Endotoxin (lipopolysaccharide) is a widespread contaminant in many environmental settings. Since the 1970s, there has been generally consistent evidence indicating reduced risks for lung cancer ...associated with occupational endotoxin exposure.
We updated a case-cohort study nested within a cohort of 267,400 female textile workers in Shanghai, China. We compared exposure histories of 1456 incident lung cancers cases diagnosed during 1989-2006 with those of a reference subcohort of 3022 workers who were free of lung cancer at the end of follow-up. We applied Cox proportional hazards modelling to estimate exposure-response trends, adjusted for age and smoking, for cumulative exposures lagged by 0, 10, and 20 years, and separately for time windows of ⩽15 and >15 years since first exposure.
We observed no associations between cumulative exposure and lung cancer, irrespective of lag interval. In contrast, analyses by exposure time windows revealed modestly elevated, but not statistically significant relative risks (∼1.27) at the highest three exposure quintiles for exposures that occurred >15 years since first exposure.
The findings do not support a protective effect of endotoxin, but are suggestive of possible lung cancer promotion with increasing time since first exposure.
Background: There is little information describing the risk of non-malignant respiratory disease and occupational exposure to diesel exhaust. Methods: US railroad workers have been exposed to diesel ...exhaust since diesel locomotives were introduced after World War II. In a retrospective cohort study we examined the association of chronic obstructive pulmonary disease (COPD) mortality with years of work in diesel-exposed jobs. To examine the possible confounding effects of smoking, multiple imputation was used to model smoking history. A Cox proportional hazards model was used to estimate an incidence rate ratio, adjusted for age, calendar year, and length of follow-up after leaving work (to reduce bias due to a healthy worker survivor effect). Results: Workers in jobs with diesel exhaust exposure had an increased risk of COPD mortality relative to those in unexposed jobs. Workers hired after the introduction of diesel locomotives had a 2.5% increase in COPD mortality risk for each additional year of work in a diesel-exposed job. This risk was only slightly attenuated after adjustment for imputed smoking history. Conclusions: These results support an association between occupational exposure to diesel exhaust and COPD mortality.
Aims: To illustrate the contribution of smoothing methods to modelling exposure-response data, Cox models with penalised splines were used to reanalyse lung cancer risk in a cohort of workers exposed ...to silica in California’s diatomaceous earth industry. To encourage application of this approach, computer code is provided. Methods: Relying on graphic plots of hazard ratios as smooth functions of exposure, the sensitivity of the curve to amount of smoothing, length of the exposure lag, and the influence of the highest exposures was evaluated. Trimming and data transformations were used to down-weight influential observations. Results: The estimated hazard ratio increased steeply with cumulative silica exposure before flattening and then declining over the sparser regions of exposure. The curve was sensitive to changes in degrees of freedom, but insensitive to the number or location of knots. As the length of lag increased, so did the maximum hazard ratio, but the shape was similar. Deleting the two highest exposed subjects eliminated the top half of the range and allowed the hazard ratio to continue to rise. The shape of the splines suggested a parametric model with log hazard as a linear function of log transformed exposure would fit well. Conclusions: This flexible statistical approach reduces the dependence on a priori assumptions, while pointing to a suitable parametric model if one exists. In the absence of an appropriate parametric form, however, splines can provide exposure-response information useful for aetiological research and public health intervention.
Background: An elevated risk of lung cancer in truck drivers has been attributed to diesel exhaust exposure. Interpretation of these studies specifically implicating diesel exhaust as a carcinogen ...has been limited because of limited exposure measurements and lack of work records relating job title to exposure-related job duties. Objectives: We established a large retrospective cohort of trucking company workers to assess the association of lung cancer mortality and measures of vehicle exhaust exposure. Methods: Work records were obtained for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. We assessed lung cancer mortality through 2000 using the National Death Index, and we used an industrial hygiene review and current exposure measurements to identify jobs associated with current and historical use of diesel-, gas-, and propane-powered vehicles. We indirectly adjusted for cigarette smoking based on an industry survey. Results: Adjusting for age and a healthy-worker survivor effect, lung cancer hazard ratios were elevated in workers with jobs associated with regular exposure to vehicle exhaust. Mortality risk increased linearly with years of employment and was similar across job categories despite different current and historical patterns of exhaust-related particulate matter from diesel trucks, city and highway traffic, and loading dock operations. Smoking behavior did not explain variations in lung cancer risk. Conclusions: Trucking industry workers who have had regular exposure to vehicle exhaust from diesel and other types of vehicles on highways, city streets, and loading docks have an elevated risk of lung cancer with increasing years of work.
Background: Workers with acute hand injuries account for over 1 000 000 emergency department visits annually in the United States. Aims: To determine potential transient risk factors for occupational ...acute hand injury. Methods: Subjects were recruited from 23 occupational health clinics in five northeastern states in the USA. In a telephone interview, subjects were asked to report the occurrence of seven potential risk factors within a 90-minute time period before an acute hand injury. Each case also provided control information on exposures during the month before the injury. The self-matched feature of the study design controlled for stable between-person confounders. Results: A total of 1166 subjects were interviewed (891 men, 275 women), with a mean age (SD) of 37.2 years (11.4). The median time interval between injury and interview was 1.3 days. Sixty three per cent of subjects had a laceration. The relative risk of a hand injury was increased when working with equipment, tools, or work pieces not performing as expected (11.0, 95% CI 9.4 to 12.8), or when using a different work method to do a task (10.5, 95% CI 8.7 to 12.7). Other transient factors in decreasing order of relative risk were doing an unusual task, being distracted, and being rushed. Wearing gloves reduced the relative risk by 60% (0.4, 95% CI 0.3 to 0.5). Occupational category, job experience, and safety training were found to alter several of these effects. Conclusion: The results suggest the importance of these transient, potentially modifiable factors in the aetiology of acute hand injury at work. Attempts to modify these exposures by various strategies may reduce the incidence of acute hand injury at work.
In this paper, we review available methods for determination of the functional form of the relation between a covariate and the log hazard ratio for a Cox model. We pay special attention to the ...detection of influential observations to the extent that they influence the estimated functional form of the relation between a covariate and the log hazard ratio. Our paper is motivated by a data set from a cohort study of lung cancer and silica exposure, where the nonlinear shape of the estimated log hazard ratio for silica exposure plotted against cumulative exposure and hereafter referred to as the exposure-response curve was greatly affected by whether or not two individuals with the highest exposures were included in the analysis. Formal influence diagnostics did not identify these two individuals but did identify the three highest exposed cases. Removal of these three cases resulted in a biologically plausible exposure-response curve.
In order to evaluate chronic effects of long-term exposure to cotton dust on respiratory health, and the role of dust and endotoxin, longitudinal changes in lung function and respiratory symptoms ...were observed prospectively from 1981 to 2001 in 447 cotton textile workers, along with 472 silk textile controls. The results from five surveys conducted over the 20-yr period are reported, including standardised questionnaires, pre- and post-shift spirometric measurements, work-area inhalable dust sample collections and airborne Gram-bacterial endotoxin analysis. Cotton workers had more persistent respiratory symptoms and greater annual declines in forced expiratory volume in one second (FEV1) and forced vital capacity as compared with silk workers. After exposure cessation, in the final 5-yr period, the rate of FEV1 decline tended to slow in nonsmoking males, but not in nonsmoking females. Workers who reported byssinotic symptoms more persistently suffered greater declines in FEV1. Chronic loss in lung function was more strongly associated with exposure to endotoxin than to dust. In conclusion, the current study suggests that long-term exposure to cotton dust, in which airborne endotoxin appears to play an important role, results in substantial adverse chronic respiratory effects.
The evolutionary rates of proteins vary over several orders of magnitude. Recent work suggests that analysis of large data sets of evolutionary rates in conjunction with the results from ...high-throughput functional genomic experiments can identify the factors that cause proteins to evolve at such dramatically different rates. To this end, we estimated the evolutionary rates of >3,000 proteins in four species of the yeast genus Saccharomyces and investigated their relationship with levels of expression and protein dispensability. Each protein's dispensability was estimated by the growth rate of mutants deficient for the protein. Our analyses of these improved evolutionary and functional genomic data sets yield three main results. First, dispensability and expression have independent, significant effects on the rate of protein evolution. Second, measurements of expression levels in the laboratory can be used to filter data sets of dispensability estimates, removing variates that are unlikely to reflect real biological effects. Third, structural equation models show that although we may reasonably infer that dispensability and expression have significant effects on protein evolutionary rate, we cannot yet accurately estimate the relative strengths of these effects.
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