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/m³ (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/m³ [0.69-12.12] and 0.21 ng/m³ [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/m³ [BD-0.59] and 0.63 ng/m³ [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.

Childhood asthma and environmental exposures at swimming pools: state of the science and research recommendations.

OBJECTIVES: Recent studies have explored the potential for swimming pool disinfection by-products (DBPs), which are respiratory irritants, to cause asthma in young children. Here we describe the state of the science on methods for understanding children's exposure to DBPs and biologics at swimming pools and associations with new-onset childhood asthma and recommend a research agenda to improve our understanding of this issue. DATA SOURCES: A workshop was held in Leuven, Belgium, 21-23 August 2007, to evaluate the literature and to develop a research agenda to better understand children's exposures in the swimming pool environment and their potential associations with new-onset asthma. Participants, including clinicians, epidemiologists, exposure scientists, pool operations experts, and chemists, reviewed the literature, prepared background summaries, and held extensive discussions on the relevant published studies, knowledge of asthma characterization and exposures at swimming pools, and epidemiologic study designs. SYNTHESIS: Childhood swimming and new-onset childhood asthma have clear implications for public health. If attendance at indoor pools increases risk of childhood asthma, then concerns are warranted and action is necessary. If there is no such relationship, these concerns could unnecessarily deter children from indoor swimming and/or compromise water disinfection. CONCLUSIONS: Current evidence of an association between childhood swimming and new-onset asthma is suggestive but not conclusive. Important data gaps need to be filled, particularly in exposure assessment and characterization of asthma in the very young. Participants recommended that additional evaluations using a multidisciplinary approach are needed to determine whether a clear association exists.

Complex interactions of pollutant and allergen exposures and their impact on people with asthma.

Pediatric asthma has many causes and can manifest differently in different children and at different times. Understanding the many factors related to the development and exacerbation of asthma is complicated by the complexity of the many environmental exposures related to asthma development and morbidity. Furthermore, the same environmental exposures that may cause increased symptoms at 1 point in time may be protective when the exposure occurs earlier or at high enough levels. We know that environmental exposures such as allergens, irritants, and pollutants are quite complex in their composition; further examination of this complexity may improve our understanding of this complex and highly prevalent disease.

Parent report of pests and pets and indoor allergen levels in inner-city homes.

BACKGROUND: Guidelines recommend allergen avoidance for patients with allergic asthma, but direct measurements of home allergen levels are not available to most physicians. Parent report of indoor allergen exposure is a potentially convenient and inexpensive surrogate measure of exposure, although validity of parent report to estimate indoor allergen levels is not well established. OBJECTIVE: To determine if parent-reported pest and pet exposures can identify patients with clinically relevant allergen exposure. METHODS: Parents of 300 inner-city children completed a survey about pests (cockroaches and mice) and furred pets (dogs and cats). Settled dust samples were obtained for Bla g 1, Mus m 1, Can f 1, and Fel d 1 from kitchens and bedrooms. RESULTS: Parent reports were associated with clinically relevant levels of Bla g 1, Mus m 1, Can f 1, and Fel d 1 (P < .001 for all). For example, when parents reported cockroaches were present, 86% of homes had settled dust Bla g 1 levels of 1 U/g or higher, and when they reported mice were present, 90% had Mus m 1 levels greater than 500 ng/g. Report of pets was also predictive of clinically meaningful allergen levels. Parent-reported absence of pets provided assurance that allergen levels were below relevant thresholds (negative predictive value, 80%-98%). However, parent-reported absence of pests did not provide assurance of low levels of these allergens (negative predictive value, 38%-75%). CONCLUSIONS: Since direct measurement of indoor allergens is not always feasible, especially in the inner city, parent report of pests and pets may be sufficient to recommend environmental control practices for sensitized children. Negative parent reports of pests are not sufficient evidence of low pest allergen exposure.

Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial.

BACKGROUND: Preliminary evidence is equivocal about the role of exhaled nitric oxide (NO) in clinical asthma management. We aimed to assess whether measurement of exhaled NO, as a biomarker of airway inflammation, could increase the effectiveness of asthma treatment, when used as an adjunct to clinical care based on asthma guidelines for inner-city adolescents and young adults. METHODS: We did a randomised, double-blind, parallel-group trial at ten centres in the USA. We screened 780 inner-city patients, aged 12-20 years, who had persistent asthma. All patients completed a run-in period of 3 weeks on a regimen based on standard treatment. 546 eligible participants who adhered to treatment during this run-in period were then randomly assigned to 46 weeks of either standard treatment, based on the guidelines of the National Asthma Education and Prevention Program (NAEPP), or standard treatment modified on the basis of measurements of fraction of exhaled NO. The primary outcome was the number of days with asthma symptoms. We analysed patients on an intention-to-treat basis. This trial is registered with clinicaltrials.gov, number NCT00114413. FINDINGS: During the 46-week treatment period, the mean number of days with asthma symptoms did not differ between the treatment groups (1.93 [95% CI 1.74 to 2.11] in the NO monitoring group vs 1.89 [1.71 to 2.07] in the control group; difference 0.04 [-0.22 to 0.29], p=0.780). Other symptoms, pulmonary function, and asthma exacerbations did not differ between groups. Patients in the NO monitoring group received higher doses of inhaled corticosteroids (difference 119 mug per day, 95% CI 49 to 189, p=0.001) than controls. Adverse events did not differ between treatment groups (p>0.1 for all adverse events). INTERPRETATION: Conventional asthma management resulted in good control of symptoms in most participants. The addition of fraction of exhaled NO as an indicator of control of asthma resulted in higher doses of inhaled corticosteroids, without clinically important improvements in symptomatic asthma control.

Does neighborhood violence lead to depression among caregivers of children with asthma?

Prior studies have related community violence to depression among children, but few studies have examined this relationship among adults. We hypothesized that victimization, awareness, and fear of neighborhood violence would increase the odds of depression among adult caregivers of children with asthma. We surveyed caregivers in the Baltimore Indoor Environment Study of Asthma in Kids (BIESAK), USA. The primary outcome was screening positive for depression on the Center for Epidemiological Studies Depression index. We assessed victimization, awareness, and fear of neighborhood violence, and conducted spatial analysis identifying subject homes within 500 ft of a homicide to validate survey measures of neighborhood violence. A multilevel logistic model with clustering by neighborhood estimated odds ratios and 95% confidence intervals. Survey responses about fear of neighborhood violence were strongly predicted by having a home within 500 ft of a homicide. Of 150 caregivers of children with asthma, 49% were aware of a neighborhood violent event, 36% were fearful of neighborhood violence, 22% reported victimization, and 27% had a homicide within 500 ft of the home. In our multilevel model, fear of violence increased the odds of depression by 6.7. Victimization was associated with a possible trend towards depression, and awareness of neighborhood violence did not increase the odds of depression. Based on our findings, personal experience with neighborhood violence may be more important than simple awareness. Health care workers should consider screening for depression among patients exposed to community violence.

Common household activities are associated with elevated particulate matter concentrations in bedrooms of inner-city Baltimore pre-school children.

Asthma disproportionately affects inner-city, minority children in the U.S. Outdoor pollutant concentrations, including particulate matter (PM), are higher in inner-cities and contribute to childhood asthma morbidity. Although children spend the majority of time indoors, indoor PM exposures have been less extensively characterized. There is a public health imperative to characterize indoor sources of PM within this vulnerable population to enable effective intervention strategies. In the present study, we sought to identify determinants of indoor PM in homes of Baltimore inner-city pre-school children. Children ages 2-6 (n=300) who were predominantly African-American (90%) and from lower socioeconomic backgrounds were enrolled. Integrated PM(2.5) and PM(10) air sampling was conducted over a 3-day period in the children's bedrooms and at a central monitoring site while caregivers completed daily activity diaries. Homes of pre-school children in inner-city Baltimore had indoor PM concentrations that were twice as high as simultaneous outdoor concentrations. The mean indoor PM(2.5) and PM(10) concentrations were 39.5+/-34.5 and 56.2+/-44.8 microg/m(3), compared to the simultaneously measured ambient PM(2.5) and PM(10) (15.6+/-6.9 and 21.8+/-9.53 microg/m(3), respectively). Common modifiable household activities, especially smoking and sweeping, contributed significantly to higher indoor PM, as did ambient PM concentrations. Open windows were associated with significantly lower indoor PM. Further investigation of the health effects of indoor PM exposure is warranted, as are studies to evaluate the efficacy of PM reduction strategies on asthma health of inner-city children.

The environment and asthma in US inner cities.

Poor, minority children living in US inner cities have increased rates of asthma morbidity and mortality. Factors that contribute to these increased rates are varied and complex, with current evidence suggesting that the environment is an important causative factor. Respiratory morbidity is often the result of allergens and air pollutants. Additionally, for children living in urban environments, underlying societal susceptibility factors specific to the inner city serve to increase asthma morbidity. Even though ambient pollutants have been declining in US cities, asthma morbidity and mortality rates have been increasing. Indoor pollutants are closely linked to increased asthma prevalence and morbidity. While the understanding of environmental influences is still relatively limited, we can say that indoor exposures are more important than ambient pollutants, and we know that bioaerosols containing allergenic proteins are especially important. Additionally, certain particulate aerosols and ozone cause inflammation individually and may act synergistically to enhance the acute and chronic IgE-mediated inflammation. The purpose of this article is to review the data relating exposure to environmental pollutants and airborne allergens, and the relationship of this exposure to asthma prevalence and morbidity in order to inform plans for public health programs to reduce an asthma burden.

Does current asthma control predict future health care use among black preschool-aged inner-city children?

OBJECTIVES: Factors predictive of future asthma must be identified among young inner-city children, who suffer disproportionately from asthma. We investigated whether current asthma control predicts future asthma-related health care use among inner-city preschool-aged children with asthma. METHODS: A total of 150 inner-city preschool-aged children with asthma were followed prospectively for 6 months. At baseline, symptom frequency and reliever-medication use were assessed to classify children into National Asthma Education and Prevention Program-derived control categories. Long-term controller-medication use was also assessed, as well as asthma-related health care use at baseline and at 3 and 6 months. RESULTS: The mean age was 4.4 years, 92% were black, and 39% reported long-term controller use. At baseline, 37% were classified as having mild-intermittent, 17% had mild-persistent, 21% had moderate-persistent, and 25% had severe-persistent asthma control. Significant changes in asthma control were observed over time, including 46% of children originally categorized with mild-intermittent asthma who had worsened asthma control by 3 months. Asthma control significantly predicted future health care use 3 months later but not 6 months later. Multivariate analyses showed that, once control status was known, reported use of long-term controller medication added little additional predictive value. CONCLUSIONS: Among inner-city preschool-aged children, significant fluctuations in asthma control occur as early as 3 months after assessment. Poor control but not long-term controller-medication use is an independent predictor of future asthma-related health care use at 3 months but is not significantly predictive of 6-month outcomes. Therefore, clinicians caring for inner-city children with asthma should consider reassessing asthma control at least every 3 months to identify those at highest future risk and to provide early interventions.

Home indoor pollutant exposures among inner-city children with and without asthma.

BACKGROUND: Evidence for environmental causes of asthma is limited, especially among African Americans. To look for systematic differences in early life domestic exposures between inner-city preschool children with and without asthma, we performed a study of home indoor air pollutants and allergens. METHODS: Children 2-6 years of age were enrolled in a cohort study in East Baltimore, Maryland. From the child's bedroom, air was monitored for 3 days for particulate matter 0.05]. Settled dust allergen levels (cat, dust mite, cockroach, dog, and mouse) were also similar in bedrooms of asthmatic and control children. CONCLUSIONS: Exposures to common home indoor pollutants and allergens are similar for inner-city preschool children with and without asthma. Although these exposures may exacerbate existing asthma, this study does not support a causative role of these factors for risk of developing childhood asthma.

Indoor environmental differences between inner city and suburban homes of children with asthma.

We conducted this study to compare environmental exposures in suburban homes of children with asthma to exposures in inner city homes of children with asthma, to better understand important differences of indoor pollutant exposure that might contribute to increased asthma morbidity in the inner city. Indoor PM(10), PM(2.5), NO(2), O(3), and airborne and dust allergen levels were measured in the homes of 120 children with asthma, 100 living in inner city Baltimore and 20 living in the surrounding counties. Home conditions and health outcome measures were also compared. The inner city and suburban homes differed in ways that might affect airborne environmental exposures. The inner city homes had more cigarette smoking (67% vs. 5%, p < .001), signs of disrepair (77% vs. 5%, p < .001), and cockroach (64% vs. 0%, p < .001) and mouse (80% vs. 5%, p < .001) infestation. The inner city homes had higher geometric mean (GM) levels (p < .001) of PM(10) (47 vs. 18 microg/m(3)), PM(2.5) (34 vs. 8.7 microg/m(3)), NO(2) [19 ppb vs. below detection (BD)], and O(3) (1.9 vs. .015 ppb) than suburban homes. The inner city homes had lower GM bedroom dust allergen levels of dust mite (.29 vs. 1.2 microg/g, p = .022), dog (.38 vs. 5.5 microg/g, p < .001) and cat (.75 vs. 2.4 microg/g, p = .039), but higher levels of mouse (3.2 vs. .013 microg/g, p < .001) and cockroach (4.5 vs. .42 U/g, p < .001). The inner city homes also had higher GM airborne mouse allergen levels (.055 vs. .016 ng/m(3), p = .002). Compared with the homes of suburban children with asthma, the homes of inner city Baltimore children with asthma had higher levels of airborne pollutants and home characteristics that predispose to greater asthma morbidity.

Mouse allergen-specific antibody responses in inner-city children with asthma.

BACKGROUND: Although mouse allergen exposure is common in inner-city homes, little is known about the relationships between exposure and humoral immune responses to mouse allergen in this population. OBJECTIVE: To examine relationships between mouse allergen exposure and allergen-specific IgE and IgG responses in inner-city children with asthma. METHODS: Inner-city children with asthma underwent skin testing and venipuncture for determination of mouse allergen-specific IgE and IgG levels. Settled dust samples were collected from their homes for allergen analysis. RESULTS: The study population (n = 112) was predominantly African American (92%) with a mean age of 4.4 years. The prevalence rate of mouse sensitization was 25% and did not consistently increase with increasing Mus m 1 levels. Instead, the prevalence rate was lowest among those exposed to <2 microg/g, increased among those exposed to 2-7.9 microg/g and 8-29.9 microg/g, and then decreased among participants exposed to >29.9 microg/g (14%, 20%, 40%, and 28%, respectively). Similarly, the prevalence rates of mouse allergen-specific IgG and IgG(4) did not increase across increasing exposure categories. Mouse allergen-specific IgG and IgG(4) were strongly associated with IgE sensitization (odds ratios [95% CI], 82.8 [20.5-334.4] and 50.4 [14.0-181.7], respectively). CONCLUSION: High-level exposure to mouse allergen in children may be associated with attenuated humoral responses of all isotypes rather than selective attenuation of IgE. CLINICAL IMPLICATIONS: Protection against allergic sensitization by high-dose allergen exposure may not be mediated by preferential production of IgG over IgE.

Room-specific characteristics of suburban homes as predictors of indoor allergen concentrations.

BACKGROUND: Room characteristics predicting indoor allergen exposure in suburban homes have not been clearly identified. OBJECTIVE: To examine relationships between room characteristics and concentrations of indoor allergens in homes of suburban asthmatic patients. METHODS: The homes of 339 asthmatic children ages 6 to 17 years were studied. Home inspections were conducted by a trained technician, and dust samples were analyzed for indoor allergen content. A high allergen concentration was defined as 8 microg (U)/g or more of fine dust. RESULTS: Infrequent sheet washing and wall-to-wall carpet were risk factors for high bedroom dust mite concentrations. Infrequent sheet washing was also a risk factor for high Fel d 1 concentrations. Food remains in the bedroom was a risk factor for high bedroom Bla g 1 levels, and exposed food, leaks, and dirty pots were all risk factors for high kitchen Bla g 1 levels. The combination of lack of mattress or pillow encasements, infrequent sheet washing, and carpeting was associated with a 24-fold increase in odds of a high dust mite concentration (odds ratio [OR], 24.1; 95% confidence interval [CI], 3.2-181.4). Among non-cat owners, the combination of stuffed toys on the bed, lack of mattress or pillow encasements, and infrequent sheet washing was associated with a 49-fold increase in odds of a high Fel d 1 level (OR, 49.4; 95% CI, 2.8-887.3). The combination of leaks, exposed food, and dirty pots was associated with a high kitchen Bla g 1 concentration (OR, 10.6; 95% CI, 2.8-40.5). CONCLUSIONS: Specific room characteristics predict high indoor allergen exposure among children with asthma, and a combination of these characteristics may further increase the risk of high allergen exposure.