Stephen A. Olenchock

Inhaled endotoxin and decreased spirometric values. An exposure-response relation for cotton 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.

Acute bronchoconstriction induced by cotton dust: dose-related responses to endotoxin and other dust factors.

Fifty-four healthy humans, selected for their acute airway responsiveness to cotton dust, had spirometric tests immediately before and after 6 hours of exposure to card-generated cotton dust from seven different cottons (of several grades and growing regions). During exposures, we measured airborne concentrations of viable fungi and bacteria (total and gram negative), vertically elutriated gravimetric dust, and vertically elutriated endotoxin. Correlation between each of these five exposure indices and exposure-related acute changes in forced expiratory volume in 1 s showed a statistically significant relationship between all of the indices except concentration of viable fungi. Of the other four indices, endotoxin was the most highly correlated (r = -0.94; p less than 0.00001), and gravimetric dust was the least correlated (r = -0.34; p less than 0.05). These findings suggest that gram-negative endotoxin may play a major role in the acute pulmonary response to inhaled cotton dust.

Organic Dust Exposures from Work in Dairy Barns

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.

Cotton dust and endotoxin exposure and long-term decline in lung function : Results of a longitudinal study

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.

A 20-year follow-up study on chronic respiratory effects of exposure to cotton dust.

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.

Environmental Study of Poultry Confinement Buildings

Environmental measurements were made in three poultry confinement buildings in order to characterize gas and particulate contaminants. Levels of total and respirable dust averaged 4.4 and 0.24 mg/m3, respectively. Particle size distribution as measured by cascade impactors was similar in the three confinement houses with a mass median aerodynamic diameter of about 15 microns and a geometric standard deviation of about 2.2. Ammonia levels measured in the active areas of the buildings averaged about 25 ppm. Ammonia concentration was quite high, however, in an unused and unventilated portion of one of the buildings (mean = 170 ppm). CO2 levels ranged from 0.05-0.1%. Levels of CO, H2S, NO2, NOx, CH4, mercaptan, formaldehyde, and hydrocarbons were all below the limit of detection for indicator tubes. Concentrations of airborne bacteria and fungi were on average about 1.5 X 10(5) and 1.0 X 10(4) colony-forming units/m3, respectively. Endotoxin analysis was also performed on the total and respirable dust samples. Endotoxin levels (expressed in air concentration) ranged from 0.77 to 61 ng/m3 for total dust and from 0.71 to 15 ng/m3 for respirable dust. Endotoxin was also measured on the collection media from the individual impactor stages. Endotoxin was detected in all size ranges with the highest concentration of endotoxin per unit of dust found in the smallest (less than approximately 3.5 microns) size fraction. The endotoxin levels tend to be lower than those previously reported in poultry operations.

Respiratory symptoms and cotton dust exposure; results of a 15 year follow up observation

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.

Occupational exposure to airborne endotoxins during poultry processing

Airborne gram-negative bacterial endotoxin levels were quantified in a live chicken hanging (shackling) room of a poultry processing plant. The mean respirable dust levels at the entrance and exit of the shackling line were 1.13 +/- 0.12 and 0.72 +/- 0.06 mg/m3, respectively, or approximately 6% of the total dust. Endotoxins constituted 43.3 +/- 2.8 micrograms per gram of respirable dust. Airborne endotoxins were present in the total dust at the mean level of 918.4 +/- 159.0 ng/m3 at the room entrance and 634.0 +/- 96.9 ng/m3 at the exit, with respirable levels of 44.3 +/- 7.8 and 33.6 +/- 2.2 ng/m3. Inhalation of gram-negative bacterial endotoxins can result in respiratory and systemic pathophysiology. The potential for adverse health effects in the working environment of the live poultry processing industry is discussed. Medical studies of workers in this area are required to confirm or deny the existence of occupationally related health effects.

Health Effects of Biological Agents: The Role of Endotoxins

Abstract Gram-negative bacteria and their endotoxins are commonly found in agricultural settings, yet they can be quantified also in environmental/occupational situations that are considered traditionally to be nondusty, such as office buildings or libraries. Endotoxins are biologically active agents that can induce respiratory and systemic reactivity after inhalation of airborne dusts which contain relatively small quantities of the toxin. Research studies with strong and compelling results are needed to lead to the prevention of lung disease caused by the inhalation of endotoxins. Olenchock, S.A.: Health Effects of Biological Agents: The Role of Endotoxins. Appl. Occup. Environ. Hyg. 9(1):62–64; 1994.

Personal Exposures to Inorganic and Organic Dust in Manual Harvest of California Citrus and Table Grapes

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/m3 for inhalable dust and 1.14 mg/m3 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.