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.     

Byssinosis Prevalence and Flax Processing

Previous evidence suggested that byssinosis in flax workers is caused by the inhalation of dust of biologically retted flax. In the present study no cases of byssinosis were found among workers in a flax plant which produces yarn by chemical degumming instead of biological retting. The absence of byssinosis in this plant could not be attributed to differences in the quantities of dust developed as compared with the conventional retting procedure.

These findings support the view that the agent in flax dust which causes symptoms of byssinosis originates during biological retting of flax and is absent from unretted flax. Chemical degumming of flax appears to be superior to biological retting procedures with respect to the health of the workers.

     

RESPIRATORY FUNCTION AND SYMPTOMS IN ROPE MAKERS

This paper gives the results of a small environmental, symptomatic, and respiratory function study of byssinosis in a rope factory. An attempt was made to relate the changes in ventilatory function during the working day to the differing dust concentrations within the factory. The tests used included the forced expiratory volume, the forced vital capacity, and, in half the subjects, other derivatives of the forced expiratory spirogram. The inspiratory airways resistance was measured by the interrupter technique.

Measurements were made at the beginning and end of a working shift on either a Monday or a Tuesday in 44 subjects, of whom 22 were in a relatively dusty part of the factory and 14, involved in making wire rope, were exposed to very little dust.

None of the subjects had symptoms of byssinosis, but significant falls were found in the F.E.V._1·0, F.V.C., and other derivatives of the forced expiratory spirogram in those in the dusty parts of the factory. There was some evidence that the peak flow rate, the maximal mid-expiratory flow, and similar indices might be a little more sensitive as measures of the acute changes in ventilatory capacity during the day than the F.E.V._1·0 and F.V.C. There were no significant changes in the airways resistance by the interrupter technique but the results were rather variable.

The fall in ventilatory capacity during the day was not greater in those with symptoms of chronic cough and sputum than in those without, nor did it seem to be related to smoking, but the number of subjects studied was small.

     

Byssinosis among Winders in the Cotton Industry

In a mill spinning coarse cotton the prevalence of byssinosis and other respiratory symptoms, and the F.E.V._1·0, were measured in a group of 29 men and 117 women employed in the winding room. All the men and 95% of the women at risk were included.

Dust concentrations, measured with a modified Hexhlet at various work points in the winding room, ranged from 1·65 to 6·05 mg./m.³ total dust. These concentrations are higher than 1·0 mg./m.³, which is the threshold limit value for cotton dust recommended by the American Conference of Governmental Industrial Hygienists. The mean dust concentration was 3·48 mg./m.³ compared with 2·85 mg./m.³ in the card room of the same mill.

The prevalence of byssinosis was 18·8% among the women and 13·8% among the men. A comparison among the women showed that those with symptoms of byssinosis had, on the average, significantly lower F.E.V.s than women of similar age without such symptoms. Four women and one man with moderately severe symptoms of byssinosis showed evidence of permanent respiratory disability with effort intolerance and a substantial diminution in F.E.V._1·0. Further studies should be carried out in other winding rooms because, if these findings are repeated elsewhere, they would indicate the necessity for medical surveillance, dust control, and extending the compensation scheme to include winding room workers.

     

A study of the acute and chronic changes in ventilatory capacity of workers in Lancashire cotton mills

Berry, G., McKerrow, C. B., Molyneux, M. K. B., Rossiter, C. E., and Tombleson, J. B. L. (1973).Brit. J. industr. Med.,30, 25-36. A study of the acute and chronic changes in ventilatory capacity of workers in Lancashire cotton mills. A prospective study of workers in 14 cotton and two man-made fibre spinning mills in Lancashire was carried out over a three-year period. A questionnaire on respiratory symptoms was completed at the start of the survey and again two years later. Up to six measurements of ventilatory capacity were made at six-monthly intervals. From these measurements the rate at which the forced expiratory volume (FEV₁) was declining (annual decline in FEV) was evaluated for 595 subjects. Six of the mills were visited on Mondays and in 199 operatives the ventilatory capacity was measured at both the beginning and end of the shift to evaluate its acute fall during work (Monday fall in FEV).

The mean annual decline in FEV for cotton workers was 54 ml/year and it was only 32 ml/year for workers in the man-made fibre mills but this lower value was attributable almost entirely to one of the two mills. For the jobs near the carding engines the annual decline was 22 ml/year higher than for speed-frame tenters. The annual decline for cigarette smokers was 19 ml/year greater than for non- and ex-smokers. The annual decline in FEV was not found to be related to symptoms of byssinosis or bronchitis, nor to present dust levels, bioactivity of the dust or air pollution, although the expected effect attributable to byssinosis turned out to be less than that which the survey was designed to detect.

The mean Monday fall in FEV was higher in cotton mills than in man-made fibre mills among those without symptoms of byssinosis and was correlated with present dust levels. For those with symptoms of byssinosis an increased Monday fall was found only in those processing coarse cotton.

For those subjects who completed the respiratory questionnaire on two occasions the chronic and acute changes in FEV were examined in relation to the change in symptoms of byssinosis. No association was found for annual decline in FEV but the Monday fall in FEV was greater for those who developed byssinosis during the survey than for those who remained free of symptoms, and was less for those who lost their symptoms than for those who retained them.

     

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.

     

BYSSINOSIS IN CARDROOM WORKERS IN SWEDISH COTTON MILLS

The prevalence of byssinosis and chronic respiratory symptoms was studied in 117 workers in four Swedish cotton mills. Changes of forced expiratory volume in 0·75 sec. (F.E.V._0·75) during a Monday and a Wednesday were assessed in 64 male workers in four cardrooms in these mills. Dust sampling was performed with weighed millipore filters.

Prevalences of byssinosis as judged from the workers' histories were 68%, 55%, 44%, and 25% in the four mills; the lowest prevalence of 25% was found in a mill spinning both high grade cotton yarn and rayon. Among 67 workers in the mills having a byssinosis prevalence of 68% and 55%, 60% were non-smokers, 70% had chronic cough, and 27% had chronic dyspnoea. The F.E.V._0·75 decreased on Monday in workers who gave a history of Monday dyspnoea, and to a lesser degree, but still significantly, in those who did not.

In spite of marked differences in fine dust (i.e., dust smaller than 2 mm. diameter) concentrations in the four cardrooms, no significant relations between dust content, byssinosis prevalence, and F.E.V._0·75 changes on Monday could be demonstrated.

The prevention and treatment of byssinosis is discussed. Workers at risk should receive a periodical medical examination including at least a spirographical pulmonary function test at intervals of one year or less.

     

Byssinosis and serum IgE concentrations in textile workers in an Italian cotton mill

ABSTRACT The relationship between serum concentrations of total IgE and byssinosis and other respiratory symptoms was evaluated in 352 textile workers (90 men, 262 women) at a cotton mill in Friuli-Venezia Giulia, Italy. The subjects were aged from 20 to 61 (mean 44) and the mean duration of employment was 20 years. One hundred and eight subjects (30·7%) were smokers. Only 2% had a positive history of atopy. A standardised questionnaire showed chronic bronchitis in 96 textile workers (27·3%) and byssinosis in 63 (17·9%). The prevalence of respiratory disorders was the same for men and women but was higher in the carding room than in other work areas. Total serum IgE concentrations (RIST, Phadebas) were analysed after log transformation. The geometric mean was 192·7 IU/ml, with no significant difference between the two sexes. This mean concentration of IgE is much higher than that reported internationally for non-atopic subjects, but similar to values found in the Italian population. The IgE concentrations of the workers in the main departments (carding, spinning, and weaving) showed no significant difference. The geometric means were not different in subsamples stratified according to respiratory diseases (cases of pure and cases of mixed forms of chronic bronchitis and byssinosis). A negative result was obtained when IgE concentrations of 289 subjects without byssinosis (¯x = 188·4 IU/ml) and 63 with byssinosis (¯x = 212·6 IU/ml) were compared; there was also no trend when the results were analysed by clinical grade of byssinosis. The same negative pattern occured when the serum IgE concentrations were examined in patients with byssinosis with different grades of chronic change in FEV₁. The results of this study support the hypothesis that there is no relationship between total serum IgE concentrations and byssinosis.     

Differential Aerosol Challenge Studies in Byssinosis

Cotton textile mill workers with conditions diagnosed as byssinosis or not byssinosis by a modified Medical Research Council (MRC) questionnaire were challenged with extracts of cotton dust fractionated by filter membrane dialysis, and volatilization. Byssinotic subjects responded with a significant decrease in FEV_1.0 and with clinical symptoms to the inhalation of whole raw cotton extract and nonvolatile, nondialyzable cotton extract compared to saline, volatile extract, and dialyzable extract. Subjects without byssinosis responded the same to saline as to all other extracts. Comparison of responses of byssinotic and nonbyssinotic subjects showed no statistically significant differences with any extract. It was concluded that the active agent in cotton dust is water soluble, filterable at 0.22μ, nonvolatile at 40C, and nondialyzable but may not be active only in that group of patients identified as byssinotic by questionnaire.     

Use of radioisotopes in the study of textile workers with byssinosis and chronic lung damage

Vaskov, L. S. (1973).British Journal of Industrial Medicine,30, 37-41. Use of radioisotopes in the study of textile workers with byssinosis and chronic lung damage. A radioisotope method of measuring separately the circulation times for the pulmonary artery and pulmonary veins is described. Combined with pulmonary scintigraphy this method has been used to investigate textile workers with lung changes.

In the workers with no evidence of heart failure there was a prolongation of the pulmonary artery circulation time but no change in the pulmonary venous circulation time. In workers with signs of right heart failure there was a prolongation of right heart filling time as well as pulmonary artery circulation time but still no prolongation of the pulmonary venous circulation time. In this group the cardiac stroke volume was reduced but the output was maintained by a tachycardia. In spite of the prolonged pulmonary circulation time there was a reduction in pulmonary blood volume and poor perfusion on the scintigram.

     

Byssinosis

A respiratory screening program, including the administration of a questionnaire and pulmonary function tests, including one-second forced expiratory volume (FEV₁) and forced vital capacity (FVC), was carried out on employees working in cotton textile plants. This identified employees with byssinosis and other pulmonary conditions. The results revealed a marked relationship between the incidence of byssinosis and bronchitis and between byssinosis and lowered pulmonary function. Cigarette smoking appeared to further increase the incidence of bronchitis and lower pulmonary function. A drop in FEV₁ during the working day, though associated with, was often present without byssinosis symptoms. A combined program of dust control with medical evaluation and surveillance is practical. Identification of reactors to cotton dust and those with other pulmonary conditions enables the employer to lessen risk by localization of areas in need of improved environmental control and by selective placement of employees.     

Studies on the aetiology of byssinosis

Taylor, G., Massoud, A. A. E., and Lucas, F. (1971).Brit. J. industr. Med.,28, 143-151. Studies on the aetiology of byssinosis. A condensed polyphenol based on leucocyanidin has been extracted from the cotton plant. The reaction between this material and human serum has been demonstrated using both a precipitin and a passive agglutination technique. Sera from 196 cardroom workers not suffering from byssinosis, 177 byssinotic cardroom workers, and 203 controls were tested for reactivity with the condensed polyphenol using the passive agglutination technique. Significant differences in mean titres were obtained between cardroom workers and controls and between byssinotic and non-byssinotic cardroom workers. It was shown that while the mean titre in non-byssinotic cardroom workers remains relatively constant with respect to duration of employment, the titre in those cardroom workers suffering from byssinosis shows a progressive rise with duration of cardroom exposure.

Inhalation of solutions of the condensed polyphenol by normal control subjects and by non-byssinotic cardroom workers produced neither symptoms nor changes in FEV_1·0 or FVC. On the other hand, inhalation of the material by byssinotic cardroom workers induced symptoms identical with those experienced on exposure in the cardroom on Mondays. Because of the subjective nature of byssinosis, this inhalational study was repeated as a double-blind trial which completely confirmed the above observations.

     

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.

     

Study of lung function changes among different grades of byssinosis

El-Sadik, Y. M., Moselhi, M., El-Hinady, A. R., and Mostafa, M. N. (1972).Brit. J. industr. Med.,29, 184-187. Study of lung function changes among different grades of byssinosis. This study comprised 80 workers of whom 50 are byssinotics, 15 are chronic asthmatic bronchitics, and 15 are free of chest symptoms.

A comparison of the changes in forced expiratory volume in one second due to exposure in the first working day in the week among them (80 workers) showed a greater reduction in byssinotics than among the others. Reduced maximum expiratory flow rates were found only in byssinotics. Independent of exposure, only third-grade byssinotic cases (22 out of 50) showed changes in predicted vital capacity, residual volume, total lung capacity, three seconds per cent vital capacity, total vital capacity timed in seconds, and air velocity index.

The pattern of changes in these lung functions is mostly obstructive; only two cases showed the pattern of restrictive disease.

This study denotes that two types of changes in pulmonary functions occur due to byssinosis. The first type is a temporary change in pulmonary functions which occurs only on exposure to the aetiological factor (cotton or flax dust). This type occurs among all grades of the disease. The nature of this type is obstructive. The second type of change is permanent. This type occurs only among the third grade of the disease and is not dependent on immediate exposure. This type of change is mostly obstructive but may show some restriction.

     

The Pharmacological Activity of Extracts of Cotton Dust

Aqueous extracts prepared from dust collected in the card-rooms of several cotton mills have been prepared and found to contain activity which contracts the smooth muscle of guinea-pig ileum, guinea-pig trachea, rat stomach strip, and rat duodenum. The extracts contained an unknown contractor substance which was dialysable, resistant to boiling for one hour, and not destroyed by the action of proteolytic enzymes. They also contained a small amount of 5-hydroxytryptamine. One of the dust samples also contained histamine, but it could not be detected in the other samples, one of which was known to possess bronchoconstrictor properties in man. The particulate material, even after repeated washing, was found to have some stimulant action on guinea-pig ileum.

There was no evidence for the release of histamine by the extracts in either cats or guinea-pigs, although a very small amount was released in rats. Jute dust is much less active than cotton dust, and the activity differs qualitatively. Cotton dust extracts were found to have pyrogenic activity but it is unlikely that pyrogens were responsible for the smooth-muscle contractor properties. Experiments with whole animals suggest that although smooth-muscle contracting substances were present in the extracts, it is possible that the symptoms of byssinosis are caused by the release of some other active bronchoconstrictor substance in the tissues. The mechanism of the release is not known; it may be caused by a soluble principle in the extract or due to the presence of particulate matter in the dust.

     

VENTILATORY CAPACITY CHANGES ON EXPOSURE TO COTTON DUST AND THEIR RELEVANCE TO BYSSINOSIS IN AUSTRALIA

The same plan of investigation as was used in a previous study of jute workers (Gandevia and Milne, 1965) has been applied to a survey of 50 workers in the blowroom and carding and spinning area of a Sydney cotton mill. Significant decreases in ventilatory capacity were recorded on Friday, Monday, and the following Thursday, with, on the average, complete `overnight' recovery, as indicated by similar morning values. Slightly, but not significantly, greater differences were observed in seven subjects with mild byssinotic symptoms and in five subjects with an observed productive cough on request. No effect of sex, shift, or history of cough and sputum was demonstrable. By contrast with the jute workers, no influence of smoking habit was apparent. The larger decreases in ventilatory capacity were observed in those with the higher F.E.V.<sub>1·0</sub>:F.V.C. ratios, whereas the reverse trend was noted in the jute workers. The occurrence of significant large decreases in those employed in the industry for less than a month, in conjunction with other evidence, suggests that a factor of `self-selection' may be operative among cotton employees in this country and may be related to the apparently low prevalence of clinically important byssinosis. Attention is drawn to two different patterns of change of ventilatory capacity over a week in subjects exposed to dusts sometimes associated with symptoms of byssinosis; the relationship of these changes and of chronic bronchitis to the development of clinical byssinosis is discussed.     

Discrimination between Byssinosis and Chronic Bronchitis in Cotton Mill Workers by Serum Immunoglobulin Patterns

A study of immunoglobulins in 29 normal (17 community and 12textile) subjects, 34 clinic patients and 74 abnormal textileworkers, revealed a significant rise in IgG and a fall in IgDand IgM in the presence of work-related chest symptoms (byssinosis).The rise in IgE levels seemed more closely related to bloodeosinophilia. There was no rise in IgG or E in textile workerswith symptoms of ‘chronic bronchitis’. These dataadd further evidence that byssinosis may be distinct from chronicbronchitis. Dr S. R. Kamat, Department of Chest Medicine, Seth G.S. Medical College and K.E.M. Hospital, Bombay 400 012, India.     

Byssinosis in the Waste Cotton Industry

This paper is of some historical interest. It describes an investigation to determine whether byssinosis occurred among workers in the waste cotton industry. It was undertaken in 1950 at the instigation of the Minister of National Insurance.

The materials used in the industry were (1) cotton that had been previously spun, and (2) waste material discarded during the preparations for spinning higher grades of yarn. A proportion of raw cotton was sometimes blended with the waste.

Twenty-two mills, representative of the industry, were surveyed. All the men in these mills, who were over 35 years of age and with at least 10 years' exposure to cotton dust, were seen. The investigations included a work history, a clinical examination, an assessment of effort dyspnoea, and a chest radiograph.

There were 140 men who had never been exposed to any dust hazard other than waste cotton. In this group were found seven (5%) men with disabling byssinosis and 35 (25%) men with lesser degrees of the same disease. There were also 15 (11%) men with bronchitis or emphysema without byssinosis.

Thus it was established that byssinosis did occur in the waste cotton industry. Insurance cover, under the National Insurance (Industrial Injuries) Act, 1946, was subsequently extended to workers in the waste cotton industry.

The survey provided no evidence that either the type of waste cotton processed or an admixture of raw cotton played a significant part in the aetiology or incidence of the disease.

     

Dust Diseases in Dundee Textile Workers: An Investigation into Chronic Respiratory Disease in Jute and Flax Industries

A survey of respiratory symptoms and function was carried out in Dundee among 123 men and women in the jute industry and 242 in the flax industry. The selection of workers was biassed in favour of those working in the dustier departments as judged by eye and those in the older age groups. A group of 72 men in a heavy engineering firm were also selected as controls for comparison.

Chronic bronchitis, as defined by Ogilvie and Newell (1957) was recorded in 27% of those interviewed, whose average age was 49. Byssinosis of various grades was recorded in 30% of all working in flax; of these 35 had cough alone worse on Monday, 34 had other respiratory symptoms worse on Monday and in only four persons did the exacerbation persist longer in the week.

In spite of the occurrence of byssinosis, chronic bronchitis was no more prevalent among flax workers than among the others, the average ventilatory function was no worse, and radiographs of the chest revealed no differences. The characteristic fall in expiratory flow rate during the course of exposure to flax dust on Mondays is similar to that found in cotton workers, and is absent in jute workers and in flax workers not admitting to symptoms of byssinosis.