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Biomedical subjects

A Cartier

Publications and source records attributed to A Cartier.

At least 91 records · Page 5Linked to original sources

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↗

Quality of life of subjects with occupational asthma.

BACKGROUND: The aim of the study was to assess the quality of life in subjects with occupational asthma after removal from exposure to the offending agent by comparison with a group of subjects paired for clinical and functional indices in order to show the separation between the two groups of subjects with a hypothesized different quality of life and relate the impairment in quality of life to anthropometric, clinical, and functional variables. METHODS: A previously described asthma quality of life questionnaire (Juniper EF, et al. Thorax 1992;47:76-83) was administered to two groups of subjects in a prospective manner. Information on the clinical and functional severity of asthma was obtained from each subject. Two groups of subjects were assessed: group 1, 134 subjects with occupational asthma who were seen more than 2 years after the diagnosis was confirmed, and group 2, 91 subjects who were seen in specialized asthma clinics of tertiary care hospitals for treatment of nonoccupational asthma and matched with 91 of the 134 subjects with occupational asthma from group 1 according to need for medication and (when available), baseline forced expiratory volume in 1 second (FEV1), and level of bronchial responsiveness. RESULTS: A statistically significant difference was seen in the four domains (asthma symptoms, limitation of activities, emotional dysfunction, environmental stimuli) and in the total score of the quality of life questionnaire between the two groups of matched subjects; the mean difference in the total score was 0.6 on a scale of 1 (no limitation or none of the time) to 7 (severe limitation or all the time). A weak but statistically significant correlation between the total score and several indices (FEV1, bronchial responsiveness and asthma severity) was generally obtained. CONCLUSION: The quality of life of subjects with occupational asthma is slightly less satisfactory than that of subjects paired for clinical and functional indices, although the magnitude of the difference is small; and quality of life is weakly correlated with clinical and functional indices.

Adult↗

Prepolymers of hexamethylene diisocyanate as a cause of occupational asthma.

BACKGROUND: Occupational asthma (OA) caused by products that contain hexamethylene diisocyanate (HDI) has been ascribed to the highly volatile monomer of HDI. Most two-component paints are now made up primarily of nonvolatile prepolymers of HDI (30% to 60%) with only trace amounts (< 0.1%) of the monomer. The respective role of the two chemical forms of HDI in causing OA has never been investigated. METHODS: Twenty workers who were consecutively referred for possible OA that resulted from exposure to spray paints underwent inhalation challenges on separate days with pure HDI monomer and the commercial formulation of HDI prepolymers to which they had been exposed at work. RESULTS: Specific inhalation challenges elicited a positive asthmatic reaction in 10 of the 20 subjects. Among these subjects, four had positive bronchial reactions (two early, one late, and one dual) to both the monomer and the prepolymers. Four other subjects had asthmatic reactions (two early, one late, and one dual) after exposure to the prepolymers but not after exposure to the monomer. The discordance in bronchial response elicited by the monomer and the prepolymers could not be due to differences in the level of baseline nonspecific bronchial reactivity or in HDI concentrations during the tests. One subject showed an atypical progressive reaction after exposure to the monomer but not after exposure to the prepolymer. In this case, the discordant response could be explained by differences in HDI concentration. CONCLUSION: These observations show that, although they are nonvolatile, the prepolymers of HDI can induce OA and that asthmatic reactions as a result of exposure to prepolymers but not the monomer is not a rare occurrence.

Adult↗

How many times per day should peak expiratory flow rates be assessed when investigating occupational asthma?

BACKGROUND: Serial peak expiratory flow rate (PEF) recording has been advocated as a sensitive and specific means of confirming work related asthma. The optimum number of recordings per day to achieve the best between-reader and within-reader reproducibility and sensitivity/specificity ratio compared with the final diagnosis determined by specific inhalation challenges is unknown. METHODS: PEF recording was carried out every two hours in 74 subjects referred for possible occupational asthma. Specific inhalation challenges performed in a hospital laboratory or at the workplace (positive in 33 subjects and negative in 41) were considered the gold standard. The duration of monitoring at work and away from work was at least two weeks each. Graphs of PEF recordings were generated in four different ways: every two hours, four times/day, three times/day, and every morning and evening. The graphs were assessed by three readers in three different centres in a blind manner. Furthermore, one third of each type of graph was read blind by the same reader one week after the initial interpretation. RESULTS: Agreement between the three readers was a little more frequent (82%) in the case of the every two hour readings than for the other types of readings (70% v 77%). Agreement between at least two of the three readers occurred in 73% of positive challenges (sensitivity) and in 78% of negative challenges (specificity) for every two hour readings. The figures varied from 61% to 70% for positive challenges and from 78% to 88% for negative challenges for the other types of readings. Within-subject reproducibility from one reading to the next (one week apart) was excellent (83% to 100%). CONCLUSIONS: Recording PEF every two hours results in a slightly more satisfactory agreement between readers and in concordance in terms of sensitivity/specificity than less frequent PEF readings, although the four times a day assessment is almost as satisfactory.

Asthma↗

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↗

Response to isocyanates: effect of concentration, duration of exposure, and dose.

There is no information on the relative role of dose, concentration, and duration of exposure in determining the magnitude of the bronchial response in subjects with isocyanate-induced asthma. Four subjects with asthma induced by toluene diisocyanate (TDI) were challenged using a recently described closed-circuit exposure chamber in which stable concentrations of TDI monomer can be generated. Each subject was challenged using various concentrations and durations of exposure on separate days. They were all exposed on three to four occasions to the same dose that had been shown to cause a 20% fall in FEV1 at a concentration of 15 ppb (DR15ppb) by varying the concentration (5, 10, 15, and 20 ppb) and durations (1 to 90 min), making sure that the total dose (concentration x duration) remained constant. They were also exposed to lower total doses by modifying the concentration and the duration on the remaining visits. Exposing subjects to the same DR15 ppb by modifying the concentration or the duration resulted in falls in FEV1 > or = 20%, except in one instance. Exposing subjects to doses lower than DR15 ppb, even at higher concentrations or for longer periods than in the challenges used for obtaining the DR15 ppb always caused falls in FEV1 < 20%. We conclude that the main determinant of bronchial responsiveness to TDI is not concentration nor duration of exposure per se but the product of both factors, that is, total dose.

Adult↗

Duration of effect of loratadine and terfenadine administered once a day for one week on cutaneous and inhaled reactivity to histamine.

STUDY OBJECTIVE: The duration of action of several new non-sedative antihistamine preparations as assessed by skin and bronchial reactivity to histamine has still not been well established. The aim of the study was to evaluate the duration of effect of loratadine (10 mg) and terfenadine (120 mg) administered once a day for one week on cutaneous and inhaled reactivity to histamine by comparison with a placebo. SUBJECTS: Twenty-four adult asthmatic subjects were included in a parallel group study that compared the duration of effect of two antihistamines and a placebo on cutaneous and inhaled reactivity to histamine. STUDY DESIGN: Baseline cutaneous and inhaled reactivity (concentration causing a fall of 20 percent in FEV1 [PC20]) to histamine was obtained on three consecutive days. Loratadine (10 mg), terfenadine (120 mg) and a placebo loratadine were administered daily for 1 week to 3 groups of subjects. The PC20 was measured at the end of the medication period, 3 days later, and weekly until PC20 returned to baseline value (upper limit of 2 SD from the mean baseline value). RESULTS: The mean blocking duration on cutaneous reactivity for loratadine was 6.9 days and for terfenadine, 7.2 days. The mean duration of the blocking effect on PC20 histamine was 8.5 days for loratadine and 7.2 days for terfenadine. These figures were significantly longer than for the placebo. CONCLUSION: These data suggest that terfenadine and loratadine have a comparable blocking effect on reactivity to cutaneous and inhaled histamine. A daily dose taken for one week will result in a mean blocking effect of one week.

Administration, Inhalation↗

[Comparative study of two methods permitting the detection of macroamylases. Application to the evaluation of macroamylasemia in a hospitalized population].

It is of great importance to be able to distinguish hyperamylasemia linked to a pathological condition of the pancreas from one due to the presence of the macroamylase in the serum of the patient. We have evaluated both gel filtration chromatography and precipitation by PEG-6000 for the detection of serum macroamylase. Our study has enabled us to define a simple detection protocol, suitable for routine laboratory use. In this protocol, macroamylasemia is detected initially by precipitation with PEG-6000; if less than 60% of amylase activity is precipitated, there is no macroamylasemia. If more than 60% of amylase activity can be precipitated by PEG-6000, macroamylasemia is confirmed by gel filtration chromatography. The incidence of macroamylasemia in hospitalized patients was studied; it was 1.3% in cases where amylasemia was normal, and 4.5% in hyperamylasemic patients.

Chromatography, Gel↗

[The Quebec system of indemnification for occupational asthma. Description, efficacy, and costs].

This study describes the Quebec system of compensation for occupational asthma, assessing the functional and social outcome of claimants and estimating the efficiency and cost. Information was obtained on the clinical, functional and social outcome as well as the estimated costs for 134/211 subjects (participation rate of 64%), who received compensation between 1986 and 1988. At the time of assessment (2 years and more after the diagnosis), 93% of participants still demonstrated significant bronchial hyperresponsiveness and 84% required anti-asthma medication. None of the participants remained exposed to the offending agent: 67% were working for the same or another employer, 16% were retired, 8% were retraining for a new job and 8% were still unemployed. Quality of life was mildly affected, more so than for a control group of subjects. The mean interval between the time claims were addressed and the first medicolegal decision was 8.1 months. The mean total cost (including temporary and permanent disability indemnities, medical and technical costs) was $CAN 49,200 (minimum and maximum values of $2,100 and $330,900). We conclude that for subjects with occupational asthma in Quebec: 1) the mean interval for a medicolegal decision to be made is eight months: 2) a minority is still unemployed two to four years after being assessed; 3) the quality of life is more affected than in a control group; 4) the mean cost is close to $CAN 50,000.

Activities of Daily Living↗

Occupational asthma due to zinc.

We describe a subject who developed asthma symptoms 2 yrs after being employed at a plant where metals were galvanized in heated zinc. The subject was not atopic. Baseline spirometry was normal three months after he left work but there was mild bronchial hyperresponsiveness to methacholine. Monitoring of forced expiratory volume in one second (FEV1) during a day at work showed a maximum fall in FEV1 of 24% at the end of the day and an increase in bronchial responsiveness on the following day. Environmental monitoring revealed that zinc and iron were present in the working environment at concentrations that were lower than the "threshold limit value-short term exposure level" (TLV-STEL) standards. Positive immediate skin tests to zinc sulphate at concentrations of 1 and 10 mg.ml-1 were obtained, although no specific immunoglobulin E (IgE) antibodies to zinc could be found. Skin tests with copper, chromium and cobalt were negative. Specific inhalation challenges were performed, having the subject inhale a solution of zinc sulphate at a 10 mg.ml-1 concentration for 6 min. An immediate reaction was elicited (maximum fall in FEV1 of 23%). We conclude that zinc can cause occupational asthma.

Asthma↗

Occupational asthma caused by a prepolymer but not the monomer of toluene diisocyanate (TDI).

Isocyanates are the most common cause of occupational asthma. Isocyanate monomers and prepolymers are widely used in the manufacture of polyurethane compounds. However, prepolymers are generating increasing interest because of their lower volatility. No distinction has yet been made between asthmatic reactions caused by the monomers and the prepolymers of isocyanates, and asthmatic reactions caused by one type of isocyanate but not the other type have not been reported. We describe two wood-roof maintenance workers who developed asthma after being exposed to a varnish containing a prepolymer of toluene diisocyanate (TDI) with only small amounts of the monomer. Specific inhalation-challenge tests with the TDI monomer did not elicit significant airway obstruction, whereas exposure to the varnish and to the purified TDI prepolymer induced late asthmatic reactions. Specific antibodies against TDI monomer human serum albumin and TDI prepolymer human serum albumin conjugates could not be demonstrated. These observations demonstrate that isocyanate prepolymers can cause occupational asthma and that asthmatic reactions caused by isocyanate prepolymers, but not to the corresponding monomer, can occur in some exposed workers.

Adult↗

Salmeterol, a new inhaled beta 2-adrenergic agonist, has a longer blocking effect than albuterol on hyperventilation-induced bronchoconstriction.

The duration of the blocking effect of salmeterol (50 micrograms), albuterol (200 micrograms), and a placebo were compared in a double-blind study in 12 adult subjects with asthma who underwent hyperventilation tests with cold dry air (-20 degrees C) on 4 study days. On the first day, the hyperventilation test was performed at various time intervals (baseline, 1, 4, 6, 8, 12, and 24 hours) with spontaneous functional recovery between each test to determine the within-day within-subject variability of the response. The response was assessed by interpolating the dose of cold dry air causing a 20% fall in FEV1. On the 3 remaining days, separated by an interval of at least 5 days, the active or placebo medication was administered after spontaneous recovery from the first hyperventilation test. Spirometry was assessed 15 minutes and 1 hour later. The hyperventilation test was then performed and repeated 4 hours after administration of the drug. The test was repeated 6, 8, 12, and 24 hours later to detect any significant blocking effect. The improvement in FEV1 15 minutes and 1 hour after the drug was administered was 19.8% and 20.4%, as compared to baseline for albuterol, and 16.3% and 16.8% for salmeterol (not significant). The mean duration of the blocking effect was 0.25 hour for the placebo, 3.5 hours for albuterol, and 15.9 hours for salmeterol (F = 24.5; p less than 0.001; Newman-Keul's test was significant for every contrast). Eight of the 12 subjects still demonstrated some blocking effect 8 hours after taking salmeterol; this was true for only one subject receiving albuterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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↗

Closed-circuit methodology for inhalation challenge tests with isocyanates.

The diagnosis of isocyanate-induced occupational asthma can be made by exposing subjects to isocyanates in small challenge rooms. There are, however, several pitfalls inherent in this procedure. Isocyanate concentrations may not remain stable throughout the exposure and may exceed the recommended TLV ceiling of 20 ppb. This can induce irritant or unduly severe bronchial reactions. To overcome these problems, a closed-circuit apparatus for generating isocyanates in a gaseous form was developed; it was assessed in 20 subjects suspected of having isocyanate-induced asthma. Subjects were tested using both the small challenge room method and the new closed-circuit method in a randomized sequential way. Isocyanate concentrations were more stable with the closed-circuit apparatus than with the challenge room method (mean of individual variance of 6.3 and 61.8, respectively; p less than 0.001). The percentage of the total exposure time during which concentrations were above 20 ppb was reduced from 11.3 to 4.5% (p less than 0.001). The two methods yielded the same number of positive and negative responses, except for one subject who did not have a positive reaction when tested with the challenge room method. The pattern and magnitude of asthmatic reactions were similar for both methods. However, the duration of exposure was shorter with the challenge room method than with the closed-circuit methods (p = 0.04).

Administration, Inhalation↗

Single-dose effect of astemizole on bronchoconstriction induced by histamine in asthmatic subjects.

STUDY OBJECTIVE: Astemizole, administered for seven days to asthmatic subjects, had an effect of bronchoconstriction induced by inhaled histamine for a mean period of 42 days. This study evaluates whether a single dose of astemizole would have the same effect. SUBJECTS: Sixteen adult asthmatic subjects took part in the study. DESIGN: They first underwent three inhalation tests and skin prick tests with histamine on three different days. On the last day, a methacholine inhalation test was also performed. They subsequently received either a placebo or an active preparation of astemizole. The histamine inhalation test was repeated one day, two days, one week, and/or ten days after administering the drug. RESULTS: Overall, no significant change in mean PC20 or in the mean diameter of the skin reaction to histamine was observed. However, three out of the eight subjects (38 percent) receiving active and none receiving placebo medication showed significant increases in PC20 histamine (p = 0.05). This effect lasted for one to two days. CONCLUSIONS: We conclude that a single dose of 10 mg/ml of astemizole can have a significant effect on bronchial but not cutaneous reactivity to histamine. This effect is of short duration (one to two days).

Adult↗

Validation of an exposure system to particles for the diagnosis of occupational asthma.

STUDY OBJECTIVE: We previously described a closed-circuit system for exposure to particles in humans. This system has three components: a particle generator, an exposure chamber connected to an orofacial mask, and monitors. We describe results of challenges in 56 subjects who underwent challenges with the apparatus using occupational sensitizers in particles. SUBJECTS: Fifty-six consecutive subjects referred for the investigation of occupational asthma to occupational sensitizers in particles were included. The agents were the following: flour and grains (n = 19), cedar (n = 10), psyllium (n = 9), guar gum (n = 9), drugs (n = 3), persulfate (n = 2), and miscellaneous (n = 4). INTERVENTION: The duration of exposure was progressive and varied from one breath to a maximum of 180 min depending on the reaction. When no significant fall in FEV1 occurred after exposure with the aerosolization device, the standard approach of tipping particles from one tray to another was used. RESULTS: Twenty-nine subjects (52 percent) had a significant (greater than or equal to 20 percent) fall in FEV1 after exposure. This includes 18 subjects with isolated immediate reactions, four with dual asthmatic reactions, and two with atypical reactions. In 20/24 instances (83 percent), the percentage of fall in FEV1 did not exceed 30 percent, thus showing that dose-response curves can generally be obtained in a safe way. In all instances except one (26/27 cases), subsequent exposures using the traditional method did not result in significant falls in FEV1. CONCLUSION: This new procedure results in safe tests in terms of the percentage of changes in FEV1 during the immediate reactions and very rare false-negative challenges.

Aerosols↗

[Duration of bronchial protective effect of salmeterol in asthma induced by hyperventilation with dry cold air].

The duration of the blocking effect of salmeterol (50 micrograms), albuterol (200 micrograms) and placebo was compared in a double-blind study carried out in 12 adult asthmatic subjects who underwent hyperventilation tests with cold dry air on 4 study days. On the first day, the hyperventilation test was carried out at various time intervals with spontaneous functional recovery between each test. The response was assessed by interpolating the dose of cold dry air causing a 20% fall in FEV1 (PD20). On the three other days, the active or placebo medications were administered. Spirometry was assessed 15 minutes and 1 hour later. The hyperventilation test was then performed and repeated at various time intervals after administering the drug. The mean duration of the blocking effect was 0.25 hour for placebo, 3.5 hours for albuterol, and of 15.9 hours for salmeterol. Eight of the 12 subjects still showed some blocking effect eight hours after salmeterol by comparison with only one subject after albuterol. The authors conclude that salmeterol has a significantly longer effect than albuterol on bronchoconstriction induced by hyperventilation.

Adrenergic beta-Agonists↗

[Salmeterol: towards new perspectives in the treatment of asthma].

Asthma is now considered as an inflammatory condition and the purpose of the treatment is directed towards the control of inflammation. Recent therapeutic guidelines have been proposed and suggested the early use of antiinflammatory preparations. Salmeterol has a prolonged bronchodilator and protective effect against physical stimuli such as exercise and exposure to cold air. Clinical studies have all shown a superiority of salmeterol by comparison with salbutamol in the treatment of asthma. Recent in vitro and in vivo studies also suggest that salmeterol may have an extra non-bronchodilator effect. Salmeterol appears to be a safe preparation if administered at a dose of 50 to 100 micrograms on a BID regimen. It has been argued that the regular use of salmeterol can mask the worsening of bronchial inflammation although clinical studies have not substantiated this potential risk. Other studies are required to answer this question. A scheme incorporating salmeterol in the guidelines for the treatment of asthma is proposed.

Adrenal Cortex Hormones↗