Risk modification and combined exposures in occupational respiratory allergy

Abstract

The main objective of the studies described in this thesis was to investigate the impact of combined exposure to allergens and non-allergenic agents on the development of respiratory allergy in occupational populations. The effect of early life exposure to the farming environment and endotoxin exposure on IgE mediated sensitization to common allergens (atopy) and respiratory symptoms was studied in farming students and adult pig farmers. Both a farm childhood and current exposure to the farming environment were associated with a much lower prevalence of atopy in farming students and non-farming controls. A low risk of sensitization to common allergens was also found in full time pig farmers, and was associated with chronic high dose exposure to endotoxin. Whether the reduced prevalence of atopy also affects risk of (allergic) respiratory disease is not clear from these studies. A farm childhood was associated with a lower prevalence of wheeze, doctor-diagnosed asthma, and bronchial hyper-reactivity (BHR), but current farming and high endotoxin exposure were associated with higher prevalences of respiratory symptoms and increased BHR in farming students and pig farmers.

The relation between disinfectant exposure and respiratory allergy was studied in pig farmers and in laboratory animal (LA) workers that had been working with LA's for more ('experienced') or less ('novice') than 4 years. Results from the study in pig farmers confirmed that disinfectant use might be a risk factor for allergic respiratory disease in this population. Prevalence of sensitization to common allergens was very low in farmers who did not use disinfectants, but strongly increased with increasing frequency of disinfectant use. Disinfectant use was also a risk factor for respiratory symptoms in atopic pig farmers, which concords with earlier findings, and was associated with signs of upper airways inflammation. Nevertheless, prevalences of sensitization to common and laboratory animal allergens were lower in 'novice' LA workers using disinfectants containing chloramine-T, and use of disinfectants other than alcohol was associated with lower prevalences of respiratory symptoms to common allergens and laboratory animals. However, no association was found between disinfectant use and sensitization or respiratory symptoms in 'experienced' workers, and there was some indication that the inverse association in 'novice' workers might be due to reversed causation.

We also investigated whether high titers of IgG4 antibody to rat urinary allergens (RUA) could be a marker for the induction of immunological tolerance in LA workers. Exposure to RUA was associated with high titers of allergen-specific IgG4 antibody. However, IgG4 was a strong risk factor for both prevalent and newly occurring sensitization and symptomatic allergy to rats in atopic and rat-sensitized workers respectively. High IgG4 to RUA is therefore not a marker for the induction of tolerance, but rather reflects aspects of exposure and susceptibility. Long-term changes in lung function in workers exposed to high molecular weight sensitizers were assessed using follow-up data from the study in LA workers. Contact with laboratory animals was a significant risk factor for accelerated annual lung function decline, but this was most pronounced in sensitized workers who continued to be exposed to the animals they were sensitized to.

Results from these studies illustrate the impact of combined exposures and interaction effects on the development of occupational respiratory allergy. Although allergen exposure is probably the most important determinant of IgE sensitization or symptomatic allergy in susceptible workers, exposure to non-allergenic agents such as endotoxin or disinfectants may significantly affect susceptibility. As combined exposures are the rule rather than the exception in the working environment, these effects are relevant to risk assessment of both allergens and non-allergenic agents.