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Major advances in diagnosis and treatment have emerged for hypertrophic cardiomyopathy (HCM), largely in major tertiary referral centers dedicated to this disease. Whether these therapeutic benefits are confined to patients in such highly selected cohorts, or can be implemented effectively in independent regional or community-based populations is not generally appreciated. We assessed management and clinical outcomes in a non-referral HCM center (n = 214 patients) in Eastern Pennsylvania. Over a 6.0 ± 3.2-year follow-up, the HCM-related mortality rate was 0.1% per year attributed to a single disease-related death, in a 49-year-old man with end-stage heart failure, ineligible for heart transplant. Fifteen patients (7%) with prophylactically placed implantable cardioverter-defibrillators (ICDs) experienced appropriate therapy terminating life-threatening ventricular tachyarrhythmias. In 23 other patients (11%; 5%/year), heart failure due to left ventricular outflow obstruction was reversed by surgical septal myectomy (n = 20) or percutaneous alcohol septal ablation (n = 3). This regional HCM cohort was similar to a comparison tertiary center referral population in terms of HCM-mortality: 0.1%/year vs 0.3%/year (p = 0.3) and ICD therapy (31% vs 16% of primary prevention implants), although more frequently with uncomplicated benign clinical course (62% vs 46%; p <0.01). In conclusion, effective contemporary HCM management strategies and outcomes in referral-based HCM centers can be successfully replicated in regional and/or non-referral settings. Therefore, HCM is now a highly treatable disease compatible with normal longevity when assessed in a variety of clinical venues not limited to tertiary centers., (Copyright © 2020. Published by Elsevier Inc.)

Amniotic fluid embolism is a rare but devastating condition associated with a very high rate of morbidity and mortality. The treatment has traditionally been aggressive supportive care. We report a case of a term pregnant woman with complete cardiovascular collapse secondary to a paradoxical amniotic fluid embolism. The embolism was seen on transesophageal echocardiogram during an emergency Cesarean section as a free-floating interatrial clot through a patent foramen ovale. She was subsequently and successfully treated with immediate cardiopulmonary bypass, thromboembolectomy, and closure of the patent foramen ovale., (Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies have suggested increased renal complications and long-term mortality with aprotinin use in coronary artery bypass grafting (CABG) patients. However, these studies have been criticized for including multiple centers and different dosing strategies. We analyzed prospectively collected registry data from a single center hospital utilizing a full-dose aprotinin regimen to evaluate if aprotinin was associated with increased mortality and adverse outcomes compared with Amicar., Methods: Data were prospectively collected from 1994 to 2006 at a teaching hospital. Long-term mortality was collected from a Social Security database. To account for differences between aprotinin and Amicar-treated patients, a propensity score was generated and propensity-stratified multivariate model for mortality were performed., Results: Compared with Amicar-treated patients (n = 1,830), aprotinin-treated patients (n = 1,507) were older, more often female, had lower creatinine clearance, and more baseline risk factors. Blood loss was lower in aprotinin-treated patients (median 715 mL vs 918 mL, p < 0.001). Postoperative renal failure was significantly higher in aprotinin patients (6.2% vs 2.7%, p < 0.001). At median 5.4-year follow-up (up to 12.2 years), aprotinin-treated patients had higher mortality versus Amicar-treated patients (Kaplan-Meier failure rates 43.5% vs 23.7% at 8 years, p < 0.0001). In a propensity-stratified model with multivariate adjustment, aprotinin remained associated with increased mortality (hazard ratio 1.62, 95% CI 1.39 to 1.90, p < 0.001). There was a stepwise relationship between weight-based aprotinin dose and mortality (p-trend < 0.001)., Conclusions: Among patients undergoing CABG in this registry, aprotinin use was associated with increased renal failure and higher mortality through 12 years in a propensity-stratified analysis. The increased mortality may be related to higher concentrations of aprotinin received.

Background: Use of saphenous vein graft (SVG) radiographic markers has been associated with shorter cardiac catheterization procedure times and reduced contrast agent volume for postoperative coronary artery bypass graft (CABG) catheterizations. Use of such markers is varied and often operator-dependent, as the effect of SVG markers has not been fully evaluated. The goal of the present analysis was to evaluate the association of SVG markers with clinical outcomes and graft patency., Methods: Data were drawn from the Project of Ex-vivo Vein Graft Engineering via Transfection (PREVENT) IV trial of patients undergoing CABG at 107 hospitals across the United States. Repeat angiography was performed within 12 to 18 months after CABG. The SVG markers were used at the discretion of the surgeon and were identified on the follow-up angiogram as any device used to mark the ostium, regardless of shape., Results: The SVG markers were present in 51.2% of evaluable patients (910 of 1,778) and 52.3% of SVGs (2,228 of 4,240). Among patients with totally occluded SVGs (n = 911), visual identification of the SVG was obtained more frequently in those with an SVG marker (90.7% vs 72.1%, p < 0.001). The SVG stenosis 70% or greater at follow-up did not differ by use of markers (25.8% with marker vs 24.4% without marker, p = not significant). These findings were also consistent in ostial lesions (n = 942). Long-term death or myocardial infarction (MI) was similar by use of marker. The perioperative CABG MI was higher in patients with SVG markers (10.1% vs 5.5%, odds ratio adjusted 1.86, p = 0.021)., Conclusions: Saphenous vein graft radiographic markers were associated with higher rates of direct visualization of totally occluded SVGs without an adverse effect on graft patency or long-term clinical outcomes, but the association of SVG markers with increased perioperative CABG MI warrants further examination.

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.

Background: Exposure to cotton dust is known to cause chronic airway obstruction, but there is little information on whether the obstructive impairment is reversible after the exposure stops., Methods: Longitudinal changes in lung function were evaluated among 429 cotton textile workers and 449 silk workers in Shanghai, China, beginning in 1981. Both active and retired workers were tested every 4 to 6 years for 15 years., Results: Overall, cotton workers had greater annual declines in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). Compared with active workers, retired cotton workers had lower annual loss of FEV1, although the retired workers had a greater loss during their active employment than the currently active workers. No such trends were detected in silk workers. Annual declines in FEV1 in retired cotton workers were smaller with increasing time since retirement. Multivariate analysis showed that retirement was a substantial contributing factor for improved FEV1 and FVC in the cotton workers, especially among those who did not smoke. Correspondingly, remission of airflow obstruction, defined as a ratio of FEV1 and FVC of less than 70%, was more common in retirees than in the active workers, and more common in nonsmokers than in smokers., Conclusion: Chronic airway obstruction related to long-term exposure to cotton dust may be partially reversible after the exposure ceases, although lung function does not return to the level found in unexposed workers.

The aim of this study was to determine characteristics of personal exposure to inorganic and organic dust during manual harvest operations of California citrus and table grapes. Personal exposures to inhalable dust and respirable dust were measured five times over a 4-month period of harvesting season. We analyzed components of the dust samples for mineralogy, respirable quartz, endotoxin, and total and culturable microorganisms. Workers manually harvesting were exposed to a complex mixture of inorganic and organic dust. Exposures for citrus harvest had geometric means of 39.7 mg/m(3) for inhalable dust and 1.14 mg/m(3) for respirable dust. These exposures were significantly higher than those for table grape operations and exceeded the threshold limit value for inhalable dust and respirable quartz. Exposures for table grape operations were lower than the threshold limit value, except inhalable dust exposure during leaf pulling. Considered independently, exposures to inhalable dust and respirable quartz in citrus harvest may be high enough to cause respiratory health effects. The degree of vigorous contact with foliage appeared to be a significant determining factor of exposures in manual harvesting.

Aims: To determine chronic effects of long term exposure to cotton dust and endotoxin on incidence of respiratory symptoms and the effect of cessation of exposure., Methods: Respiratory health in 429 Chinese cotton textile workers (study group) and 449 silk textile workers (control group) was followed prospectively from 1981 to 1996. Byssinosis, chest tightness, and non-specific respiratory symptoms were assessed by means of identical standardised questionnaires at four time points. Exposures to cotton dust and endotoxin were estimated using area samples collected at each survey. Incidence and persistence of symptoms were examined in relation to cumulative exposure and exposure cessation using generalised estimating equations (GEE)., Results: Among cotton workers, the cumulative incidence of byssinosis and chest tightness was 24% and 23%, respectively, and was significantly more common in smokers than in non-smokers. A high proportion of symptoms was found to be intermittent, rather than persistent. Among silk workers, no typical byssinosis was identified; the incidence of chest tightness was 10%. Chronic bronchitis, cough, and dyspnoea were more common and persistent in the cotton group than in the silk group. Significantly lower odds ratios for symptoms were observed in cotton workers who left the cotton mills; risk was also related to years since last worked. Multivariate analysis indicated a trend for higher cumulative exposure to endotoxin in relation to a higher risk for byssinosis., Conclusion: Chronic exposure to cotton dust is related to both work specific and non-specific respiratory symptoms. Byssinosis is more strongly associated with exposure to endotoxin than to dust. Cessation of exposure may improve the respiratory health of cotton textile workers; the improvement appears to increase with time since last exposure.

Background: Quality improvement in health care, which relies on appropriate strategies to evaluate and compare provider performance, has spawned the propagation of many public report cards or provider profiles for cardiac surgery. These risk-adjusted prediction models allow for the computation of a provider's expected outcome event rate compared with observed outcome events. The aim of this study was to assess the accuracy and reliability of 5 risk-adjusted predictive models for mortality in an independent population of patients in a community hospital who underwent coronary artery bypass graft surgery., Methods: Five nonproprietary models were selected for evaluation (Parsonnet, Canadian, Cleveland, New York, and the Northern New England)., Results: The C-statistic for the 5 models was 0.752, 0.693, 0.748, 0.735, and 0.722 for the Parsonnet, Canadian, Cleveland, New York, and Northern New England models respectively. The H-L c2 calibration statistics were 4.948, P =.763; 1.616, P =.899; 11.96, P =.035; 10.23, P =.249; and c2 = 12.14, P =.145 for the Parsonnet, Canadian, Cleveland, New York, and Northern New England models respectively., Conclusions: Comparing hospital-specific or surgeon-specific mortality/morbidity rates will remain a challenge. This analysis reaffirms the concept of risk-adjusting outcomes and emphasizes the importance of the risk-adjustment process for CABG surgery in a community hospital.

Background: Public "report cards" for cardiac surgery have been freely available from a variety of sources. These risk-adjusted indices serve as a means of benchmarking outcomes performances, allowing comparisons of outcomes between surgical programs, and quantifying quality improvement programs. We examined two alternative strategies for using previously developed risk-adjusted mortality models in a community hospital: (1) using the model "off the shelf" (OTS) and (2) recalibrating the existing model (RM) to fit the institution-specific population., Methods: Six OTS models were used: Parsonnet (PA), Canadian (CA), Cleveland (CL), Northern New England (NNE), New York (NY), and New Jersey (NJ). The RM models were created by each model's independent variables and definitions and adjusting the weighting with logistic regression methods. The accuracy, the C statistic, and the precision of each model were assessed for in-hospital mortality. We compared the OTS version of each model to the RM version with methods detailed by Hanley and McNeil., Results: The RM C statistic was improved for all risk-adjusted models, most notably in the statistical improvement seen in the PA (0.053 improvement) and NJ (0.052 improvement) indices. Statistical gains in precision were also seen in the RM models for the PA, CL, and NNE indices. Conversely, one model, the CA model, was more poorly calibrated in the RM model compared with the OTS model, despite an improved C statistic (0.062)., Conclusions: The RM strategy provides institution-explicit models that demonstrate a higher degree of accuracy and precision than the OTS models.

A 55-year-old woman underwent coronary artery bypass grafting and mitral valve repair using intraoperative transesophageal echocardiography (TEE). Postoperatively she had hemodynamic instability associated with an increase in abdominal size and a drop in hemoglobin. At laparotomy, a splenic hilar laceration was discovered, which was presumed to be associated with intraoperative TEE. She underwent emergent splenectomy. This case demonstrates that although rare, serious complications can occur with TEE.

To evaluate the chronic effects of exposure to cotton dust, a 15-yr follow-up study in cotton textile workers was performed in Shanghai, China from 1981 to 1996. Testing occurred four times during the 15-yr period. The achieved follow-up rates were 76-88% of the original 447 cotton textile workers, and 70-85% of the original 472 silk textile workers (as a control group). Identical questionnaires, equipment, and methods were used throughout the study. The prevalence of byssinosis increased over time in cotton workers, with 15.3% at the last survey versus 7.6% at the baseline, whereas no byssinosis was found in silk workers. More workers in the cotton group consistently reported symptoms than in the silk group, although symptom reporting varied considerably from survey to survey. Cotton workers had small, but significantly greater, adjusted annual declines in FEV(1) and FVC than did the silk workers. Years worked in cotton mills, high level of exposure to endotoxin, and across-shift drops in FEV(1) were found to be significant determinants for longitudinal change in FEV(1), after controlling for appropriate confounders. Furthermore, there were statistically significant associations between excessive loss of FEV(1) and byssinosis, chest tightness at work, and chronic bronchitis in cotton workers. Workers who consistently (three or four of the surveys) reported byssinosis or chest tightness at work had a significantly greater 15-yr loss of FEV(1). We conclude that long-term exposure to cotton dust is associated with chronic or permanent obstructive impairments. Consistent reporting of respiratory symptoms, including byssinosis and chest tightness at work, is of value to predict the magnitude and severity of chronic impairments in textile workers.

Background: To evaluate the relationship between long-term exposure to cotton dust and Gram-negative bacterial endotoxin on lung function, we conducted an 11-year follow-up study of cotton textile workers in Shanghai, China., Methods: Workers at a nearby silk-thread manufacturing mill were used as a referent population. Ninety percent of the original cohort of 445 cotton and 467 silk textile workers--both active and retired--were identified for testing in the 11th year. Questionnaires and spirometric testing were performed, as well as cotton dust and endotoxin sampling at three points over the 11-year follow-up period: at baseline, at Year 5, and at Year 11. After excluding deaths and subjects on sick-leave, 84% of the original cohort had complete health and environmental data., Results: The data were reanalyzed using generalized estimating equations feedback model which allow for subject transfer over time between work areas, various exposure levels to dust and endotoxin, and FEV1. Cotton workers had a larger loss of FEV1 during the first 5 years of study (-40 mls/yr) as compared with the second 6 years of follow-up (-18 mls/yr). During the same periods, the average decline among silk workers was slightly higher in the first period, but was more consistent (-30 mls/yr vs. -27 mls/yr), and these differences could not be explained by worker selection or dropout. When cumulative exposure to dust and endotoxin were estimated and used in a multivariate model (GEE) for FEV1 loss, cumulative dust, but not endotoxin, was associated with 11-year loss in FEV1 after adjustments for confounders. There was evidence of feedback between dust-exposure levels and FEV1, indicating the existence of a healthy-worker survivor effect. After accounting for a healthy-worker survivor effect, we found a significant relationship between dust exposure and FEV1 decline., Conclusions: Our results suggest that cotton dust is more strongly associated with chronic airflow limitation than associated endotoxins. Further work is needed to clarify potential reversibility after cessation of exposure, and the relative contributions of dust, endotoxin, and tobacco to chronic respiratory impairment in cotton and other vegetable-exposed workers.

Environmental surveys were conducted in 85 barns, predominantly dairy, in central Wisconsin to characterize exposures to organic dusts and dust constituents from routine barn work. Environmental analytes included airborne dusts (total, inhalable inlet, and respirable), particle size distributions, endotoxins, total spore and bacteria counts, viable bacteria and fungi, histamine, cow urine antigen, mite antigen, ammonia, carbon dioxide, and hydrogen sulfide. The geometric mean (GM) concentration of airborne dusts include area total, 0.74 mg/m3; personal inhalable inlet, 1.78 mg/m3, and area respirable, 0.07 mg/m3. Viable bacteria and fungi, spores, endotoxins, histamine, cow urine antigen, and mite antigen were quantifiable constituents of these organic dusts and potential respiratory exposure hazards from routine dairy barn work. Endotoxin concentrations from the inhalable inlet samples ranged from 25.4 endotoxin units per cubic meter of air (EU/m3) to 34,800 EU/m3. The GM endotoxin concentration from these samples, 647 EU/m3, exceeds estimated threshold exposure levels for respiratory health effects. Ammonia was a common irritant quantified in most dairy barns. There were significant correlations between the concentrations of organic dusts and certain dust constituents, although in most instances these correlations were not strong. These sampling results demonstrate the complex nature of organic dusts and provide quantitative description of the exposures to toxic and immunogenic dust constituents during routine barn work.

Study Objective: To determine if inhalation of grain sorghum dust in the laboratory would cause neutrophilic upper and lower respiratory tract inflammation in human volunteers, as well as systemic signs of illness., Design: Prospective., Setting: University of Nebraska Medical Center., Participants: Thirty normal volunteers., Interventions: Inhalation challenge with 20 mL of a nebulized solution of filter-sterilized grain sorghum dust extract (GSDE). One group received prednisone, 20 mg for 2 days, prior to the challenge., Measurements and Results: Bronchoscopy with bronchoalveolar lavage (BAL) was performed 24 h after challenge, with samples collected as bronchial and alveolar fractions. Findings included visible signs of airways inflammation, quantified as the bronchitis index. The percentage of bronchial neutrophils was significantly increased in those challenged with GSDE vs the control solution, Hanks' balanced salt solution (40.3 +/- 4.5% vs 14.3 +/- 5.1%, p < or = .01). Similar findings were seen in the alveolar fraction. Pretreatment with corticosteroids did not prevent the rise in neutrophils recovered by BAL. Peripheral blood neutrophils were also increased in volunteers challenged with the grain dust extract. To explain the increase in peripheral blood neutrophil counts, the capacity of the peripheral blood neutrophils to migrate in chemotaxis experiments was examined. The results demonstrate an increase in peripheral blood neutrophils and an increase in chemotactic responsiveness., Conclusions: Inhalation challenge with a grain dust extract causes respiratory tract inflammation and a peripheral blood neutrophilia. One reason for this may be an increase in activated peripheral blood neutrophils.

To identify the role of endotoxin in grain dust-induced lung disease, we conducted a population-based, cross-sectional investigation among grain handlers and postal workers. The study subjects were selected by randomly sampling all grain facilities and post offices within 100 miles of Iowa City. Our study population consisted of 410 grain workers and 201 postal workers. Grain workers were found to be exposed to higher concentrations of airborne dust (p = 0.0001) and endotoxin (p = 0.0001) when compared with postal workers. Grain workers had a significantly higher prevalence of work-related (cough, phlegm, wheezing, chest tightness, and dyspnea) and chronic (usual cough or phlegm production) respiratory symptoms than postal workers. Moreover, after controlling for age, gender, and cigarette smoking status, work-related respiratory symptoms were strongly associated with the concentration of endotoxin in the bioaerosol in the work setting. The concentration of total dust in the bioaerosol was marginally related to these respiratory problems. After controlling for age, gender, and cigarette smoking status, grain workers were found to have reduced spirometric measures of airflow (FEV1, FEV1/FVC, and FEF25-75) and enhanced airway reactivity to inhaled histamine when compared with postal workers. Although the total dust concentration in the work environment appeared to have little effect on these measures of airflow obstruction, higher concentrations of endotoxin in the bioaerosol were associated with diminished measures of airflow and enhanced bronchial reactivity. Our results indicate that the concentration of endotoxin in the bioaerosol may be particularly important in the development of grain dust-induced lung disease.

To assess whether working in a swine confinement facility causes an excess or accelerated decline in lung function, we conducted a population-based study to evaluate the determinants of longitudinal changes in airflow in a population of swine confinement operators. Spirometric measures of lung function were compared between swine confinement operators (N = 168) and neighborhood farmer control subjects (N = 127). Study subjects were randomly selected from a cohort of swine confinement operators in eastern Iowa. The control farming population was matched by geographic location, age, and sex to the swine confinement operators. On average, the follow-up time was approximately 2 yr, with a range of follow-up between 56 and 1,900 d. Although swine confinement operators and neighborhood farmers had similar demographic characteristics (age, gender, racial background, smoking history, and atopy status), swine confinement operators tended to have less farming experience and were more extensively followed (more measures of lung function and longer periods of observation) than the neighborhood farmer control group. Swine confinement operators were also exposed to higher environmental dust concentrations and other irritants than the farmer control subjects. Interestingly, the cross-sectional data indicated that swine confinement operators tended to have slightly lower measures of airflow and greater workshift declines in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and mid-expiratory flow (FEF25-75) than the neighborhood farmer control group.(ABSTRACT TRUNCATED AT 250 WORDS)

We conducted an assessment of respiratory health status including questionnaire and spirographic measurements in 54 male swine producers age 36.3 +/- 11.1 years (mean +/- SD) who worked an average of 10.7 +/- 6.3 years in the industry and spent 4.7 +/- 2.1 hours per day in the swine barns, and we also measured atmospheric contaminants including carbon dioxide, ammonia, total dust, respirable dust, and airborne endotoxin. Mean atmospheric dust contaminant levels were as follows: carbon dioxide, 2632 +/- 807 ppm; ammonia, 11.3 +/- 4.2 ppm; total dust, 2.93 +/- 0.92 mg/m3; respirable dust, 0.13 +/- 0.05 mg/m3; and endotoxin, 11,332 +/- 13,492 endotoxin units/m3. Of these, endotoxin related to forced vital capacity (P < .05) and endotoxin x hours per day was related to forced vital capacity (P < .05) and to forced expiratory volume in 1 second (P = .06). Respiratory symptoms and lung function studies did not relate to categories of low, medium, and high exposure to respirable dust. However, categories of endotoxin (available on 46 workers) related to respiratory symptoms (cough, P = .02; chronic bronchitis, P = .06; and to forced vital capacity, P < .01). These data suggest that respiratory health status relates to endotoxin levels but not to dust level exposures in the presence of low dust levels and indicates that control measures should include endotoxin as well as dust control.

Gram-negative bacteria and their endotoxins have been shown to cause profound changes in the structure and function of mammalian lungs. Airborne exposures in humans have resulted in bronchoconstriction and symptoms of chest tightness and dyspnea. Cotton dust is often heavily contaminated and endotoxin has been postulated to be the agent in cotton dust which is responsible for the byssinosis syndrome. Previous studies of cotton dust have revealed variable amounts of contamination by bacterial endotoxin, with the variability determined in large part by botanical and climatic characteristics. We report here the results of an environmental study conducted in a cotton mill located in the tropics of Central America using locally grown cotton. Results indicate that airborne endotoxin was present in all yarn preparation and weaving areas and ranged from a low of 18 EU/m3 in weaving to a high of 3138 EU/m3 in opening areas. Airborne levels and the amount of endotoxin per nanogram of dust were not higher than values obtained in temperate climates.

Exposure to cotton dust is known to cause both acute and chronic respiratory illness. A specific pattern of symptoms called byssinosis is well described to occur among workers in the cotton processing (e.g., yarn preparation) industry. Recent studies have implicated Gram-negative bacterial endotoxin as one of the agents responsible for acute, and possibly chronic, respiratory illness. Laboratory experiments using a model cardroom have found poor correlations between airborne dust and associated endotoxin. This study reports the results of vertical elutriated dust and endotoxin levels in 11 work areas of 2 cotton textile mills in 1986 in Shanghai, China. The overall correlation between dust and endotoxin was strong, rs = 0.66 and 0.79 (p < 0.0001) for mills 1 and 2, respectively. The dust-endotoxin correlation was relatively poor in early yarn preparation in the workshops and improved in the later preparation areas. Our findings suggest that in these mill settings, dust and endotoxin levels may be well correlated in most work areas. Therefore, dust may be a useful index for monitoring populations employed in the cotton textile industry throughout the world. Additional field studies need to be performed which consider the various determinants of dust and endotoxin levels.

Three distinct samples collected from a barn in which an outbreak of respiratory problems occurred were examined for possible etiologic agents. No causal relationship could be established from the results of this study; however histamine concentrations as high as 0.5 ng/mg for bulk hay (in the absence of measurable creatinine levels) along with 6138.3 endotoxin units/mg of hay were present in the samples. Both endotoxin and histamine could be recovered from respirable hay dust. The authenticity of the histamine found in the hay was evaluated with high-performance liquid chromatography and radioimmunoassay. Histamine release caused by hay extracts was evaluated with the use of leukocytes from the farmer and a referent. Histamine is known to modulate the immune system, but the role of occupational or environmental exposure to histamine in respiratory disease is unknown.

Symptoms commonly defined as the sick building syndrome were studied in a cross-sectional investigation of 147 office workers in five building areas using a linear-analog self-assessment scale questionnaire to define symptoms at a specific point in time. At the same time, the environment in the breathing zone was characterized by measuring thermal parameters (dry-bulb temperature, relative humidity, air speed, and radiant temperature), volatile organic compounds, respirable suspended particulates, noise and light intensity, and carbon dioxide and carbon monoxide levels. Demographic characteristics of the occupants and building characteristics were recorded. Up to 25% of the variance in regression models could be explained for mucous membrane irritation and central nervous system symptoms. These two symptom groups were related to the concentrations of volatile organic compounds, to crowding, to layers of clothing, and to measured levels of lighting intensity. Chest tightness was also related to lighting intensity. Skin complaints were related only to gender. Gender, age, and education failed to demonstrate a consistent relationship with symptom categories. This study suggests that the sick building syndrome may have specific environmental causes, including lighting and volatile organic compounds.

As part of a multidisciplinary longitudinal approach to assess the roles of airborne cotton dust and endotoxins in affecting the respiratory health of cotton textile workers, this study was designed to quantify the endotoxin contamination of airborne vertically elutriated and total dusts. Yarn preparation areas (opening through fine spinning) were studied at two cotton textile mills which had been studied 5 years previously in Shanghai. People's Republic of China, Filter, with vertically elutriated (VE) or total dusts were mailed to the United States and endotoxin analyses were performed for each filter in duplicate with the quantitative chromogenic modification of the Limulus amebocyte lysate assay. Dusts from all areas of the textile mills contained endotoxins. Endotoxin burdens in VE dusts from the carding area were similar in both milk while the endotoxin contamination of total dust from carding in Mill 1 was over threefold greater than that of total dust from carding in Mill 2. All other areas differed between milk in both VE and total dust endotoxin burdens. Mean endotoxin levels in VE dusts from all areas of both mills were well above the reported threshold of 90 EU/m3 for acute pulmonary function effects in humans. Comparison of selected areas of both mills from the present study with the same work areas from the previous study showed that, in general, the airborne endotoxin burden was higher than levels found 5 years ago in these two mills. The data suggest that even with reduced or unchanged gravimetric dust levels in these two cotton textile mills, airborne endotoxin levels were higher and provided an increased potential for adverse respiratory response in exposed workers.

Fourteen samples of settled dust from two factories processing rice and wheat straw near Shanghai, China, were examined by dilution plating for total bacteria, gram-negative bacteria, thermophilic actinomycetes, and fungi. They were also examined for aflatoxin, endotoxin, and potential to stimulate production of human interleukin 1 beta (IL-1 beta) and to consume complement. The concentrations of total microorganisms were consistently greater than 10(7) CFU/g and ranged from 10(7) to 10(9) CFU/g. In general, the level of microbial contamination was greater in the hay dust samples than in the rice dust samples, with bacteria being the most numerous microorganisms observed followed by molds, thermophilic actinomycetes, and yeasts. The predominant fungi were species of Aspergillus, Cladosporium, Penicillium, Trichosporon, and Cryptococcus. No significant levels of aflatoxin were observed and the isolates of A. flavus examined lack significant aflatoxigenic potential. The levels of microorganisms in these samples, the types of organisms found, and the inflammatory mediators such as endotoxin suggest that workers exposed to these dusts may be at risk for respiratory illness.

The in vitro study of mast cell degranulation utilises the measurement of histamine as a quantitative marker of this process. Histamine is most commonly assayed, following organic extraction, by condensing it with o-phthalaldehyde (OPT) and thereby obtaining a highly fluorescent adduct. A number of variables that might affect the performance of this assay, including assay conditions, stability and purity, were evaluated during the course of developing this assay for use in our laboratory. We observed the stability of OPT-histamine and found it to be very stable at 0 and 25 degrees C, following acidification. Derivatisation conditions and the purity of the leukocyte histamine extract were also assessed, and indicated that derivatisation at low temperatures slows down decay, providing a greater over-all fluorescence intensity. Extraction procedures are necessary, prior to condensation with OPT, to eliminate both positive and negative interfering substances from leukocyte preparations.

Basophil activation studies commonly rely on the measurement of histamine following extraction and condensation to o-phthalaldehyde (OPT) as a quantitative measurement of degranulation. Specificity has long been recognized as a problem with this method. We have described a new high-performance liquid chromatographic method that allows for both a qualitative and a quantitative check of the purity of the OPT-histamine adduct. This method was sensitive (limit of detection = 2.55 pmol) and linear over a wide range (5 to 1000 ng/ml).

Zymogen-stimulated neutrophils release many pre- and non-preformed factors including proteolytic enzymes, oxygen free radicals and arachidonic acid metabolites. Measurement of the histamine concentration of a supernatant fluid commonly employs an organic extraction procedure followed by condensation to o-phthalaldehyde. Diamine oxidase digestion studies and high-performance liquid chromatographic analysis suggest that a factor(s) derived from zymogen-stimulated neutrophils can produce a positive interference in the fluorometric determination of histamine.

Gram-negative bacterial endotoxins are contaminants of dusts from agricultural products. They represent a potential health hazard for farmers working in many different processes. However, the occurrence of endotoxins has not been well characterized in the various farming operations. Therefore, two farming activities with potential for generating airborne endotoxins were studied: 1) chopping of baled corn stalks or straw for bedding in New York State, and 2) oat bin unloading in Alabama. Actual airborne endotoxin levels in dusts obtained during bedding chopper operations far exceeded [90 endotoxin units (EU)/m3] the level at which acute pulmonary function decrements occur in cotton dust-exposed individuals. Endotoxin contamination of laboratory-generated dust from an oat sample likewise exceeded these levels. This study documents the presence of potentially hazardous exposures to endotoxins in two common farm processes, which expands the knowledge of airborne endotoxin exposures on the farm.

Grain dusts contain a variety of materials which are potentially hazardous to the health of workers in the grain industry. Because the characterization of grain dusts is incomplete, we are defining the botanical, chemical, and microbial contents of several grain dusts collected from grain elevators in the Duluth-Superior regions of the U.S. Here, we report certain of the carbohydrate and protein contents of dusts in relation to dust morphology. Examination of the gross morphologies of the dusts revealed that, except for corn, each dust contained either husk or pericarp (seed coat in the case of flax) fragments in addition to respirable particles. When viewed with the light microscope, the fragments appeared as elongated, pointed structures. The possibility that certain of the fragments within corn, settled, and spring wheat were derived from cell walls was suggested by the detection of pentoses following colorimetric assay of neutralized 2 N trifluoroacetic acid hydrolyzates of these dusts. The presence of pentoses together with the occurrence of proteins within water washings of grain dusts suggests that glycoproteins may be present within the dusts. With scanning electron microscopy, each dust was found to consist of a distinct assortment of particles in addition to respirable particles. Small husk fragments and "trichome-like" objects were common to all but corn dust.

The early stages of byssinosis, the chronic lung disorder caused by the inhalation of cotton dust, are characterized by repeated episodes of mild and reversible obstruction of airways on exposure to cotton dust. To define the relation between exposure to endotoxin and the airway response to inhaled cotton dust, we pooled and analyzed data from several previous studies of experimental exposure. The pooled data set involved a total of 108 separate sessions of exposure to dust and 32 different cottons. Each dust-exposure session had involved exposing a group of 24 to 35 prescreened healthy subjects to dust from one of the cottons for six hours. The following data were obtained for each session: average concentrations of airborne dust (range, 0.12 to 0.55 mg per cubic meter) and endotoxin (range, 6 to 779 ng per cubic meter) as determined in air samples collected by vertical elutriators, and group mean percentage change in forced expiratory volume in one second (range, +0.5 to -9.1 percent), as determined by preexposure and postexposure spirometry. When data from the 108 exposure sessions were pooled, the dust concentration was not correlated with the group mean percentage change in forced expiratory volume in one second (r = -0.08; P = 0.43). In contrast, a clear exposure-response relation was observed between endotoxin concentration and group mean percentage change in forced expiratory volume in one second (r = -0.74; P less than 0.0001). Logarithmic transformation of endotoxin values clarified this relation at low-exposure concentrations and improved the correlation (r = -0.85; P less than 0.0001). Our observations strongly support the hypothesis that endotoxin has a causative role in the acute pulmonary response to inhaled cotton dust.

Epidemiological investigations of grain workers have suggested the presence of biological hazards in terminal grain elevators. Immunological assessments of the involved individuals, however, have produced inconclusive results. We have recently demonstrated in vitro a potential biological mechanism which could occur in vivo upon inhaling airborne graon dust, thereby constituting a potential inflammatory insult to the respiratory tracts of grain workers. Airborne dusts of similar size distributions generated by transporting grain in terminal grain elevators have been shown to activate the alternative pathway of complement in precipitin-negative pooled normal human serum. These dusts consumed hemolytic complement in a dose-response manner as quantified by both CH100 immunodiffusion and CH50 tube methods. The proactivator of C3 was converted to the activator form in the presence of the chelator EGTA, but conversion was prevented by EDTA. Likewise, serum from guinea pigs genetically deficient in C4, thereby lacking a functional classical complement pathway, showed complement consumption by grain dusts via the alternative pathway. Relative CH50 toxicity ranking of the various dusts was found to be unrelated to the amount of endotoxin present. Of interest, aged settled dust (20-30 years) remained relatively active against the alternative complement pathway as did 15 min aqueous extracts of ground whole rye.

Three samples of silage taken from the surface of a silo and from depths of 20 and 45 cm in the silo were studied for identification of the potential agents causing symptoms of organic dust toxic syndrome. The samples were examined by dilution plating before and after aerosolization in an acoustical dust generator. Aerosol samples were collected by liquid impinger and filter cassettes. The samples were examined for total aerobic bacteria, anaerobic bacteria, gram-negative bacteria, lactobacilli, listeriae, thermophilic actinomycetes, fungi, and endotoxin. Very high levels of total aerobic bacteria and fungi were found in the surface sample (up to 10(9) CFU/g in the bulk sample and up to 10(9) CFU/m3 after aerosolization), whereas the corresponding values from the deepest site were 100 to 50,000 times lower. Aspergillus fumigatus predominated among the fungi, whereas Bacillus and gram-negative organisms (Pseudomonas, Alcaligenes, Citrobacter, and Klebsiella species) prevailed among bacteria. Thermophilic actinomycetes occurred in numbers up to 10(7) CFU/g in the bulk samples, whereas anaerobic bacteria, lactobacilli, and listeriae were only few or absent. The concentration of endotoxin was high in the surface sample (up to 211.4 Endotoxin Units/mg) and about 200-fold lower in the sample from the deepest site. The results show that contact with dust from the surface of silage carries the risk of exposure to high concentrations of microorganisms, of which A. fumigatus and endotoxin-producing bacteria are the most probable disease agents.

The inhalation of grain dust by grain workers is responsible for a large number of pulmonary pathophysiologies. These problems may be acute or chronic and may be mediated by the chronic activation of the immune system. Constant inflammatory states in the lung may eventually lead to tissue damage and respiratory deficit. This study was designed to measure the changes in the relative number of inflammatory cells in peripheral blood, bronchoalveolar spaces, and lung interstitium that occur in response to intratracheally instilled airborne spring wheat dust in rats. It was found that 6 h after instillation with dust, neutrophils were present in greater numbers in the blood and bronchoalveolar spaces than in lung interstitium. After 24 h, there appeared to be a larger number of neutrophils in the lung interstitium in dust-instilled animals than in saline-instilled controls. These results indicate that intratracheal instillation of grain dust initiates an acute inflammatory reaction, and that there is an initial influx of neutrophils into the air spaces of the lung followed by transit of these cells into the lung interstitium.

The elemental composition of a group of airborne and settled grain dusts is reported. This survey was undertaken as part of a study to systematically describe the chemistry and morphology of these representative dusts. Our data show that airborne or settled grain dusts differ from each other with respect to elemental composition. Such fundamental differences may be related to previously observed differences in the biological activities of the dusts.

Settled grain dust was collected from several active grain elevators in the Superior-Duluth areas of the United States. Particle size distribution (47% less than 5 micrometer) and endotoxin contamination (429 ng/gm) of the dust were similar to those reported for the airborne parent dust. Human complement uas activated in vitro in a dose-response manner which could be quantified. This hemolytic consumption was via the alternative pathway as defined by ethylenediaminetertraacetic acid/ethylene-glycol-bis-(beta-amino-ethyl ether) N,N'-tetraacetic acid (EDTA/EGTA) differential serum chelation, factor B conversion, and complement reductions in serum from guinea pigs deficient in C4. It is proposed that continuous low-dose exposure to aerosolized, biologically active rafter dust could contribute to the respiratory insult of grain workers.

Previous studies have demonstrated that grain dust can stimulate lymphocyte proliferation and the production of interleukin-1 by macrophages. This study was undertaken to investigate whether grain dust could stimulate the production of histamine-releasing factor (HRF) by guinea pig spleen cells. We also studied the direct action of grain dust on guinea pig lung mast cells and basophils. Plastic nonadherent cells from immunized animals were cultured for 24 hours in the presence of grain dust or lipopolysaccharide, and the cell-free supernatants were assayed for HRF activity in the mast cell and basophil histamine release test. Lung mast cells were isolated by enzymatic digestion and discontinuous Percoll gradient centrifugation. It has been demonstrated that grain dust stimulated the production of HRF by spleen cells from the immunized animals but not from the control animals. Stimulation of spleen cells with lipopolysaccharide did not enhance the HRF production. Gel chromatography of grain dust-stimulated supernatant revealed that HRF has a molecular weight in the range of 50 to 70 kd and 5 to 8 kd. We also found that grain dust directly released significant amount of histamine from both mast cells and basophils. The results of this study suggest that grain dust contains some potent active substances that can activate lymphocytes, mast cells, and basophils.

Ground whole rye and airborne rye dust of comparable size distribution were tested for their ability to activate the complement cascade via the alternative pathway. Precipitin-negative pooled normal human serum was incubated with increasing amounts of the two rye dusts. Electrophoresis of the resultant supernatant fluids demonstrated the conversion of the proactivator of the third component of complement to the gamma-migrating activator of the third component. This activation was completely prevented by pre-treating the serum with the chelator EDTA, while pre-treatment with EGTA allowed suboptimal arc conversion, strongly implying that complement was activated via the alternative pathway. Quantification of the supernanant fluids showed dose-dependent complement consumption as defined by both CH100 immunodiffusion and CH50 tube haemolytic techniques. Airborne rye dust showed a greater quantitative potential than ground whole rye for activating the alternative pathway. These results indicate the possibility of the direct action of airborne organic dusts on the induction of inflammatory sequelae in the lungs of both sensitized and unsensitized individuals.

Gram-negative bacterial endotoxins, implicated in adverse worker health responses, were found in settled and airborne dust samples obtained from poultry and swine confinement units. Results of the Limulus amebocyte lysate gel test found endotoxin levels in dust samples ranged from 4.5 to 47.7 micrograms of FDA Klebsiella endotoxin equivalents/gm. Differences in endotoxin levels between dust samples may have been due to variables in time, geographic locations, confined animals, confinement buildings and equipment, and methods of sample collection. Animal confinement workers are potentially exposed to large amounts of gram-negative bacterial endotoxins; however, the respiratory health effects of such exposures to animal confinement workers have yet to be determined.

Aqueous extracts of silage samples from four farms in up-state New York were reacted in vitro with normal human serum. Hemolytic levels of complement component C3 were consumed in a dose-dependent fashion, and the four extracts differed in their relative activity rankings. Studies with chelated serum indicate that the alternative complement pathway is involved in the activation, and the active fragment C3b was demonstrated. Serum levels of hemolytic C3 and C4 in vivo were quantified before and after farmers performed their normal silo unloading operations. Although the study groups were small, suggestive evidence of in vivo complement consumption was found. IgE-related allergy did not appear to be of significance to the study groups. Complement activation may be an initiator of or contributor to adverse reactions in farmers who are exposed to airborne silage dusts.