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Biomedical subjects

M Chan-Yeung

Publications and source records attributed to M Chan-Yeung.

At least 19 recordsLinked to original sources

Five cross-sectional studies of grain elevator workers.

Five cross-sectional studies were conducted on grain workers in all the terminal elevators in British Columbia, Canada, at 3-year intervals from 1976 to 1988. Civic workers were studied in the same manner as a referent group. The studies consisted of questionnaires, spirometry using the same spirometers, allergy skin tests, and measurement of dust concentration by personal sampling. Although the dust concentration in the elevators was reduced progressively over the years, grain workers had more respiratory symptoms and lower lung function compared with the civic workers in each of the five cross-sectional studies. Exposure to grain dust was associated with significant reduction in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) but not in maximal midexpiratory flow rate or FEV1/FVC, suggesting reduction in volume which may be due to lesions in the lung parenchyma or in the small airways. Cigarette smoking was associated with significant reduction in FEV1, maximal midexpiratory flow rate, and FEV1/FVC due to airflow obstruction, but had no influence on FVC. Workers who took part in all five surveys tended to be a "healthier" selected group, but the grain workers still had lower lung function compared with the civic workers. This study confirmed previous findings that grain dust has adverse effects on the lungs. Cross-sectional study of the grain elevator workers proved to be a consistent and useful method to evaluate occupational health hazards.

Adult

Polyphosphoinositide hydrolysis and protein kinase C activation in guinea pig tracheal smooth muscle cells in culture by leukotriene D4 involve a pertussis toxin sensitive G-protein.

Leukotriene D4 (LTD4) at concentrations greater than 1 nM induced phosphatidylinositol bisphosphate (PIP2) hydrolysis and protein kinase C (PKC) activation in primary culture of airway smooth muscle cells. Within seconds of activation, an increase in inositol 1,4,5-trisphosphate (IP3) was observed reaching a maximum at 5 min. The level of IP3 decreased after 5 min and was followed by an increase in inositol 1,4-bisphosphate (IP2) and inositol 1-monophosphate (IP1). LTD4-induced PIP2 hydrolysis was inhibited by 1 h pretreatment of cells with 10 micrograms/ml of pertussis toxin (PTX). LTD4 activated both soluble and particulate forms of PKC by 2-3-fold. The LTD4-induced PKC activation was blocked by treatment of cells with PTX, suggesting the involvement of a PTX-sensitive G-protein. To assess the involvement of G(i) in smooth muscle cell receptor activation, the modulation of adenylyl cyclase activity was investigated. LTD4 did not stimulate cAMP formation in smooth muscle cells, and did not inhibit forskolin-induced cAMP formation. These data suggest that the LTD4 receptor in airway smooth muscle cells is coupled to a PTX-sensitive G-protein, possibly G(o).

Adenylate Cyclase Toxin

Natural history of occupational asthma: relevance of type of agent and other factors in the rate of development of symptoms in affected subjects.

It is unknown whether factors such as the nature of the agent, gender, age, atopy, smoking habits, continuous or noncontinuous exposure, and pattern of asthmatic reaction can influence the rate of development of symptoms in subjects with occupational asthma. We compared several clinical and functional parameters among three groups of subjects with occupational asthma caused by Western red cedar (group 1, n = 433), isocyanates (group 2, n = 107), and high molecular weight agents acting through an IgE-mediated mechanism (group 3, n = 121). Survival analysis showed that the three curves relating years of exposure before onset of symptoms to the proportion of subjects without symptoms were significantly different in two respects: (1) almost 40% of subjects in groups 1 and 2 as compared with 20% of subjects in group 3 became symptomatic within 1 year of exposure; (2) after 5 years of exposure, the rate of sensitization was slower for subjects in groups 2 and 3 as compared with those in group 1. Having a nonimmediate reaction at the time of specific inhalation challenges, being continuously exposed and being younger slightly increased the risk at each time point on the curve of developing symptoms in subjects with occupational asthma. These data suggest that the natural history for onset of occupational asthma is different depending on the sensitizing agent. Factors such as age, type of exposure, and pattern of reaction on exposure to the agent also modulate the rate of development of this condition.

Adult

Methacholine responsiveness, smoking, and atopy as risk factors for accelerated FEV1 decline in male working populations.

Longitudinal lung function data from four occupational health surveys was used to explore the relationship between nonspecific bronchial responsiveness (NSBR) and the rate of decline of FEV1 (RDFEV) and to address other factors that may predict or influence RDFEV. Of the 1,203 subjects with baseline methacholine and lung function data, follow-up data were available for 733 individuals (61%). The data-available and data-unavailable groups were well matched with respect to baseline lung function, atopy, and smoking status. Compared with the unavailable group, those available for follow-up were younger (42.5 versus 37.7 yr; p less than 0.0001) and slightly less responsive to methacholine (p less than 0.01). Somewhat unexpectedly, RDFEV was lower in the 30 asthmatic subjects than in the nonasthmatics. Among the nonasthmatic subgroup (96% of those available for follow-up), age, occupational group, and baseline FEV1 (% predicted) were independent predictive factors for RDFEV. When these factors were included in the model, RDFEV was found to be increased among current smokers compared with never-smokers or ex-smokers. In the final regression model, a relationship was found between methacholine sensitivity (calculated as a dose-response slope) and RDFEV in nonasthmatics (p less than 0.05). Stratification by smoking status revealed that the relationship between RDFEV and bronchial responsiveness was confined to current smokers and that atopy was an additional risk factor in this subgroup only. This relationship was valid among current smokers in each of the three occupational groups studies. However, reinclusion of the 30 asthmatic subjects in the study population obscured the relationship between NSBR and RDFEV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Bronchial hyperresponsiveness and level of exposure in occupational asthma due to western red cedar (Thuja plicata). Serial observations before and after development of symptoms.

Four workers from a cedar sawmill who developed red cedar asthma are described. They had serial measurements of lung function and nonspecific bronchial hyperresponsiveness (NSBH) several years before and after the development of chest symptoms. Measurements of dust concentration and specific IgE antibodies to plicatic acid-human serum albumin (PA-HSA) conjugate were also carried out before the onset of disease. NSBH developed in parallel with the development of asthma and was not present in any of the workers beforehand, indicating that it is not a predisposing host factor. Nasal symptoms preceded chest symptoms in three workers, suggesting that this may be an early marker of the disease. Although dust concentrations for jobs located both inside and outside the sawmill were low, jobs associated with somewhat higher exposures were associated with the initiation of asthma symptoms.

Adult

First-aid reports of acute chlorine gassing among pulpmill workers as predictors of lung health consequences.

Workers in pulpmills can be exposed to a multitude of gases hazardous to respiratory function, the most common of which is chlorine gas. First-aid reports of acute gas overexposure incidents ("gassings") over an 8 year period were used to generate exposure data on a group of pulpmill workers whose respiratory function had been studied cross-sectionally in 1981 and 1988. Three hundred forty-eight incidents representing 174 workers were identified, 78% of these being treated solely by the first-aid attendant with the administration of O2 and cough suppression medication. Among 316 workers tested during a 1988 respiratory health survey, 78 had at least one chlorine or chlorine dioxide "gassing" incident. There was a significant decrease in the FEV1/FVC ratio (p less than .05) as well as increased risk for workplace associated chest symptoms in this group with at least one "gassing" incident. In an age- and smoking-matched analysis, among workers tested both in 1981 and 1988, there was a greater decline in FEV2/FVC ratio and MMF (p less than .05) in the "gassed" group than in the nonexposed group over the 7 year period of observation. These results emphasize the need for worker protection against accidental chlorine gas exposures.

Analysis of Variance

Lung function and chest radiograph abnormalities among construction insulators.

We carried out a prevalence survey of pulmonary health parameters among current and retired construction insulators (50 years old and older) from all areas of British Columbia, Canada. The study population included 59 active workers (81 percent participation in this group) and 29 workers who were retired or inactive due to illness (69% participation). Radiograph results were compared to those from actively working bus mechanics from the same age group, and retired grain and civic workers, who were all tested in the same manner. Chest radiographs were read independently by two readers and were graded according to the ILO classification system. Pleural abnormalities alone were found in 34% (20) of active workers (5% in comparison group) and 45% (13) of non-active workers (14% in comparison group). Rates for parenchymal abnormalities for these same groups (ILO grade 1/0 or higher) were 17% (5%) and 20% (5%), respectively. Airflow obstruction was present in 35% (31) of the insulators and was associated with age and the presence of diffuse pleural thickening, and 5 or more years of employment in pulp mills. Restrictive lung function was present in 22% (19) of the insulator population and was associated with age and radiographic evidence of parenchymal fibrosis. The results indicate that construction insulators, a group at high risk for asbestos-related lung disease, also have a high prevalence of airflow obstruction. This was associated not only with smoking, but also with diffuse pleural thickening and a history of pulp-mill employment, suggesting that airflow obstruction in this population is also partly work related.

Aged

Differences in mediator release between allergic rhinitis and asthma.

To determine why patients with allergic rhinitis alone differ in their airway response to inhaled allergen compared to patients with allergic asthma, bronchial lavage was performed in 10 subjects with allergic asthma and in five subjects with allergic rhinitis, before and after inhalation challenge with antigen to produce an immediate asthmatic reaction. Before antigen challenge, the subjects with asthma had higher absolute neutrophil counts in the lavage fluid. After antigen challenge, the subjects with asthma released significant amounts of bronchoconstrictive mediators, such as histamine and thromboxane B2 into the lavage fluid, whereas subjects with rhinitis alone did not. There was also a significant increase in prostaglandin E2 in the subjects with asthma after antigen challenge. Nonimmunologic bronchoconstriction with methacholine inhalation challenge in six other subjects with asthma did not demonstrate an increase in any of the lavage fluid mediator levels that were measured. A positive correlation was found between methacholine provocative concentration causing a 20% drop in FEV1 and the concentration of prostaglandin E2 in the lavage fluid before challenge. The significance of this observation has yet to be determined. The results suggest that subjects with allergic asthma differ from subjects with rhinitis alone in their capacity to release more mediators into the airways on antigen challenge. It is not known whether this increase in mediators is due to increase in the number of mast cells in the airways or due to increase in mediator releasability from the mast cells of subjects with asthma.

Adult

Reassessment of the temporal patterns of bronchial obstruction after exposure to occupational sensitizing agents.

Typical asthmatic reactions after exposure to common or occupational allergens have been classified as isolated immediate, early late, late, and dual (Pepys and Hutchcroft, 1975). Atypical reactions can also occur, but their temporal behavior and frequency are unknown. We analyzed 69 bronchospastic reactions after exposure to three types of occupational sensitizers in the laboratory: isocyanates, western red cedar, and IgE sensitizing agents. Graphs of the reactions were presented to three observers in a blind, randomized way. Reactions were defined as follows: (1) typical patterns, that is, isolated immediate, early late, late, and dual, as put forward by Pepys and Hutchcroft, and (2) atypical patterns including progressive (onset, during, or minutes after exposure, progressing to a maximum reaction 5 to 6 hours later) and square waved (similar to a dual reaction but with only partial recovery [less than 10%] between the immediate and late falls in FEV1). Some curves were also analyzed by polynomial regression. The three observers agreed in 59/69 cases (86%), and a consensus was reached after discussion for the remaining subjects. Fifteen of 63 (22%) reactions were atypical. IgE-mediated reactions and reactions to red cedar were, respectively, mainly of the immediate and late types. The distribution of reactions to isocyanates, however, was significantly different (chi-square, 6.1; p = 0.01), the "progressive" pattern occurring in 7/23 instances (30%). There was a satisfactory concordance between visual assessment and polynomial fit analysis in distinguishing dual from square-waved reactions. We conclude that isocyanates frequently cause atypical progressive bronchospastic reactions that are rarely observed after exposure to IgE agents and western red cedar.

Adult

The release of platelet-activating factor into plasma during allergen-induced bronchoconstriction.

Plasma histamine and platelet-activating factor (PAF) were measured in six subjects with mild seasonal asthma before and after allergen-induced bronchoconstriction, and in six other patients with asthma before and after methacholine-induced bronchoconstriction. A significant increase in plasma histamine and PAF levels was found in patients with mild seasonal asthma after allergen-induced bronchoconstriction but not in patients with asthma after bronchoconstriction induced by methacholine. There was a significant correlation between the baseline plasma PAF levels and the degree of bronchial hyperresponsiveness to methacholine. These findings suggests that PAF may be an important mediator in the pathogenesis of asthma and bronchial hyperresponsiveness.

Biological Assay

Occupational asthma caused by exposure to neurospora in a plywood factory worker.

A 24 year old man developed severe asthma two years after starting to work in a plywood plant. Four years later the patient had to stop working because of the increasing severity of his asthma. Three months after leaving his job, the patient's asthma was greatly improved. His job consisted of placing plywood sheets into a drying machine. The plywood sheets had stayed outside in wet conditions for at least four to six weeks and were usually covered with moulds. Drying the plywood sheets changed the mould into a fine orange powder. Exposure to this in the laboratory induced an isolated immediate asthmatic reaction. The same reaction was seen when the patient was challenged with an extract of the mould powder at a 0.1% w/v concentration. Skin prick test with the mould extract induced a weal and flare reaction and IgE antibodies against the dry mould powder were identified. A control patient with the same degree of bronchial hyperreactivity did not have any asthmatic reaction when challenged with the same mould extract. Culture of the dry mould powder on Sabouraud agar plates grew pure Neurospora sp. This mould has not been previously reported as a cause of occupational asthma. The immunological mechanism is probably related to an IgE mediated mast cell allergy.

Adult

Lung health consequences of reported accidental chlorine gas exposures among pulpmill workers.

The long-term consequences of accidental chlorine gas exposure have been investigated, mainly in the community setting, among persons exposed as a result of a nearby chlorine spill. This circumstance is not analogous to the more frequent chlorine or chlorine dioxide gas overexposures that occur commonly in pulpmills over a background of a low level of gas exposure. To investigate the respiratory health consequences of these accidental exposures ("chlorine gassing") in the industrial setting, we carried out a cross-sectional respiratory health survey among workers at a British Columbia coastal pulpmill and a nearby rail maintenance yard. A greater proportion of pulpmill workers were unavailable for study because of illness (10.5% versus 2.4% in the railyard, p less than 0.01). Procedures involved simple spirometry, respiratory symptom assessment, and measurement of average levels of air contaminants. Average chlorine levels in the pulpmill were below 1 ppm; however, 60% of the pulpmill workers reported one or more accidental "chlorine gassing" incidents. Pulpmill workers who reported being "gassed" were significantly more likely to report wheezing on occasion than were other pulpmill workers and railyard workers (rate for these three groups: nonsmokers: 8, 2, 1%; ex-smokers: 17, 11, 7%; current smokers: 42, 21, 19%; p less than 0.05). No significant lung function differences were found between the overall pulpmill group and the railyard workers; however, nonsmoking and formerly smoking pulpmill workers who reported being "gassed" had significantly lower average midmaximal flow rate and FEV1/FVC ratio than did their counterparts in the remainder of the pulpmill population (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Occupational

Grain dust and lung function. Dose-response relationships.

Grain dust exposure has been associated with both acute and chronic respiratory abnormalities. We sought to answer two questions with regard to this exposure: (1) is there a dose-response relationship between grain dust and respiratory abnormalities, and (2) is there evidence to suggest that the allowable exposure (currently 10 mg/m3 in Canada) be lowered? We compared respiratory symptoms and lung function among 454 grain elevator workers and 55 civic workers to estimates of lifetime average grain dust exposure. A total of 781 personal air samples representing 20 different job titles over a 15-yr period were used to construct a job title-time period matrix for average dust exposure levels. The matrix was applied to each worker's detailed job history to obtain a value for estimated cumulative and average dust exposure. Significant dose-response relationships were seen for chronic phlegm production, breathlessness on exertion, FEV1, and FVC; and dose-response trends were evident for the longitudinal change in both FEV1 and FVC. Workers with estimated average exposure between 4 and 9 mg/m3 were found to have significantly lower values for FEV1 and FVC compared to both grain workers exposed to less than 4 mg/m3 on average and civic workers, despite no difference in duration of employment among these groups. The results indicate a strong dose-response relationship between grain dust exposure and both respiratory symptoms and lung function and also suggest that the current Canadian allowable exposure level of 10 mg/m3 is too high.

British Columbia

Characterization of health effects of wood dust exposures.

Exposure to wood dust is a common occurrence in all countries and may cause various diseases. These include extrinsic allergic alveolitis, organic dust toxic syndrome, occupational asthma, non-asthmatic chronic airflow obstruction, and simple chronic bronchitis (mucus hypersecretion). Of these conditions, the most common are simple chronic bronchitis and non-asthmatic chronic airflow obstruction. The level and pattern of occurrence of these conditions varies with the type of wood dust, climatic conditions, and the manner in which it is handled, particularly the use of fungicides. The prevalence and characteristics of the conditions associated with wood dust exposure are very similar to those due to grain dust exposure.

Alveolitis, Extrinsic Allergic

Sensitivity and specificity of PC20 and peak expiratory flow rate in cedar asthma.

The diagnosis of red cedar asthma is usually confirmed by a specific challenge with plicatic acid, the compound responsible for the disease. We performed this study to determine the sensitivity and specificity of two other diagnostic tests, prolonged recording expiratory flow rate (PEFR) and measurement of bronchial responsiveness (provocative dose of methacholine causing a 20% fall in FEV1 [PC20 methacholine]). Twenty-three patients with suspected cedar asthma participated in the study. The patients recorded PEFR during 2 weeks away from work and 3 weeks at work. PC20 was measured both at the end of the nonworking and working period. An obvious decrease in PEFR in 2 of 3 working weeks, when PEFRs of weekends or holidays were compared (by visual inspection of the PEFR recording), and a decrease in PC20 by more than a twofold dilution, when the patient returned to work, were considered as positive tests for cedar asthma. Plicatic acid challenge test was performed at the end of the study; 14 patients reacted, whereas nine patients did not. With the results of the plicatic acid challenge test as the gold standard, the sensitivity and specificity of PEFR recordings were 86% and 89%; changes in PC20, 62% and 78%; and 93% and 45% for a positive clinical history. The combination of PEFR and clinical history revealed a 100% sensitivity with a 45% specificity. Combination of PEFR and PC20 did not improve the diagnostic accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens

Outcome of patients with cedar asthma with continuous exposure.

After an average follow-up of 6.5 yr (range 1 to 13), 48 of 48 patients with cedar asthma, who were still working in the same industry, were re-examined. In all of them, the diagnosis of cedar asthma had been confirmed with a specific challenge inhalation test with plicatic acid. We graded the severity of asthma symptoms and the requirement for antiasthma medications at the time of diagnosis and at the time of follow-up visit. Spirometry and measurement of airway responsiveness to methacholine (PC20 methacholine) were also done on both visits. The increase or decrease in asthma symptoms, medications requirement, FEV1 and PC20 methacholine between the follow-up and the diagnostic visit were used to determine the outcome of the patients. Using these parameters, 10.4% of patients improved, 62.5% remained stable, 37.5% deteriorated, and none recovered. Among the characteristics of the patients observed at the time of diagnosis, the age of the patient, the atopic status, smoking habit, and the presence of specific IgE to plicatic acid were not useful in predicting the eventual outcome. Reduction of exposure by transfer to a less dusty job and the use of an airstream helmet did not prevent deterioration of asthma. Only the use of the twin-cartridge respirator was associated with a favorable outcome. We conclude that among cedar asthmatics who remained exposed to cedar dust for an average of 6.5 yr, over one-third showed marked deterioration of their asthma symptoms. There is also no way to predict who will deteriorate. A decrease in the amount of exposure to cedar dust does not prevent deterioration of asthma. This suggests that the ideal management of cedar asthma is removal from exposure.

Allergens