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J L Malo

Publications and source records attributed to J L Malo.

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↗

Diagnosing occupational asthma: how, how much, how far?

Diagnosing occupational asthma is still a challenge because it is based on a stepwise approach in which the depth of investigative means may vary depending on resources. The authors herewith review the existing investigative means from the approach of outlining controversies and queries. There is no validated clinical questionnaire for diagnosing occupational asthma. Immunological investigation is limited by the lack of standardised extracts for skin-prick testing and specific immunoglobulin E assessments. Criteria for interpretation of changes in peak expiratory flow rates and bronchial responsiveness to pharmacological agents are still open to discussion. It is worth improving the methodology of specific inhalation challenges, either in the laboratory or in the workplace, to facilitate more extensive use of these tests. Validation of new means that assess airway inflammation, such as exhaled nitric oxide and induced sputum, needs to be performed. There is a need to increase the use of these diagnostic tests because the diagnosis is still too often based on "clinical impression".

Asthma↗

Incidence of probable occupational asthma and changes in airway calibre and responsiveness in apprentice welders.

The majority of cross-sectional studies have shown a higher prevalence of ventilatory impairment in welders while only few longitudinal studies were able to detect chronic effects on spirometry or bronchial responsiveness. The aim of the study was to determine the incidence of probable occupational asthma (OA), bronchial obstruction and hyperresponsiveness among 286 students entering an apprenticeship programme in the welding profession. This epidemiological prospective cohort study consisted of a baseline assessment survey and two follow-up assessments. A respiratory symptom questionnaire was administered at each visit. Spirometry and methacholine bronchial challenge test results, conducted once prior to onset of exposure and later after an average of 15 months of apprenticeship, were available for 194 subjects. The incidence of probable OA was approximately 3% (6 of 194). The incidence of bronchial hyperresponsiveness, defined as a > or = 3.2-fold decrease in the provocative concentration causing a 20% fall in the forced expiratory volume in one second from baseline to the end of the study was 11.9%. A statistically significant difference was found between the baseline and end of study for the lung function values. In particular, the forced expiratory volume per cent predicted had significantly dropped by 8.4% on average. The significance of these early pulmonary function changes in relation to possible chronic effects of exposure to welding fumes and gases remains to be explored.

Adult↗

Controversies in epidemiology of occupational asthma.

Epidemiology is the study of the distribution, determinants and outcome of disease. In this article, the recently acquired knowledge of the epidemiology of occupational asthma is described, as well as current areas of controversy. Incidence figures obtained from field studies in high-risk workplaces, medicolegal statistics and sentinel programmes indicate that approximately 10% of adult-onset asthma is attributable to the workplace. The strategy to identify cases through questionnaires and tools that address functional, immunological and physiopathological issues needs to be improved. Although few in number and limited to a handful of workplaces, cohort studies found that the risk of developing occupational asthma is determined less by individual susceptibility (e.g. atopy, tobacco smoking, human leukocyte antigen phenotype) and more by the level of exposure to its causes; in general, the higher the exposure, the greater the risk, and, by implication, lowering the level of exposure reduces the incidence of disease. Occupational asthma can be used as a satisfactory model for the development of adult-onset asthma. There is a great need to develop intervention strategies through adequate surveillance programmes in high-risk workplaces.

Adult↗

Definitions and types of work-related asthma: a nosological approach.

The workplace can trigger or induce asthma and cause the onset of different types of work-related asthma. Analysis of previous definitions of occupational asthma (OA) led to the conclusion that evidence of a direct causal relationship between workplace exposure and the development of asthma remains the key element for defining OA. Based on clinical features and pathophysiological mechanisms, the following conditions should be distinguished in the spectrum of work-related asthma: 1) immunological OA characterised by a latency period necessary to acquire immunologically induced sensitisation; 2) nonimmunological OA characterised by the rapid onset of asthma following single or multiple exposures to high concentrations of irritant compounds; 3) work-related asthma defined by exacerbation of symptoms in workers with pre-existing or coincident asthma; and 4) variant syndromes including eosinophilic bronchitis, potroom asthma, and asthma-like disorders caused by organic dusts. The issues and controversies relating to this approach are critically reviewed in order to stimulate the consensus development of operational definitions of work-related asthma.

Asthma↗

Assessment and evaluation of symptomatic steroid-naive asthmatics without sputum eosinophilia and their response to inhaled corticosteroids.

Eosinophilic airway inflammation is one of the hallmarks of asthma. Sputum eosinophilia has been suggested as a predictor of the response to inhaled corticosteroids in asthma. This study sought to investigate the proportion of steroid-naive uncontrolled asthmatics without significant sputum eosinophilia (< or = 1%) and to examine whether sputum eosinophilia could predict the response to inhaled corticosteroids. A total of 51 mild uncontrolled steroid-naive asthmatics who had not been treated with oral or inhaled corticosteroids for at least 3 months were investigated. The evaluation included a spirometry, methacholine inhalation challenge and sputum induction on two occasions, one at baseline and the other after 1 month of treatment with 250 microg twice-daily fluticasone propionate. Of the 51 subjects, 15 had an eosinophil count < or = 1%, and 46 completed the two visits. Patients with baseline sputum eosinophils < or = 1% (n=14) were compared with those with sputum eosinophils > 1% (n=32). The baseline characteristics of these two groups were similar. After 1 month of treatment, respiratory symptoms, quality of life, forced expiratory volume in one second (FEV1) and provocative concentration causing a 20% fall in FEV1 improved in both groups. The absence of sputum eosinophilia does not seem to be an indicator of poor response to inhaled corticosteroid treatment in steroid-naive asthmatics. However, this finding needs to be investigated further in a double-blind, placebo-controlled study, entirely designed to answer this question.

Administration, Inhalation↗

Host determinants for the development of allergy in apprentices exposed to laboratory animals.

The aim of this study was to evaluate whether determinants of work-related symptoms, skin sensitization and diseases differ between atopic and nonatopic subjects starting a career with exposure to laboratory animals (LA). A cohort of 417 apprentices in animal-health technology was prospectively followed during 32 or 44 months. The effect on the study outcomes of variables derived from questionnaire, skin reactivity, and lung function assessments at baseline were compared in atopic (n=212) and nonatopic (n=183) subjects. Eighty-five incident cases of sensitization to a LA-derived allergen were identified, 67 among atopic and 18 among nonatopic subjects. Baseline rhinitis symptoms in contact with pets and skin sensitization to pets were associated with the development of work-related rhinoconjunctivitis (RC) symptoms in atopic subjects, whereas perannual rhinitis symptoms and having a PC20 (provocative concentration causing a 20% fall in forced expiratory volume in one second) < or = 32 mg x mL(-1) were associated in nonatopic subjects. Baseline rhinitis symptoms on contact with pets and a PC20 value < or = 32 mg x mL(-1) were significant determinants for developing sensitization to a specific allergen in atopic subjects only. Finally, baseline rhinitis symptoms in contact with pets and perannual rhinitis symptoms were associated with the development of occupational RC in atopic subjects, whereas in nonatopic subjects this was associated with having a PC20 value < or = 32 mg x mL(-1). In conclusion, the determinants for the development of specific skin sensitization, symptoms and disease are different between atopic and nonatopic apprentices starting occupational exposure to laboratory-animal-derived allergens.

Animals↗

Family size, day-care attendance, and breastfeeding in relation to the incidence of childhood asthma.

A hypothesis has been suggested stating that children exposed early to infections are less likely to develop atopy or asthma. The authors investigated the relation between risk of childhood asthma and number of siblings as well as day-care attendance, as factors possibly increasing the likelihood of early infections, and breastfeeding as a factor reducing them. A case-control study was carried out in Montréal, Canada, between 1988 and 1995 that included 457 children diagnosed with asthma at 3--4 years of age and 457 healthy controls. Cases followed for 6 years were later classified as persistent or transient by the symptoms and use of medication after diagnosis. Among cases diagnosed at 3--4 years of age, the adjusted odds ratio for asthma was 0.54 (95% confidence interval (CI): 0.36, 0.80) for one sibling and 0.49 (95% CI: 0.30, 0.81) for two or more. The adjusted odds ratio for day-care attendance before 1 year of age was 0.59 (95% CI: 0.40, 0.87). Results were similar with persistent cases. Among transient cases (who possibly had an infection with wheezing at 3--4 years of age), day-care attendance and a short duration of breastfeeding resulted in increased risk. The results support the hypothesis that opportunity for early infections reduces the risk of asthma.

Asthma↗

Incidence of sensitization, symptoms, and probable occupational rhinoconjunctivitis and asthma in apprentices starting exposure to latex.

Latex is a well-known sensitizer. Prospective studies in apprentices beginning to be exposed to latex have not been carried out. We wanted to determine the incidence of skin reactivity, cutaneous symptoms, rhinoconjunctivitis (RC) symptoms, respiratory symptoms, probable occupational RC, and asthma in apprentices in dental hygiene. A total of 122 students starting a program in dental hygiene technology were recruited between 1993 and 1995. A questionnaire, skin-prick tests with common aeroallergens and latex, and assessment of spirometry and responsiveness to methacholine were carried out on entry and at follow-up visits at 20 and 32 months after the start of exposure. Of the 110 subjects who participated for at least 1 follow-up visit, skin reactivity to latex developed in 7. Cutaneous symptoms developed in 6 of the 7, RC symptoms developed in 2, and respiratory symptoms developed in 1. Five of the 7 subjects had significant changes in methacholine responsiveness and fulfilled the definition of probable occupational asthma. Sensitized subjects were more likely to be atopic and to have a previous history of asthma and respiratory symptoms on exercise than were nonsensitized subjects. Three subjects at the 20-month assessment and 4 subjects at the 32-month visit showed skin reactivity. The cumulative incidences for skin sensitization, probable occupational RC, and occupational asthma to latex were 6.4%, 1.8%, and 4.5%, respectively.

Adolescent↗

Changes in sputum cell counts after exposure to occupational agents: what do they mean?

BACKGROUND: Exposure to occupational agents can induce eosinophilic inflammation in subjects with occupational asthma (OA). It might also induce nonspecific changes in airway inflammation in subjects without OA. OBJECTIVES: We sought to investigate the changes in airway inflammation induced by exposure to occupational agents in subjects with and without OA and to determine which changes in sputum eosinophil numbers and bronchial responsiveness to methacholine should be regarded as clinically significant for predicting a 20% fall in FEV(1). METHODS: We performed specific inhalation challenges (SICs) in 3 groups of subjects: subjects reporting a history consistent with OA with a positive SIC response (n = 17); subjects reporting a history consistent with OA with a negative SIC response (n = 14); and asthmatic subjects without any history of OA (n = 10). Induced sputum and methacholine challenges were performed at the end of the control day and again at the end of the last day of exposure; the last day of exposure was always performed in the laboratory. RESULTS: There was an increase in median sputum eosinophil and neutrophil numbers in subjects with positive SIC responses. Cell counts remained unchanged after exposure in asthmatic subjects without OA. A combination of a greater than 0.26 10(6)/mL increase in sputum eosinophil numbers and a decrease in the concentration of methacholine inducing a 20% fall in FEV(1) of at least 1.8-fold compared with baseline values predicted a 20% fall in FEV(1) in 96% (95% CI, 70%-99%) of patients. CONCLUSION: Exposure to occupational agents per se does not induce airway inflammation. Changes in both sputum eosinophil counts and methacholine responsiveness are satisfactory predictors of a significant bronchial responsiveness to occupational agents.

Adult↗

Occupational asthma.

The workplace can be responsible for approximately one in 10 cases of adult-onset asthma. Two types of occupational asthma (OA) are distinguished by whether they arise after a latency period that is necessary for acquiring sensitization or as a result of acute exposure to irritant materials (irritant-induced asthma). The pathophysiology of OA with a latency period is similar to that of nonoccupational asthma, whereas the mechanism of irritant-induced asthma is still uncertain. HLA haplotypes and other genetic polymorphisms have been found to be associated with OA. According to various sources of data, the overall frequency of OA has remained stable in the last 10 years, although the frequency of causal agents vary. Registers of causal occupations and agents have been issued on Web sites (eg, www.asmanet.com ). Improved sampling methods have shown that the degree of exposure plays a key role in the onset of the disease, whereas prospective data collected in high-risk workplaces have also identified personal risk factors (eg, atopy, smoking, and rhinoconjunctivitis). A diagnosis of OA should no longer be based on a compatible history only but should be confirmed by means of objective testing. Once the diagnosis is confirmed, the worker should be removed from exposure, and satisfactory compensation programs should be offered, the most important being retraining programs with financial compensations because affected workers are generally young. The cost-effectiveness of prevention programs in high-risk workforces should be assessed.

Asthma↗

Incidence and host determinants of probable occupational asthma in apprentices exposed to laboratory animals.

Laboratory animal (LA) workers are frequently affected with allergic sensitization and occupational asthma (OA). The role of preexposure host factors, in particular airway responsiveness, on the incidence of OA has not been satisfactorily studied. A prospective cohort study of 417 apprentices in animal-health technology was conducted to investigate the incidence and determinants of probable OA. Questionnaire and skin-prick tests with common and work-specific allergens were administered on entry and at follow-up visits (up to three) from 8 to 44 mo after starting apprenticeship. Responsiveness to inhaled methacholine was assessed at baseline and at follow-up in apprentices who developed a new specific skin sensitization and in control subjects. Preexposure host characteristics and the school attended were compared between cases and all cohort subjects not meeting the criteria for probable OA. Twenty-eight apprentices satisfied the definition for probable OA, i.e., onset of immediate skin reactivity to > 1 occupational inhalant and > 3.2-fold decrease in the provocative concentration causing a 20% reduction in FEV(1) (PC(20)). The incidence of probable OA was 2.7% (28/1,043 person-years). Baseline immediate skin reactivity to pets (rate ratio [RR] 4.1, 95% confidence interval [CI] = 1.6 to 10.8), and bronchial responsiveness (PC(20) < or = 32 versus PC(20) > 32 mg/ ml) (RR = 2.5, 95% CI = 1.0 to 5.8) were associated with an increased risk of probable OA; a lower FEV(1) had an apparent, protective effect (RR = 0.58, 95% CI = 0.43 to 0.78). It is concluded that apprentices in animal health show a high incidence of probable OA, and that preexposure airway caliber and responsiveness as well as sensitization to pets are associated with an increased risk.

Adult↗

Natural history of sensitization, symptoms and occupational diseases in apprentices exposed to laboratory animals.

The natural history of the development of sensitization and disease due to high-molecular-weight allergens is not well characterized. This study describes the time-course of the incidence of work-related symptoms, skin reactivity and occupational rhinoconjunctivitis (RC) and asthma (OA); and assesses the predictive value of skin testing and RC symptoms in apprentices exposed to laboratory animals, in a 3-4-yr programme. Four-hundred and seventeen apprentices at five institutions were assessed prospectively with questionnaire, skin-testing with animal-derived allergens, spirometry and airway responsiveness (n=373). Depending on the school, students were seen 8 (n=136), 20 (n=345), 32 (n=355) and 44 (n=98) months after starting the programme. At all visits, the incidence was greater for work-related RC symptoms followed in order by skin reactivity, occupational RC, and, almost equally, OA and work-related respiratory symptoms. The incidence-density figures were comparable for each follow-up period and for most indices up to 32 months after entry into the study and then tended to decrease. The positive predictive values (PPVs) of skin reactivity to work-related allergens for the development of work-related RC and respiratory symptoms were 30% and 9.0%, respectively, while the PPVs of work-related RC for the development of OA was 11.4%. Sensitization, symptoms and diseases occur maximally in the first 2-3 yrs after starting exposure to laboratory animals. Skin reactivity to work-related allergens and rhinoconjuctivitis symptoms have low positive predictive values.

Adolescent↗

Occurrence and risk factors of oral candidiasis treated with oral antifungals in seniors using inhaled steroids.

Oral candidiasis (OC) is a frequent side effect of inhaled corticosteroids (iCSTs). This study estimated occurrence and significance of risk factors of OC treated with antifungals in users of iCSTs under conditions of normal use. This retrospective analysis used data drawn from drug insurance plan records in Quebec, Canada. The sample contained 27,000 seniors using anti-asthma medications during 1990. Three years of data (1989-1991) were searched for use of oral antifungals concurrent with exposure to iCSTs. A case-control study examined factors leading to increased probability of first incidence of OC in new users of iCSTs. Three-year occurrence for OC was 7%. Increased risk for a first occurrence of OC was significantly associated with higher doses of iCST, increased length of iCST exposure, use of antibiotics, use of oral steroids, having three or more prescribers, a history of use of both high and low strengths of iCST, and concurrent use of oral steroids and diabetes medications. The occurrence of OC is relatively high. Knowledge of factors leading to increased risk could facilitate the targetting of patients who need timely intervention, under conditions of normal use.

Aged↗

Frequency and determinants of exaggerated bronchoconstriction during shortened methacholine challenge tests in epidemiological and clinical set-ups.

The European Respiratory Society guidelines on bronchial provocation testing have proposed time-saving procedures, which may lead to unwanted exaggerated responses. The frequency and determinants of exaggerated bronchoconstriction in response to methacholine inhalation testing in clinical and epidemiological settings have not been assessed. The authors evaluated: 1) the prevalence of exaggerated bronchoconstriction, 2) its relation to time-saving measures (starting methacholine concentration and skipping concentrations); and 3) associations between such reactions and risk factors, respiratory symptoms and/or lung function parameters. Clinical (n=408) and epidemiological (n=711) groups were included. Exaggerated bronchoconstriction was defined as either a fall > or =20% following saline or a > or =30% fall in forced expiratory volume in one second (FEV1) after methacholine inhalations. Cases were compared with two groups of subjects: 1) with measurable bronchial responsiveness (MBR); and 2) without MBR. In the epidemiological group, 84 subjects (12%) presented exaggerated bronchoconstriction. Skipped concentrations accounted for an exaggerated bronchoconstriction in 18 of these. In the clinical group, 41 subjects (10%) experienced exaggerated reactions. Skipped concentrations accounted for an exaggerated bronchoconstriction in five of these. The provocative concentration of methacholine causing a 20% fall in FEV1 values were marginally lower in subjects with exaggerated bronchoconstriction. Questionnaire analysis in epidemiological subjects showed some symptoms of asthma and rhinitis to be more prevalent in cases than in subjects without MBR. In conclusion, methacholine inhalation tests with time-saving measures result in a 10% risk of exaggerated bronchoconstriction as defined in this study and bronchial responsiveness is more prominent in subjects with exaggerated bronchoconstriction.

Adult↗

What is the respiratory retention of inhaled hexamethylene di-isocyanate?

Isocyanates are a frequent cause of occupational asthma. Specific inhalation challenges are often required to confirm the diagnosis. The inhaled concentration has to be assessed during this procedure. However, the respiratory retention of di-isocyanate has not, to the authors knowledge, been evaluated in humans. The existence of a closed-circuit apparatus, designed to carry out these challenges, makes it possible to assess the dose. The respiratory retention of hexamethylene di-isocyanate (HDI) generated in vapour form, in both normal subjects (n=4) and subjects referred for the investigation of occupational asthma due to HDI in whom the diagnosis was excluded (n=5), was assessed. The latter group included four subjects with nonoccupational asthma. The HDI was generated at concentrations varying 5.1-15.2 ppb. The expired concentrations of HDI during such challenges varied 1.4-5.3 ppb. Therefore, the respiratory retention was 61-90%. To conclude, the majority of inhaled hexamethylene di-isocyanate vapour is retained within the airways and/on lung parenchyma.

Asthma↗