Denyse Gautrin

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.

Is reactive airways dysfunction syndrome a variant of occupational asthma

BACKGROUND Reactive airways dysfunction syndrome (RADS) or irritant-induced asthma is a syndrome that leaves subjects with asthma-like symptoms after one or more exposures to a high concentration of an irritant substance. The degree of reversibility of airway obstruction in subjects with RADS is nevertheless unknown, as is the degree of associated lesions at the airway level. METHODS We compared the acute reversibility of forced expiratory volume in 1 second (FEV1) after inhalation of albuterol (200 micrograms) in 15 subjects with RADS (12 cases caused by chlorine inhalation) with that of 30 subjects with occupational asthma (OA) caused by various agents. They were paired according to baseline airway obstruction (61% and 63% of predicted value in the RADS and OA groups), requirement for medication (bronchodilator only--7 of 15 subjects with RADS and 14 of 30 subjects with OA--as compared with bronchodilator + inhaled steroids in 8 of 15 subjects with RADS and 16 of 30 subjects with OA, respectively), and interval since removal from exposure (means of 30 and 24 months in the RADS and OA groups). In addition, five nonsmokers with RADS who had not received inhaled steroids underwent bronchoscopy with lavage and bronchial biopsies less than 2 years after the exposure. RESULTS The percentage increase in FEV1 over baseline after inhalation of albuterol was 10% +/- 9% in the RADS group and 19% +/- 16% in the OA group (p = 0.005). Only 2 of 15 subjects (13%) with RADS and 12 of 30 subjects (40%) with OA showed an improvement in FEV1 of 20% or greater after inhalation of albuterol. Bronchoalveolar lavage showed an increased number of cells with a predominance of lymphocytes, and biopsy specimens showed increased basement membrane thickness in the five subjects with RADS who underwent bronchoscopy. CONCLUSION Subjects with RADS are generally left with less airway reversibility than those with OA. We suggest that this difference is secondary to distinct pathologic changes.

EAACI position paper on occupational rhinitis

The present document is the result of a consensus reached by a panel of experts from European and non-European countries on Occupational Rhinitis (OR), a disease of emerging relevance which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio-economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored on that of occupational asthma, as well as a diagnostic algorithm based on steps allowing for different levels of diagnostic evidence are proposed. The needs for future research are pointed out. Key messages are issued for each item.

Long-Term Outcomes in a Prospective Cohort of Apprentices Exposed to High-Molecular-Weight Agents

RATIONALE We conducted a long-term (8-yr) follow-up of 408 apprentices entering programs involving exposure to high-molecular-weight allergens. OBJECTIVES The objectives were to assess the frequency of new and persisting sensitization, symptoms, and bronchial hyperresponsiveness in relation with job history after ending apprenticeship and to examine characteristics significantly associated with the incidence and remission of these occupational outcomes. METHODS A respiratory symptom questionnaire, skin prick tests with work-related allergens (laboratory animals, flour, and latex), spirometry, and methacholine challenge were administered. The association between incidence or remission of these outcomes and individual characteristics at baseline and end of apprenticeship was examined. MEASUREMENTS AND MAIN RESULTS In subjects who at any time during follow-up held a job related to their training (78%), the incidence of sensitization, rhinoconjunctival and chest symptoms, and bronchial hyperresponsiveness at follow-up was 1.3, 1.7, 0.7, and 2.0 per 100 person-years, respectively. The remission of these outcomes acquired during apprenticeship was 18.5, 9.6, 9.6, and 12.4 per 100 person-years, respectively, in subjects no longer in a job related to training. Several clinical, immunological, and functional characteristics at baseline and acquired during apprenticeship were found to be significantly associated with the incidence and remission of the outcomes. CONCLUSIONS The incidence of sensitization, symptoms, and bronchial hyperresponsiveness was lower while at work than during the apprenticeship period. A high proportion of subjects in a job not related to training experienced remission of symptoms acquired during apprenticeship.

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 ∼3% (6 of 194). The incidence of bronchial hyperresponsiveness, defined as a ≥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.

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 ∼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.

Prevalence and association of welding related systemic and respiratory symptoms in welders

Background: The prevalence of welding related respiratory symptoms coexisting with welding related systemic symptoms in welders is unknown. Aims: To determine in a sample of welders the prevalence of coexisting welding related systemic symptoms indicative of metal fume fever (MFF) and welding related respiratory symptoms suggestive of occupational asthma (OA), and the strength and significance of any association between these two groups of symptoms. Methods: A respiratory symptoms questionnaire, a systemic symptoms questionnaire, and a questionnaire on occupational history were administered by telephone to 351 of a sample of 441 welders (79.6%) from two cities in Québec, Canada. Results: The co-occurrence of possible MFF (defined as having at least two symptoms of fever, feelings of flu, general malaise, chills, dry cough, metallic taste, and shortness of breath, occurring at the beginning of the working week, 3–10 hours after exposure to welding fumes) together with welding related respiratory symptoms suggestive of OA (defined as having at least two welding related symptoms of cough, wheezing, and chest tightness) was 5.8%. These two groups of symptoms were significantly associated (χ2 = 18.9, p < 0.001). Conclusion: There is a strong association between welding related MFF and welding related respiratory symptoms suggestive of OA. As such, MFF could be viewed as a pre-marker of welding related OA, a hypothesis that requires further investigation.

Incidence and host determinants of work‐related rhinoconjunctivitis in apprentice pastry‐makers

Background: The authors recently assessed the incidence and determinants of immunologic sensitization to flour in apprentice pastry‐makers. The aim of this work was to determine the incidence of work‐related rhinoconjunctivitis (RC) symptoms and their determinants.

Occupational rhinitis in workers investigated for occupational asthma

Background: The links between asthma and rhinitis are now referred to as united airways disease (UAD). Current evidence shows that the UAD model seems to be applicable to occupational rhinitis (OR) and occupational asthma (OA). A study was undertaken to objectively assess, in the context of specific inhalation challenge (SIC) testing, the concomitance of bronchial and nasal reaction in the investigation of OR and OA. Methods: 43 subjects with a history of work-related asthma symptoms underwent SIC for confirmation of OA and investigation of OR. Changes in bronchial calibre were measured by spirometry and nasal patency and airway inflammation were assessed by acoustic rhinometry and nasal lavage. Results: A positive nasal challenge was observed in 25 SIC tests and a positive bronchial challenge was observed in 17 SIC tests. A concomitant positive nasal and bronchial challenge was observed in 13 instances. This association was significant (risk ratio = 1.7; 95% CI 1.0 to 2.4; p = 0.04) and more frequent in subjects challenged with high molecular weight agents (n = 11/22) than with low molecular weight agents (n = 2/21). In subjects with a positive nasal challenge, nasal lavage showed a significant increase in eosinophils 30 min after exposure which correlated with changes in nasal patency. Conclusion: The results of this study provide objective evidence to support the concept of UAD using OR and OA as a model to demonstrate a significant concomitant physiological reaction of the nose and lungs after challenge. This study shows that OR can be assessed by objective means; it often coexists with OA but can be present without OA.

Occupational asthma and allergy in snow crab processing in Newfoundland and Labrador

Background: Risk factors and prevalence of occupational asthma (OA) and occupational allergy (OAl) in the snow crab-processing industry have been poorly studied. Objective: To estimate the prevalence of OA and OAl in snow crab-processing workers and determine their relationship with exposure to snow crab allergens and other potential risk factors. Methods: A total of 215 workers (120 female/95 male) were recruited from four plants in Newfoundland and Labrador, Canada in 2001–2002. Results from questionnaires, skin-prick tests to snow crab meat and cooking water, specific IgEs against the latter, spirometry and peak flow monitoring were used to develop a diagnostic algorithm. An index based on work history and exposure measurements of snow crab aeroallergens was developed to estimate the cumulative exposure for each worker. Results: The prevalences of almost certain or highly probable OA and OAl were 15.8% and 14.9%, respectively. A high cumulative exposure to crab allergens, in jobs mostly held by women, was associated with OA (odds ratio (OR) = 14.0, 95% CI 3.0 to 65.8) (highest vs lowest Cumulative Exposure Index) and with OAl (OR = 7.1, 95% CI 1.9 to 29.0); job held when symptoms started (cleaning, packing, freezing) also predicted OA (OR = 3.9, 95% CI 1.6 to 8.7) and OAl (OR = 3.2, 95% CI 1.4 to 7.5). Atopy (OR = 2.8, 95% CI 1.2 to 6.8), female gender (OR = 10.7, 95% CI 3.6 to 32.1) and smoking were significant determinants for OA (OR = 3.1, 95% CI 1.3 to 7.4). Conclusions: The prevalences of OA and OAl are high in snow crab-processing workers of Canada’s East Coast. Cumulative exposure to snow crab allergens was related to the prevalences of OA and OAl in a dose–response manner taking into account atopy, gender and smoking.