Role of histamine in the aetiology of byssinosis. I Blood histamine concentrations in workers exposed to cotton and flax dusts.

The formation or the accumulation, or both, of histamine in the lungs may be potentiated by agent(s) present in cotton dust at higher level(s) than in flax dust and negligible in cottonseed dust. It has been suggested that such potentiation may be due to the activation of the ability of the lung to produce histamine and/or produce or recruit mast cells; this may present an acceptable explanation of the mechanism by which the propagation of the chronic effect of the dust proceeds in cotton and flax workers. Histamine accumulated in the lung over the weekend is released on exposure to dust causing the symptoms of byssinosis. The difference in the rate of histamine metabolism relative to the rate of histamine formation in byssinotic subjects leads to a more prolonged histamine accumulation than in symptom free subjects, with the consequent appearance of the symptoms of byssinosis. Continuous exposure to dust, without weekend interruption, leads to equivalent rates of histamine formation and metabolism with non-considerable histamine accumulation in the lungs and consequent absence of the symptoms of byssinosis.     

Role of histamine in the aetiology of byssinosis. I Blood histamine concentrations in workers exposed to cotton and flax dusts

The formation or the accumulation, or both, of histamine in the lungs may be potentiated by agent(s) present in cotton dust at higher level(s) than in flax dust and negligible in cottonseed dust. It has been suggested that such potentiation may be due to the activation of the ability of the lung to produce histamine and/or produce or recruit mast cells; this may present an acceptable explanation of the mechanism by which the propagation of the chronic effect of the dust proceeds in cotton and flax workers. Histamine accumulated in the lung over the weekend is released on exposure to dust causing the symptoms of byssinosis. The difference in the rate of histamine metabolism relative to the rate of histamine formation in byssinotic subjects leads to a more prolonged histamine accumulation than in symptom free subjects, with the consequent appearance of the symptoms of byssinosis. Continuous exposure to dust, without weekend interruption, leads to equivalent rates of histamine formation and metabolism with non-considerable histamine accumulation in the lungs and consequent absence of the symptoms of byssinosis.     

Some Pharmacological Actions of Cotton Dust and Other Vegetable Dusts

Aqueous extracts of cotton and other vegetable dusts cause contraction of the isolated ileum and tracheal muscle of the guinea-pig, and of isolated human bronchial muscle. The levels of this contractor activity place the dusts of cotton, flax, and jute in the order of the probable incidence of byssinosis occurring in the mills spinning these fibres.

Extracts of cotton dust possess a histamine-liberating activity and contain a permeability-increasing component. These actions are of plant origin and are found in the pericarp and bracts of the cotton boll. Histamine and 5-hydroxytryptamine have also been found in some cotton dust samples. The formation of histamine by bacterial action in cotton dust does not take place under conditions found in cotton mills. The smooth muscle contractor substance is organic in nature, relatively heat-stable, and dialysable. The relevance of these results to the symptoms of byssinosis is discussed.

     

Comparative study of the smooth muscle contractor activity of airborne dusts and of dustiness in cotton, flax, and jute mills.

A bioassay technique using isolated guinea-pig ileum was employed to compare the smooth muscle contractor activity of various dusts from mills in which the prevalence of byssinosis was known. The activity of dust from a mill spinning a coarse grade of cotton was several times greater than that in dust from a mill processing a fine grade of cotton. There was a similar order in the difference of the prevalence of byssinosis in these mills. However, the activities of fine cotton, flax, and jute dusts were very similar to each other, in spite of marked differences in the prevalence of byssinosis in these mills. For cotton dust, smooth muscle contractor activity was associated with all particle sizes, although the lowest level of activity was found in the largest sized fraction (less than 2 mm). Activity in the cotton dust extracts was not correlated with nitrogen, carbohydrate, or potassium content. However, about one-fifth of the activity of a cotton dust extract was associated with an insoluble particulate fraction. The possible chemical nature of the water-soluble contractor agent is discussed. It is concluded that, until the role of this agent in the pathogenesis of byssinosis has been established, the bioassay technique cannot be employed as a means of assessing the byssinogenic potential of cotton dust.     

Comparative study of the smooth muscle contractor activity of airborne dusts and of dustiness in cotton, flax, and jute mills.

A bioassay technique using isolated guinea-pig ileum was employed to compare the smooth muscle contractor activity of various dusts from mills in which the prevalence of byssinosis was known. The activity of dust from a mill spinning a coarse grade of cotton was several times greater than that in dust from a mill processing a fine grade of cotton. There was a similar order in the difference of the prevalence of byssinosis in these mills. However, the activities of fine cotton, flax, and jute dusts were very similar to each other, in spite of marked differences in the prevalence of byssinosis in these mills. For cotton dust, smooth muscle contractor activity was associated with all particle sizes, although the lowest level of activity was found in the largest sized fraction (less than 2 mm). Activity in the cotton dust extracts was not correlated with nitrogen, carbohydrate, or potassium content. However, about one-fifth of the activity of a cotton dust extract was associated with an insoluble particulate fraction. The possible chemical nature of the water-soluble contractor agent is discussed. It is concluded that, until the role of this agent in the pathogenesis of byssinosis has been established, the bioassay technique cannot be employed as a means of assessing the byssinogenic potential of cotton dust.     

Histamine-related reactions in patients with byssinosis

The purpose of the study was to analyze the mechanism of histamine action in histamine-dependent reactions of neutrophils and lymphocytes in patients with byssinosis and chronic asthmatic bronchitis under cotton and flax dust effect. The appraisal of histamine content in blood serum, receptor/histamine distribution of lymphocyte and neutrophil subpopulations (rosette-forming double and triple reactions), determination of histamine modeling effect on lymphocyte-neutrophil cooperation in the inhibition reaction of leukocyte migration revealed that under cotton dust effect neutrophils and the complement system were involved into the histamine liberation process in byssinosis patients, lymphocytes were most likely not involved into the process. Flax dust-affected histamine reactions were not so distinct: lymphocyte and neutrophil reactivity in byssinosis patients did not exceed the standards. Patients with chronic asthmatic bronchitis had high blood concentration of histamine and experienced some changes in cells' migration characteristics. It was assumed that primarily nonimmune mechanisms of histamine liberation and activation of the complement system were involved into byssinosis pathological process in patients exposed to cotton and flax dust effect. In patients with chronic asthmatic bronchitis there occurred all 3 activation mechanisms of biologically active substances, i.e., allergic and nonantigenic ways of histamine liberation and activation of the complement system.     

Histamine release by Western red cedar (Thuja plicata) from lung tissue in vitro

Evans, Elizabeth and Nicholls, P. J. (1974).British Journal of Industrial Medicine,31, 28-30. Histamine release by Western red cedar(Thuja plicata)from lung tissue in vitro. Various respiratory symptoms have previously been observed in workers exposed to dust from Western red cedar (Thuja plicata). Although an allergic basis for these effects has been proposed, the possibility that the dust may contain a pharmacologically active agent was investigated. Aqueous extracts of two samples of red cedar released significant amounts of histamine from pig and human lung in vitro. For one of these samples, using pig lung, a dose-response relation was found over a narrow range of concentrations. These dusts possessed the same order of histamine-releasing activity as a sample of cotton dust. Potassium cyanide reduced the release of histamine caused by low concentrations of Western red cedar. Similar effects of cyanide on the histamine-releasing activity of cotton dust and compound 48/80 were observed. It is possible that release of histamine in the lungs and upper respiratory tract occurs on inhalation of dust from Western red cedar and this may be a contributory factor to the development of respiratory symptoms in workers exposed to the dust of this wood.     

Characterisation of textile dust extracts: I. Histamine release in vitro.

Cotton, flax, hemp, and cotton bracts extracts did not release histamine from mouse, rat, guinea pig, horse, cow, and monkey lung. Neither rat peritoneal mast cells nor mouse mastocytoma cells released histamine when incubated with textile dust extracts. Compound 48/80 caused a considerable release of histamine from all these tissues and the extracts released histamine from pig and human lung tissues. Whereas dusts that cause bronchospasm in man released histamine--for instance, cotton--those that are inactive, such as pericarps, did not. Histamine release was not quantitatively related to the concentration of extract used. Cotton bracts extract released histamine from pig lung tissue whereas in the same preparations methyl piperonylate was inactive. The active releasing agent was highly water soluble but could not be steam distilled from, nor extracted by, ether from bracts extract. These physicochemical properties are not characteristic of methyl piperonylate. There was no correlation between the induction of histidine decarboxylase and the histamine releasing capacity of the extracts. We conclude that pig lung is a useful qualitative assay tissue for the further characterisation of the histamine releasing agent(s) in textile dust extracts.     

Characterisation of textile dust extracts: I. Histamine release in vitro

Cotton, flax, hemp, and cotton bracts extracts did not release histamine from mouse, rat, guinea pig, horse, cow, and monkey lung. Neither rat peritoneal mast cells nor mouse mastocytoma cells released histamine when incubated with textile dust extracts. Compound 48/80 caused a considerable release of histamine from all these tissues and the extracts released histamine from pig and human lung tissues. Whereas dusts that cause bronchospasm in man released histamine--for instance, cotton--those that are inactive, such as pericarps, did not. Histamine release was not quantitatively related to the concentration of extract used. Cotton bracts extract released histamine from pig lung tissue whereas in the same preparations methyl piperonylate was inactive. The active releasing agent was highly water soluble but could not be steam distilled from, nor extracted by, ether from bracts extract. These physicochemical properties are not characteristic of methyl piperonylate. There was no correlation between the induction of histidine decarboxylase and the histamine releasing capacity of the extracts. We conclude that pig lung is a useful qualitative assay tissue for the further characterisation of the histamine releasing agent(s) in textile dust extracts.     

Comparison of the effects of organic dusts on respiratory organs of rats using a morphometric method

The contributors studied changes in the respiratory organs in rats induced by lucerne, maize, cotton, flax and flour dusts. The dusts were administered intratracheally by 10 mg dosages. Histological studies of the lung parenchyma were performed in 3 months, which revealed granuloma formations caused by the dusts. Automized planimetry was used to measure the surfaces, both individual and total, of the granuloma formations. To this criterion, cotton dust proved most affective (2.423 +/- 0.772), followed by lucerne (1.739 +/- 0.694), maize (1.434 +/- 0.558), flax (1.420 +/- 0.329), and flour (0.565 +/- 0.171) dusts.     

Respiratory disability in ex-cotton workers.

A high proportion of textile workers handling cotton and flax complain of respiratory symptoms and show a loss in lung function. These effects are reversible in the early stages but the degree to which they lead to permanent respiratory disability is unknown. Two surveys were therefore conducted in which respiratory function and symptoms were compared in ex-textile workers and in control subjects who had never been exposed to textile dusts. One survey was of ex-flax workers in Northern Ireland. The present survey was of ex-cotton workers in Lancashire. A survey of random population samples in Oldham and Bolton, in both of which cotton had formerly been the most important source of employment, was conducted. After allowing for age, height, and smoking, lung function was about 2-8% lower in the ex-textile workers than in controls who had never been exposed to any dust. Ex-textile workers were slightly shorter than the controls, suggestive of past social and nutritional deprivation which may have contributed to the decrement in lung function. There was evidence of a small but increasing decrement in lung function with an increase in a "dust exposure" score. For men, about 15 years of heavy dust exposure was associated with a loss in FEV1 equivalent to that shown by light or ex-smokers. For women, 15 years of heavy dust exposure appeared to be associated with a decrement in FEV1 about half that of light smoking.     

Histamine Liberation by Cotton Dust Extracts: Evidence Against its Causation by Bacterial Endotoxins

The recently stated hypothesis that histamine liberation by cotton dust extracts is caused by endotoxins from gram-negative bacteria contained in cotton was studied experimentally in various animals. It was shown clearly that such amounts of endotoxin as were found in cotton dust did not give rise to histamine liberation which was provoked by extracts from cotton card-room dusts. Further arguments are given which testify against the endotoxin hypothesis.     

Blood histamine levels in cotton-dust exposed workers in a textile mill of Ahmedabad

Blood histamine levels were measured by the bioassay of histamine (on an isolated strip of guinea pig ileum) in workers exposed to cotton dust in a textile mill in Ahmedabad. Byssinotic subjects showed very high levels of blood histamine as compared to nonbyssinotic and control subjects. The blood histamine levels were not well correlated to the dust concentrations or duration of exposure but rather to the day of the week (ie, first, second, third, etc., after weekend break) on which the samples were collected. The blood histamine levels were high on the first day of the work week, when byssinotics complained most of their symptoms.     

Effects of different vegetable dust exposures

Valić, F., and Žuškin, E. (1972).Brit. J. industr. Med.,29, 293-297. Effects of different vegetable dust exposures. In order to establish the rank of biological activity of vegetable dusts, five groups of non-smoking female workers exposed to similar concentrations of hemp, flax, cotton, sisal, and jute airborne dust, respectively, were compared as to the prevalence of byssinosis, chronic respiratory symptoms, and one-second expiratory volume changes over the Monday shift. The groups were selected in such a way as to differ in the distribution of age and length of exposure to the respective dust as little as possible.

The prevalence of byssinosis in hemp and flax workers was approximately equal (44% and 43% respectively), in cotton workers it was considerably lower (27%), while no byssinosis was caused by either sisal or jute dust. The highest prevalence of other chronic respiratory symptoms was recorded in hemp workers (39%), followed by flax (36%) and cotton workers (27%), while in sisal (13%) and jute workers (13%) it was the lowest.

Significant mean FEV_1·0 reductions over the shift were recorded in all the groups of textile workers with the largest reductions in hemp workers (19%) followed by flax (11%), cotton (8%), sisal (7%), and jute workers (5%). The application of orciprenaline before the shift diminished the mean acute FEV_1·0 falls over the work shift in all the groups studied.

     

Respiratory disability in ex-cotton workers

A high proportion of textile workers handling cotton and flax complain of respiratory symptoms and show a loss in lung function. These effects are reversible in the early stages but the degree to which they lead to permanent respiratory disability is unknown. Two surveys were therefore conducted in which respiratory function and symptoms were compared in ex-textile workers and in control subjects who had never been exposed to textile dusts. One survey was of ex-flax workers in Northern Ireland. The present survey was of ex-cotton workers in Lancashire. A survey of random population samples in Oldham and Bolton, in both of which cotton had formerly been the most important source of employment, was conducted. After allowing for age, height, and smoking, lung function was about 2-8% lower in the ex-textile workers than in controls who had never been exposed to any dust. Ex-textile workers were slightly shorter than the controls, suggestive of past social and nutritional deprivation which may have contributed to the decrement in lung function. There was evidence of a small but increasing decrement in lung function with an increase in a "dust exposure" score. For men, about 15 years of heavy dust exposure was associated with a loss in FEV1 equivalent to that shown by light or ex-smokers. For women, 15 years of heavy dust exposure appeared to be associated with a decrement in FEV1 about half that of light smoking.     

Endotoxins in cotton: Washing effects and size distribution

Endotoxin contamination was measured in washed and unwashed cottons from three distinct growing areas, California, Mississippi, and Texas. The data show differences in endotoxin contamination based upon the geographic source of the cotton. It is also shown that washing bulk cotton before the carding process results in lower endotoxin in the cotton dust. Washing conditions can affect the endotoxin levels, and all size fractions of the airborne dust contain quantifiable endotoxin contamination. Endotoxin analyses provide a simple and reliable method for monitoring the cleanliness of cotton or airborne cotton dusts.     

Respiratory disability in ex-flax workers.

Acute respiratory effects occur in a high proportion of subjects exposed to textile dusts. The extent to which these lead to permanent respiratory symptoms and loss of lung function is unknown. A survey of random population samples was therefore conducted in ten towns in Northern Ireland in which flax processing had been a major source of employment. The MRC questionnaire on respiratory symptoms was administered and Vitalograph tracings recorded on subjects aged 40 to 74 inclusive. An occupational history was taken at the end of each interview. Lung function in ex-flax workers was slightly lower than in control subjects never exposed to flax dust, but the presence of a positive interaction with age meant that differences were apparent only in the younger subjects. Over about the age of 65 the lung function in the ex-flax workers was comparable with that of the controls and overall the loss was at most about half that due to light smoking (1-14 cigarettes a day). The association between a "dust exposure score" and lung function was inconsistent in the two sexes. In men there was a small decrement with increasing dust exposure. In women there was also a small decrement, but a positive interaction with age meant that the women with the highest dust exposure scores had a lower loss with increasing age than the women with the least dust exposure. There was an excess in symptoms in the ex-flax workers but the size of the excess was greater than would be expected from the lung function results. It is possible that, although the survey was conducted without explicit reference to the flax industry, knowledge throughout Northern Ireland that many flax workers have been awarded compensation on the grounds of respiratory disablement may have led to an increased reporting of symptoms in the ex-flax workers.     

Histamine release from platelets for assay of byssinogenic substances in cotton mill dust and related materials.

Previous reports suggest that byssinosis, an asthma-like condition among textile workers, may be mediated in part by histamine liberated following inhalation of dust. A simple, sensitive, and reliable procedure using pig platelets which contain the unusually high concentration of 0.8-1.6 microgram histamine/10(9) cells has been devised for the assay of histamine-releasing factors in cotton mill dust and related materials, and has yielded results generally in accordance with earlier assays using chopped lung tissue. As little as 50--100 microgram of total extractable substances from cotton mill dust can be measured. The activity of the extract is associated with the non-dialysable high molecular weight portion. However, conditions of acid hydrolysis do not destroy the activity. Extracts of leaves from different varieties of plant are highly potent, which suggests that the factors responsible for byssinosis are widely distributed plant components, present in textile fibre plants and converted to a respirable form by handling processes. Ellagic acid and sodium metasilicate release histamine from pig platelets, and represent new classes of compounds with possible roles in the aetiology of byssinosis.     

Histamine release from platelets for assay of byssinogenic substances in cotton mill dust and related materials.

Previous reports suggest that byssinosis, an asthma-like condition among textile workers, may be mediated in part by histamine liberated following inhalation of dust. A simple, sensitive, and reliable procedure using pig platelets which contain the unusually high concentration of 0.8-1.6 microgram histamine/10(9) cells has been devised for the assay of histamine-releasing factors in cotton mill dust and related materials, and has yielded results generally in accordance with earlier assays using chopped lung tissue. As little as 50--100 microgram of total extractable substances from cotton mill dust can be measured. The activity of the extract is associated with the non-dialysable high molecular weight portion. However, conditions of acid hydrolysis do not destroy the activity. Extracts of leaves from different varieties of plant are highly potent, which suggests that the factors responsible for byssinosis are widely distributed plant components, present in textile fibre plants and converted to a respirable form by handling processes. Ellagic acid and sodium metasilicate release histamine from pig platelets, and represent new classes of compounds with possible roles in the aetiology of byssinosis.     

Byssinosis: The Acute Effect on Ventilatory Capacity of Dusts in Cotton Ginneries, Cotton, Sisal, and Jute Mills

Studies of ventilatory capacity change in small groups of employees during a shift in a cotton mill and in three cotton ginneries in Uganda, a sisal factory in Kenya, and a jute mill in England, have demonstrated that an effect is produced by the dust in the cotton mill and in a very dusty ginnery but not in two other less dusty ginneries. No significant effect was detected in the sisal factory or in the jute mill despite much higher dust concentrations than in the cotton mill.

The dust sampling instruments gave the weight in three sizes: Coarse (>2 mm.), medium (7μ to 2 mm.), and fine (<7μ). The samples were analysed for protein, mineral (ash), and cellulose (by difference). The fine and medium sisal and jute dusts contain less protein than cotton dusts. The physiological changes observed in the employees in the cotton mill indicate the need for general dust measurement and control, even when new carding machinery is installed in a new mill.