Introduction

Laboratory animal allergy (LAA) is a common health problem in biomedical research and the prevalence of allergy has been found to be as high as 56% of animal-exposed workers.1 Sensitization to laboratory animal allergens can give rise to both severe, acute (anaphylactic) reactions2 and disabling chronic illnesses (dermatitis and asthma). Both acute and chronic reactions to allergen exposure can have a significant adverse impact on affected workers and their employers. Several authors have reviewed this topic.3-5

Allergy to many different animals has been described.6 The allergens are present in hair, skin, feces, urine, and other material from the animals.3 The most important laboratory animal allergens have been identified and characterized.7 These include the major rat and mouse allergens, which are urinary proteins.

The immunological mechanisms that give rise to symptoms of allergy have been characterized.5 Allergen exposure can lead to the production of specific immunoglobulin E (IgE) against allergens. The interaction between an allergen and specific IgE initiates a cascade of events that leads to the symptoms of allergy. This cascade will be repeated on each subsequent exposure to the allergen. The allergy may present as disorders of the nose and eyes (rhinoconjunctivitis), skin (urticaria and contact dermatitis), and chest (asthma) or, more rarely, as acute anaphylactic reactions.

There is conflicting evidence for personal risk factors for development of LAA, especially tobacco smoking and a family history of allergic reactions.8 The majority of studies have indicated that workers who have a tendency to produce IgE against allergens and to develop allergic symptoms (atopics)9 are more likely to develop LAA.10 Also, atopics appear to develop LAA after a shorter time of exposure.11 However, even atopy is not a sufficiently good predictor of LAA to be used in pre-placement selec-tion.6,12-14

A number of occupational risk factors for exposure to allergen have been identified, which include high-risk tasks (such as handling animals or cleaning cages)15,16 and some work practices (e.g., choice of bedding).17 Studies have demonstrated a positive relationship between exposure to animal allergens and the prevalence of sensitization.18-20 The combination of preexisting allergy or atopy and environmental risk factors (e.g., exposure level) may further increase the risk for LAA.18,21,22 The exposure-response relationship is not linear, and further work is needed before the role of different features of exposure, such as peak and troughs of exposure, in the development of allergy is fully understood.

The prevention of allergy is a significant challenge while uncertainty remains about which are the critical characteristics of exposure to control. Allergy-prevention strategies have generally focused on measures to control total exposure to allergens, through a combination of engineering, procedural, and personal controls. The cost of measures to reduce allergen exposure, such as robots and sophisticated ventilation, may be prohibitive, while their ability to reduce the incidence of allergy is uncertain. No studies of the cost effectiveness of allergen-control programs have been reported.

Although a high incidence and prevalence of LAA has been reported, where comprehensive measures have been introduced to reduce personal exposure to allergen, this has led to a decrease in the incidence of allergy to low levels.12,23 These reports suggest that for the majority of workers exposed to animals, the development of allergy can be prevented by effective control of allergen exposure.

EPIDEMIOLOGY AND PATHOGENESIS Prevalence: How Many People have LAA?

Many cross-sectional studies have investigated the proportion of cases of work-related allergy in laboratory animal-exposed populations. Pooled data from the studies of 4,988 persons at risk has indicated a prevalence of LAA of about 20%, although the spread of reported prevalence was broad.3 Many factors contribute to the wide variation in prevalence, including differences in investigators' methods and definitions of allergy, the tendency to retain unaffected workers in the exposed population, employment policies for workers already allergic to laboratory animals, and the nature and degree of allergen exposure.10

Incidence: The Risk of Getting LAA

There have been few studies of the number of newly developing cases of LAA in exposed populations, but in those published, incidences of LAA among subjects in the first years of animal work vary between 5 to 40%, when no special prevention strategies have been employed.10, 14,24 Where comprehensive programs have been introduced, a reducing incidence of allergy has been observed.12,23 Nose, eye, and skin symptoms have a higher incidence than chest symptoms.25 In a recent study of 373 apprentices, the incidence of probable occupational asthma was 2.7% after 8 to 44 months of follow-up.26 This incidence is similar to that reported elsewhere.25,27,28

Most workers who develop LAA do so within the first three years of exposure (see Figure 7.1).3,29 The mean exposure before symptoms develop is shortest for nasal symptoms and longest for chest symptoms.19 However, there is great variation in the length of the period before allergy is clinically present. While some workers develop almost immediate symptoms, others may have contact with the animals for 15 to 20 years before they react.3 However, the time to development of symptoms appears to depend upon atopic status, as was demonstrated in a retrospective study, in which atopics developed LAA after a median time of 2.2 years and nonatopics after 8.2 years.11

Exposure-Response Relationship

Exposure as a risk factor for LAA has been studied, but only recently using actual aeroallergen measurements in cohorts of exposed subjects. Exposure proxies, such as job title, work years, or hours of animal work per week, have been used in many studies, with partially contradictory results. For instance, some studies have found an inverse relationship between exposure intensity or length of employment and LAA.27,30 This has usually been attributed to healthy worker selection: those in the highest exposure groups who develop LAA have left the workforce. This may, however, suggest that length of exposure (i.e., cumulative exposure) is less important than intensity.

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