Total and Cause-Specific Mortality Risk Associated With Low-Level Exposure to Crystalline Silica: A 44-Year Cohort Study From China.

The association between low-level crystalline silica (silica) exposure and mortality risk is not well understood. We investigated a cohort of 44,807 Chinese workers who had worked in metal mines or pottery factories for at least 1 year from January 1, 1960, to December 31, 1974, and were followed through 2003. Low-level silica exposure was defined as having a lifetime highest annual mean silica exposure at or under a permissible exposure limit (PEL). We considered 3 widely used PELs, including 0.05 mg/m3, 0.10 mg/m3, and 0.35 mg/m3. Cumulative silica exposure was estimated by linking a job exposure matrix with each participant's work history. For the 0.10-mg/m3 exposure level, Cox proportional hazards models showed significantly increased risk of mortality from all diseases (for each 1-ln mg/m3-years increase in logged cumulative silica exposure, hazard ratio (HR) = 1.05, 95% confidence interval (CI): 1.03, 1.07), malignant neoplasms (HR = 1.06, 95% CI: 1.03, 1.09), lung cancer (HR = 1.08, 95% CI: 1.02, 1.14), ischemic heart disease (HR = 1.09, 95% CI: 1.02, 1.16), pulmonary heart disease (HR = 1.08, 95% CI: 1.00, 1.16), and respiratory disease (HR = 1.20, 95% CI: 1.14, 1.26). The 0.05-mg/m3 and 0.35-mg/m3 exposure levels yielded similar associations. Long-term exposure to low levels (PELs ≤0.05 mg/m3, ≤0.10 mg/m3, or ≤0.35 mg/m3) of silica is associated with increased total and certain cause-specific mortality risk. Control of ambient silica levels and use of personal protective equipment should be emphasized in practice.

Prevalence of Airflow Obstruction in U.S. Adults Aged 40-79 Years: NHANES Data 1988-1994 and 2007-2010.

BACKGROUND: The study evaluated the change in the prevalence of airflow obstruction in the U.S. population 40-79 years of age from years 1988-1994 to 2007-2010. METHODS: Spirometry data from two representative samples of the U.S. population, the National Health and Nutrition Examination Surveys (NHANES) conducted in 1988-1994 and 2007-2010, were used. The American Thoracic Society/European Respiratory Society (ATS/ERS) criteria were used to define airflow obstruction. RESULTS: Based on ATS/ERS criteria, the overall age-adjusted prevalence of airflow obstruction among adults aged 40-79 years decreased from 16.6% to 14.5% (p < 0.05). Significant decreases were observed for the older age category 60-69 years (20.2% vs. 15.4%; p < 0.01), for males (19.0% vs. 15.4%; p < 0.01), and for Mexican American adults (12.7% vs. 8.4%; p < 0.001). The prevalence of moderate and more severe airflow obstruction decreased also (6.4% vs. 4.4%; p < 0.01). Based on ATS/ERS criteria, during 2007-2010, an estimated 18.3 million U.S. adults 40-79 years had airflow obstruction, 5.6 million had moderate or severe airflow obstruction and 1.4 million had severe airflow obstruction. CONCLUSIONS: The overall age-adjusted prevalence of airflow obstruction among U.S. adults aged 40-79 years decreased from 1988-1994 to 2007-2010, especially among older adults, Mexican Americans, and males.

Changes in prevalence of chronic obstructive pulmonary disease and asthma in the US population and associated risk factors.

Chronic lower airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma, are currently the third leading cause of death in the United States. We aimed to evaluate changes in prevalence of and risk factors for COPD and asthma among the US adult population. We evaluated changes in prevalence of self-reported doctor-diagnosed COPD (i.e. chronic bronchitis and emphysema) and asthma and self-reported respiratory symptoms comparing data from the 1988-1994 and 2007-2010 National Health and Nutrition Examination Surveys. To investigate changes in the severity of each outcome over the two periods, we calculated changes in the proportions of spirometry-based airflow obstruction for each outcome. Prevalence of doctor-diagnosed chronic bronchitis and emphysema decreased significantly mainly among males, while asthma increased only among females. The self-reported disease and the respiratory symptoms were associated with increased prevalence of airflow obstruction for both periods. However, the prevalence of airflow obstruction decreased significantly in the second period among those with shortness of breath and doctor-diagnosed respiratory conditions (chronic bronchitis, emphysema, and asthma). COPD outcomes and asthma were associated with lower education, smoking, underweight and obesity, and occupational dusts and fumes exposure. Chronic lower airway diseases continue to be major public health problems. However, decreased prevalence of doctor-diagnosed chronic bronchitis and emphysema (in males) and decreased prevalence of airflow obstruction in those with respiratory symptoms and doctor-diagnosed respiratory diseases may indicate a declining trend and decrease in disease severity between the two periods. Continued focus on prevention of these diseases through public health interventions is prudent.

Occupational risk factors for COPD phenotypes in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.

INTRODUCTION: The contribution of occupational exposure to the risk of chronic obstructive pulmonary disease COPD in population-based studies is of interest. We compared the performance of self-reported exposure to a newly developed JEM in exposure-response evaluation. METHODS: We used cross-sectional data from Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of 45-84 year olds free of clinical cardiovascular disease at baseline. MESA ascertained the most recent job and employment, and the MESA Lung Study measured spirometry, and occupational exposures for 3686 participants. Associations between health outcomes (spirometry defined airflow limitation and Medical Research Council-defined chronic bronchitis) and occupational exposure [self-reported occupational exposure to vapor-gas, dust, or fumes (VGDF), severity of exposure, and a job-exposure matrix (JEM)-derived score] were evaluated using logistic regression models adjusted for non-occupational risk factors. RESULTS: The prevalence of airflow limitation was associated with self-reported exposure to vapor-gas (OR 2.6, 95%CI 1.1-2.3), severity of VGDF exposure (P-trend < 0.01), and JEM dust exposure (OR 2.4, 95%CI 1.1-5.0), and with organic dust exposure in females; these associations were generally of greater magnitude among never smokers. The prevalence of chronic bronchitis and wheeze was associated with exposure to VGDF. The association between airflow limitation and the combined effect of smoking and VGDF exposure showed an increasing trend. Self-reported vapor-gas, dust, fumes, years and severity of exposure were associated with increased prevalence of chronic bronchitis and wheeze (P < 0.001). CONCLUSIONS: Airflow limitation was associated with self-reported VGDF exposure, its severity, and JEM-ascertained dust exposure in smokers and never-smokers in this multiethnic study.

Exposure-response analysis and risk assessment for lung cancer in relationship to silica exposure: a 44-year cohort study of 34,018 workers.

Crystalline silica has been classified as a human carcinogen by the International Agency for Research on Cancer (Lyon, France); however, few previous studies have provided quantitative data on silica exposure, silicosis, and/or smoking. We investigated a cohort in China (in 1960-2003) of 34,018 workers without exposure to carcinogenic confounders. Cumulative silica exposure was estimated by linking a job-exposure matrix to work history. Cox proportional hazards model was used to conduct exposure-response analysis and risk assessment. During a mean 34.5-year follow-up, 546 lung cancer deaths were identified. Categorical analyses by quartiles of cumulative silica exposure (using a 25-year lag) yielded hazard ratios of 1.26, 1.54, 1.68, and 1.70, respectively, compared with the unexposed group. Monotonic exposure-response trends were observed among nonsilicotics (P for trend < 0.001). Analyses using splines showed similar trends. The joint effect of silica and smoking was more than additive and close to multiplicative. For workers exposed from ages 20 to 65 years at 0.1 mg/m(3) of silica exposure, the estimated excess lifetime risk (through age 75 years) was 0.51%. These findings confirm silica as a human carcinogen and suggest that current exposure limits in many countries might be insufficient to protect workers from lung cancer. They also indicate that smoking cessation could help reduce lung cancer risk for silica-exposed individuals.

Estimating the U.S. prevalence of chronic obstructive pulmonary disease using pre- and post-bronchodilator spirometry: the National Health and Nutrition Examination Survey (NHANES) 2007-2010.

BACKGROUND: During 2007-2010, the National Health and Nutrition Examination Survey (NHANES) conducted a spirometry component which obtained pre-bronchodilator pulmonary lung function data on a nationally representative sample of US adults aged 6-79 years and post-bronchodilator pulmonary lung function data for the subset of adults with airflow limitation. The goals of this study were to 1) compute prevalence estimates of chronic obstructive pulmonary disease (COPD) using pre-bronchodilator and post-bronchodilator spirometry measurements and fixed ratio and lower limit of normal (LLN) diagnostic criteria and 2) examine the potential impact of nonresponse on the estimates. METHODS: This analysis was limited to those aged 40-79 years who were eligible for NHANES pre-bronchodilator spirometry (n=7,104). Examinees with likely airflow limitation were further eligible for post-bronchodilator testing (n=1,110). Persons were classified as having COPD based on FEV1/FVC < 70% (fixed ratio) or FEV1/FVC < lower limit of normal (LLN) based on person's age, sex, height, and race/ethnicity. Those without spirometry but self-reporting both daytime supplemental oxygen therapy plus emphysema and/or current chronic bronchitis were also classified as having COPD. The final analytic samples for pre-bronchodilator and post-bronchodilator analyses were 77.1% (n=5,477) and 50.8% (n=564) of those eligible, respectively. To account for non-response, NHANES examination weights were adjusted to the eligible pre-bronchodilator and post-bronchodilator subpopulations. RESULTS: In 2007-2010, using the fixed ratio criterion and pre-bronchodilator test results, COPD prevalence was 20.9% (SE 1.1) among US adults aged 40-79 years. Applying the same criterion to post-bronchodilator test results, prevalence was 14.0% (SE 1.0). Using the LLN criterion and pre-bronchodilator test results, the COPD prevalence was 15.4% (SE 0.8), while applying the same criterion to post-bronchodilator test results, prevalence was 10.2% (SE 0.8). CONCLUSIONS: The overall COPD prevalence among US adults aged 40-79 years varied from 10.2% to 20.9% based on whether pre- or post-bronchodilator values were used and which diagnostic criterion (fixed ratio or LLN) was applied. The overall prevalence decreased by approximately 33% when airflow limitation was based on post-bronchodilator as compared to pre-bronchodilator spirometry, regardless of which diagnostic criterion was used.

Longitudinal decline in lung function in former asbestos exposed workers.

BACKGROUND: This study was designed to assess the effect of asbestos exposure on longitudinal lung function decline. METHODS: A group of 502 former asbestos-cement workers with at least two spirometry tests 4 years apart. Repeated evaluations included respiratory symptoms questionnaire, spirometry and chest imaging. Asbestos exposure was ascertained as years of exposure, an index of cumulative exposure and latency time. The mixed effects model was used to evaluate the effect of exposure on the level and rate of change in forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC). RESULTS: Mean age at entry was 51 (SD 9.9) years, mean latency time 25.6 (SD 10.0) years, mean follow-up time 9.1 (SD 2.8) years and mean number of spirometry tests 3.5. The FEV(1) level was significantly related to pack-years of smoking at entry and during the follow-up, the index of cumulative asbestos exposure at entry, and the presence of asbestosis at follow-up. The FVC level was significantly related to pack-years of smoking during the follow-up, cumulative asbestos exposure at entry, asbestosis and pleural thickening at follow-up, and body mass index at entry. Asbestos exposure was not associated with increasing rates of FEV(1) and FVC decline. However, FEV(1) regression slopes with age, estimated by terciles of cumulative exposure, showed significant differences. Combined effects of smoking and exposure conferred further acceleration in lung function decline. CONCLUSIONS: Occupational exposure in asbestos-cement industry was a risk factor for increased lung function decline. The effect seems to be mostly concentrated during the working period. Smoking and exposure had synergic effects.

COPD causation and workplace exposures: an assessment of agreement among expert clinical raters.

BACKGROUND: Although occupational exposure is a known risk factor for Chronic Obstructive Pulmonary Disease (COPD), it is difficult to identify specific occupational contributors to COPD at the individual level to guide COPD prevention or for compensation. The aim of this study was to gain an understanding of how different expert clinicians attribute likely causation in COPD. METHODS: Ten COPD experts and nine occupational lung disease experts assigned occupational contribution ratings to fifteen hypothetical cases of COPD with varying combinations of occupational and smoking exposures. Participants rated the cause of COPD as the percentage contribution to the overall attribution of disease for smoking, occupational exposures and other causes. RESULTS: Increasing pack-years of tobacco smoking was associated with significantly decreased proportional occupational causation ratings. Increasing weighted occupational exposure was associated with increased occupational causation ratings by 0.28% per unit change. Expert background also contributed significantly to the proportion of occupational causation rated, with COPD experts rating on average a 9.4% greater proportion of occupational causation per case. CONCLUSION: Our findings support the notion that respiratory physicians are able to assign attribution to different sources of causation in COPD, taking into account both smoking and occupational histories. The recommendations on whether to continue to work in the same job also differ, the COPD experts being more likely to recommend change of work rather than change of work practice.

Long-term exposure to silica dust and risk of total and cause-specific mortality in Chinese workers: a cohort study.

BACKGROUND: Human exposure to silica dust is very common in both working and living environments. However, the potential long-term health effects have not been well established across different exposure situations. METHODS AND FINDINGS: We studied 74,040 workers who worked at 29 metal mines and pottery factories in China for 1 y or more between January 1, 1960, and December 31, 1974, with follow-up until December 31, 2003 (median follow-up of 33 y). We estimated the cumulative silica dust exposure (CDE) for each worker by linking work history to a job-exposure matrix. We calculated standardized mortality ratios for underlying causes of death based on Chinese national mortality rates. Hazard ratios (HRs) for selected causes of death associated with CDE were estimated using the Cox proportional hazards model. The population attributable risks were estimated based on the prevalence of workers with silica dust exposure and HRs. The number of deaths attributable to silica dust exposure among Chinese workers was then calculated using the population attributable risk and the national mortality rate. We observed 19,516 deaths during 2,306,428 person-years of follow-up. Mortality from all causes was higher among workers exposed to silica dust than among non-exposed workers (993 versus 551 per 100,000 person-years). We observed significant positive exposure-response relationships between CDE (measured in milligrams/cubic meter-years, i.e., the sum of silica dust concentrations multiplied by the years of silica exposure) and mortality from all causes (HR 1.026, 95% confidence interval 1.023-1.029), respiratory diseases (1.069, 1.064-1.074), respiratory tuberculosis (1.065, 1.059-1.071), and cardiovascular disease (1.031, 1.025-1.036). Significantly elevated standardized mortality ratios were observed for all causes (1.06, 95% confidence interval 1.01-1.11), ischemic heart disease (1.65, 1.35-1.99), and pneumoconiosis (11.01, 7.67-14.95) among workers exposed to respirable silica concentrations equal to or lower than 0.1 mg/m(3). After adjustment for potential confounders, including smoking, silica dust exposure accounted for 15.2% of all deaths in this study. We estimated that 4.2% of deaths (231,104 cases) among Chinese workers were attributable to silica dust exposure. The limitations of this study included a lack of data on dietary patterns and leisure time physical activity, possible underestimation of silica dust exposure for individuals who worked at the mines/factories before 1950, and a small number of deaths (4.3%) where the cause of death was based on oral reports from relatives. CONCLUSIONS: Long-term silica dust exposure was associated with substantially increased mortality among Chinese workers. The increased risk was observed not only for deaths due to respiratory diseases and lung cancer, but also for deaths due to cardiovascular disease. Please see later in the article for the Editors' Summary.

Combined effect of lung function level and decline increases morbidity and mortality risks.

Lung function level and decline are each predictive of morbidity and mortality. Evaluation of the combined effect of these measurements may help further identify high-risk groups. Using Copenhagen City Heart Study longitudinal spirometry data (n = 10,457), 16-21 year risks of chronic obstructive pulmonary disease (COPD) morbidity, COPD or coronary heart disease mortality, and all-cause mortality were estimated from combined effects of level and decline in forced expiratory volume in one second (FEV(1)). Risks were evaluated using Cox proportional hazards models for individuals grouped by combinations of baseline predicted FEV(1) and quartiles of slope. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using stratified analysis by gender, smoking status, and baseline age (≤45 and >45). For COPD morbidity, quartiles of increasing FEV(1) decline increased HRs (95 % CI) for individuals with FEV(1) at or above the lower limit of normal (LLN) but below 100 % predicted, reaching 5.11 (2.58-10.13) for males, 11.63 (4.75-28.46) for females, and 3.09 (0.88-10.86) for never smokers in the quartile of steepest decline. Significant increasing trends were also observed for mortality and in individuals with a baseline age ≤45. Groups with 'normal' lung function (FEV(1) at or above the LLN) but excessive declines (fourth quartile of FEV(1) slope) had significantly increased mortality risks, including never smokers and individuals with a baseline age ≤45.

Health outcomes associated with lung function decline and respiratory symptoms and disease in a community cohort.

BACKGROUND: In workplace respiratory disease prevention, a thorough understanding is needed of the relative contributions of lung function loss and respiratory symptoms in predicting adverse health outcomes. METHODS: Copenhagen City Heart Study respiratory data collected at 4 examinations (1976-2003) and morbidity and mortality data were used to investigate these relationships. With 15 or more years of follow-up for a hospital diagnosis of chronic obstructive pulmonary disease (COPD) morbidity, COPD or coronary heart disease (CHD) mortality, and all-cause mortality, risks for these outcomes were estimated in relation to asthma, chronic bronchitis, shortness of breath, and lung function level at examination 2 (1981-1983) or lung function decline established from examinations 1 (1976-1978) to 2 using 4 measures (FEV(1) slope, FEV(1) relative slope, American College of Occupational and Environmental Medicine's Longitudinal Normal Limit [LNL], or a limit of 90 milliliters per year [ml/yr]). These risks were estimated by hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, height-adjusted baseline forced expiratory volume in 1 second (FEV(1)/height(2)), and height. RESULTS: For COPD morbidity, the increasing trend in the HR (95% CI) by quartiles of the FEV(1) slope reached a maximum of 3.77 (2.76-5.15) for males, 6.12 (4.63-8.10) for females, and 4.14 (1.57-10.90) for never-smokers. Significant increasing trends were also observed for mortality, with females at higher risk. CONCLUSION: Lung function decline was associated with increased risk of COPD morbidity and mortality emphasizing the need to monitor lung function change over time in at-risk occupational populations.

Effect of occupational exposures on decline of lung function in early chronic obstructive pulmonary disease.

RATIONALE: Several occupational exposures adversely affect lung function. OBJECTIVES: This study reports the influence of continued occupational dust and fume exposures on the rate of decline of lung function in participants with early chronic obstructive pulmonary disease (COPD) studied in a population-based study. METHODS: Subjects consisted of 5,724 participants in the Lung Health Study, a multicenter study of smoking cessation and anticholinergic bronchodilator administration in smokers with early COPD (3,592 men; 2,132 women). Average post-bronchodilator FEV1 at entry was 78.4% predicted for men and 78.2% predicted for women; all participants had an FEV1/FVC ratio less than 0.70. MEASUREMENTS AND MAIN RESULTS: Participants underwent a baseline evaluation and five annual follow-up assessments, including questionnaires and spirometry. The effect of ongoing dust or fume exposure on FEV1 in each follow-up year was statistically evaluated with a mixed-effects regression model, which was adjusted for FEV1 at entry, age, airway responsiveness to methacholine, baseline smoking intensity, and time-varying (yearly) smoking status during each follow-up year. In men with early COPD, each year of continued fume exposure was associated with a 0.25% predicted reduction in post-bronchodilator FEV1% predicted. Continued smoking and airway hyperresponsiveness were also associated with reduction in FEV1 during each year of follow-up in both men and women. Statistically significant effects of dust exposure on the rate of decline were not found, nor were effects of fume exposure noted in women. CONCLUSIONS: These results suggest a need for secondary prevention by controlling occupational fume exposures.

Decline in lung function and mortality: implications for medical monitoring.

AIM: To investigate the risk of death associated with selected cut-off points for rate of decline of forced expiratory volume in one second (FEV(1)). METHODS: Mortality rates of a cohort of 1730 coal miners who had performed two pulmonary function tests 12.8 years apart were followed up for an additional 12 years. Based on previous studies, cut-off points for FEV(1) rate of decline (ml/year) were selected as 30, 60 and 90 ml/year. Cox proportional hazard regression was used to estimate multivariate risk ratio of death in each category. RESULTS: The risk ratios (compared to "below 30 ml/year") were 1.39 (95% CI 0.99 to 1.97) in the "60 to less than 90 ml/year" category and 1.90 (95% CI 1.32 to 2.76) in the "90 ml/year and above" category. Rates of decline above 90 ml/year were consistently related to excess mortality. In non-smokers and those with neither restrictive nor obstructive patterns at the first survey, rates of decline above 60 ml/year were significantly associated with increased mortality. CONCLUSIONS: Risk of death increases in individuals with rates of decline above about 60 ml/year and is statistically significant with declines of 90 ml/year or more. These results should be useful to healthcare providers in assessing lung function declines observed in individuals.

Limits of longitudinal decline for the interpretation of annual changes in FEV1 in individuals.

OBJECTIVE: Spirometry-based screening programmes often conduct annual assessment of longitudinal changes in forced expiratory volume in 1 second (FEV1) to identify individuals with excessive rates of decline. Both the American Thoracic Society (ATS) and the American College of Occupational and Environmental Medicine (ACOEM) recommend a reference limit value of > or =15% for excessive annual decline. Neither the ATS nor the ACOEM adjust this limit for the precision of the existing spirometry data. The authors propose an improved method of defining the reference limit of longitudinal annual FEV1 decline (LLD) based on the precision of the spirometry data. METHOD: The authors used data from four monitoring programmes and measured their data precision using a pair-wise within-person variation statistic. They then derived programme- and gender-specific absolute and relative LLD values and validated these against the 95th percentiles for observed yearly changes in FEV1. RESULTS: The relative limit for annual decline was more practical than the absolute limit as it adjusted for gender differences in the magnitude of FEV1. The programme-specific relative limit values were in good agreement with 95th percentiles for year-to-year FEV1 changes and ranged from 6.6% to 15.8%. For individuals with COPD and bronchial hyperreactivity the 95th percentiles for year-to-year changes were about 15% and higher. CONCLUSIONS: The relative longitudinal limit for annual FEV1 decline based upon precision of measurements is valid and can be generalised to different gender and population groups. A relative limit of approximately 10% appears appropriate for good quality workplace monitoring programmes, whereas a limit of about 15% appears appropriate for clinical evaluation of individuals with an obstructive airway disease. Computer software based on the method described is available from the corresponding author.

Longitudinal limits of normal decline in lung function in an individual.

OBJECTIVES: The objectives of this study were to propose a method of calculating longitudinal limits of normal decline (LND) in forced expiratory volume in 1 second to identify individuals with an excessive decline in lung function and to compare the method with other published LND methods. METHODS: We used longitudinal data from 11 workplace-based spirometric monitoring programs conducted from 1987 to 2001 on 12,729 workers to evaluate effectiveness of each LND method in identifying a "true" excessive decline in forced expiratory volume in 1 second defined using two criteria: slope >60 mL/year or >90 mL/year estimated over 5 or more years of follow up. RESULTS: In comparison to the LND proposed by the American College of Occupational and Environmental Medicine, the proposed method had 5.0 to 2.7 times higher sensitivity over years 1 through 5 for the >60-mL/yr criterion. CONCLUSIONS: The proposed LND method was more effective than the other methods for identifying excessive declines.

Change in prevalence of restrictive lung impairment in the U.S. population and associated risk factors: the National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 2007-2010.

BACKGROUND: Data for the U.S adult population from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate risk factors for a restrictive pattern on spirometry and estimate the change in its prevalence from the 1988-1994 to 2007-2010 sampling periods. Several previous epidemiologic studies used the Global Initiative for Chronic Obstructive Lung Disease fixed forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 0.70 criteria for classifying restrictive pattern rather than the age-defined American Thoracic Society (ATS)/European Respiratory Society (ERS) lower limit of normal (LLN) criteria, which may lead to misclassification. METHODS: Spirometry measurements from NHANES data for the 1988-1994 and 2007-2010 periods were analyzed to estimate the age-standardized prevalence of a restrictive pattern on spirometry and the change in prevalence over time for adults aged 20-79. A restrictive pattern was defined based on ATS/ERS LLN criteria as FEV1/FVC > LLN and FVC < LLN, and a moderate to more severe restrictive pattern was further evaluated using FEV1 < 70% predicted. The associations between demographic and other individual risk factors for restrictive lung impairment were examined using multivariable logistic regression models for the two consecutive time periods. RESULTS: The overall age-standardized prevalence of restrictive pattern decreased significantly from 7.2% (1988-1994) to 5.4% (2007-2010) (p = 0.0013). The prevalence of moderate to more severe restrictive pattern also decreased significantly from 2.0% to 1.4% (p = 0.023). Factors positively associated with restrictive pattern on spirometry included age, female sex, white race, lower education, former and current smoking, and comorbidities including doctor-diagnosed cardiovascular disease, doctor-diagnosed diabetes, and abdominal obesity. CONCLUSIONS: The overall prevalence of restrictive pattern and moderate to more severe restrictive pattern decreased between the 1988-1994 and 2007-2010 survey periods despite a population increase in the proportion of comorbidities associated with restrictive pattern (i.e. diabetes and abdominal obesity). This suggests a decline in individual risk factors for restrictive pattern and a need for future research.

New-onset asthma associated with exposure to 3-amino-5-mercapto-1,2,4-triazole.

OBJECTIVE: The authors conducted an investigation of a cluster of eight new-onset asthma cases identified in a chemical plant through the Sentinel Event Notification Systems for Occupational Risks (SENSOR) program. METHODS: Workplace investigation involved interviews with the asthma cases, review of medical records, and medical and industrial hygiene surveys in the plant. RESULTS: Altogether, 11 work-related asthma cases were identified among the plant workers-approximately 10% of the workers exposed to the potential causative agents: 3-amino-5-mercapto-1,2,4-triazole (AMT) or N-(2,6-difluorophenyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide (DE-498; trade name Flumetsulam). Of these cases, six had physician-diagnosed occupational asthma (OA) based on work-related respiratory symptoms and nonspecific bronchial hyperresponsiveness (NSBH), and of these, three had work-related expiratory peak flow changes. CONCLUSIONS: The findings of this investigation, together with findings from concurrent animal studies, suggest that this outbreak of new-onset asthma was associated with exposure to AMT. CLINICAL SIGNIFICANCE: A cluster of eight new-onset asthma cases was identified in a chemical plant through the SENSOR program. Subsequent workplace investigation identified AMT, used in the production of a herbicide N-(2,6-difluorophenyl)-5-methyl- [1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide, as the most likely causal agent.