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Jean-Luc Malo

Publications and source records attributed to Jean-Luc Malo.

14 recordsLinked to original sources

An effective strategy for diagnosing occupational asthma: use of induced sputum.

Monitoring airway inflammation by means of induced sputum cell counts seems to improve the management of asthma. We sought to assess whether such monitoring at the end of periods at and away from work combined with the monitoring of PEF could improve the diagnosis of occupational asthma. We enrolled subjects suspected of having occupational asthma. Serial monitoring of PEF was performed during 2 weeks at and away from work. At the end of each period, induced sputum was collected. Specific inhalation challenge was subsequently performed. PEF graphs were interpreted visually by five independent observers. Forty-nine subjects, including 23 with positive specific inhalation challenge, completed the study. The addition of sputum cell counts to the monitoring of PEF increased the specificity of this test, respectively, by 18 (range [r] 13.7-25.5) or 26.8% (r 24.8-30.4) depending if an increase of sputum eosinophils greater than 1 or 2% when at work was considered as significant. The sensitivity increased by 8.2% (r 4.1-13.4) or decreased by 12.3% (r 3.1-24.1) depending on the cutoff value in sputum eosinophils chosen (greater than 1 or 2%, respectively). The addition of sputum cell counts to PEF monitoring is useful to improve the diagnosis of occupational asthma.

Adult↗

Recovery of methacholine responsiveness after end of exposure in occupational asthma.

Recent data suggest that responsiveness to methacholine continues to improve 2 and more years after cessation of exposure to agents causing occupational asthma (OA). The goal of this study was to characterize further the curve of improvement to methacholine responsiveness in subjects with OA. Eighty subjects with confirmed OA who had at least two assessments of a provocative concentration of histamine causing a 20% drop in FEV(1) (PC(20)) and were seen for at least 2 years after cessation of exposure. The shape of recovery of PC(20) was assessed by CARMA (James K. Lindsey, Liège, Belgium) analysis. Slopes of recovery were compared in the first 2.5 years in 55 subjects and from 2.5 years until the end of observation in 56 subjects. Recovery curves showed progressive improvements in PC(20) significantly influenced by time lapse since end of exposure, sex, baseline PC(20), and FEV(1). The slopes of recovery were significantly different from zero both for the first 2.5 years after cessation of exposure (0.27 +/- 0.05 SEM natural logarithm of PC(20) per year) and later (0.09 +/- 0.008 SEM natural logarithm of PC(20) per year), with the slope significantly steeper for the first 2.5 years. This study shows that improvement in responsiveness to methacholine continues for years after cessation of exposure but that the improvement is more rapid in the first 2.5 years.

Adult↗

Occupational asthma.

PURPOSE OF REVIEW: The scientific literature on occupational asthma is steadily increasing and no longer only describes case reports with prevalence figures and limited physiopathologic and immunologic data. Prospective cohort studies are currently carried out with relevant incidence figures and risk factors. Genetic susceptibility is explored. New diagnostic means are described. Surveillance programs are conducted and preventive measures are proposed. RECENT FINDINGS: A relevant account was published on the respiratory consequences (irritant-induced asthma, a type of occupational asthma) of exposure of firefighters at the World Trade Center site. Glutathione-S-transferase appears to be an interesting susceptibility gene for occupational asthma as a result of isocyanates. Inflammation caused by neutrophils and not only by eosinophils is more often associated with occupational asthma. Examination of induced sputum and assessment of exhaled nitric oxide are becoming useful diagnostic tools. Cleaners are at increased risk of developing occupational asthma, although the causal agents are unknown. Surveillance programs currently combine strategies that aim to reduce exposure and identify cases early. SUMMARY: New scientific information provides better, accurate figures on the frequency of occupational asthma and on risk factors, proposes relevant diagnostic tools more directly related to the physiopathology of the disease, and suggests effective surveillance programs in high-risk workplaces.

Asthma↗

Airway inflammation after cessation of exposure to agents causing occupational asthma.

Subjects with occupational asthma (OA) generally present asthma symptoms and airway hyperresponsiveness after cessation of exposure. We hypothesized that they are also left with airway inflammation. We assessed 133 subjects with OA at a mean interval of 8.7 years (0.5-20.8 years) after cessation of exposure by questionnaire, airway caliber, and responsiveness to methacholine. Satisfactory samples of induced sputum were obtained from 98 subjects. We defined three groups of subjects: (1) cured: normalization of the concentration of methacholine provoking a 20% decrease in FEV1 (PC20), (2) improved: increase in PC20 by 3.2-fold or more but PC20 still abnormal, and (3) not improved: no significant change in PC20. In all, 9/28 subjects (32.1%) with no improvement versus 6/56 (10.7%) subjects with partial and complete improvements had sputum eosinophils equal to or greater than 2% and 11/28 (39.3%) subjects versus 11/56 (19.6%) subjects showed sputum neutrophils equal to or greater than 61%. Levels of interleukin-8 and of the neutrophil-derived myeloperoxidase were significantly more elevated in sputum of subjects with no improvement. Those in the cured or improved groups had a significantly longer time lapse since diagnosis and a higher PC20 at the time of diagnosis. We conclude that failure to improve after cessation of exposure to an agent causing OA is associated with airway inflammation at follow-up.

Adult↗

Chlorine-induced injury to the airways in mice.

Exposure to chlorine gas (Cl2) causes occupational asthma that we hypothesized occurs through the induction of airway inflammation and airway hyperresponsiveness by oxidative damage. Respiratory mechanics and airway responsiveness to methacholine were assessed in A/J mice 24 hours after a 5-minute exposure to 100, 200, 400, or 800 ppm Cl2 and 2 and 7 days after inhalation of 400 ppm Cl2. Airway responsiveness was higher 24 hours after 400 and 800 ppm Cl2. Responsiveness after inhalation of 400 ppm Cl2 returned to normal by 2 days but was again elevated at 7 days. Airway epithelial loss, patchy alveolar damage, proteinaceous exudates, and inflammatory cells within alveolar walls were observed in animals exposed to 800 ppm Cl2. Macrophages, granulocytes, epithelial cells, and nitrate/nitrite levels increased in lung lavage fluid. Increased inducible nitric oxide synthase expression and oxidation of lung proteins were observed. Epithelial cells and alveolar macrophages from mice exposed to 800 ppm Cl2 stained for 3-nitrotyrosine residues. Inhibition of inducible nitric oxide synthase with 1400W (1 mg/kg) abrogated the Cl2-induced changes in responsiveness. We conclude that chlorine exposure causes functional and pathological changes in the airways associated with oxidative stress. Inducible nitric oxide synthase is involved in the induction of changes in responsiveness to methacholine.

Administration, Inhalation↗

Incidence of occupational rhinoconjunctivitis and risk factors in animal-health apprentices.

BACKGROUND: Exposure to laboratory animals often causes the appearance of immunologic sensitization and symptoms. OBJECTIVE: Our aim was to determine the incidence of occupational rhinoconjunctivitis and the timing of symptoms and their determinants in apprentices starting exposure to laboratory animals. METHODS: Data from 387 (92.8%) of 417 students entering career programs in animal health in 5 schools were kept for analysis. Questionnaires and skin prick tests with common and occupational inhalants were carried out on entry and at follow-up visits scheduled at 8, 20, 32, and 44 months, depending on the schools. Responsiveness to inhaled methacholine was assessed at entry. RESULTS: Ninety-three (24%) subjects showed incident occupational rhinoconjunctivitis symptoms, and 37 (9.6%) had symptoms combined with skin sensitization to an animal-derived allergen. Symptoms such as sneezing, rhinorrhea, and itchy eyes tended to develop early in the course of exposure. In two thirds of the subjects, symptoms persisted at subsequent visits. In a multivariate analysis the determinants of the appearance of rhinoconjunctivitis with or without allergic sensitization included sensitization to grass pollens (odds ratio [OR], 1.78; 95% CI, 0.99-3.19), as well as nasal (rhinorrhea in contact with dust: OR, 1.79; 95% CI, 1.05-3.05) and bronchial symptoms (chest tightness: OR, 3.31; 95% CI, 0.98-11.25; cough on exposure to strong odors: OR, 1.88; 95% CI, 0.98-3.59). CONCLUSION: The incidence of occupational rhinoconjunctivitis symptoms with or without immunologic sensitization is high in apprentices starting exposure to laboratory animals. Symptoms related to histamine release are common in the early course of exposure. Determinants include immunologic and target-organ susceptibility.

Adolescent↗

Does clinical trial subject selection restrict the ability to generalize use and cost of health services to "real life" subjects?

OBJECTIVES: To explore one aspect of the external validity of the randomized controlled trial (RCT), specifically how being selected for inclusion in a trial and having participated has influenced the use and cost of asthma-related health services. METHODS: Services used by asthmatic users of inhaled corticosteroids (iCSTs) having previously participated in an RCT (TS, n = 46) were compared with individuals who had never participated (NS, n = 51). RESULTS: TS were more likely to use higher (> or = 400 microg) daily doses of iCSTs than NS (OR, 3.3; 95% Cl, 1.1-8.3) but less likely to visit emergency departments (OR, 0.3; 95% Cl, 0.1-0.7). Total asthma-related costs did not differ significantly. CONCLUSIONS: Subject differences may impede generalizing from RCTs to real life.

Adrenal Cortex Hormones↗

Time course of onset of sensitization to common and occupational inhalants in apprentices.

BACKGROUND: Incident sensitization to common allergens in the setting of sensitization to an occupational allergen has not been described. OBJECTIVE: Our aim was to determine the risk and timing of development of sensitization to common allergens in subjects with incident sensitization to a work-related allergen. METHODS: Data from a cohort of 769 apprentices in animal-health technology, pastry making, and dental hygiene were used. Skin prick tests to work-related allergens (laboratory animal, flour, and latex) and common allergens (mites, molds, pets, and pollen) were administered at baseline and at up to 3 subsequent annual visits. Risk ratios (RRs) and 95% CIs were calculated. RESULTS: Eighty-three subjects had sensitization to a work-related allergen. Four (4.8%) subjects became sensitized to common and then occupational allergens. Nine (10.8%) subjects had sensitization to a common allergen after sensitization to a work-related allergen. In 20 (24.1%) subjects new sensitizations to specific and common allergens were detected simultaneously. Fifty subjects remained free from new sensitization to occupational allergen during development of sensitization to common allergens. An increased risk of development of sensitization to molds (RR = 3.49) and pets (RR = 2.51) was found in subjects with incident sensitization to occupational allergens relative to the risk in subjects without sensitization. CONCLUSION: New sensitization to common aeroallergens is frequent in subjects not previously exposed to work-related allergens; it often occurs around the same time as sensitization to work-related agents. Subjects with new occupational sensitization are at a greater risk of development of sensitization to common aeroallergens than subjects without sensitization.

Administration, Inhalation↗

Diisocyanate antigen-stimulated monocyte chemoattractant protein-1 synthesis has greater test efficiency than specific antibodies for identification of diisocyanate asthma.

We previously reported that diisocyanate-human serum albumin (DIISO-HSA) stimulated production of monocyte chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cells is significantly associated with a clinical diagnosis of diisocyanate asthma (DA). Others have reported that antibodies for DIISO-HSA are specific but insensitive markers of DA. This study was performed to evaluate test characteristics of the in vitro MCP-1 assay compared with DIISO-HSA-specific immunoglobulin (Ig) G and IgE in identifying workers with DA. MCP-1 was quantitated in peripheral blood mononuclear cell supernatants 48 hours after incubation with DIISO-HSA antigens. Assay results were compared with outcomes of specific inhalation challenge (SIC) testing. Nineteen of 54 (35%) workers assayed for antibodies and MCP-1 stimulation had SIC-confirmed DA. Mean MCP-1 produced by SIC-positive workers was greater than SIC-negative workers (p < or = 0.001). Diagnostic sensitivity, specificity, and test efficiency for specific IgG were 47%, 74%, and 65%, respectively, and for specific IgE were 21%, 89%, and 65%, respectively. Sensitivity, specificity, and test efficiency of the MCP-1 test were 79%, 91%, and 87%, respectively. This study indicates that the MCP-1 stimulation assay has greater sensitivity and specificity than the specific antibody assays in correctly identifying DA.

Adult↗

Airway inflammation and functional changes after exposure to different concentrations of isocyanates.

BACKGROUND: Isocyanates are a common cause of occupational asthma (OA). OBJECTIVES: We sought (1) to examine whether asthmatic reactions to isocyanates could be induced at concentrations as low as 1 ppb in subjects with OA caused by isocyanates previously diagnosed in our center and (2) to compare the inflammatory and functional changes after exposure to 1 and 15 ppb of isocyanates with similar total doses (concentration of isocyanates x duration of exposure). METHODS: Specific inhalation challenges were performed in 12 asthmatic subjects with previously confirmed OA caused by isocyanates. Eight subjects were exposed to 1 ppb at 10% of the dose of isocyanates that induced an asthmatic reaction at the time of the diagnosis. Seven subjects were exposed to the same total dose of isocyanates by using concentrations of 1 and 15 ppb 1 month apart. RESULTS: Exposure to 1 ppb at 10% of the dose that had induced functional changes at the time of diagnosis induced an asthmatic reaction in 3 of 8 subjects. There was a significant correlation between the percentage of maximum decrease in FEV(1) after exposure to 1 ppb and the increase in sputum neutrophils (rho = 0.8). By keeping the total dose (concentration of isocyanates x duration of exposure) of isocyanates similar, 4 of 7 subjects experienced an asthmatic reaction after exposure to 1 ppb, whereas only one subject experienced an 18.5% decrease in FEV(1) after exposure to 15 ppb. CONCLUSION: Isocyanates can induce functional and inflammatory changes (mainly neutrophilic) at concentrations as low as 1 ppb. For the same total dose of exposure, low concentrations of isocyanates are as harmful as or even more harmful than higher concentrations for subjects with OA to isocyanates.

Administration, Inhalation↗

Socioeconomic status and utilization of health care services among asthmatic children.

We evaluated the relation between socioeconomic factors and hospitalization as well as emergency department (ED) visits among asthmatic children who had universal access to health care. Newly diagnosed asthmatic children 3-4 years of age were followed up for a period of 6 years. Information on hospitalization and ED visits was obtained by interviewing parents. Socioeconomic status (SES) was measured by paternal occupation, race, type of dwelling, and an index of crowding. After adjusting for asthma severity, logistic regression analysis showed that children with fathers in the economically least advantaged occupations were more likely to be hospitalized due to their asthma [father's occupation group 3 (FOG3), odds ratio (OR)=2.1, 95% confidence interval (95% CI)=0.2-19.8; father's occupation group 4 (FOG4), OR=13.9, 95% CI=1.1-181.4]. The probability of emergency department visits was not significantly different according to the studied variables. Emergency department visits were not influenced by SES variables, probably due to the absence offinancial barriers to access health care. However, SES differences in hospitalization may suggest differential management and/or treatment practices according to socioeconomic status at the emergency departments.

Adult↗

Utilization of pulmonary function measurements in the assessment of occupational asthma.

Lung function assessments that include spirometry and bronchial responsiveness are now often coupled to immunological assessment and an evaluation of inflammation in the investigation of occupational asthma. For diagnostic purposes, evidence points out that specific inhalation challenges are the gold standard, as previously suspected. In the epidemiological setting, both spirometry and bronchial responsiveness are feasible and safe. The role of lung function assessments in surveillance programmes is still open to discussion.

Asthma↗