Henry Lynn

Relationship of indoor allergen exposure to skin test sensitivity in inner-city children with asthma

BACKGROUNDnIt is important to understand the relationship between environmental allergen exposure dose and the risk of atopic individuals becoming sensitized to that allergen if we are to change the risk of sensitization and morbidity from allergic disease.nnnOBJECTIVEnThe objective of these studies was to determine whether there was a dose response between current exposure to mite, cockroach, and cat allergen in inner-city children and to determine the prevalence of sensitization to these allergens.nnnMETHODSnA sample of 500 children was selected from the 1528 children enrolled in the National Cooperative Inner City Asthma Study. Children were selected who had a sample of home dust and valid skin test responses performed with a MultiTest skin test device. The samples of home dust were collected from the floor and furniture in the kitchen, bedroom, and television/living room and were assayed for Der p 1, Der f 1, Bla g 1, and Fel d 1 allergens.nnnRESULTSnEach allergen level correlated significantly between rooms in individual homes. Mite (Der p 1 and Der f 1) and cat (Fel d 1) allergen levels were frequently below the detection limit of the assay. Cockroach allergen (Bla g 1) concentrations in the childs bedroom were related to the prevalence of positive skin test responses to cockroach allergen extract among the children, with an odds ratio for sensitization of 1.45 (1.11-1.92). Positive skin test responses to cockroach allergen were seen in 15% of children exposed to bedroom dust with a Bla g 1 concentration below the level of detection compared with a rate of 32% in bedrooms with Bla g 1 levels of 1 to 2 U/g and 40% to 44% among those in rooms with 4 U/g or greater. The relationship between exposure and positive skin test responses was clearly stronger among atopic children with a greater number of positive skin test responses.nnnCONCLUSIONSnDespite widespread exposure to household allergens, the strongest relationship between exposure and sensitization was seen in the bedroom. The dose response between exposure to cockroach allergen and sensitization suggested that exposure to low doses of allergen, 2 U/g or less, was a risk factor and that the risk plateaus above 4 U/g. Atopy modified the relationship of exposure to sensitization.

Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children

BACKGROUNDnWheezing illnesses cause major morbidity in infants and are frequent precursors to asthma.nnnOBJECTIVEnWe sought to examine environmental factors associated with recurrent wheezing in inner-city environments.nnnMETHODSnThe Urban Environment and Childhood Asthma study examined a birth cohort at high risk for asthma (n = 560) in Baltimore, Boston, New York, and St Louis. Environmental assessments included allergen exposure and, in a nested case-control study of 104 children, the bacterial content of house dust collected in the first year of life. Associations were determined among environmental factors, aeroallergen sensitization, and recurrent wheezing at age 3 years.nnnRESULTSnCumulative allergen exposure over the first 3 years was associated with allergic sensitization, and sensitization at age 3 years was related to recurrent wheeze. In contrast, first-year exposure to cockroach, mouse, and cat allergens was negatively associated with recurrent wheeze (odds ratio, 0.60, 0.65, and 0.75, respectively; P ≤ .01). Differences in house dust bacterial content in the first year, especially reduced exposure to specific Firmicutes and Bacteriodetes, was associated with atopy and atopic wheeze. Exposure to high levels of both allergens and this subset of bacteria in the first year of life was most common among children without atopy or wheeze.nnnCONCLUSIONSnIn inner-city environments children with the highest exposure to specific allergens and bacteria during their first year were least likely to have recurrent wheeze and allergic sensitization. These findings suggest that concomitant exposure to high levels of certain allergens and bacteria in early life might be beneficial and suggest new preventive strategies for wheezing and allergic diseases.

Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis

BACKGROUNDnAtopic dermatitis (AD) is a common inflammatory skin disease with a global prevalence ranging from 3% to 20%. Patients with AD have an increased risk for complications after viral infection (eg, herpes simplex virus), and vaccination of patients with AD with live vaccinia virus is contraindicated because of a heightened risk of eczema vaccinatum, a rare but potentially lethal complication associated with smallpox vaccination.nnnOBJECTIVEnWe sought to develop a better understanding of immunity to cutaneous viral infection in patients with AD.nnnMETHODSnIn a double-blind randomized study we investigated the safety and immunogenicity of live attenuated yellow fever virus (YFV) vaccination of nonatopic subjects and patients with AD after standard subcutaneous inoculation or transcutaneous vaccination administered with a bifurcated needle. Viremia, neutralizing antibody, and antiviral T-cell responses were analyzed for up to 30 days after vaccination.nnnRESULTSnYFV vaccination administered through either route was well tolerated. Subcutaneous vaccination resulted in higher seroconversion rates than transcutaneous vaccination but elicited similar antiviral antibody levels and T-cell responses in both the nonatopic and AD groups. After transcutaneous vaccination, both groups mounted similar neutralizing antibody responses, but patients with AD demonstrated lower antiviral T-cell responses by 30 days after vaccination. Among transcutaneously vaccinated subjects, a significant inverse correlation between baseline IgE levels and the magnitude of antiviral antibody and CD4(+) T-cell responses was observed.nnnCONCLUSIONSnYFV vaccination of patients with AD through the transcutaneous route revealed that high baseline IgE levels provide a potential biomarker for predicting reduced virus-specific immune memory after transcutaneous infection with a live virus.

Development of a standardized approach for environmental microbiota investigations related to asthma development in children

Standardized studies examining environmental microbial exposure in populations at risk for asthma are necessary to improve our understanding of the role this factor plays in disease development. Here we describe studies aimed at developing guidelines for high-resolution culture-independent microbiome profiling, using a phylogenetic microarray (PhyloChip), of house dust samples in a cohort collected as part of the NIH-funded Inner City Asthma Consortium (ICAC). We demonstrate that though extracted DNA concentrations varied across dust samples, the majority produced sufficient 16S rRNA to be profiled by the array. Comparison of array and 454-pyrosequencing performed in parallel on a subset of samples, illustrated that increasingly deeper sequencing efforts validated greater numbers of array-detected taxa. Community composition agreement across samples exhibited a hierarchy in concordance, with the highest level of agreement in replicate array profiles followed by samples collected from adjacent 1×1 m(2) sites in the same room, adjacent sites with different sized sampling quadrants (1×1 and 2×2 m(2)), different sites within homes (living and bedroom) to lowest in living room samples collected from different homes. The guidelines for sample collection and processing in this pilot study extend beyond PhyloChip based studies of house-associated microbiota, and bear relevance for other microbiome profiling approaches such as next-generation sequencing.

Patterns of immune development in urban preschoolers with recurrent wheeze and/or atopy

Background Disadvantaged urban children have high rates of allergic diseases and wheezing, which are diseases associated with type 2–biased immunity. Objective We sought to determine whether environmental exposures in early life influence cytokine responses that affect the development of recurrent wheezing illnesses and allergic sensitization. Methods A birth cohort of 560 urban families was recruited from neighborhoods with high rates of poverty, and 467 (83%) children were followed until 3 years of age. Cytokine responses were measured in blood cell samples obtained at birth (cord blood) and ages 1 and 3 years. Cytokine responses were examined in relation to personal characteristics and environmental exposures to allergens and endotoxin and to the development of allergic sensitization and recurrent wheeze assessed at age 3 years. Results Cytokine responses generally increased with age, but responses at birth were poorly predictive for those at ages 1 and 3 years. Exposure to certain allergens (cockroach, mouse, dust mite) was significantly associated with enhanced cytokine responses at age 3 years, including IFN‐&agr; and IL‐10 responses to certain stimulants and responses to phytohemagglutinin. Regarding the clinical outcomes, reduced LPS‐induced IL‐10 responses at birth were associated with recurrent wheeze. In contrast, reduced respiratory syncytial virus–induced IL‐8 responses and increased 5′—cytosine—phosphate—guanine—3′ (CpG)‐induced IL‐12p40 and allergen‐induced IL‐4 responses were associated with atopy. Conclusions These findings suggest that diverse biologic exposures, including allergens and endotoxin, in urban homes stimulate the development of cytokine responses in early life, and that cytokine responses to specific microbial and viral stimuli are associated with the development of allergic sensitization and recurrent wheeze.

SITE-SPECIFIC VARIATION IN ACCESS TO HEALTH CARE FOR INNER CITY CHILDREN WITH ASTHMA. † 619

SITE-SPECIFIC VARIATION IN ACCESS TO HEALTH CARE FOR INNER CITY CHILDREN WITH ASTHMA. † 619

AN INDEX OF ACCESS TO CARE FOR INNER CITY CHILDREN WITH ASTHMA. † 639

Poor access to care has been frequently mentioned as a possible cause for the rapid increase in asthma morbidity among children of the inner-city. For a sample of 1528 inner city children ages 4 to 9, the NCICAS project conducted an extensive assessment including more than 150 questions concerning health care access. This assessment included a wide range of access factors which could potentially be related to asthma morbidity. Using global measures, access to care appeared to be quite high with approximately 95% reporting that they had a usual place for attack and/or follow-up care. However, several specific elements of access were related to the childrens asthma morbidity. Those access issues were; 1) having a place to call about the childs asthma problems; 2) finding it hard to get asthma attack care; 3) finding it hard to get follow-up care; 4) having to pay for medical costs; 5) having difficulty getting appointments for care. Responses to these five items were combined into an `access index (AI) which was verified in a split sample canonical analysis. As expected, dividing the children into high and low AI groups revealed that those children with high access had fewer unscheduled and emergency room visits over a one year follow-up (p<.002); better over all functional status (p<.0001); fewer school days missed because of asthma(p<.0001), less wheeze (p<.01), less sleep loss (p<.02) and less reduction in play activities (p<.001) because of their asthma. Additionally, the AI show quite strong relationships for a rather broad range of other factors. Those scoring high on the AI showed less life stress on the PERI life events scale (6.77 vs. 8.77, p <.0001) and greater social support(p<.0001). The psychological adjustment of the child, as indicted by the Child Behavior Check List (CBCL), and the adjustment of the caretaker, as measured by the Brief Symptom Inventory (BSI) both revealed greater adjustment among those with high access (CBCL p <.0001, BSI p <.0001). The population studied by the NCICAS project includes a wide range of asthma severity. When these access issues are analyzed within severity strata, these dramatically strong access relationships were typically more pronounced among the severe children. The NCICAS Phase II intervention study which is currently underway will provide an opportunity to validate this measure and its morbidity relationship in a more direct, prospective design.