Beverly Paigen

Control strategies for aeroallergens in an animal facility

BACKGROUND Prevalence of the occupational disease laboratory animal allergy could be reduced if aeroallergen reduction strategies are identified. OBJECTIVE To reduce worker exposure to Mus m 1, an allergen from laboratory mice, the effect of filter cage tops, increased room ventilation, negatively pressurized ventilated cages, and ventilated cage-changing tables were evaluated. METHODS Aeroallergen was collected in the ambient air and in the breathing zone and quantified by using a competitive immunoassay. RESULTS When mice were housed in unventilated cages, ambient allergen was reduced from 5.1 ng/m3 with no cage top to 1.3 ng/m3 with a simple filter-sheet top and 0.8 ng/m3 with a fitted filter-bonnet top (P <. 05). Room ventilation was increased from 6 to 10, 15, and 20 air changes per hour and had little effect on aeroallergen levels and no impact on airborne particulate matter. When mice were housed in ventilated cages, ambient allergen was significantly reduced from 1. 1 ng/m3 at positive cage pressure to 0.3 ng/m3 at negative cage pressure (P <.05). Negative cage pressure combined with handling animals under a ventilated table reduced breathing zone allergen from 28 ng/m3 with neither control strategy in place to 9 ng/m3 (P <. 05). Use of a ventilated table controlled bacterial contamination, measured as colony forming units, found in negatively pressurized cages. CONCLUSION Three aeroallergen control strategies are use of filter cage tops, operation of negatively pressurized cages, and use of ventilated changing tables.

The effect of relative humidity on mouse allergen levels in an environmentally controlled mouse room.

To determine the effect of humidity on the levels of the mouse allergen Mus m 1, an experimental animal room was constructed to control environmental variables. The sex, strain, age, and number of mice was constant in the room, so that the average daily production of Mus m 1 would not vary greatly. Six different levels of relative humidity from 15% to 65% were maintained for a minimum of a week each. Daily collections of airborne particulates were eluted from filters and Mus m 1 content measured by immunological assay. Increasing relative humidity caused a decrease in Mus m 1 levels from a high of 3 ng/m3 at 15% humidity to a low of 0.5 ng/m3 at 65% humidity. Thus, reduction of airborne allergen levels can be achieved by careful attention to humidity control, especially during the winter heating season when humidity levels may be low. This experimental room can be used to measure the effect of other variables such as ventilation rate, caging, bedding, and work practices on the levels of mouse allergen in an animal facility.

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

BACKGROUND The role of natural aeroallergen exposure in modulating allergen-specific immune responses is not well understood. OBJECTIVE We sought to examine relationships between mouse allergen exposure and mouse-specific immune responses. METHODS New employees (n = 179) at a mouse facility underwent repeated assessment of mouse allergen exposure, skin prick tests (SPTs), and measurement of mouse-specific IgG levels. Relationships between the mean level of exposure, variability of exposure (calculated as log deviation), and time to development of immunologic outcomes were examined by using Cox proportional hazards models. RESULTS By 24 months, 32 (23%) participants had experienced a positive SPT response, and 10 (8%) had mouse-specific IgG₄. The incidence of a positive SPT response increased as levels of exposure increased from low to moderate, peaking at 1.2 ng/m³, and decreased beyond this point (P = .04). The more variable the exposure was across visits, the lower the incidence of a positive SPT response (hazard ratio [HR], 0.17; 95% CI, 0.07-0.41). Variability of exposure was an independent predictor of a positive SPT response in a model that included both exposure metrics. In contrast, the incidence of mouse-specific IgG₄ increased with increasing levels of mouse allergen exposure (HR, 2.9; 95% CI, 1.4-6.0), and there was evidence of a higher risk of mouse-specific IgG₄ with greater variability of exposure (HR, 6.3; 95% CI, 0.4-95.2). CONCLUSION Both the level and variability of mouse allergen exposure influence the humoral immune response, with specific patterns of exposure associated with specific immunophenotypes. Exposure variability might be a more important predictor of a positive SPT response, whereas the average exposure level might be a more important predictor of mouse-specific IgG₄.

Occupational Mouse Allergen Exposure Among Non-Mouse Handlers

This study assessed mouse allergen exposure across a range of jobs, including non-mouse handling jobs, at a mouse facility. Baseline data from 220 new employees enrolled in the Jackson Laboratory (JAXCohort) were analyzed. The baseline assessment included a questionnaire, allergy skin testing, and spirometry. Exposure assessments consisted of collection of two full-shift breathing zone air samples during a 1-week period. Air samples were analyzed for mouse allergen content, and the mean concentration of the two shifts represented mouse allergen exposure for that employee. The mean age of the 220 participants was 33 years. Ten percent reported current asthma and 56% were atopic. Thirty-eight percent were animal caretakers, 20% scientists, 20% administrative/support personnel, 10% materials/supplies handlers, and 9% laboratory technicians. Sixty percent of the population handled mice. Eighty-two percent of study participants had detectable breathing zone mouse allergen, and breathing zone mouse allergen concentrations were 1.02 ng/m 3 (0.13–6.91) (median [interquartile range (IQR)]. Although mouse handlers had significantly higher concentrations of breathing zone mouse allergen than non-handlers (median [IQR]: 4.13 ng/m 3 [0.69–12.12] and 0.21 ng/m 3 [below detection (BD)–0.63], respectively; p < 0.001), 66% of non-handlers had detectable breathing zone mouse allergen. Mouse allergen concentrations among administrative/support personnel and materials/supplies handlers, jobs that generally do not entail handling mice, were median [IQR]: 0.23 ng/m 3 [BD–0.59] and 0.63 ng/m 3 [BD–18.91], respectively. Seventy-one percent of administrative/support personnel, and 68% of materials/supplies handlers had detectable breathing zone mouse allergen. As many as half of non-mouse handlers may have levels of exposure that are similar to levels observed among mouse handlers.

Air Quality in an Animal Facility: Particulates, Ammonia, and Volatile Organic Compounds

Concentrations of ammonia, volatile organic compounds, particles, and mouse allergen were measured in an animal facility. Ammonia concentrations averaged less than 1 ppm, below any health-based standards. The concentrations of volatile organic compounds were in the 5-15 micrograms/m3 range. Among the volatile organic compounds found, only the terpenes a-pinene and a-terpinol (which may be derived from the pine shavings used as bedding) were consistently present in concentrations greater than outdoor air. The primary air contaminant present at concentrations high enough to be of known physiological significance was the mouse allergen, Mus ml. To determine which activities in an animal room generated the highest concentrations of airborne Mus ml, a monitor that counted particles continuously was used. The particle counts were correlated with allergen levels in the workers breathing zone (r50.83,p,0.05). Thus, a particle counter can be used effectively in an animal facility to identify specific activities that generate high levels of both particles and allergen. Such activities included changing mice from soiled to clean cages, cleaning floors, and changing foam inserts in pressurized individually ventilated cages. To reduce exposure to allergen during cage changing, which is the major activity for an animal caretaker, a capture-type ventilated changing table was designed and tested. Use of such a table reduced exposure to allergen in the workers breathing zone from 4.961.1 to 2.160.3 ng Mus ml/m3, a level comparable to background levels.

Atopy as a Modifier of the Relationships Between Endotoxin Exposure and Symptoms Among Laboratory Animal Workers

Background Exposure to endotoxin is known to trigger airway inflammation and symptoms, and atopy may modify the relationship between endotoxin exposure and symptom development. Objective To test the a priori hypothesis that atopic status modifies the relationship between endotoxin exposure and respiratory symptom development. Methods A prospective study of laboratory workers at The Jackson Laboratories was conducted. Allergy skin testing was performed and population demographic and clinical information was obtained at baseline. Personal exposure assessments for airborne endotoxin and surveys of self-reported symptoms were performed every 6 months. Cox proportional hazards models were used to examine the relationship between endotoxin exposure and development of mouse-associated symptoms and multivariate regression was used to test for interaction. Results Overall, 16 (9%) of 174 worker-participants developed mouse-associated rhinoconjunctivitis symptoms by 24 months and 8 (5%) developed mouse-associated lower respiratory symptoms by 24 months. Among workers with endotoxin exposure above the median (≥2.4 EU m-3), 5 (6% of 80) atopics reported mouse-associated rhinoconjunctivitis symptoms at 24 months as compared to 3 (3% of 94) non-atopics. Among workers below the median endotoxin exposure (<2.4 EU m-3), 1 (1% of 80) atopic reported mouse-associated rhinoconjunctivitis symptoms at 24 months as compared to 7 (7% of 94) non-atopics. For the combination of symptoms, the adjusted hazard ratio was 6.8 (95% confidence interval: 0.7-67.2) for atopics and 0.07 (95% confidence interval: 0.01-0.5) for non-atopics. Conclusion In this occupational cohort, atopic workers may be more susceptible to, and non-atopic workers protected from, endotoxin-associated upper and lower respiratory symptoms.

Physician-diagnosed eczema is an independent risk factor for incident mouse skin test sensitization in adults.

BACKGROUND The disrupted skin barrier in eczema has been associated with an increased risk of immunoglobulin E (IgE) sensitization in childhood. However, it is unclear whether eczema, independent of atopy, is a risk factor for the development of allergic sensitization in adulthood. OBJECTIVE To determine if skin barrier dysfunction, independent of atopy, is a risk factor for incident sensitization in adult workers at a mouse production and research facility. METHODS New employees at The Jackson Laboratory enrolled in a cohort study and underwent skin-prick testing (SPT) at baseline and every 6 months to mouse and to a panel of aeroallergens (net wheal ≥3 mm indicated a positive SPT result). Mouse allergen exposure was measured every 6 months by using personal air monitors. Physician-diagnosed eczema was defined as self-reported physician-diagnosed eczema. Cox proportional hazard modeling was used to examine the association between baseline physician-diagnosed eczema and incident mouse skin test sensitization and adjusted for potential confounders. RESULTS The participants (N = 394) were followed up for a median of 24 months. Fifty-four percent were women, 89% were white, and 64% handled mice. At baseline, 7% of the participants reported physician-diagnosed eczema and 9% reported current asthma; 61% had at least one positive skin test result. At 30 months, 36% of those with eczema versus 14% of those without eczema had developed a positive mouse skin test result (p = 0.02, log-rank test). After adjusting for age, race, sex, smoking status (current, former, never), current asthma, hay fever, the number of positive SPT results at baseline, and mouse allergen exposure, physician-diagnosed eczema was an independent risk factor for incident mouse SPT sensitization (hazard ratio 5.6 [95% confidence interval, 2.1-15.2]; p = 0.001). CONCLUSION Among adult workers at a mouse production and research facility, physician-diagnosed eczema was a risk factor for incident mouse sensitization, independent of atopy, which indicated that a defect in skin barrier alone may increase the risk of skin sensitization, not just in childhood, but throughout life.

Reducing exposure to laboratory animal allergens

Laboratory animal allergy is a serious health problem. We examined several possible allergen-reducing strategies that might be effective in the working mouse room. Ambient allergen concentrations were measured when mice were maintained under several conditions: conventional housing versus ventilated cage racks operated under negative or positive pressure. We found that housing mice in ventilated cages operated under negative pressure and using ventilated changing tables reduced ambient mouse allergen (Mus m 1) concentrations tenfold, compared with values when mice were housed in conventional caging and using a conventional (non-ventilated) changing table. Housing mice in positively pressurized cages versus conventional cages did not reduce ambient allergen values. Cleaning mouse rooms at an accelerated frequency also did not reduce ambient Mus m 1 concentration. We also quantified ambient allergen values in several areas of The Jackson Laboratory. A facility-wide survey of Mus m 1 concentrations indicated that allergen concentrations were undetectable in control areas, but ranged from a mean (+/- SEM) 0.11 +/- 0.02 ng/m3 to 5.40 +/- 0.30 ng/m3 in mouse rooms with different cage types. The percentage of animal caretakers reporting allergy symptoms correlated significantly with ambient allergen concentrations: 12.9% reported symptoms in the rooms with the lowest allergen concentration (0.14 +/- 0.02 ng/m3), but 45.9% reported symptoms in rooms with the highest concentration (2.3 +/- 0.4 ng/m3). These data indicate that existing technology can significantly reduce exposure to laboratory animal allergens and improve the health of animal caretakers.