Indoor Environmental Factors May Modify the Response to Mouse Allergen Reduction Among Mouse-Sensitized and Exposed Children with Persistent Asthma.

BACKGROUND: Whether concomitant home exposures modify the effectiveness of mouse allergen reduction among mouse-sensitized children with asthma is unknown. OBJECTIVE: To determine whether a lower baseline home mouse allergen level, lower particulate matter 10 µ or less (PM10), and the absence of sensitization and exposure to other indoor allergens are associated with greater improvements in asthma associated with mouse allergen reduction. METHODS: A secondary analysis of a randomized clinical trial of a home mouse allergen intervention was performed to examine the effect of 3 indoor factors on the relationship between mouse allergen reduction and a range of asthma outcomes. RESULTS: Participants (N = 297) were predominantly minority (78% African American, 22% Hispanic) and publicly insured (88%). Higher baseline mouse allergen levels were associated with a greater response to mouse allergen reduction for several symptom and exacerbation outcomes. Lower indoor PM10 levels were associated with a greater response to mouse allergen reduction for several symptom outcomes, but not exacerbation outcomes. Overall, sensitization and exposure to other indoor allergens did not appear to modify the effect of mouse allergen reduction. CONCLUSIONS: In this population of predominantly low-income children with persistent asthma and mouse sensitization, mouse allergen reduction was associated with improvements in asthma, especially among those with high baseline mouse allergen exposure. Lower indoor PM10 was associated with greater improvements in asthma symptoms.

Do Baseline Asthma and Allergic Sensitization Characteristics Predict Responsiveness to Mouse Allergen Reduction?

BACKGROUND: Mouse allergen reduction is associated with improvements in asthma among sensitized and exposed children, but whether clinical characteristics predict responsiveness to allergen reduction is unclear. OBJECTIVE: To examine the effects of clinical characteristics on relationships between mouse allergen reduction and asthma outcomes. METHODS: We performed a secondary analysis of data from a randomized clinical trial of a mouse allergen intervention, examining the effects of atopy, demographic characteristics, lung function, asthma control, and asthma severity on relationships between mouse allergen reduction and asthma outcomes. RESULTS: Participants were predominantly low-income and minority (78% black, 22% Hispanic), and had persistent asthma. Among less atopic participants (<6 positive skin prick test results), each 50% reduction in mouse allergen was associated with fewer symptoms (incidence rate ratio [95% CI]: maximal symptoms: 0.94 [0.92-0.96]). There was little effect of mouse allergen reduction on symptoms among more atopic participants (P > .05). The interactions between atopic status and mouse allergen reduction were statistically significant for all symptom outcomes; however, there was no evidence that atopic status influenced the effect of mouse allergen reduction on exacerbation-related outcomes. Older children (≥9 years) tended to experience greater improvement in some asthma outcomes with reduction in mouse allergen exposure than younger children. There was no evidence that either mouse-specific IgE or lung function influenced the effect of mouse allergen reduction on any asthma outcomes. CONCLUSIONS: Although there may be variability in the clinical response to mouse allergen reduction among low-income, minority children with asthma, there were no clinical characteristics that clearly identified a subgroup at which the intervention should be targeted.

Reduction in mouse allergen exposure is associated with greater lung function growth.

BACKGROUND: Current childhood asthma therapies have little effect on lung function trajectory. OBJECTIVE: We sought to determine whether mouse allergen exposure reduction is associated with lung function growth in mouse-sensitized/exposed asthmatic children. METHODS: Three hundred fifty mouse-sensitized/exposed asthmatic children (5-17 years old) were enrolled in a 1-year randomized trial of integrated pest management plus education versus education alone. Prebronchodilator/postbronchodilator spirometry was performed at baseline and 6 and 12 months, and bedroom floor mouse allergen levels were measured every 3 months. Mouse allergen reduction was defined as a 75% or greater decrease in mouse allergen levels from baseline. Treatment groups were combined for analyses because there were no differences in outcomes between groups. Changes in lung function over time were modeled, adjusting for age, sex, race, atopy, group, and bronchodilator reversibility and including an interaction term (allergen reduction*time). RESULTS: The study population was predominantly black (79.4%) and low income (66.3% [<$30,000]). At baseline, the median mouse allergen level was 5.7 µg/g (interquartile range, 1.5-22.8 µg/g), and the mean (SD) prebronchodilator FEV1/forced vital capacity ratio was 80.2% (9.0%). Ninety-two (26.3%) participants had 75% or greater reduction in mouse allergen levels. For a 10-year-old black boy, 75% or greater allergen reduction was associated with an increase in prebronchodilator FEV1 of 238 mL/y (95% CI, 177-299 mL/y), whereas less than 75% allergen reduction was associated with an increase in prebronchodilator FEV1 of 131 mL/y (95% CI, 97-166 mL/y). Estimated differences in prebronchodilator and postbronchodilator FEV1 growth were as follows: 107 mL/y (95% CI, 37-177 mL/y; Pint = .003) and 48 mL/y (95% CI, -17 to 113 mL/y; Pint = .15), respectively. Estimated differences in prebronchodilator and postbronchodilator forced expiratory flow at 25% to 75% of vital capacity growth were as follows: 182 mL/y (95% CI, 61-304 mL/y; Pint = .003) and 181 mL/y (95% CI, 48-314 mL/y; Pint = .008), respectively. CONCLUSION: Mouse allergen reduction is associated with greater increases in prebronchodilator FEV1 and prebronchodilator/postbronchodilator forced expiratory flow at 25% to 75% of vital capacity over 1 year among sensitized/exposed asthmatic children.

Caregiver-Reported Asthma Control Predicts Future Visits, Independent of Guideline-Based Control Measures.

BACKGROUND: It is unknown whether caregiver perception of a child's asthma control, independent of guideline-based asthma control assessment, is a predictor of future acute visits. OBJECTIVE: To determine whether caregiver-reported asthma control is an indicator of future risk of acute visit. METHODS: Two study populations of low-income, minority 5- to 17-year-old children with persistent asthma were included. Questionnaires administered at baseline and at 3, 6, 9, and 12 months captured symptoms, short-acting ß-agonist use, acute visits in the previous 3 months, and caregiver-reported asthma control. Well-controlled, not well-controlled, and very poorly controlled asthma were defined using National Asthma Education and Prevention Program guideline-based assessment. Relationships between caregiver-reported control and acute visits in the subsequent 3 months were examined. RESULTS: At baseline, both populations were predominantly black/African American (91% and 79%) with public insurance (85% and 88%) and very poorly controlled asthma (47% and 50%). In both populations, most caregivers reported that their child's asthma was well controlled (73% and 69%). In both populations, participants whose caregivers reported that their child had uncontrolled asthma had greater odds of having an acute visit in the following 3 months as compared with participants whose caregivers reported that their child's asthma was well controlled, independent of guideline-based control, age, sex, race, controller medication, insurance, and atopy (odds ratio [95% CI], 2.4 [1.4-4.2] and 1.6 [1.1-2.4]). CONCLUSIONS: Among predominantly low-income minority children with asthma, caregiver-reported asthma control may provide information about the risk of future acute visit for asthma that is complementary to guideline-based control assessment.

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.

A pilot feeding study for adults with asthma: The healthy eating better breathing trial.

RATIONALE: Evidence from observational studies and to a lesser extent clinical trials suggest that a healthy diet may improve symptoms and lung function in patients with asthma. We conducted a pilot study to determine the feasibility of conducting a larger scale dietary trial and to provide preliminary evidence on the impact of a healthy diet on asthma outcomes. METHODS: In a randomized, two period cross-over trial, participants with asthma received a 4-week dietary intervention followed by a usual diet (or vice versa), separated by a 4-week washout. The dietary intervention was a healthy diet rich in unsaturated fat. During the dietary intervention, participants ate three meals per week on site at the Johns Hopkins ProHealth Research Center. All remaining meals and snacks were provided for participants to consume off-site. During the control diet, participants were instructed to continue their usual dietary intake. Relevant biomarkers and asthma clinical outcomes were assessed at 0, 2, and 4 weeks after starting each arm of the study. RESULTS: Eleven participants were randomized, and seven completed the full study protocol. Among these seven participants, average age was 42 years, six were female, and six were African American. Participant self-report of dietary intake revealed significant increases in fruit, vegetable, and omega-3 fatty acid intake with the dietary intervention compared to usual diet. Serum carotenoids (eg. lutein and beta-cryptoxanthin) increased in the intervention versus control. Total cholesterol decreased in the intervention versus control diet. There was no consistent effect on asthma outcomes. CONCLUSIONS: The findings suggest that a feeding trial in participants with asthma is feasible. Larger trials are needed to definitively assess the potential benefits of dietary interventions on pulmonary symptoms and function in patients with asthma.

Predictors of polycyclic aromatic hydrocarbon exposure and internal dose in inner city Baltimore children.

Polycyclic aromatic hydrocarbons (PAHs), the by-products of incomplete combustion of organic materials, are commonly found on particulate matter (PM) and have been associated with the development of asthma and asthma exacerbation in urban populations. We examined time spent in the home and outdoors as predictors of exposures to airborne PAHs and measured urinary 1-hydroxypyrene-glucuronide (1-OHPG) as internal dose of PAHs in 118 children aged 5-12 years from Baltimore, MD. During weeklong periods (Saturday-Saturday) in each of four seasons: daily activities were assessed using questionnaires, indoor air nicotine and PM concentrations were monitored, and urine specimens were collected on Tuesday (day 3) and Saturday (day 7) for measurement of 1-OHPG. Time spent in non-smoking homes was associated with significantly decreased 1-OHPG concentration in urine (ß=-0.045, 95% CI (-0.076, -0.013)), and secondhand smoke (SHS) exposures modified these associations, with higher urinary 1-OHPG concentrations in children spending time in smoking homes than non-smoking homes (P-value for interaction=0.012). Time spent outdoors was associated with increased urinary 1-OHPG concentrations (ß=0.097, 95% CI (0.037, 0.157)) in boys only. Our results suggest that SHS and ambient (outdoor) air pollution contribute to internal dose of PAHs in inner city children.

Mouse allergen is the major allergen of public health relevance in Baltimore City.

BACKGROUND: Cockroach and mouse allergens have both been implicated as causes in inner-city asthma morbidity in multicenter studies, but whether both allergens are clinically relevant within specific inner-city communities is unclear. OBJECTIVE: Our study aimed to identify relevant allergens in Baltimore City. METHODS: One hundred forty-four children (5-17 years old) with asthma underwent skin prick tests at baseline and had clinical data collected at baseline and 3, 6, 9, and 12 months. Home settled dust samples were collected at the same time points for quantification of indoor allergens. Participants were grouped based on their sensitization and exposure status to each allergen. All analyses were adjusted for age, sex, and serum total IgE level. RESULTS: Forty-one percent were mouse sensitized/exposed, and 41% were cockroach sensitized/exposed based on bedroom floor exposure data. Mouse sensitization/exposure was associated with acute care visits, decreased FEV1/forced vital capacity percentage values, fraction of exhaled nitric oxide levels, and bronchodilator reversibility. Cockroach sensitization/exposure was only associated with acute care visits and bronchodilator reversibility when exposure was defined by using bedroom floor allergen levels. Mouse-specific IgE levels were associated with poor asthma health across a range of outcomes, whereas cockroach-specific IgE levels were not. The relationships between asthma outcomes and mouse allergen were independent of cockroach allergen. Although sensitization/exposure to both mouse and cockroach was generally associated with worse asthma, mouse sensitization/exposure was the primary contributor to these relationships. CONCLUSIONS: In a community with high levels of both mouse and cockroach allergens, mouse allergen appears to be more strongly and consistently associated with poor asthma outcomes than cockroach allergen. Community-level asthma interventions in Baltimore should prioritize reducing mouse allergen exposure.

Guideline-recommended fractional exhaled nitric oxide is a poor predictor of health-care use among inner-city children and adolescents receiving usual asthma care.

BACKGROUND: American Thoracic Society guidelines support using fractional exhaled nitric oxide (FENO) measurements in patients with asthma and highlight gaps in the evidence base. Little is known about the use of FENO levels to predict asthma exacerbations among high-risk, urban, minority populations receiving usual care. METHODS: Children with persistent asthma (n = 138) were enrolled in a prospective, observational cohort study and skin tested at baseline (a wheal ≥ 3 mm indicated a positive skin-prick test). FENO levels, lung function, and asthma-related health-care use were assessed at baseline and every 3 months thereafter for 1 year. Relationships between FENO levels and health-care use in the subsequent 3 months were examined. Final models accounted for repeated outcome measures and were adjusted for age, sex, and lung function. RESULTS: The mean age of the children was 11 years (range, 5-17 years), and most were male (57%), black (91%), and atopic (90%). At baseline, the median FENO level was 31.5 parts per billion (interquartile range, 16-61 ppb) and mean FEV1/FVC was 80.7% (SD, ± 9.6%). There were 237 acute asthma-related health-care visits, 105 unscheduled doctor visits, 125 ED visits, and seven hospitalizations during the follow-up period. FENO level was not a significant predictor of acute visits, ED visits, unscheduled doctor visits, or hospitalization in either unadjusted or adjusted analyses. Use of recommended cut points did not improve the predictive value of the FENO level (positive predictive value, 0.6%-32.8%) nor did application of the guideline-based algorithm to assess change over time. CONCLUSIONS: FENO level may not be a clinically useful predictor of health-care use for asthma exacerbations in urban minority children with asthma.

Outdoor exposure and vitamin D levels in urban children with asthma.

BACKGROUND: The inner-city pediatric population in the United States has a disproportionate burden of asthma. Recent attention has focused on the immunomodulatory role of vitamin D, which may be protective against disease morbidity. As the primary determinant of vitamin D status in humans is exposure to sunlight, we aimed to determine if 25-OH vitamin D levels in urban preschool children with asthma were low, influenced by time spent outdoors, and associated with asthma morbidity. METHODS: Serum 25-OH vitamin D levels were measured at baseline in a cohort of 121 inner-city children ages 2-6 years with asthma in Baltimore, MD. Participants were followed longitudinally at 3 and 6 months to assess time spent outdoors, asthma symptoms through questionnaires and daily diaries, and allergic markers. RESULTS: In a predominantly black population of preschool children, the median 25-OH vitamin D level was 28 ng/mL (IQR 21.2-36.9), with 54% of the children below the traditionally sufficient level of 30 ng/mL and 7.4% in the range associated with risk of rickets (< 15 ng/mL). The median time spent outdoors was 3 hours/day (IQR 2-4), and greater time spent outdoors was not associated with higher vitamin D levels. 25-OH vitamin D did not show seasonal variation in our cohort (p = 0.66). Lower 25-OH levels were correlated with higher IgE levels. CONCLUSIONS: Urban African-American preschool children with asthma have high rates of vitamin D insufficiency, and increased outdoor exposure is unlikely to correct these low 25-OH vitamin D levels. Repletion in this population may require dietary supplementation.

Effects of allergic phenotype on respiratory symptoms and exacerbations in patients with chronic obstructive pulmonary disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) guidelines make no recommendations for allergy diagnosis or treatment. OBJECTIVES: To determine whether an allergic phenotype contributes to respiratory symptoms and exacerbations in patients with COPD. METHODS: Two separate cohorts were analyzed: National Health and Nutrition Survey III (NHANES III) and the COPD and domestic endotoxin (CODE) cohort. Subjects from NHANES III with COPD (n = 1,381) defined as age > 40 years, history of smoking, FEV1/FVC < 0.70, and no diagnosis of asthma were identified. The presence of an allergic phenotype (n = 296) was defined as self-reported doctor diagnosed hay fever or allergic upper respiratory symptoms. In CODE, former smokers with COPD (n = 77) were evaluated for allergic sensitization defined as a detectable specific IgE to perennial allergens. Bivariate and multivariate models were used to determine whether an allergic phenotype was associated with respiratory symptoms and exacerbations. MEASUREMENTS AND MAIN RESULTS: In NHANES III, multivariate analysis revealed that individuals with allergic phenotype were more likely to wheeze (odds ratio [OR], 2.1; P < 0.01), to have chronic cough (OR, 1.9; P = 0.01) and chronic phlegm (OR, 1.5; P < 0.05), and to have increased risk of COPD exacerbation requiring an acute doctor visit (OR, 1.7; P = 0.04). In the CODE cohort, multivariate analysis revealed that sensitized subjects reported more wheeze (OR, 5.91; P < 0.01), more nighttime awakening due to cough (OR, 4.20; P = 0.03), increased risk of COPD exacerbations requiring treatment with antibiotics (OR, 3.79; P = 0.02), and acute health visits (OR, 11.05; P < 0.01). An increasing number of sensitizations was associated with a higher risk for adverse health outcomes. CONCLUSIONS: Among individuals with COPD, evidence of an allergic phenotype is associated with increased respiratory symptoms and risk of COPD exacerbations.

Being overweight increases susceptibility to indoor pollutants among urban children with asthma.

BACKGROUND: Both being overweight and exposure to indoor pollutants, which have been associated with worse health of asthmatic patients, are common in urban minority populations. Whether being overweight is a risk factor for the effects of indoor pollutant exposure on asthma health is unknown. OBJECTIVES: We sought to examine the effect of weight on the relationship between indoor pollutant exposure and asthma health in urban minority children. METHODS: One hundred forty-eight children (age, 5-17 years) with persistent asthma were followed for 1 year. Asthma symptoms, health care use, lung function, pulmonary inflammation, and indoor pollutants were assessed every 3 months. Weight category was based on body mass index percentile. RESULTS: Participants were predominantly African American (91%) and had public health insurance (85%). Four percent were underweight, 52% were normal weight, 16% were overweight, and 28% were obese. Overweight or obese participants had more symptoms associated with exposure to fine particulate matter measuring less than 2.5 µm in diameter (PM2.5) than normal-weight participants across a range of asthma symptoms. Overweight or obese participants also had more asthma symptoms associated with nitrogen dioxide (NO2) exposure than normal-weight participants, although this was not observed across all types of asthma symptoms. Weight did not affect the relationship between exposure to coarse particulate matter measuring between 2.5 and 10 µm in diameter and asthma symptoms. Relationships between indoor pollutant exposure and health care use, lung function, or pulmonary inflammation did not differ by weight. CONCLUSION: Being overweight or obese can increase susceptibility to indoor PM2.5 and NO2 in urban children with asthma. Interventions aimed at weight loss might reduce asthma symptom responses to PM2.5 and NO2, and interventions aimed at reducing indoor pollutant levels might be particularly beneficial in overweight children.

Predicting future asthma morbidity in preschool inner-city children.

BACKGROUND AND AIMS: Children living in the inner city are particularly vulnerable to asthma. While we know much about factors that affect near-term outcomes in inner-city children, there is little evidence to guide clinicians on what to expect in the coming years, especially in preschool children. The purpose of our study was to determine which clinical and environmental factors are predictive of poor long-term asthma control in preschool inner-city children. MATERIALS AND METHODS: Baseline characteristics determined to be potential predictors of asthma severity were examined: demographics, asthma symptoms, medication use, healthcare utilization, early life medical history, family history, allergen exposure and allergic disease, and pollutant exposure. Bivariate and multivariate analyses were performed using logistic regression to examine the association of predictors of asthma severity with healthcare utilization at 2 years. RESULTS: Of the 150 children at baseline, the follow-up rate was 83% at 2 years; therefore, 124 children were included in final analyses. At baseline, the mean age was 4.4 years and participants were predominantly African-American (90%). Most of the children were atopic and 32.5% reported using inhaled corticosteroids. Nighttime awakening from asthma and a history of pneumonia were predictive of future poor control. CONCLUSION: Preschool children with nighttime awakening from asthma and a history of pneumonia may deserve closer monitoring to prevent future asthma morbidity.

A randomized trial of air cleaners and a health coach to improve indoor air quality for inner-city children with asthma and secondhand smoke exposure.

OBJECTIVE: To test an air cleaner and health coach intervention to reduce secondhand smoke exposure compared with air cleaners alone or no air cleaners in reducing particulate matter (PM), air nicotine, and urine cotinine concentrations and increasing symptom-free days in children with asthma residing with a smoker. DESIGN: Randomized controlled trial, with randomization embedded in study database. SETTINGS: The Johns Hopkins Hospital Children's Center and homes of children. PARTICIPANTS: Children with asthma, residing with a smoker, randomly assigned to interventions consisting of air cleaners only (n = 41), air cleaners plus a health coach (n = 41), or delayed air cleaner (control) (n = 44). MAIN OUTCOME MEASURES: Changes in PM, air nicotine, and urine cotinine concentrations and symptom-free days during the 6-month study. RESULTS: The overall follow-up rate was high (91.3%). Changes in mean fine and coarse PM (PM(2.5) and PM(2.5-10)) concentrations (baseline to 6 months) were significantly lower in both air cleaner groups compared with the control group (mean differences for PM(2.5) concentrations: control, 3.5 µg/m(3); air cleaner only, -19.9 µg/m(3); and air cleaner plus health coach, -16.1 µg/m(3); P = .003; and PM(2.5-10) concentrations: control, 2.4 µg/m(3); air cleaner only, -8.7 µg/m(3); and air cleaner plus health coach, -10.6 µg/m(3); P = .02). No differences were noted in air nicotine or urine cotinine concentrations. The health coach provided no additional reduction in PM concentrations. Symptom-free days were significantly increased [corrected] in both air cleaner groups compared with the control group (P = .03). CONCLUSION: Although the use of air cleaners can result in a significant reduction in indoor PM concentrations and a significant increase in symptom-free days, it is not enough to prevent exposure to secondhand smoke.

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.

Indoor particulate matter increases asthma morbidity in children with non-atopic and atopic asthma.

BACKGROUND: Compared with atopic asthma, fewer environmental modifications are recommended for non-atopic asthma in children. OBJECTIVE: To better understand the role of indoor pollutants in provoking non-atopic asthma, we investigated the effect of in-home particulate matter on asthma symptoms among non-atopic and atopic children living in inner-city Baltimore. METHODS: A cohort of 150 children ages 2 to 6 years with asthma underwent home environmental monitoring for 3-day intervals at baseline, 3, and 6 months. Children were classified as non-atopic if they were skin test negative to a panel of 14 aeroallergens. Caregivers completed questionnaires assessing symptoms and rescue medication use. Longitudinal data analysis included regression models with generalized estimating equations. RESULTS: Children were primarily African American from lower socioeconomic backgrounds and spent most of their time in the home. Thirty-one percent were non-atopic, and 69% were atopic. Among non-atopic and atopic children, increased in-home fine (PM2.5) and coarse (PM2.5-10) particle concentrations were associated with significant increases in asthma symptoms and rescue medication use ranging from 7% (95% confidence interval [CI], 0-15) to 14% (95% CI, 1-27) per 10 µg/m(3) increase in particle concentration after adjustment for confounders. CONCLUSIONS: In-home particles similarly cause increased symptoms of asthma in non-atopic and atopic children. Environmental control strategies that reduce particle concentrations may prove to be an effective means of improving asthma outcomes, especially for non-atopic asthma, for which there are few environmental control practice recommendations.

Household smoking behavior: effects on indoor air quality and health of urban children with asthma.

The goal of the study was to examine the association between biomarkers and environmental measures of second hand smoke (SHS) with caregiver, i.e. parent or legal guardian, report of household smoking behavior and morbidity measures among children with asthma. Baseline data were drawn from a longitudinal intervention for 126 inner city children with asthma, residing with a smoker. Most children met criteria for moderate to severe persistent asthma (63%) versus mild intermittent (20%) or mild persistent (17%). Household smoking behavior and asthma morbidity were compared with child urine cotinine and indoor measures of air quality including fine particulate matter (PM(2.5)) and air nicotine (AN). Kruskal-Wallis, Wilcoxon rank-sum and Spearman rho correlation tests were used to determine the level of association between biomarkers of SHS exposure and household smoking behavior and asthma morbidity. Most children had uncontrolled asthma (62%). The primary household smoker was the child's caregiver (86/126, 68%) of which 66 (77%) were the child's mother. Significantly higher mean PM(2.5), AN and cotinine concentrations were detected in households where the caregiver was the smoker (caregiver smoker: PM(2.5) µg/m(3): 44.16, AN: 1.79 µg/m(3), cotinine: 27.39 ng/ml; caregiver non-smoker: PM(2.5): 28.88 µg/m(3), AN: 0.71 µg/m(3), cotinine:10.78 ng/ml, all P ≤ 0.01). Urine cotinine concentrations trended higher in children who reported 5 or more symptom days within the past 2 weeks (>5 days/past 2 weeks, cotinine: 28.1 ng/ml vs. <5 days/past 2 weeks, cotinine: 16.2 ng/ml; P = 0.08). However, environmental measures of SHS exposures were not associated with asthma symptoms. Urban children with persistent asthma, residing with a smoker are exposed to high levels of SHS predominantly from their primary caregiver. Because cotinine was more strongly associated with asthma symptoms than environmental measures of SHS exposure and is independent of the site of exposure, it remains the gold standard for SHS exposure assessment in children with asthma.

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.

Skin test sensitivity to mouse predicts allergic symptoms to nasal challenge in urban adults.

Epidemiologic studies have shown an association between mouse allergen exposure and asthma morbidity among urban populations, but confirmatory challenge studies in community populations have not been performed. This study was designed to examine the clinical relevance of mouse sensitization using a nasal challenge model. Forty-nine urban adults with asthma underwent skin-prick testing (SPT) and intradermal testing (IDT) with mouse epithelia extract. A positive SPT was defined as a net wheal size ≥3 mm and a positive IDT was defined as a net wheal size ≥6 mm using a 1:100 dilution of extract (1:10 w/v was obtained from Greer Laboratories (Lenoir, NC) as a single lot [Mus m 1 concentration = 2130 ng/mL]). Mouse-specific IgE (m-IgE) was measured by ImmunoCAP (Phadia, Uppsala, Sweden). Nasal challenge was performed with increasing concentrations of mouse epithelia extract and symptoms were assessed by visual analog scale. A positive challenge was defined as a 20-mm increase in the scale. The age range of the 49 participants was 18-50 years; 41% were men and 86% were black. Fourteen participants were SPT(+) to mouse, 15 participants were SPT(-) but (IDT(+)), and 20 participants were negative on both SPT(-) and IDT(-) (SPT(-)/IDT(-)). Sixty-four percent of the SPT(+) group, 40% of the IDT(+) group, and 20% of the SPT(-)/IDT(-) group had a positive nasal challenge. Sixty-seven percent (10/15) of those who were either SPT(+) or m-IgE(+) had a positive nasal challenge. SPT or the combination of SPT plus m-IgE performed best in diagnosing mouse allergy. The great majority of mouse-sensitized urban adults with asthma appear to have clinically relevant sensitization. Urban adults with asthma should be evaluated for mouse sensitization using SPT or SPT plus m-IgE testing.