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Biomedical subjects

A Desjardins

Publications and source records attributed to A Desjardins.

At least 19 recordsLinked to original sources

Exaggerated bronchoconstriction due to inhalation challenges with occupational agents.

Inhalation challenges with occupational agents are used to confirm the aetiology of occupational asthma. It has been proposed that using closed-circuit equipment rather than the realistic challenge method would improve the methodology of these tests. Changes in forced expiratory volume in one second (FEV1) were examined in 496 subjects with "positive specific inhalation challenges", i.e. changes in FEVI of > or = 20% after exposure to an occupational agent, including 357 subjects exposed by the realistic method, 108 using the closed-circuit method and 31 by both methods. For immediate reactions, 18 of 95 (19%) showed changes in FEV1 of > or = 30% with the closed-circuit method, whereas a significantly larger proportion, i.e. 77 of 200 (38.5%), showed such changes using the realistic method. As regards nonimmediate reactions, changes in FEV1 of > or = 30% occurred in 16 of 43 (37%) cases with the closed-circuit method as compared to a larger proportion, i.e. 87 of 180 (48%) cases, using the realistic method. This favourable effect was significantly more pronounced in workers with higher levels of bronchial hyperresponsiveness to methacholine. It is concluded that, for agents that can be generated using the closed-circuit method, use of such apparatus results in a smaller proportion of exaggerated bronchoconstriction than does the realistic method, this being particularly true for low-molecular weight agents.

Administration, Inhalation↗

Differential behaviour of fluid liposomes toward mammalian epithelial cells and bacteria: restriction of fusion to bacteria.

Previous work demonstrated that fluid liposomes developed in our laboratory are able to fuse with bacterial outer membranes. This fusion improved the penetration and activity of liposome-encapsulated antibiotics and antisense oligonucleotides into the bacterial cells. Because it is anticipated that fluid liposome encapsulated antibiotics will be administered by aerosols to patients with chronic pulmonary infections or cystic fibrosis (CF), we conducted comparative studies in E. coli, P. aeruginosa and human lung epithelial cells using lipid-mixing assays to investigate the possibility that fluid liposomes might fuse with surrounding epithelial cells. After a 2 h incubation at 4 and 37 degrees C, no fusion between fluid liposomes and human lung epithelial cells was observed, whereas mean levels of 71 and 37% of fusion were observed at 37 degrees C with E. coli and P. aeruginosa cells, respectively. No fusion was observed at 4 degrees C in any cells. A kinetic study where temperature was gradually increased from 7 to 37 degrees C indicated that the fusion process in the two bacteria starts between 28 and 31 degrees C with a mean fusion rate of 0.60%/min at 31 degrees C to reach 1.18%/min at 37 degrees C. The present work suggests that it is unlikely that fluid liposomes fuse with host cells lining the human respiratory tract and further elucidates the fusogenic properties of fluid liposomes with respect to prokaryotes and eukaryotes.

Bacteria↗

Encapsulation of DNA in negatively charged liposomes and inhibition of bacterial gene expression with fluid liposome-encapsulated antisense oligonucleotides.

Antisense therapy for the treatment of bacterial infections is a very attractive alternative to overcome drug resistance problems. However, the penetration of antisense oligonucleotides into bacterial cells is a major huddle that has delayed research and application in this field. In the first part of this study, we defined efficient conditions to encapsulate plasmid DNA and antisense oligonucleotides in a fluid negatively charged liposome. Subsequently, we evaluated the potential of liposome-encapsulated antisense oligonucleotides to penetrate the bacterial outer membrane and to inhibit gene expression in bacteria. It was found that 48.9+/-12% and 43.5+/-4% of the purified plasmid DNA and antisense oligonucleotides were respectively encapsulated in the liposomes. Using fluorescence-activated cell sorting analysis, it was shown, after subtraction of the fluorescence values due to the aggregation phenomenon measured at 4 degrees C, that about 57% of bacterial cells had integrated the encapsulated antisense oligonucleotides whereas values for free antisenses were negligible. The uptake of the encapsulated anti-lacZ antisense oligonucleotides resulted in a 42% reduction of beta-galactosidase compared to 9% and 6% for the encapsulated mismatch antisense oligonucleotides and the free antisense oligonucleotides respectively. This work shows that it is possible to encapsulate relatively large quantities of negatively charged molecules in negative fluid liposomes and suggests that fluid liposomes could be used to deliver nucleic acids in bacteria to inhibit essential bacterial genes.

DNA↗

Prevalence and intensity of rhinoconjunctivitis in subjects with occupational asthma.

Subjects with occupational asthma may also report symptoms of rhinoconjunctivitis. The aims of this study were: 1) to assess the prevalence of rhinoconjunctivitis in association with occupational asthma, and the severity of rhinoconjunctivitis according to the type of agent (high (HMW) and low (LMW) molecular weight agents) causing occupational asthma; and 2) to evaluate the timing of occurrence of symptoms of rhinoconjunctivitis in relation to those of occupational asthma. A questionnaire on symptoms of rhinoconjunctivitis and its timing in relation to the development of chest symptoms was prospectively addressed to 143 subjects consecutively referred to an occupational asthma clinic. Objective testing through specific inhalation challenges confirmed the diagnosis of occupational asthma in 40 subjects. Symptoms of rhinitis were reported at some time by 37 of the 40 subjects (92%), and of conjunctivitis by 29 of the 40 subjects (72%). The prevalence of symptoms was not different for HMW and LMW agents, although rhinitis was more intense for HMW (19 out of 24 subjects with three or more of the following symptoms: runny nose, itchy nose, nasal blockage, and sneezing) than for LMW (5 out of 14 subjects) (p<0.01). There were significantly fewer subjects with occupational asthma due to LMW agents, with rhinitis appearing before asthma (p=0.03). Figures for conjunctivitis showed a similar trend, but did not reach statistical significance. In conclusion, symptoms of rhinoconjunctivitis are often associated with occupational asthma. Rhinitis is less pronounced in the case of low molecular weight agents, but more often appears before occupational asthma in the case of high molecular weight agents.

Adult↗

Fever and leucocytosis accompanying asthmatic reactions due to occupational agents: frequency and associated factors.

Fever is sometimes associated with asthmatic reactions following specific inhalation challenges with occupational agents. Our aims were to estimate the prevalence of fever in subjects with occupational asthma confirmed by specific inhalation challenge and to examine the characteristics and clinical correlates of subjects who develop fever on specific inhalation challenge. We performed a retrospective analysis of 317 subjects who had positive specific inhalation challenge to occupational agents and a comparison of subjects who developed fever after specific inhalation challenge with a random sample of those who did not. Fifteen subjects (5%) developed fever associated with positive specific inhalation challenge. They were compared with a random sample of 60 subjects who did not develop fever. The fever group: 1) showed a larger increase in absolute number of blood neutrophils, and a larger decrease both of blood lymphocytes and forced vital capacity after specific inhalation challenge; 2) included fewer atopics; 3) had been exposed more frequently to low rather than high molecular compounds; and 4) always experienced a late reaction and had more atypical reactions. We conclude that after positive specific inhalation challenge; fever occurs infrequently, and is associated with an increase in blood neutrophils and a decrease in blood lymphocytes and forced vital capacity. Such reactions seem more likely to occur in nonatopic subjects exposed to low molecular weight agents.

Adult↗

Occupational IgE-mediated sensitization and asthma caused by clam and shrimp.

BACKGROUND: To confirm occupational asthma caused by clam and shrimp in a food company worker, the following investigation was planned in 60 other exposed workers (56 participants). METHODS: Before the production period of clam and shrimp, a medical and occupational questionnaire was carried out and skin and RAST testing were done with common inhalants and clam, shrimp, crab, and lobster extracts. During the production period, environmental monitoring was performed with personal and general samplers; inhalation testing with methacholine was proposed to subjects with immediate skin reactivity to clam, shrimp, or both. After the production period, all subjects with an immediate skin reactivity to clam, shrimp, or both and either a history of rhinoconjunctivitis, asthma, or bronchial hyperresponsiveness were seen by a specialist. RESULTS: Including the index case in whom occupational asthma to clam and shrimp had been confirmed, four (7%) subjects had a history of rhinoconjunctivitis and two (4%) had a history of asthma during the period of clam production, whereas three (5%) subjects had rhinoconjunctivitis and two (4%) had asthma during the shrimp production. Three (5%) subjects had immediate skin reactivity to clam, and nine (16%) subjects to shrimp. Four (7%) subjects had increased specific IgE antibodies (RAST binding > or = 3%) to clam and eight (14%) to shrimp. Significant associations were found between immunologic reactivity to clam and shrimp on the one hand and to crab and lobster on the other. Environmental monitoring demonstrated clam and shrimp on the air sampling filters. Occupational asthma caused by clam was confirmed by specific inhalation challenges in one subject in addition to the index case. These two subjects had skin reactivity and increased specific IgE antibodies to clam, shrimp, or both. CONCLUSION: By including the initial subject, the prevalence of immediate sensitization is 5% to 7% to clam and 14% to 16% to shrimp. Two (4%) subjects had occupational asthma caused by clam, and one (2%) had occupational asthma caused by shrimp.

Adult↗

Occupational asthma caused by dry metabisulphite.

A case is described of occupational asthma in a worker with no previous history of asthma who sprinkled dried metabisulphite powder onto potatoes and developed work-related symptoms. Occupational asthma was confirmed by specific inhalation challenges.

Adult↗

Occupational asthma caused by oak wood dust.

Three cases of occupational asthma caused by oak wood dust are presented. The diagnosis was confirmed by specific inhalation challenges, which induced a dual asthmatic reaction in two subjects and an atypical prolonged immediate reaction in one subject.

Adult↗

Occupational asthma due to formaldehyde resin dust with and without reaction to formaldehyde gas.

We report the cases of three subjects who developed asthma after being exposed to formaldehyde dust or gas. For two subjects, specific bronchial provocation tests with formaldehyde gas did not cause significant bronchoconstriction, whereas exposure to formaldehyde resin dust did. One subject experienced asthmatic reaction after being exposed to formaldehyde resin dust and gas. These findings suggest that the physical and chemical properties of formaldehyde are relevant to its likelihood of causing asthma.

Adult↗

Assessment of respiratory limitation in activities of daily life among retired workers.

Epidemiologic studies of occupational lung diseases generally compare symptoms and pulmonary function between groups with differing exposure risks. However, the functional consequences (e.g., on activities of daily life) of statistically significant group differences in either symptoms or pulmonary function are rarely addressed. An understanding of this is important for both the scientific investigators and users of these public health investigations. To address this issue, we developed a 15-item questionnaire to assess breathing-related limitations in activities of daily life, and applied this in a study of 112 retired workers. For each subject, we calculated a limitation score as the number of items associated with breathing difficulty divided by the total number of applicable items. Results from this questionnaire were compared to respiratory symptoms, the Sickness Impact Profile (SIP), lung function test results, 6-min walking distance, and participants' assessment of breathing effort after the walk. The limitation score was significantly higher in subjects reporting dyspnea (22% versus 4%, p < 0.01) or occasional wheeze (27% versus 6%, p < 0.01), and correlated negatively with FEV1, MMEF, and FEV1/FVC (R2 = -0.47, -0.36, and -0.45, respectively, p < 0.0001) and breathing effort after the 6-min walk (R2 = 0.31, p < 0.01). Breathing related limitation in daily activities was also associated with a general health related limitation in household maintenance and ambulation in the SIP (p < 0.01). For each questionnaire item, we compared the responses among subjects with a normal FEV1 to those of subjects with an abnormal FEV1 (below the lower 95% confidence limit).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

Respiratory health among retired grain elevator workers.

Previous studies of grain elevator workers have shown exposure-related increased rates for respiratory symptoms and reduced levels of lung function compared with those of other employed populations. However, some reports have suggested that this effect may be reversible after cessation of exposure. To investigate this, we conducted a respiratory health survey among 75 retired grain elevator workers and 37 retired civic workers. Methods included a standard respiratory questionnaire, routine spirometry, chest radiography, a 6-min walk test, and a specialized questionnaire to assess the impact of breathing trouble on the activities of daily life. Grain retirees were slightly older than civic retirees (69 versus 67 yr, p < 0.05) and less likely to be atopic (7 versus 35%, p < 0.01). Grain elevator retirees reported more dyspnea (44 versus 11%, p < 0.01) and had significantly lower levels for both FEV1 (78.6 versus 88.2% pred) and FVC (90.0 versus 97.7% pred) (both p < 0.05). Compared with civic retirees, grain retirees reported the same average level of breathlessness after the 6-min walk test, but they walked a significantly shorter distance (p < 0.01); they also scored higher on the impairment of activities scale and had a greater proportion of persons reporting impairment of daily activities caused by breathing trouble (p < 0.05). Comparison of the changes in lung function from 1975 to the present study (i.e., from active employment to retirement) showed that grain workers had consistently lower levels of lung function than did civic workers while still employed, with no reversibility after retirement.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

Aluminium potroom asthma confirmed by monitoring of forced expiratory volume in one second.

Chronic airflow obstruction has long been seen among aluminium potroom workers. Currently referred to as "potroom asthma," it is debatable as to whether it is occupational asthma or nonspecific airway obstruction. A 35-yr-old male lifelong nonsmoker, with no history of asthma or atopy, was hired by an aluminium plant that had begun its operation in 1986. Preemployment screening, consisting of spirometry and a chest radiograph, was normal. During his 12-h shifts, he replaced 10 to 20 anodes (prebake type), spending 5 min each time close to open pots releasing hot fumes. The patient experienced episodes of cough and dyspnea, which were resolved during withdrawal from work in January and December 1991. He resumed work in the potrooms in March 1992, his dyspnea recurred at work and at night with 25% drops in peak expiratory flow rates (PEFR), associated with mild-to-moderate bronchial hyperresponsiveness (PC20 histamine, 1.0 mg/ml). After a chest physician's assessment, he was withdrawn from the potroom department. Assessment of the bronchial response to the occupational exposure in potrooms carried out in November 1992 revealed a pattern of dual asthmatic response, paralleled by a drop in PC20 methacholine from 5.1 to 0.7 mg/ml. A similar pattern was seen again during repeat workplace challenges 3 wk later. Spirometry obtained on control days was stable. We conclude that asthmatic reactions can exist among workers in aluminium smelters.

Adult↗

Occupational asthma due to heated polypropylene.

A 35 year-old nonatopic woman was referred to the hospital for possible work-related asthma. She had worked as an operator, at a plant producing polypropylene bags, for the previous four yrs. Her main complaint was a productive cough with dyspnoea and wheezing, as well as rhinitis over the past 3 yrs. She had been absent from work for 6 months on maternity leave, and had improved greatly. She was on a beta 2-adrenergic agent and had to take it at least four times daily. Baseline spirometry whilst at work showed marked airflow obstruction (forced expiratory volume in one second (FEV1) of 43% predicted (pred). After two months away from work FEV1 improved to 89% pred; provocative concentration of histamine causing a 25% fall in FEV1 (PC20) was 3.6 mg.ml-1 (mild airway hyperresponsiveness). Return to work resulted in a marked deterioration in FEV1, and serial peak expiratory flow (PEFR) values. PC20 was 0.11 mg.ml-1 (severe airway hyperresponsiveness) one week after she had returned to work. Specific inhalation challenges with polypropylene heated to 250 degrees C resulted in a late asthmatic reaction. As formaldehyde is one of the degradation products of heating polypropylene, we exposed her to it for up to 2 h, but we elicited no bronchospastic reaction. We conclude that heated polypropylene should be listed as one of the agents that causes occupational asthma.

Adult↗

Exposure to domestic animals and risk of immunologic sensitization in subjects with asthma.

BACKGROUND: The objective of the study was to determine whether exposure to domestic animals plays a significant role, beyond atopy, in the development of immediate sensitization to animal-derived antigens. METHODS: To test this hypothesis, 200 subjects with asthma (85 male subjects and 115 female subjects; mean age, 37 +/- 16 years) seen consecutively in an asthma clinic were enrolled in a cross-sectional survey. Each subject answered a questionnaire about allergy symptoms and past and current exposure to domestic animals. Skin prick testing with extracts of common inhalant allergens including antigens from eight species of animal (cat, dog, horse, rabbit, rat, mouse, guinea pig, and hamster) were also carried out. RESULTS: Seventy-nine percent of subjects were atopic, and 91% had kept animals at home at some point (figures were 80% for dogs, 68% for cats, 23% for rabbits, and 20% for rodents). Using two-by-two tables, we showed that skin reactivity to at least one animal antigen was strongly linked to atopy (86% of atopic subjects had skin reactions as compared with 34% of nonatopic subjects: p < 0.001) but not to previous and current exposure to domestic animals (78% of both exposed and never exposed subjects). However, with the use of logistic regression, the determinants of skin reactivity to animals were atopy (p < 0.001), followed by cumulative duration of exposure to domestic animals (p < 0.01). The number of animals times the number of species times the duration of exposure was also a significant determinant of skin reactivity (p = 0.05). CONCLUSIONS: We conclude that beyond the predominant role of atopy, cumulative duration of exposure to domestic animals is a significant determinant for immediate sensitization to animal-derived antigens in subjects with asthma.

Adult↗

Hypersensitivity pneumonitis-like reaction among workers exposed to diphenylmethane [correction to piphenylmethane] diisocyanate (MDI).

Isocyanates are well documented as a cause of occupational asthma. A hypersensitivity pneumonitis type of reaction has also been reported but only in a few isolated cases. We investigated nine subjects who complained of respiratory and general symptoms related to workplace exposure. All the subjects had worked in a plant where a resin based on diphenylmethane diisocyanate (MDI) is used in the manufacture of woodchip boards. They underwent inhalation challenges using the MDI resin for progressively increasing periods of time on separate days. In eight subjects, exposure to subirritant amounts of MDI induced a pattern of reaction consistent with hypersensitivity pneumonitis, i.e., significant falls in both FEV1 and FVC associated with a rise in body temperature (> 38 degrees C) and an increase in blood neutrophils (> +2,500/mm3). Bronchoalveolar lavage, performed in two subjects 24 h after the end of challenge exposure, revealed an increase in lymphocytes and neutrophils. Specific immunoglobulin G (IgG) and IgE antibodies to MDI human serum albumin (HSA) conjugates were present in all subjects. We conclude that the MDI resin caused an hypersensitivity pneumonitis type of reaction in at least eight (4.7%) of the 167 potentially exposed workers employed in the plant. These findings indicate that in some workplaces, a hypersensitivity pneumonitis type of reaction may be a more frequent consequence of isocyanate exposure than is usually thought.

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↗