The effects of urban green space and road proximity to indoor traffic-related PM2.5, NO2, and BC exposure in inner-city schools.

BACKGROUND: Since there are known adverse health impacts of traffic-related air pollution, while at the same time there are potential health benefits from greenness, it is important to examine more closely the impacts of these factors on indoor air quality in urban schools. OBJECTIVE: This study investigates the association of road proximity and urban greenness to indoor traffic-related fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) in inner-city schools. METHODS: PM2.5, NO2, and BC were measured indoors at 74 schools and outdoors at a central urban over a 10-year period. Seasonal urban greenness was estimated using the Normalized Difference Vegetation Index (NDVI) with 270 and 1230 m buffers. The associations between indoor traffic-related air pollution and road proximity and greenness were investigated with mixed-effects models. RESULTS: The analysis showed linear decays of indoor traffic-related PM2.5, NO2, and BC by 60%, 35%, and 22%, respectively for schools located at a greater distance from major roads. The results further showed that surrounding school greenness at 270 m buffer was significantly associated (p < 0.05) with lower indoor traffic-related PM2.5: -0.068 (95% CI: -0.124, -0.013), NO2: -0.139 (95% CI: -0.185, -0.092), and BC: -0.060 (95% CI: -0.115, -0.005). These associations were stronger for surrounding greenness at a greater distance from the schools (buffer 1230 m) PM2.5: -0.101 (95% CI: -0.156, -0.046) NO2: -0.122 (95% CI: -0.169, -0.075) BC: -0.080 (95% CI: -0.136, -0.026). These inverse associations were stronger after fully adjusting for regional pollution and meteorological conditions. IMPACT STATEMENT: More than 90% of children under the age of 15 worldwide are exposed to elevated air pollution levels exceeding the WHO's guidelines. The study investigates the impact that urban infrastructure and greenness, in particular green areas and road proximity, have on indoor exposures to traffic-related PM2.5, NO2, and BC in inner-city schools. By examining a 10-year period the study provides insights for air quality management, into how road proximity and greenness at different buffers from the school locations can affect indoor exposure.

Age-specific Metabolomic profiles in children with food allergy.

BACKGROUND: Food allergy (FA) in young children is often associated with eczema, frequently directed to egg/cow milk allergens and has a higher chance of resolution, while FA that persists in older children has less chance of resolution and is less clearly associated with atopy. METHODS: Children with FA (n = 62) and healthy controls (n = 28) were categorized into "younger" (≤5 years) and "older" (>5 years). Mass spectrometry-based untargeted metabolomic profiling as wells as cytokine profiling were performed on plasma samples in FA children in each age group. RESULTS: Younger FA children manifested unique alterations in bile acids, polyamine metabolites and chemokines associated with Th2 responses, while older FA children displayed pronounced changes in long chain fatty acids, acylcarnitines and proinflammatory cytokines. CONCLUSIONS: FA children of different ages manifest unique metabolic changes which may reflect at least in part pathogenic mechanisms and environmental influences operative at different time points in the disease course.

ß-2 adrenergic receptor gene methylation is associated with decreased asthma severity in inner-city schoolchildren: asthma and rhinitis.

BACKGROUND: Genetic variation in the ß-2 adrenergic receptor gene (ADRB2) has been implicated in asthma severity and control with conflicting results. Epigenetic variation in the ADRB2 may play an important role in asthma phenotype. OBJECTIVE: We aimed to evaluate whether DNA methylation of ADRB2 is associated with asthma phenotypes in inner-city school-aged children. METHODS: Multiple CpG sites in the promoter region of ADRB2 gene were analysed in 177 children enrolled in the School Inner-City Asthma Study. Blood- or saliva-derived DNA was measured by bisulphite-polymerase chain reaction pyrosequencing assay. Average percentage DNA methylation across the sites was evaluated for association with asthma severity (report of dyspnoea, night-time symptoms, rescue medication use, and baseline spirometry) and morbidity (school absences and unscheduled healthcare visits). Three clades composed of highly correlated methylation sites within the methylated segment of ADRB2 were further analysed. RESULTS: Methylation of individual sites generally ranged from 0% to 6% with average percentage methylation across sites of 2.4%. Univariate analyses strongly favoured the association of higher percentage methylation with lower asthma severity measured by report of dyspnoea. Furthermore, there was a non-significant trend towards less rescue medication use, night-time symptoms, school absences, activity limitation due to asthma, and improved lung function measurements with increased methylation. Multivariate analysis demonstrated methylation of ADRB2 gene significantly associated with less dyspnoea (odds ratio (OR) 0.2, 95% confidence interval (CI), 0.1-0.6, P = 0.002). Each of the three clades of methylation sites showed a strong, but not statistically significant, effect on decreased dyspnoea. CONCLUSIONS AND CLINICAL RELEVANCE: DNA methylation in the ADRB2 gene is associated with decreased asthma symptom severity, suggesting a role for methylation in asthma phenotypes.

Mouse allergen exposure, wheeze and atopy in the first seven years of life.

BACKGROUND: Little is known about mouse allergen exposure in home environments and the development of wheezing, asthma and atopy in childhood. OBJECTIVE: To examine the relation between mouse allergen exposure and wheezing, atopy, and asthma in the first 7 years of life. METHODS: Prospective study of 498 children with parental history of allergy or asthma followed from birth to age 7 years, with longitudinal questionnaire ascertainment of reported mouse exposure and dust sample mouse urinary protein allergen levels measured at age 2-3 months. RESULTS: Parental report of mouse exposure in the first year of life was associated with increased risk of transient wheeze and wheezing in early life. Current report of mouse exposure was also significantly associated with current wheeze throughout the first 7 years of life in the longitudinal analysis (P = 0.03 for overall relation of current mouse to current wheeze). However, early life mouse exposure did not predict asthma, eczema or allergic rhinitis at age 7 years. Exposure to detectable levels of mouse urinary protein in house dust samples collected at age 2-3 months was associated with a twofold increase in the odds of atopy (sensitization to >=1 allergen) at school age (95% confidence interval for odds ratio = 1.1-3.7; P = 0.03 in a multivariate analysis. CONCLUSIONS: Among children with parental history of asthma or allergies, current mouse exposure is associated with increased risk of wheeze during the first 7 years of life. Early mouse exposure was associated with early wheeze and atopy later in life.

Predictors of indoor exposure to mouse allergen in urban and suburban homes in Boston.

BACKGROUND: Mouse allergen exposure is prevalent among urban children with asthma. Little is known about mouse allergen exposure in children at risk for the development of allergic diseases. AIMS OF THE STUDY: To assess indoor mouse allergen exposure in early life among children with parental history of asthma or allergies. METHODS: Prospective birth cohort study of 498 children with a history of allergy or asthma in at least one parent living in metropolitan Boston. RESULTS: Of the 498 participating children, 357 (71.7%) resided outside the city of Boston and 439 (90.7%) lived in households with incomes > 30,000 dollars. Mouse allergen was detected in 42% of the homes of study participants. In a multivariate analysis adjusting for sex, income, and endotoxin, black race [odds ratio (OR) = 3.0; 95% confidence interval (CI) = 1.3-6.6, P = 0.009], signs of mice in the home at age 2-3 months (OR = 3.0; 95% CI = 1.6-5.6, P = 0.0006), and kitchen cockroach allergen levels > or = 0.05 to < 2 U/g (OR = 1.8; 95% CI = 1.1-3.2, P = 0.02) were associated with detectable mouse allergen in the kitchen. In this model, living in a single detached house was inversely associated with detectable kitchen mouse allergen levels (OR = 0.4; 95% CI = 0.2-0.6, P = 0.0001). CONCLUSION: Infants with a parental history of asthma or allergies are commonly exposed to mouse allergen in their homes. Among infants at high risk for atopy, predictors of increased mouse allergen levels included black race, reported mice exposure, and moderate levels of cockroach allergen.

Successful treatment of enterovirus infection with the use of pleconaril in 2 infants with severe combined immunodeficiency.

Two patients with severe combined immunodeficiency and enterovirus infections were successfully treated with pleconaril. There were no adverse affects.

Animal allergens and their control.

Animal allergens play a significant role in the pathogenesis of asthma and allergic rhinitis, and are potent causes of acute and chronic symptoms. Although cat and dog allergens are the most important, exposure to a wide variety of other furred animals is not uncommon. Recent reports state that 60% to 70% of households in the western world have at least one pet. Because of this significant exposure, hypersensitivity to animals has become increasingly important. This review focuses on the importance of animal allergens, concentrating on cat and dog allergens, but including others as well. It also discusses the pathogenesis, diagnosis, prevention, and management of animal allergy.

Mouse allergen. I. The prevalence of mouse allergen in inner-city homes. The National Cooperative Inner-City Asthma Study.

BACKGROUND: Although mouse allergen is a well-defined cause of IgE-mediated hypersensitivity in occupational settings, it has not been well studied in the general population. OBJECTIVE: We sought to determine the prevalence of mouse allergen in inner-city homes. METHODS: A subset of 608 homes from the National Cooperative Inner-City Asthma Study population had dust samples adequate for analysis of mouse allergen. In addition, data regarding the demographics and housing of the subjects were related to the mouse allergen levels. RESULTS: Ninety-five percent of all homes had detectable mouse allergen (Mus m 1) in at least one room, with the highest levels found in kitchens (kitchen: range, 0-618 microg/g; median, 1.60 microg/g; bedroom: range, 0-294 microg/g; median, 0.52 microg/g; television-living room: range, 0-203 microg/g; median, 0. 57 microg/g). By city, 100% of the kitchens in Baltimore had detectable mouse allergen, with the lowest percentage (74%) in Cleveland. Mouse allergen levels correlated among rooms (R = 0.65-0. 75). Forty-nine percent of the homes had reported problems with mice within the last year, and 29% of the homes had evidence of mice in one or more rooms on home inspection and had higher levels of mouse allergen (P =.0001). Higher allergen levels were also associated with evidence of cockroach infestation in any room (P =.006). None of the other subject or housing demographics evaluated were associated with a higher prevalence or level of mouse allergen. CONCLUSIONS: We conclude that mouse allergen is widely distributed in inner-city homes and that cockroach infestation is associated with high mouse allergen levels.

Mouse allergen. II. The relationship of mouse allergen exposure to mouse sensitization and asthma morbidity in inner-city children with asthma.

BACKGROUND: Although mouse allergen is known to cause occupational asthma in laboratory workers, its potential significance in home environments has never been studied. OBJECTIVE: This study was designed to define the prevalence of mouse sensitivity and its relationship to mouse allergen exposure and disease activity in inner-city children with asthma. METHODS: A subset of 499 subjects from the National Cooperative Inner-City Asthma Study had dust samples adequate for mouse allergen analysis, as well as valid puncture skin test (PST) results. Data were analyzed to relate mouse allergen exposure and other risk factors to mouse sensitization and asthma morbidity. RESULTS: Eighty-nine (18%) of the 499 children had a positive mouse skin test response. Children whose homes had mouse allergen levels above the median (1.60 microg/g) in the kitchen had a significantly higher rate of mouse sensitization (23% vs 11%, P =. 007). Atopy was also significantly related to mouse sensitization, with 40% of those with more than 4 positive PST responses having mouse sensitivity compared with 4% of those with no other positive PST responses (P <.0001). When atopy and exposure were considered together, 53% of those with more than 4 positive PST responses and allergen levels above the median had a positive PST response to mouse allergen compared with 22% of those with more than 4 positive PST responses and allergen levels below the median (P <.0001). The relationship among mouse allergen exposure, sensitization, and any measures of asthma morbidity was not statistically significant. CONCLUSIONS: Mouse allergen may be an important indoor allergen in inner-city children with asthma, with exposure and atopy contributing to mouse sensitization.

A randomized, double-blind, placebo-controlled trial of the effect of zafirlukast on upper and lower respiratory responses to cat challenge.

BACKGROUND: Zafirlukast, a leukotriene antagonist, has been shown to have protective effects against a variety of asthma triggers. OBJECTIVE: Our purpose was to evaluate zafirlukast's effects on upper and lower airway responses to cat allergen exposure with use of a well-characterized cat exposure model. METHODS: In a double-blind, placebo-controlled, cross-over trial 18 subjects with cat-induced asthma were randomly assigned to receive 1 week each of zafirlukast or placebo followed by a 1-hour cat challenge. Upper and lower respiratory symptoms were rated and spirometry and acoustic rhinometry were performed. Challenges were stopped early if the subject was too uncomfortable or had a >50% decrease in FEV(1). RESULTS: Overall changes in FEV(1) were significantly different with zafirlukast treatment (P = .02). Significant differences in FEV(1) change were detected at 15 and 30 minutes (P = .027 and .05, respectively) but not at 45 and 60 minutes. Changes in acoustic rhinometry were also significantly different at 15 and 30 minutes (P =.05 and .0005, respectively) but not at 45 and 60 minutes. Challenge length was significantly longer with zafirlukast versus placebo after adjustment for differences in allergen exposure (P = .022). Respiratory symptom scores were significantly different (lower respiratory, P < .001; upper respiratory, P = .038) through the first 30 minutes of the challenge after adjustment for allergen exposure. CONCLUSIONS: Zafirlukast was significantly more effective than placebo in preserving pulmonary function and nasal anatomy and extending challenge length when cat-sensitive asthmatic subjects were exposed to high levels of cat allergen.

A comparison of skin prick tests, intradermal skin tests, and RASTs in the diagnosis of cat allergy.

BACKGROUND: Skin testing and RASTs are the most commonly used methods for the diagnosis of allergy. Questions remain, however, as to the accuracy of these tests, particularly with regard to the role of intradermal skin tests (IDSTs) in the evaluation of respiratory allergy. OBJECTIVE: The purpose of this study was to determine the predictive value of skin prick tests (SPTs), IDSTs, and RASTs in the diagnosis of cat allergy. METHODS: Patients were challenged with a well-characterized cat exposure model after evaluation by history, SPTs, IDSTs (if SPT results were negative), and RASTs. All patients were evaluated with respect to their upper respiratory responses, although only those patients with asthma were included in the analysis of lower airway responses. Challenge results were considered positive if the mean upper respiratory symptom score was 0.5 or more, the mean lower respiratory symptom score was 0.4 or more, or the maximum fall in FEV1 value was 15% or more. RESULTS: One hundred twenty patients were evaluated. SPT values were positive in 81 patients; of the remaining 39 patients, IDST values were positive in 26 patients. RASTs were performed in 89 patients; the values were positive in 45 of 51 patients with a positive SPT value and were negative in all patients with a negative SPT value. When any positive challenge outcome was considered, positive challenge results were seen in 38 of 41 patients with a positive SPT score, in 10 of 39 patients with a negative SPT score, in 6 of 26 patients with a positive IDST score, in 4 of 13 patients with a negative IDST score, in 27 of 27 patients with a positive RAST score, and in 12 of 44 patients with a negative RAST score. CONCLUSION: Although both SPT and RAST values exhibited excellent efficiency in the diagnosis of cat allergy, IDST scores added little to the diagnostic evaluation.

The value of acoustic rhinometry in assessing nasal responses to cat exposure.

BACKGROUND: Acoustic rhinometry (AR) uses sonar principles to map the anatomy of the nasal cavity and has been used in other studies to assess acute airway responses to allergen exposure. OBJECTIVE: The purpose of this study was to evaluate the utility of AR in assessing acute airway responses to cat allergen exposure by using a well-characterized cat exposure model. METHODS: Thirty subjects with a history of cat-induced rhinitis and a positive skin prick test response to cat allergen underwent an environmental cat challenge. Of these 30 subjects, 10 also had repeat challenges at lower levels of antigen to determine whether there was a dose response. Five subjects with negative skin test responses to cat were recruited as control subjects. During the 1-hour cat exposure, upper and lower respiratory symptoms were scored every 5 minutes, and spirometry and AR were obtained every 15 minutes. RESULTS: Although 29 of 30 subjects had changes in AR measurements, no correlations were detected between upper respiratory symptom scores and any of the changes observed in AR. In comparing the baseline challenges with lower antigen level challenges, upper respiratory symptom scores differed significantly (P = .002), whereas AR responses were nearly identical. Subjects without cat allergy did exhibit less response by AR (P = .05 to .13), but the greatest differences remained in the upper respiratory symptoms scores (P < .0001). CONCLUSION: We conclude that although AR does provide an objective measure of nasal response to allergen exposure, it has significant limitations. These are evidenced by the lack of correlation with symptoms, the inability to measure a dose response, and the changes noted even among the control subjects.

The fallacy of evaluating biomaterial wear-rates with water as lubricant: a hip simulator study of alumina-PTFE nd CoCr-PTFE combinations.

Controversy surrounds wear data from hip-simulator studies, whether from the choice of lubricants or other parameters such as the particular biomaterial combinations used, and whether any such interactions could bias the resulting wear predictions. To investigate these phenomena, we studied the wear performance of CoCr and alumina femoral heads, in water and serum-based lubricants, using as our standard the polytetrafluoroethylene wear data derived clinically by Charnley. To model Charnley's clinical experience, PTFE acetabular cups were used in sets of three each with each size of femoral head for 22.25, 28, and 42-mm diameters in a nine-channel hip simulator. From the serum-based tests, the CoCr-PTFE wear data were consistently linear with duration of test, exhibited very large wear rates of 3,000-8,400 mm3/10(6), cycles had a precision within +/- 4% for each set of three cups, and copious amounts of small particulate were clearly seen circulating. The wear data clearly demonstrated Charnley's thesis that volume of wear increased with regard to size of femoral head. From the water-based tests, the CoCr-PTFE wear data were nonlinear with duration of test, had much reduced wear rates compared to the serum tests, lost the clinical relationship with ball size, and precision deteriorated to +/- 27% for each set. The wear debris appeared as 1-2 cm long ribbons which floated to the surface. For the alumina-PTFE combination in serum, the wear data appeared identical in performance to the CoCr-PTFE data in serum. Thus, the PTFE wear rates were not sensitive to the choice of femoral-head material. The most surprising outcome in this study was the zero-wear performance of the ceramic-PTFE combination in water. This contrasted remarkably with the large wear rates established for the same combinations run in serum. The zero-wear performance of the ceramic-PTFE combination in water was unexpected, but a similar phenomenon was noted in published simulator tests of ceramic-UHMWPE run in water. It now seems likely that such data may reflect the capricious behavior of water lubrication rather than any other variables under evaluation. The water-based experiments clearly favored the ceramic's superior tribological performance and placed metal bearings at a decided disadvantage. Therefore, for an in vitro simulation of materials wear-ranking of clinical relevance, it may be advisable to use a serum-based lubricant.