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Biomedical subjects

A Cartier

Publications and source records attributed to A Cartier.

At least 37 records · Page 2Linked to original sources

Persistent specific bronchial reactivity to occupational agents in workers with normal nonspecific bronchial reactivity.

Specific bronchial reactivity (SBR) to common inhalants is related to the degree of nonspecific bronchial reactivity (NSBR) and to specific allergen sensitivity. We investigated 16 workers with normal NSBR who had been previously diagnosed with occupational asthma caused by high-molecular-weight agents. The agents were flour in seven workers, psyllium in five, and guar gum in four. The subjects had been removed from exposure to these agents for a mean of 5.7 (+/- 4.0 SD) yr, no longer showed evidence of persisting asthma, and had a normal lung function. In the present study, the workers were reexposed to the sensitizing agent by specific inhalation challenges, in the same way they were as at the time of the diagnosis, to assess their current SBR to the sensitizer. SBR was estimated as the duration of exposure that induced a 20% decrease in FEV(1). Eleven of the 16 subjects had an asthmatic reaction at the time of the study; the duration of exposure necessary to induce the asthmatic reaction was the same as that needed at the time of diagnosis (3.55 +/- 0.5 min and 4.2 +/- 0.7 min, respectively, p = 0.8). The decrease in specific IgE levels between the two events was much greater in the subjects who failed to react to the second challenge test (from 24.2 +/- 37.5% to 3.0 +/- 16.9% binding) than in those who reacted on both occasions (from 31.2 +/- 27.0% to 21.6 +/- 36.7% binding); however, in both groups the change was significant (p = 0.05 and 0.04, respectively). We conclude that SBR to high-molecular-weight agents persists in most cases despite a normalization of NSBR, and that this persistence is associated with a persistence of specific immunization to the agent.

Adult↗

Comparison of peak expiratory flows and FEV1 in assessing immediate asthmatic reactions due to occupational agents.

BACKGROUND: FEV1 is more sensitive than PEF in assessing late asthmatic responses (LAR) after specific inhalation challenges (SIC) with occupational agents. As immediate asthmatic reactions (IAR) mainly involve proximal airways, PEF may, however, be as valid as FEV1. METHODS: Thirty-seven subjects who experienced an immediate fall in FEV1 of > or =20% during SIC with occupational agents and 20 subjects with fall of < or =10% in FEV1 were included. Both FEV1 and PEF were measured in a random order every 10 min for 1 h after exposure. We corrected PEF (PEFc) for inaccuracies of the mini-Wright meters by the Miller equation. RESULTS: Maximum changes in PEFc (30+/-11%) were not significantly different from changes in FEV1 (27+/-5%) (P=0.13). Their timings after exposure were 14+/-11 min and 17+/-17 min, respectively (P=0.4). High sensitivity (92%), specificity (95%), accuracy (93%), and positive predictive value (97%) were found for a 20% fall in PEFc to detect a significant IAR. Results were better and not influenced by meter inaccuracies with a cutoff point of 15% change in noncorrected PEF (PEFnc). An absolute decrease in PEF of 70 l/min gave a good discrimination between reactions with and without an asthmatic response. CONCLUSIONS: PEF is as satisfactory as FEV1 for detecting a significant IAR after exposure to an occupational agent if one considers a cutoff point of 1) 15% fall in PEF 2) 20% fall in PEFc 3) 20% fall and/or 70 l/min decrease in PEFnc.

Adult↗

Skin bruising, adrenal function and markers of bone metabolism in asthmatics using inhaled beclomethasone and fluticasone.

Fluticasone propionate (FP) is generally considered to have twice the efficacy of beclomethasone dipropionate (BDP) on a weight-to-weight basis for the control of asthma, and may have lesser effects on adrenal function. However, the effects of FP and BDP on skin integrity and bone metabolism markers require further examination. Sixty-nine asthmatic subjects were enrolled in a double-blind crossover study in which, after a baseline period, they received BDP or FP (at half the dose of BDP) for two 4-month periods each. A questionnaire on skin bruising, a skin examination, tests of adrenal function and of markers of bone metabolism were performed after 2 months of each period. The number of asthma exacerbations was not significantly different for the two treatment periods (eight for BDP and nine for FP), nor were various indices of asthma control. Whereas the frequency of bruising reported by the questionnaire was not different, there were more bruises on examination for BDP (1.6+/-2.5) than for FP (1.2+/-2.3) (p=0.04). Although baseline serum cortisol was not significantly different for the two drugs, the increase in cortisol after cortrosyn was lower for BDP (357+/-158 micromol x dL(-1)) than for FP (422+/-144 micromol x dL(-1)) (p<0.01). Serum osteocalcin levels were significantly lower in subject on BDP (2.8+/-1.7 microg x mL(-1)) than on FP (3.5+/-1.9 ng x mL(-1)) (p=0.003). Other markers of bone metabolism were not significantly altered. The three major side-effects were loosely, but significantly correlated with the periods on BDP and FP. However, skin bruises, increase in cortisol after Cortrosyn and osteocalcin were not significantly correlated for the period on either BDP or FP. In conclusion, whereas fluticasone propionate used at half the dose of beclomethasone dipropionate has a comparable effect on the control of asthma, fluticasone propionate demonstrated fewer side-effects in terms of skin bruising, adrenal suppression and bone metabolism.

Administration, Inhalation↗

Mechanism of inhibition of rat liver bilirubin UDP-glucuronosyltransferase by triphenylalkyl derivatives.

A series of potent and competitive inhibitors of UDP-glucuronosyltransferase derived from 7,7,7-triphenylheptanoic acid has been synthesized in order to probe the active site of the isozyme involved in the glucuronidation of the endogenous toxic compound, bilirubin IX alpha. Like triphenylalkylcarboxylic acids, triphenyl alcohols were found to be very effective competitive inhibitors of the reaction (Ki 12 to 180 microM). Superimposition of the best inhibitors with bilirubin by computer modeling showed a marked spatial similarity, which accounts for the observed competitive-type inhibition. The bulky triphenylmethyl moiety of the inhibitor superimposed well on the part of the bilirubin molecule containing three of the four pyrrole rings. In agreement, substitution of the triphenylmethyl moiety by planar structures such as fluorenyl or indenyl rings completely suppressed the inhibition. In addition, the weak inhibition exerted by the shortest carboxylic acids could be related to the higher acidity of these molecules. The inhibition potency depended on the acidity of the molecules; the more acidic, the less inhibitory, suggesting that the presence of a negative charge on the inhibitor molecule prevents bilirubin glucuronidation. Based on these results, a reaction mechanism for bilirubin glucuronidation is postulated.

Animals↗

Occupational asthma: what have we learned?

Occupational asthma is one of the most frequent work-related diseases and may represent between 2% and 6% of all cases of asthma. It is defined as asthma causally and specifically related to exposure to airborne dusts, gases, vapors, or fumes in the working environment. Because it may cause long-lasting disability, it is important to properly identify affected workers and to withdraw them from exposure to the sensitizing agent as soon as possible. Although the history is the clue to the diagnosis, it is not sensitive or specific. The diagnosis should be confirmed by objective means, essentially by monitoring of peak expiratory flow and nonallergic bronchial responsiveness or by specific inhalation challenges. In this article the author reviews the investigation of occupational asthma.

Asthma↗

Can reactive airways dysfunction syndrome (RADS) transform into occupational asthma due to "sensitisation" to isocyanates?

The case history is described of a worker who presented with a history suggestive of reactive airways dysfunction syndrome which occurred after an acute high level inhalation of diphenylmethane diisocyanate. Further exposure at work, at a time when concentrations of isocyanates were no longer "irritant", suggested occupational asthma; this diagnosis was confirmed by a specific inhalation challenge test.

Allergens↗

Tolerance to the protective effects of salmeterol on methacholine-induced bronchoconstriction: influence of inhaled corticosteroids.

Long-acting beta2-adrenoceptor agonists such as salmeterol reduce airway responsiveness for at least 12 h, but this effect seems to decrease with regular use. We evaluated the time-course of the protective effects of salmeterol on methacholine-induced bronchoconstriction, its modulation by inhaled corticosteroids (ICS) and its influence on asthma control. Thirty two subjects (13 males and 19 females) with mild to moderate stable asthma were divided into two groups according to their medication needs: bronchodilators (BD) alone (n=16) or with ICS (n=16). After a 2 week run-in period, a double-blind crossover study was conducted. Subjects from both groups received salmeterol 50 microg b.i.d. or a placebo for 4 weeks each in random order, separated by a 2 week washout period. The provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) was measured before and after each treatment period, 1 h prior to inhalation of salmeterol or placebo and 1 and 12 h after. Baseline forced expiratory volume in one second (FEV1) increased significantly after salmeterol, both after the first dose and at 4 weeks (BD group: 19 and 17%; ICS: 22 and 13%). On the first day of administration, salmeterol provided significant protection in both groups up to 12 h with a PC20 before and 1 and 12 h postdose of 2.2, 21.7 and 12.4, mg x mL(-1), respectively, in the BD group and 2.1, 11.6 and 55 mg x mL(-1), respectively, in the ICS group. After 4 weeks, this effect was significantly attenuated in both groups with a PC20 before, 1 and 12 h postdose of 3.3, 10.9 and 7.1 mg x mL(-1), respectively, in the BD group and 2.1, 5.0 and 2.3 mg x mL(-1), respectively, in the ICS group. This loss of protective effect was of similar magnitude in both groups. Respiratory symptoms, rescue beta2-agonist use and baseline FEV1 did not change significantly throughout the study in both groups. In conclusion, the bronchoprotective effect of salmeterol decreased with regular use both 1 and 12 h postdose; inhaled corticosteroids did not prevent this reduction. However, the development of tolerance was not associated with loss of asthma control.

Administration, Inhalation↗

Compliance with peak expiratory flow monitoring in home management of asthma.

BACKGROUND: The recent consensus reports on asthma management emphasize the importance of using peak flowmeters to accurately assess the degree of airflow obstruction. However, the optimal way to use those devices has not yet been determined. OBJECTIVES: To assess compliance with peak expiratory flow (PEF) measurements in the long-term management of asthma, and identify the characteristics of patients with poor compliance. SETTING: Asthma clinics from three tertiary-care hospitals. DESIGN: A descriptive and prospective study of 1-year duration. PATIENTS: Twenty-six patients with moderate to severe asthma taking part in an asthma education program. MAIN OUTCOME MEASURES: Patients were asked to measure morning and evening PEF using an electronic peak flowmeter with a 3-month memory; they were unaware that PEF values were being recorded by this device. RESULTS: Compliance with PEF measurements was relatively good during the first month (63% of the measurements done) but even with regular reinforcement, fell to 50% at 6 months and to 33% at 12 months. Right from the beginning, 8 of 26 subjects (30%) never or almost never (<5% of the readings done) measured PEF, with seven of these subjects writing fabricated results in their diaries most of the time. At 12 months, 60% of the subjects were measuring PEF <25% of the time, and most of them continued writing fabricated PEF values in their diaries. None of the subjects' characteristics helped us to identify those who had poor compliance with these measurements. CONCLUSIONS: While short-term compliance with PEF measurements is fairly good, most patients with moderate to severe asthma are not interested in measuring PEF twice daily over a prolonged period. In the current management of asthma, PEF measurement devices can be suggested to those showing a strong personal interest in using them, but should be limited to short periods of time. Furthermore, this study outlines the usefulness of electronic peak flowmeters when doing clinical research where PEF improvement is an important outcome.

Adult↗

Influence of beclomethasone and salmeterol on the perception of methacholine-induced bronchoconstriction.

BACKGROUND: Patient evaluation of asthma severity and medication needs is mostly based on respiratory symptoms and may be influenced by changes in perception of bronchoconstriction-induced sensations. However, the influence of asthma medication on the ability to perceive symptoms is still to be documented. This study evaluated the effects of short-term and regular use of salmeterol on the perception of methacholine-induced bronchoconstriction (MIB) in subjects with mild asthma, using inhaled salbutamol on an "as required" basis (n=15), and in subjects with moderate asthma, using daily inhaled beclomethasone (mean daily dose, 640 microg; n=15) in addition to salbutamol to control their asthma. METHODS: Methacholine challenges (MC) were performed at entry into the study, and then before, 1, and 12 h following inhalation of 50 microg of salmeterol or a placebo, after a 15-day baseline period; and after 4 weeks of twice daily use of those treatments. The measurements were then repeated with the alternate treatment after a 15-day washout period. Finally, a last MC was performed after another 15-day washout period. For each MC, the perception score of bronchoconstriction-associated breathlessness at 20% fall in FEV1 (PS20) was evaluated on a modified Borg scale from 0 to 10. RESULTS: Subjects using regular beclomethasone had a higher baseline PS20 than those using only salbutamol (means: 3.06 0.06 and 2.01+/-0.07, p=0.0001). Short- and long-term use of salmeterol did not change significantly the PS20 compared with placebo (p>0.05) in either group (with or without corticosteroid). Although there were some intraindividual variations, mean PS20 did not vary significantly throughout the study. CONCLUSION: These observations show that the perception of bronchoconstriction-associated breathlessness is not influenced by regular use of salmeterol. Patients using inhaled corticosteroids show a greater perception of MIB.

Administration, Inhalation↗

Follow-up of occupational asthma after removal from or diminution of exposure to the responsible agent: relevance of the length of the interval from cessation of exposure.

STUDY OBJECTIVE: We set the hypothesis that follow-up surveys of occupational asthma (OA) could now show better improvement in the asthmatic condition because of a more prolonged interval since removal from exposure than in previously reported studies. PATIENTS/METHODS: Ninety-nine subjects with OA were assessed and were separated into two groups according to the duration of cessation of exposure: (1) group removed for > or = 5 years: 48 subjects studied 8.9+/-2.2 years after cessation of exposure; (2) group removed for <5 years: 51 subjects with OA, comparable in terms of history and functional results at time of diagnosis, with a time lapse from last exposure of 3.1+/-1.2 years. On the follow-up visit, questionnaires including information on the current and previous use of inhaled steroids, spirometry, and methacholine tests were administered and results were compared with those obtained at the time of diagnosis. RESULTS: At the follow-up visit, no significant changes in spirometry were observed in the two groups. However, a significant improvement in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) from a mean value of 1.5 to 3.7 mg/mL was documented (p<0.001). The proportion of subjects having normal PC20 at the follow-up visit was significantly higher in the group removed from exposure for >5 years than in the group removed for < or = 5 years (16/33 vs 8/42; p=0.01). Stepwise logistic regression showed that follow-up PC20 could be predicted from baseline PC20 (p<0.001, odds ratio [OR]=4.1, 95% confidence interval [CI]=1.8 to 9.1), duration of exposure (p=0.04, OR=0.9, 95% CI=0.8 to 1.0), the interval since removal from exposure (p=0.002, OR=1.7, 95% CI=1.2 to 2.5), and the type of agent; subjects with OA due to high-molecular-weight agent showed a less favorable outcome (p=0.04, OR=0.2, 95% CI=0.03 to 1.0). Current and past treatments with inhaled steroids were not significant predictors. CONCLUSION: Results obtained in the group of this study removed for >5 years show better prognostic figures than those reported in most previous studies. Comparison with the group removed for a shorter interval and the stepwise logistic regression analysis suggest that the longer duration of the interval from cessation of exposure appears to be a factor determining this difference.

Adult↗

Directives de la Societe canadienne de thoracologie pour l'asthme professionnel canadian thoracic society guidelines for occupational asthma

OBJECTIVE: To provide broad guidelines and principles to help primary care physicians, occupational physicians, allergists and respirologists with the recognition, diagnosis and management of patients with occupational asthma (OA). OPTIONS: These guidelines are mainly directed towards OA induced by a workplace sensitizing agent. However, irritant-induced asthma and workplace aggravation of underlying asthma are also addressed, and some consideration is given to other differential diagnoses. OUTCOMES: To enable the assessing physician to investigate patients with possible OA appropriately and to provide guidelines for appropriate early referral when specialized investigations are required. To provide an understanding of the appropriate management strategies following objective diagnosis. EVIDENCE: The key diagnostic and management recommendations were based on a critical review of the literature and by specialist consensus meetings. VALUES: Evidence was categorized as follows. Level 1: Evidence from at least one randomized, controlled trial. Level 2: Evidence from at least one well-designed clinical trial without randomization, from cohort or case-control analytical studies, preferably from more than one centre, from multiple time series or from dramatic results in uncontrolled experiments. Level 3: Evidence from the opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees. Evidence was further subdivided as follows: A. Good evidence to support a recommendation for use; B. Moderate evidence to support a recommendation for use; C. Poor evidence to support a recommendation for or against use; D. Moderate evidence to support a recommendation against use; E. Good evidence to support a recommendation against use. BENEFITS, HARM AND COSTS: The medical and socioeconomic risks and benefits of an incorrect diagnosis of OA and of failure to diagnose true OA were considered in the recommendations. VALIDATION: The document has been reviewed and endorsed by the Canadian Thoracic Society, the Canadian Society of Allergy and Clinical Immunology, and The College of Family Physicians of Canada. CONCLUSIONS: There is good evidence for rapid investigation and objective categorization of presented symptoms into OA, aggravation of underlying asthma, unrelated asthma or other diagnoses. OA should be suspected in all adult onset asthmatics whose asthma begins or worsens while they are working. Investigations should be directed to an objective assessment of asthma and then to an assessment of the work relationship, using a combination of investigations as feasible, which may include immunological tests, pulmonary function assessed during work and away from work, and specific challenge tests. Early specialist referral is recommended for diagnosis. Management strategies include general asthma management in addition to measures to avoid further exposure to a relevant workplace sensitizer. Compensation issues and other workers at risk of developing OA also need to be considered when the diagnosis is made.

Journal Article↗

Alexithymia and impoverished dream recall in asthmatic patients: evidence from self-report measures.

Early clinical impressions that alexithymia is associated with diminished dream recall have been supported by more recent research. The present study was designed to examine this association using self-report measures and a carefully screened clinical population. Thirty-three male and 43 female asthmatics from an outpatient clinic were administered the Toronto Alexithymia Scale, the Eysenck Personality Questionnaire, and a questionnaire concerning retrospective recall of dreams and nightmares. Multiple regression analyses revealed that, among men, dream recall was negatively related to alexithymia, especially to the TAS analytical mode of thinking subscale, independent of age and neuroticism. Among women, dream and nightmare recall were positively correlated with neuroticism. These results are consistent with early clinical observations of pensée opératoire, with some research findings, and with the notion that dream recall may be differentially associated with components of alexithymia in men and women patients.

Adolescent↗

Influence on asthma morbidity of asthma education programs based on self-management plans following treatment optimization.

The objective of this study was to evaluate the effectiveness of an asthma education program on morbidity, knowledge, and compliance with inhaled corticosteroid treatment using a prospective, randomized, controlled, one-year-before/one-year-after protocol. After rigorous optimization of asthma therapy under the care of respirologists, patients were assigned to one of three groups: Group C (control group: no formal education), Group P (education and action plan based on peak-flow monitoring), and Group S (education with action plan based on monitoring of asthma symptoms). A total of 188 subjects with moderate to severe asthma were enrolled and 149 completed the study. Asthma morbidity decreased significantly in all groups (p = 0.001). Mean values one-year-before/one-year-after in Groups C, P, and S were: unscheduled medical visits, 2.4/0.8, 2.3/0.7, and 1.9/ 0.7; hospitalizations, 0.21/0.04, 0.24/0.04, and 0.40/0.09; oral steroid treatments; 1.3/0.5, 1.2/0.7, and 1.3/0.9; absenteeism from work/school, 9.6/5.2, 8.8/2.2, and 6.3/2.9. Between-group differences did not reach statistical significance (p > 0.05). Asthma knowledge increased in both educated groups compared with the control group (p < 0.001) as did short-term compliance with inhaled corticosteroids. These results confirm that treatment optimization coupled with sustained high quality care in motivated patients can lead to a significant decrease in asthma morbidity. In such clinical settings, structured asthma education significantly improved short-term compliance with treatment and knowledge about asthma, although it could not add extra benefit with regard to morbidity. Nevertheless, this study does not refute the potential benefit of educational interventions aimed at improving asthma-related morbidity over a longer time period or in patients with less optimal care or with high-risk factors.

Absenteeism↗