. For example, the total [3H]eicosanoid release increased 3.9-fold after refractory ceramic fiber, 4.6-fold after asbestos, and 8.7-fold after silica. Refractory ceramic fiber and asbestos also have similar particle dimensions (diameter, length, and surface area). Inasmuch as macrophage-derived LTB4 and TNF are potent mediators in inflammatory events, including migration and activation of neutrophils, these findings suggest that refractory ceramic fiber can activate macrophages in vitro to release mediators relevant to in vivo findings of inflammation and fibrotic lung disease in laboratory animals.

Induction of nuclear aberrations by smokeless tobacco in epithelial cells of human oral mucosa.

Cytologic and cytogenetic studies were performed to assess the prevalence of somatic cell genetic damage in 48 young adults equally divided to represent users and nonusers of smokeless tobacco. Exposure was ascertained by measuring saliva cotinine using capillary gas chromatography. Squamous epithelial cells sampled from the oral mucosa demonstrated significant cytologic alterations associated with tobacco exposure. The frequency of micronucleated cells was significantly (P less than .01) higher in the labial mucosa of exposed (2.22%) compared to unexposed (0.27%) individuals. The frequency of micronuclei varied widely between exposed subjects but was higher in heavily (2.48%) compared to lightly (1.29%) exposed individuals as measured by saliva cotinine levels. Morphologic classification of epithelial cell nuclei showed that the frequency of cells with normal nuclear structure was significantly (P less than .01) reduce in exposed individuals. Analysis of oral epithelial cells of five additional nonusers of smokeless tobacco but wearers of orthodontic appliances to stimulate abrasion demonstrated no difference from the nonexposed control group. Unlike the case with cigarette smokers, peripheral lymphocyte sister-chromatid exchange frequency was not affected by exposure to smokeless tobacco. The oral cytology data, however, support an interpretation of exposure-dependent nuclear alterations, including micronuclei, in the oral epithelium associated with the use of smokeless tobacco. Altogether, results suggest that use of smokeless tobacco may cause genetic damage to cells in the oral epithelium.

Health effects of synthetic vitreous fibers.

This article reviews the terminology and manufacturing process for synthetic vitreous fibers. The in vitro and in vivo animal experimental data that correlate fiber toxicity with dose, dimensions, and durability are summarized. Occupational exposure data are presented as well as the potential irritant effects of synthetic vitreous fibers. The ongoing human morbidity and mortality studies are summarized along with current occupational exposure standards. The discussion correlates physical properties related to fiber toxicity and the types of synthetic vitreous fibers.

Male reproductive effects of solvent and fuel exposure during aircraft maintenance.

Few studies have addressed the effects of mixed, low-level exposures to complex mixtures on a man's reproductive potential. In this prospective study, each subject was evaluated before first exposure and at 15 and 30 weeks after exposures had begun. A total of 50 men working on aircraft maintenance at an Air Force installation were included in the study. In addition, eight unexposed men were concurrently sampled. Industrial hygiene (IH) sampling and expired breath samples were collected for jet fuel as measured by total napthas, benzene--a component of jet fuel, 1,1,1-trichloroethane, methyl ethyl ketone, xylenes, toluene, and methylene chloride. Sperm production, structure, and function (sperm concentration, sperm motion, viability, morphology, morphometrics, and stability of sperm chromatin) were evaluated. Exposures were low. All mean IH measures were below 6 ppm, which is less than 10% of the Occupational Safety and Health Administration standard for all chemicals except benzene. Sheet metal workers had the highest mean breath levels for both total solvents (24 ppb) and fuels (28.3 ppb). For most sperm measures, mean values remained in the normal range throughout the 30 weeks of exposure. When jobs were analyzed by exposure groups, some adverse changes were observed. The paint shop group had a significant decline in motility of 19.5% at 30 weeks. Internal dose measures, however, did not show a significant association with spermatogenic changes.

Balancing cost and precision in exposure assessment studies.

Because of the cost involved both for personnel and laboratory analyses, it is incumbent that industrial hygiene (IH) sampling plans be both precise and cost effective. The purpose of this paper is to describe a method of balancing two opposing objectives, increasing precision and decreasing the cost by manipulating the number and nature of IH sample collections. Data from a pilot study were used to obtain an optimum sampling scheme for exposure assessment. The design that obtains the highest precision while controlling costs serves as the model of choice. An approach is illustrated with data from an ongoing study examining health effects of workers exposed to solvents. It is shown that there is a large variation in precision for identical IH measurements, depending on the efficiency of the sampling schedule.

Weight change and lung function: implications for workplace surveillance studies.

This study evaluated the relationship between weight change and longitudinal measurement of lung function among 361 men providing at least five pulmonary function tests. The men in this study were participants in a workplace pulmonary surveillance program for subjects with exposure to refractory ceramic fibers (RCFs). Occupational and environmental studies are generally designed to evaluate factors suspected of causing excess decline in lung function. Failure to adequately account for all significant factors may lead to erroneous conclusions regarding change in lung function. This study utilized two different statistical models to evaluate longitudinal changes in a cohort of RCF workers. What was unique to this study was the modeling of longitudinally measured initial weight, weight change, and longitudinal exposure before and during the period of observation. Results showed a strong relationship between weight gain and longitudinal loss in lung function that approximated forced vital capacity declines of 16 mL for every kilogram of weight gain per year in both models. This value is comparable or greater in magnitude and significance to other factors known to be inversely related to lung function, such as age and pack-years smoking to time of initial testing. In conclusion, weight gain was found to have a significant impact on longitudinal change in lung function. Therefore, weight gain becomes a very important variable that requires consideration whenever longitudinal studies of pulmonary function are conducted.

Increased incidence of menstruation-associated bactericidal defects in neutrophils from women who have recovered from toxic shock syndrome.

There is a growing suspicion that a host abnormality may contribute to the pathogenesis of toxic shock syndrome (TSS). We found that females (5 of 5) who had recovered from TSS had transient, menstruation-associated decreases (greater than or equal to 9%) in the ability of their neutrophils to kill Staphylococcus aureus. 502A in vitro more often (P = 0.040 by Fisher's exact test) than non-TSS-affected control subjects (5 of 12). In addition, the average decrease in bactericidal activity in neutrophils obtained during menstruation from recovered TSS patients was 30 +/- 9% compared to 7 +/- 7% for neutrophils from non-TSS-affected control subjects. The results are consistent with the possibility that transient menstruation-associated decreases in neutrophil bactericidal function may indicate susceptibility and/or contribute to the development of TSS.

What is the potential measurement error in occupational exposure studies?

This paper demonstrates statistical methods that estimate measurement error from available industrial hygiene data. Errors in measuring a continuous exposure variable may arise when all individuals in a work area are assigned the same exposure. An example is when the mean of exposure measurements obtained on a sample of individuals is assigned to all workers with similar jobs. This may lead to inaccurate point and interval estimates in exposure-response modeling. A method of simulating the distribution of true (i.e., unobserved) individual exposures is described in order to estimate the mean and variance of measurement error. The minimum variance unbiased estimator approximates the mean of lognormally distributed exposure measurements. The distribution of true individual exposures is approximated by the distribution of simulated estimates of mean exposure. The methodology is illustrated by exposure data from work areas manufacturing refractory ceramic fiber (RCF) and RCF products. Results show that exposure is slightly underestimated in work areas with between 25 and 113 exposure measurements; measurement error variance averages about 1.3% of the total variance.

Reversible beryllium sensitization in a prospective study of beryllium workers.

Chronic beryllium disease is a granulomatous and fibrotic pulmonary disorder with increased numbers and percentage of lymphocytes in bronchoalveolar lavage fluid similar to that found in hypersensitivity pneumonitis. Blastogenic lymphocyte transformation (LT) to beryllium salts has been described in lavage and blood lymphocytes in patients with chronic beryllium disease. We conducted a 3-yr prospective study to evaluate the relationship between LT and beryllium exposure and pulmonary changes consistent with chronic beryllium disease. There were 15.9% (13/82) positive LTs in 1979 and 8.2% (5/61) in 1982. Of 11 positive LTs in 1979, 8 were negative in 1982, concomitant with a significant reduction in exposure. A positive LT was not associated with reduced pulmonary function, and no radiographic changes consistent with beryllium disease were identified. We propose that LT in beryllium workers is related to exposure and is reversible when exposure levels are reduced through diligent industrial hygiene measures.

Radon and man-made vitreous fibers.

Epidemiologic studies of miners have established a causal association between radon exposure and development of lung cancer. During the past decade the focus of attention has turned to the potential risks from exposure to radon in indoor air. Governmental involvement thus far has primarily been aimed at gathering further data and issuing voluntary guidelines for radon control in the indoor environment. The federal government's most recent risk assessment for exposure to indoor radon published in 1992 concluded that exposure to indoor radon results in 13,600 radon-induced lung cancer deaths in the United States each year. As public awareness of such environmental issues continues to grow, physicians will be faced with the need to respond to inquiries regarding potential health effects. Man-made vitreous fibers are silicate glass that have a noncrystalline structure. They have been in production for more than 100 years and are used in numerous applications in residential and commercial settings. The health risks from man-made vitreous fibers that are used in residential and commercial settings are limited to skin and occasional respiratory tract irritation under circumstances of improper installation or maintenance. When glass fiber contaminates an indoor environment, proper repair measures and thorough cleaning of the indoor environment will lead to resolution of any resultant irritant symptoms.

Indoor air quality medicolegal issues.

The regulatory and legal communities have begun only recently to address the medicolegal issues surrounding indoor air quality. No single governmental agency is responsible for indoor air quality issues. The focus of the federal government's indoor air quality programs is on the gathering and dissemination of information rather than on the regulation of indoor air pollution. State and local regulatory controls vary but may include antismoking ordinances, building codes, and contractor certification programs. Numerous lawsuits involving various parties and legal theories have been filed on the basis of illness allegedly related to indoor air quality. Further regulatory and legal review of indoor air problems will likely occur in the near future, particularly as a result of the characterization of environmental tobacco smoke as a class A carcinogen.

Pulmonary function testing in pulmonary prevention.

Pulmonary function testing plays an important role in the prevention of environmental lung disease when used in surveillance programs, research programs, and clinical practice. This paper focuses upon the interpretation of lung function data acquired during occupational disease surveillance and examines several potential pitfalls in spirometry surveillance programs.