Mechanisms of allergy and clinical immunology
Associations between pre-employment immunologic and airway mucosal factors and the development of occupational allergy

https://doi.org/10.1016/j.jaci.2008.12.021Get rights and content

Background

Sensitization to occupational allergens is frequently found in laboratory animal workers (LAWs) and can cause serious health problems. Atopy is a major risk factor for sensitization, but it is considered insufficient to advise against working with animals.

Objective

We investigated whether immunologic measures, including serology and cytokine production profiles of blood cells, and parameters for airway inflammation are associated with the development of occupational sensitization.

Methods

In a prospective cohort study 110 starting LAWs were followed for 2 years. At inclusion, results of health questionnaires, skin test results, lung function measures, methacholine threshold levels, and nasal lavage fluid were obtained. Blood was taken for measuring total IgE and allergen-specific IgE antibodies. Cytokine production profiles were measured in whole blood.

Results

Twenty-two new cases of sensitization were identified during follow-up. In multivariate logistic regression analysis a model including atopy and total IgE level predicted sensitization best. This was corroborated in a separate validation cohort. Parameters for airway inflammation or cytokine production profiles did not further contribute to the prediction of sensitization. Based on these results, pre-employment counseling aimed at applicant LAWs with atopy and a total IgE level of greater than 100 IU/mL might be able to reduce occupational sensitization by up to 45% to 50% with less than 10% false-positive predictions.

Conclusion

The combination of atopy and total IgE level offered the best model to predict development of occupational sensitization. Other immunologic parameters and parameters of airway inflammation did not contribute significantly.

Section snippets

Study design and characteristics

In this prospective longitudinal cohort study 110 starting LAWs working with rats, mice, or both were followed for 2 years. The protocol was approved by the Institutional Review Board of the Academic Medical Center of the University of Amsterdam. Written informed consent was obtained from all participants. At inclusion, participants should have had less than 18 months of occupational contact with animals and no sensitization to the animals with which they were working.

The outcome of the study

Study population and occupational setting

Characteristics of the cohort are shown in Table I. At the start of the study, 4 subjects reported previous occupational sensitization to animals or plants. During the study, they had no contact with these allergens. As expected, atopic subjects had significantly higher levels of total IgE (P < .001) and tended to have a lower methacholine threshold (P = .06). At the start of the study, IL-8 and myeloperoxidase levels in the nasal lavage fluid were significantly higher in nonatopic subjects (P

Discussion

In this cohort the incidence of sensitization was very similar to the incidence of laboratory animal allergy reported in previous studies.1, 2, 3 It is described in the literature that sensitization is frequently followed by the development of occupational allergy, which is usually defined as having work-related allergic symptoms in the presence of sensitization.19 This was confirmed in our study. Symptoms of rhinoconjunctivitis were encountered most frequently (73%), and asthma symptoms were

References (21)

There are more references available in the full text version of this article.

Cited by (22)

  • Long term effect and allergic sensitization in newly employed workers in laboratory animal facilities

    2015, Respiratory Medicine
    Citation Excerpt :

    We also showed that low bronchial responsiveness to methacholine was associated with a lower risk of developing LAA. These findings are in line with previous results in a 2 years follow-up cohort study [22] where atopy in addition with family history of allergy, bronchial methacholine threshold, IgE level and working with rats were associated with an increased risk of becoming sensitized to rat and mice. We observed increased bronchial responsiveness during follow up only in those who were atopic whereas bronchial responsiveness remained unaltered in subjects who were non-atopic at study entry.

  • Historic overview of allergy research in the Netherlands

    2014, Immunology Letters
    Citation Excerpt :

    Work-related allergic symptoms are of concern both for employers and employees. Some examples of Dutch contributions to the occupational allergy field are the investigations in the laboratory animal workers [147,148], pig farmers [149], the baking industry [150] and the greenhouse workers [151]. Allergen exposure in the home environment has been investigated in many studies.

  • Both the variability and level of mouse allergen exposure influence the phenotype of the immune response in workers at a mouse facility

    2011, Journal of Allergy and Clinical Immunology
    Citation Excerpt :

    Relationships observed between the exposure metrics and a positive SPT response and mouse-specific IgG4 levels were robust to adjustment for potential confounders, including age, sex, smoking status, total IgE levels, and respiratory protection use (see Tables E2, E3, and E4 in this article’s Online Repository). In addition, atopy, which has been shown to be a risk factor for sensitization and allergen-specific IgG4 in previous studies,8,23,24 was also a predictor of these outcomes in this study population (see this article’s Online Repository). Most study participants had neither skin test sensitivity nor mouse-specific IgG4.

  • Advances in environmental and occupational respiratory diseases in 2009

    2010, Journal of Allergy and Clinical Immunology
    Citation Excerpt :

    Induced sputum cell counts may be another useful method for evaluating OA. In a prospective study of laboratory animal workers, Krop et al6 found that new sensitization was correlated most closely with pre-existing evidence of atopy (positive skin test to inhaled allergens) and a total IgE level <100 IU/mL. Pre-employment counseling aimed at such individuals may be able to reduce occupational sensitization by up to 45% to 50%.

View all citing articles on Scopus

Supported by research grand no. 99-25 of the Dutch Asthma Foundation.

Disclosure of potential conflict of interest: D. J. J. Heederik has a research contract with the European Union and the Dutch government. R. Lutter received grant support from AstraZeneca. The rest of the authors have declared that they have no conflict of interest.

Dr Krop is currently affiliated with the Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.

View full text