Pantoea agglomerans: a marvelous bacterium of evil and good.Part I. Deleterious effects: Dust-borne endotoxins and allergens - focus on cotton dust.

The ubiquitous Gram-negative bacterium Pantoea agglomerans (synonyms: Enterobacter agglomerans, Erwinia herbicola) is known both as an epiphytic microbe developing on the surface of plants and as an endophytic organism living inside the plants. The bacterium occurs also abundantly in plant and animal products, in the body of arthropods and other animals, in water, soil, dust and air, and occasionally in humans. From the human viewpoint, the role of this organism is ambiguous, both deleterious and beneficial: on one side it causes disorders in people exposed to inhalation of organic dusts and diseases of crops, and on the other side it produces substances effective in the treatment of cancer and other diseases of humans and animals, suppresses the development of various plant pathogens, promotes plant growth, and appears as a potentially efficient biofertilizer and bioremediator. P. agglomerans was identified as a predominant bacterium on cotton plant grown all over the world, usually as an epiphyte, rarely as pathogen. It is particularly numerous on cotton bract after senescence. During processing of cotton in mills, bacteria and their products are released with cotton dust into air and are inhaled by workers, causing respiratory and general disorders, usually defined as byssinosis. The most adverse substance is endotoxin, a heteropolymer macromolecule present in the outermost part of the cell wall, consisting of lipopolysaccharide (LPS) as a major constituent, phospholipids and protein. The numerous experiments carried out in last quarter of XXth century on laboratory animals and human volunteers supported a convincing evidence that the inhaled endotoxin produced by P. agglomerans causes numerous pathologic effects similar to those elicited by cotton dust, such as influx of free lung cells into airways and activation of alveolar macrophages which secrete mediators (prostaglandins, platelet-activating factor, interleukin-1, tumor necrosis factor) that cause accumulation of platelets in pulmonary capillaries initiating an acute and chronic inflammation resulting in endothelial cell damage and extravasation of cells and fluids into the lung interstitium. These changes cause bronchoconstriction, the decrement of lung function expressed as reduction of forced expiratory volume in one second (FEV1) and/or diffusion capacity, increase in the airway hyperreactivity and subjective symptoms such as fever, airway irritation and chest tightness. The conclusions from these experiments, performed mostly 2-3 decades ago, did not loose their actuality until recently as so far no other cotton dust component was identified as a more important work-related hazard than bacterial endotoxin. Though also other microbial and plant constituents are considered as potential causative agents of byssinosis, the endotoxin produced by Pantoea agglomerans and other Gram-negative bacteria present in cotton dust is still regarded as a major cause of this mysterious disease.

The prevalence of byssinosis among cotton workers in the north of Benin.

BACKGROUND: Cotton is the main agricultural export product in Benin. Cotton dust is thus present in the air during the handling and processing of cotton. This dust contains a mixture of substances including ground up plant matter, fibres, bacteria, fungi, soil, pesticides, noncotton matter, and other contaminants. While cotton processing is decreasing in industrialized countries, it is increasing in developing countries. Cotton processing, particularly in the early processes of spinning, can cause byssinosis. OBJECTIVE: To determine the respiratory effects of cotton dust exposure among cotton mill workers in Benin. METHODS: In a cross-sectional study, 109 workers exposed to cotton dust and 107 unexposed workers were studied. The International Commission on Occupational Health (ICOH) questionnaire was used for data collection on respiratory symptoms. For each worker, crossshift pulmonary function was performed with a dry spirometer. Based on the severity of respiratory symptoms and spirometry byssinosis was defined and classified according to the criteria of Schilling, et al. RESULTS: The mean ± SD age of the exposed and unexposed workers was 46.3 ± 7.8 and 37.0 ± 8.3 years, respectively (p<0.001). The mean FEV1 predicted value for the exposed and unexposed workers was 76.3% and 77.3%, respectively. The prevalence of grade 3 byssinosis was 21.1% (95% CI: 13.4-28.9) in exposed workers and 8.4% (95% CI: 3.1-13.7) in unexposed workers (p=0.006). On Mondays, the exposed workers had more respiratory symptoms than unexposed workers; for grade 3 byssinosis, the prevalence was 13.8% in exposed and 4.7% in unexposed workers (p=0.011). CONCLUSION: The prevalence of respiratory symptoms and byssinosis among cotton mill workers in Benin is high and needs prompt attention of health care workers and policymakers.

Cross-shift airway responses and long-term decline in FEV1 in cotton textile workers.

RATIONALE: Acute airway response, measured as cross-shift change in FEV(1), to cotton dust may lead to subsequent chronic loss of lung function in exposed workers. OBJECTIVES: To explore the association between the magnitude and frequency of cross-shift change and chronic loss of FEV(1). METHODS: Four hundred eight cotton workers and 417 silk workers from Shanghai textile mills were observed prospectively for 20 years, with cross-shift measurements at baseline and follow-up surveys at approximate 5-year intervals. To account for repeated measures of 5-year change, generalized estimating equations were used to estimate the relationship between the magnitude of cross-shift change in FEV(1) (DeltaFEV(1)) and subsequent 5-year annualized change. Linear regression models were used to examine the association between the number of drops in cross-shift FEV(1) (DeltaFEV(1) < 0) and annualized change over the entire study period. MEASUREMENTS AND MAIN RESULTS: Exposure to cotton dust was associated with a 10 ml/year decrement in 5-year annualized FEV(1) decline. In addition, every 10 ml in DeltaFEV(1) drop was associated with an additional 1.5 ml/year loss in annualized FEV(1) decline. The association between the frequency of drops and annualized decline was stronger for cotton workers than for silk workers over the entire study period. CONCLUSIONS: Cotton workers had larger and more frequent drops, as well as excessive chronic declines in FEV(1), than did silk workers. The magnitude and frequency of cross-shift drops were associated with chronic loss in FEV(1) over the entire 20-year period examined.

Natural history and risk factors of early respiratory responses to exposure to cotton dust in newly exposed workers.

OBJECTIVE: A prospective study of newly exposed cotton workers was performed to investigate the natural history of respiratory symptoms and lung function changes. METHODS: A total of 157 workers naive to cotton dust exposure were investigated by questionnaire, spirometry, and skin tests. They were examined before employment (baseline) and at the end of the first week, and the first, third, sixth, and 12th month after starting work. Acute airway response was defined as either a cross-first-shift or a cross-week fall in forced expiratory volume in one second (FEV1). The longitudinal change of lung function over the year was also calculated. Five hundred seventy-two personal dust sampling and 191 endotoxin measurements were performed to assess the exposure. RESULTS: Forty percent of workers reported work-related symptoms in the first week of the study. Smoking, endotoxin, and dust concentrations were risk factors for all work-related symptoms. Acute airway responses were witnessed after immediate exposure. Female status was the only factor found to be predictive of acute airway response. The mean longitudinal fall in FEV1 at 1 year was 65.5 mL (standard error = 37.2). Age, early respiratory symptoms, and early fall in cross-week FEV1 were found to predict the 12-month fall in FEV1. Cross-first-shift and cross-week falls in FEV1 reduced in magnitude during the course of the study. CONCLUSIONS: This study of workers naive to cotton dust exposure has demonstrated that respiratory symptoms and acute airway responses develop early following first exposure, and a tolerance effect develops in those workers with the continued exposure. Current smoking and increasing exposure predicts the development of work-related lower respiratory tract symptoms, while early symptoms and acute airway changes across the working week predict the longitudinal loss of lung function at 1 year.

TNF polymorphisms modify endotoxin exposure-associated longitudinal lung function decline.

OBJECTIVES: Endotoxin exposure induces airway inflammation, hyper-responsiveness and higher expression of tumour necrosis factor (TNF). This study was conducted to investigate whether TNF polymorphisms modify the effect of endotoxin exposure on chronic declines in lung function. METHODS: Associations between TNF and LTA polymorphisms, endotoxin exposure and lung function were analysed in 263 cotton workers and 230 silk workers as a reference group, who were prospectively followed for 20 years. Multiple linear regression models were used to assess the association, with adjustment for smoking and other covariates. RESULTS: Endotoxin exposure was associated with faster lung function decline among genotypes associated with higher TNF expression levels, with estimates of annual FEV1 change in relation to endotoxin exposure of -2.9 ml and -6.8 ml in the G/G and G/A+AA genotypes, respectively, for the TNF polymorphism; and -2.0 ml, -4.0 ml and -3.6 ml in A/A, A/G and G/G genotypes, respectively, for the LTA polymorphism. When joint effects of endotoxin exposure and smoking were considered, the effect modification of TNF and LTA polymorphisms was prominent in never smokers. CONCLUSIONS: TNF and LTA polymorphisms may modify the association between occupational endotoxin exposure and longitudinal lung function decline, which was more clearly observed in never smokers.

Airway responses to the inhalation of cotton dust and cotton bract extracts.

BACKGROUND: Exposure to dust in the cotton industry is associated with respiratory dysfunction. Healthy subjects challenged with cotton bract extract (CBE) develop transient airway hyperresponsiveness. CBE, a major component of cotton dust, is potentially an important agent for studying byssinosis. OBJECTIVES: To compare airway responses to cotton dust extract (CDE) and CBE in healthy subjects. METHODS: In 21 healthy, non-smoking subjects we compared the effects of CBE and CDE in a double-blind random order, following a 10-min aerosol inhalation. The response to methacholine (MCh) 2 h following CBE or CDE was measured. Lung function was recorded using maximal (MEFV) and partial expiratory flow volume (PEFV) curves, measuring MEF at 60% of baseline vital capacity below total lung capacity [MEF40%(P)] on the PEFV curve. Responders were subjects who developed a 20% or greater fall in MEF40%(P) following extract challenge. Endotoxin levels were low for CBE (5.71 EU/mg) and CDE (31.88 EU/mg). RESULTS: There were 18 responders to CBE and 17 responders to CDE. The average maximal falls in MEF40%(P) were 70 +/- 4.9 and 70 +/- 4.4% of baseline (nonsignificant) following CBE and CDE, respectively. All subjects enhanced their MCh response following CBE or CDE. The MCh dose which reduced MEF40%(P) by 40% was identical for CBE and CDE (1.3 microg/ml). CONCLUSIONS: We conclude that CBE and CDE exert similar physiologic effects.

Byssinosis among jute mill workers.

Although byssinosis in jute mill workers remains controversial, studies in a few jute mills in West-Bengal, India, revealed typical byssinotic syndrome associated with acute changes in FEV1 on the first working day after rest. The present study on 148 jute mill workers is reported to confirm the occurrence of byssinosis in jute mill workers. Work related respiratory symptoms; acute and chronic pulmonary function changes among exposed workers were studied on the basis of standard questionnaire and spirometric method along with dust level, particle mass size distributions and gram-negative bacterial endotoxins. The pulmonary function test (PFT) changes were defined as per the recommendation of World Health Organization and of Bouhys et al. Total dust in jute mill air were monitored by high volume sampling, technique (Staplex, USA), Andersen cascade impactor was used for particle size distribution and personal exposure level was determined by personal sampler (Casella, London). Endotoxin in airborne jute dust was analysed by Lymulus Amebocyte Lysate (LAL) "Gel Clot" technique. Batching is the dustiest process in the mill. Size distribution showed that about 70-80% dust in diameter of < 10 microm, 40-50%, < 5 microm and 10-20%, < 2 microm. Mean endotoxin levels found in hatching, spinning and weaving, and beaming were 2.319 microg/m3, 0.956 microg/ m3, 0.041 microg/m3 respectively and are comparable to the values obtained up to date in Indian cotton mills. Respiratory morbidity study reported typical byssinotic symptoms along with acute post shift FEV1 changes (31.8%) and chronic changes in FEV1 (43.2%) among exposed workers. The group with higher exposure showed significantly lower FVC, FEV1, PEFR and FEF25-75% values. The study confirmed the findings of the earlier studies and clearly indicated that the Indian jute mill workers are also suffering from byssinosis as observed in cotton, flask and hemp workers.

Respiratory effects of long-term exposure to cotton dust.

Traditionally, the concept of cotton dust-related disease focused on acute airway responses. A possible connection of long-term exposure to cotton dust with chronic obstructive airway disease was not addressed until the past two decades. This review summarizes the latest findings relevant to this topic that were observed from longitudinal cohort studies and discusses the relation between acute airway responses and chronic losses of lung function.

A longitudinal observation of early pulmonary responses to cotton dust.

AIMS: To examine early adverse pulmonary effects of exposure to cotton dust, and to identify potential risk factors, including atopy for pulmonary responses to cotton dust. METHODS: Spirometry, methacholine challenge testing, and questionnaire; performed among 101 non-smoking newly hired textile workers at baseline (prior to starting work), and at 3, 12, and 18 months after starting work. Concentrations of airborne cotton dust in various work areas were measured at each follow up survey using vertical elutriators. RESULTS: The incidence of non-specific respiratory symptoms was 8% at three months, then diminished afterwards. Substantial acute cross shift drops in FEV(1) at each follow up survey, and longitudinal declines in FVC and FEV(1) after 12 months of exposure were observed. Airway responsiveness to methacholine increased with follow up time, and was more pronounced among atopics. Increasing airway responsiveness was strongly correlated with cross shift drops in FEV(1). In addition, one or more respiratory symptoms at three months was significantly, and pre-existing atopy marginally significantly, associated with cross shift drops in FEV(1) after adjusting for other covariates and confounders. CONCLUSION: Results suggest that non-specific respiratory symptoms, decreasing lung function, and increasing airway responsiveness are early pulmonary responses to cotton dust. In addition, the occurrence of respiratory symptoms and increasing airway responsiveness, as well as atopy, may be important predictors for acute changes in lung function among cotton textile workers.

Respiratory symptoms, lung function and cell surface markers in a group of hemp fiber processors.

BACKGROUND: Hemp dust exposure is associated with byssinosis and accelerated lung loss in longitudinal studies. The immunological changes associated with hemp dust exposure are less well understood. METHODS: We studied a small group of current male hemp processors with a mean age of 43 years. Questionnaire data, lung function, serial FEV(1) and blood were collected from all workers. RESULTS: In total, seven workers (64%) complained of at least one respiratory symptom (one with byssinosis). The mean percentage predicted FEV(1) was 91.5, FVC 97.7, PEF 92.1, and FEF(25-75) 79.5. Serial FEV(1) measurements in the two workers with work-related respiratory symptoms revealed a mean change in FEV(1) on the first working day of -12.9%. This contrasted with +6.25% on the last working day. Respective values for the two workers without work-related symptoms were -1.4 and +3.2%. CONCLUSIONS: Lung function changes and abnormalities in a profile of cell surface activation markers and antibodies were noted to relate to the presence of work-related respiratory symptoms, not seen in the control group.

Byssinosis.

Byssinosis as a nonspecific chronic respiratory disease in textile workers exposed to cotton, flax, jute, hemp and sisal is described. Opinions about aetiopathogenesis are presented. The following chapters are focused on clinical symptoms and functional lung changes. Classification of the disease is described afterwards. Finally, the necessity of medical and technical measures to prevent the development of this disease in textile workers is emphasised.

[Byssinosis--an occupational disease of textile workers]. / Bisinoza--professionalna bolest tekstilnih radnika.

Byssinosis as a nonspecific chronic respiratory disease in textile workers exposed to cotton, hemp and flax is described. Pathogenesis and ethiologic factors responsible for bissynosis are listed. Clinical symptoms of byssinosis and differential diagnosis with occupational asthma are presented. Characteristic functional changes of ventilatory capacity in textile workers are described. Clinical and functional criteria for diagnosis of byssinosis are presented. Particular emphasis is given to preventive medical and technical measures in order to prevent the development of respiratory diseases in textile workers.

Lung function in Lancashire cotton and man made fibre spinning mill operatives.

OBJECTIVES: This survey was conducted to investigate current lung function levels in operatives working with cotton and man made fibres. Dust concentrations, smoking history, and occupational details were recorded so that factors influencing lung function could be identified. METHODS: A cross sectional study of respiratory symptoms and lung function was made in 1057 textile spinning operatives of white caucasian extraction. This represented 96.9% of the total available working population to be studied. Most (713) worked currently with cotton. The remainder worked with man made fibre. Lung function was assessed by measuring forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Exposure to cotton dust was measured in the work area and personal breathing zones, and retrospective exposure to cotton dust over a working life was estimated with accurate work history and best available hygiene data. RESULTS: 3.5% of all operatives had byssinosis, 55 (5.3%) chronic bronchitis, 36 (3.5%) work related persistent cough, 55 (5.3%) non-byssinotic work related chest tightness, and 56 (5.3%) work related wheeze. A total of 212 static work area dust samples (range 0.04-3.23 mg/m3) and 213 personal breathing zone samples (range 0.14-24.95 mg/m3) were collected. Percentage of predicted FEV1 was reduced in current smokers (mean 89.5, 95% confidence interval (95% CI) 88-91) in comparison with non-smokers (93.1, 90.5-94.1) and FVC was reduced in operatives currently working with man made fibre (95.3, 93.8-96.9) in comparison with cotton (97.8, 96.6-99.0). Regression analysis identified smoking (P < 0.01), increasing age (P < 0.01), increasing time worked in the waste room (P < 0.01), and male sex (P < 0.05) as being associated with a lower FEV1 and FVC. Current and retrospective cotton dust exposures did not appear as predictor variables in the regression analysis although in a univariate analysis, FEV1 was reduced in those operatives exposed to high dust concentrations assessed by personal and work area sampling. DISCUSSION: This study has documented loss of lung function in association with exposure to cotton dust. Those operatives with work related symptoms had significantly lower FEV1 and FVC than asymptomatic workers. Although lung function seemed to be affected by high dust exposures when operatives were stratified into high and low exposure groups, regression analysis did not identify current dust concentrations as an independent factor influencing loss. Smoking habit was found to explain most of the measured change in FEV1 and FVC. It is likely that smoking and dust exposure interact to cause loss of lung function in cotton textile workers.

Effect of cotton, hemp, and flax dust extracts on lung permeability in the guinea pig.

Byssinosis is an occupational lung disease in textile mill workers exposed to the respirable dusts of cotton, hemp, and flax. This study investigated the influence of aqueous extracts from these dusts on overall lung permeability in the guinea pig as an index of respiratory epithelial damage. Lung permeability was assessed by absorption into blood from the lung of inhaled technetium-99m diethylenetriamine penta-acetate (Tc-DTPA) using gamma-scintigraphy. The half-life for Tc-DTPA absorption (t1/2) was significantly reduced following a 4-week inhalation treatment with cotton, hemp, or flax dust extracts when compared to saline control. There was at least a partial return to normal permeability 7 days after stopping treatment. A single inhalation of extract did not affect the t1/2, but increased the number of neutrophils in bronchoalveolar lavage fluid 24 h postexposure. Neutrophil migration into the airspaces therefore appeared to precede the increased lung permeability. Long-term exposure was not associated with respiratory epithelial shedding, suggesting that the increased permeability reflects a loss of epithelial tight junction integrity arising from repeated exposure to as yet undefined agents in these dusts.

Byssinosis and other respiratory disorders among textile mill workers in Bahr Dar northwest Ethiopia.

The prevalence of byssinosis and other respiratory symptoms were studied among 433 workers who were occupationally exposed to cotton dust in Bahr Dar Textile Mill. One-hundred-one nonexposed workers living in the same geographical area were included as controls. All of the subjects completed the British Medical Research Council Questionnaire. Pulmonary function tests were administered on a vitalograph spirometer before starting the shift for all subjects, and after at least four hours of exposure for exposed subjects. Among the cotton dust exposed workers, byssinotics behaved distinctly and showed the maximum acute and chronic changes in pulmonary functions. The overall prevalence of byssinosis was 45.5%. The highest prevalence was found in carding (57.9%) and in ring frame (57.1%) operatives and the lowest in weaving preparatory section (32.1%). Unlike bronchial asthma, chronic cough and chronic bronchitis were significantly higher (p < 0.01) in cotton dust exposed subjects compared with controls. The mean measured values of ventilatory capacity (FEV1 and FVC) are to a significant extent reduced in the exposed groups compared with controls (p < 0.01). In view of the above findings, preventive measures are of paramount importance in minimizing the prevalence of byssinosis and other respiratory disorders.

Cotton dust and across-shift change in FEV1 as predictors of annual change in FEV1.

In this report of a 5-yr longitudinal study of workers employed at six cotton textile mills, exposure and across-shift FEV1 change were evaluated as possible predictors of the annual change in FEV1 for yarn manufacturing workers. A total of 611 workers had three repeatable spirometric tests, over at least 3 yr, and at least one (average of three) across-shift test, while always working the same shift. The "same shift" criterion controlled for the effect of diurnal variation. Average exposure was determined from measures of lint-free elutriated cotton dust in combination with job histories. This study found a significant association between the acute and chronic effects of cotton dust exposure. Both exposure and across-shift change proved to be significant predictors of annual change, and excess annual declines in FEV1 were predicted even for exposures of 200 micrograms/m3 and across-shift drops in FEV1 of 200 ml. These results suggest that, to prevent dust-related chronic decline in lung function, current smokers should be excluded from yarn manufacturing work and exposures should be reduced below 200 micrograms/m3, to approximately 100 micrograms/m3.