Research plan:
Occupational asthma is reported to account for 2-15% of all new cases of asthma. By analogy with the increase in allergy to ubiquitous environmental allergens, the incidence of occupational allergy also appears to be rising. Allergy and asthma caused by large molecular weight occupational (glyco)proteins resembles allergy and asthma caused by ubiquitous aero-allergens from e.g. house dust mites and cats with respect to allergen characteristics, IgE-mediated mechanism, type of bronchial inflammation and symptoms. Respiratory allergy to natural rubber (latex, Hevea brasiliensis proteins), laboratory animals (rats and mice) and plant allergens (flour in baker's asthma and vegetables and flowers in greenhouse employees) quantitatively dominate the 5-30% prevalence of sensitization among exposed employees. Although atopy is an established risk for the development of occupational allergy and asthma, a significant proportion of non-atopic employees also develop occupational airways disease. In this prospective study we will investigate which baseline parameters are associated with airway mucosal reactivity and which immunological parameters at the beginning of employment as a laboratory animal worker or entering a health care job with daily use of latex gloves are associated with the development of sensitization and occurrence of airway symptoms (rhinitis and asthma). Established risk factors i.e. level of exposure, atopy, smoking and gender will be analysed as covariates. Humoral and cellular immune responses to the occupational allergens and control antigens (tetanus toxoid) will be followed during the first 2 years of occupational exposure. Immunological parameters include peripheral blood monocyte function as determined by stimulated IL-12 production in whole blood and allergen-specific and polyclonal activation of peripheral blood mononuclear cell fractions. The Th1-Th2 polarization of the T lymphocyte response will be determined by quantitative PCR on IL-4, IL-5, IL-13 and IFN-mRNA. Isotype switching (IgG1, IgG4, IgE) of antibody responses to allergens and control antigens will be studied and related to the cellular immune response. In this study we aim to characterise the mechanisms that contribute to the development of occupational allergic sensitization and occupational asthma in order to improve the identification of individuals at risk. Moreover, the mechanisms to be studied are likely to be relevant to the development of allergy to ubiquitous allergens and naturally occurring asthma and may therefore contribute to the understanding of allergy and asthma in general. |
