SummaryBackgroundAtopy is an established risk factor for asthma, and an elevated eosinophil level is a hallmark of atopic and non‐atopic asthma. Whether atopy and eosinophils act independently or interact to influence asthma has clinical and public health implications.ObjectiveTo investigate the relationship between atopy and eosinophils in asthma.MethodsData on current asthma, atopy (IgE positive to ≥ 1 allergen), and blood eosinophil percent (dichotomized at the median) were obtained for persons aged ≥ 6 years from the National Health and Nutrition Examination Survey 2005–2006. Interaction on an additive scale was evaluated by estimating the prevalences of asthma for combinations of atopy (yes or no) and eosinophil percent (high or low) and calculating the excess prevalence due to interaction.ResultsFor all ages combined, the adjusted prevalences of asthma were 4.6%, 7.6%, 6.9% and 17.2% for persons with neither factor, atopy alone, a high eosinophil percent alone and both factors respectively. The excess prevalence of asthma due to interaction was 7.2%, indicating synergism. The excess prevalence was greatest in children aged 6–17 years (15.3%), and it decreased with each older age category until it was absent in adults aged ≥ 55 years (−0.2%). In children, 94% of asthma cases attributable to the 2 factors were attributable to the interaction, whereas in the oldest adults, no cases were attributable to the interaction.Conclusions and Clinical RelevanceInteraction between atopy and an elevated eosinophil level in asthma cases was very strong in children but absent in the oldest adults, which suggests different mechanistic pathways for these factors by age and supports the notion that asthma is a heterogeneous disease. In addition, the age‐dependent interaction between the factors has potential implications for the selection of asthma patients for treatments that would target either IgE or a high eosinophil level.

RATIONALE: Previous studies have shown adult obesity to be associated with asthma, but whether this differs by gender and the extent to which this depends on allergic status is unclear. METHODS: Nationally representative U.S. data from the 2001-2006 National Health and Nutrition Examination and Survey (NHANES) were used to examine the relationship between obesity (BMI ≥ 30) and self-reported doctor diagnosis of current asthma among 13,970 adults age 20 and above with a logistic regression model controlling for age, race/ethnicity, gender, poverty income ratio, and current smoking. Specific IgE levels available in 2005-2006 for 4,025 adults were used to examine the relationship between obesity and atopy (≥ 1 positive specific IgE result) and to stratify the asthma analysis by atopic status. RESULTS: Obese adults were more likely to report current asthma than adults of normal weight (10.3% vs. 6.4%; OR: 1.67, 95% CI: 1.44-1.94). The association did not differ by gender (OR in men: 1.43, 95% CI: 1.13-1.82 vs. OR in women: 1.83, 95% CI: 1.54, 2.18; interaction p-value = 0.15, nor did it differ significantly by atopic status (OR in atopic adults: 1.95, 95% CI: 1.29, 2.95 vs. OR: 1.66, 95% CI: 0.97-2.83; interaction p-value = 0.66). BMI was not associated with atopy. C-reactive protein levels were associated with both obesity and asthma, but not with atopy. CONCLUSIONS: Obesity was related to the prevalence of asthma in U.S. men and women and may involve an inflammatory mechanism. BMI was not related to atopy, but was related to asthma in both atopic and non-atopic adults.

RATIONALE: The Head-off Environmental Asthma in Louisiana (HEAL) Study examined both environmental and clinical data from children with asthma in post-Hurricane Katrina New Orleans.METHODS: 182 children ages 4-12 years with moderate-severe asthma living in the New Orleans area were enrolled from March 2007-March 2008. Prick skin testing was performed to inhalants including the commonly tested molds Alternaria, Cladosporium, Penicillium, and Aspergillus as well as to an additional 10 fungal species.RESULTS: In the post-Katrina population, sensitivity to Alternaria was found in 53% (95/180), Penicillium 48%, Cladosporium 29%, and Aspergillus fumigatus 24%. Children frequently reacted to the other fungal species tested, with 48% sensitized to Neurospora, 40-44% positive to each of Acremonium, Chaetomium, Dreschlera, Epicoccum, Paecilomyces, and Trichoderma, and 25-33% to each of Bipolaris, Fusarium, and Aspergillus niger. Reactivity to at least one of the 14 fungal species tested was present in 72% with the average number of mold sensitivities 5.34+0.38. In contrast, the results of the Inner-City Asthma Study (ICAS) of 937 atopic children with moderate-severe asthma enrolled in 7 U.S. cities revealed sensitivity to Alternaria of 36%, Aspergillus 27%, Cladosporium 18%, and Penicillium 13%. Reactivity to at least one of these 4 species was 50% in ICAS and 67% in HEAL.CONCLUSIONS: Children enrolled in HEAL demonstrate sensitivity to a wide variety of fungi and have increased reactivity to mold when compared to the results of ICAS. Environmental sampling from the homes of HEAL participants will help to clarify the differences between these study populations. RATIONALE: The Head-off Environmental Asthma in Louisiana (HEAL) Study examined both environmental and clinical data from children with asthma in post-Hurricane Katrina New Orleans. METHODS: 182 children ages 4-12 years with moderate-severe asthma living in the New Orleans area were enrolled from March 2007-March 2008. Prick skin testing was performed to inhalants including the commonly tested molds Alternaria, Cladosporium, Penicillium, and Aspergillus as well as to an additional 10 fungal species. RESULTS: In the post-Katrina population, sensitivity to Alternaria was found in 53% (95/180), Penicillium 48%, Cladosporium 29%, and Aspergillus fumigatus 24%. Children frequently reacted to the other fungal species tested, with 48% sensitized to Neurospora, 40-44% positive to each of Acremonium, Chaetomium, Dreschlera, Epicoccum, Paecilomyces, and Trichoderma, and 25-33% to each of Bipolaris, Fusarium, and Aspergillus niger. Reactivity to at least one of the 14 fungal species tested was present in 72% with the average number of mold sensitivities 5.34+0.38. In contrast, the results of the Inner-City Asthma Study (ICAS) of 937 atopic children with moderate-severe asthma enrolled in 7 U.S. cities revealed sensitivity to Alternaria of 36%, Aspergillus 27%, Cladosporium 18%, and Penicillium 13%. Reactivity to at least one of these 4 species was 50% in ICAS and 67% in HEAL. CONCLUSIONS: Children enrolled in HEAL demonstrate sensitivity to a wide variety of fungi and have increased reactivity to mold when compared to the results of ICAS. Environmental sampling from the homes of HEAL participants will help to clarify the differences between these study populations.

RATIONALE: The allergy component of the NHANES 2005-2006 survey was the first nationwide assessment of allergen-specific IgEs in the U.S. population. The NHANES sample offers a unique opportunity to explore groupings or dependencies among the specific IgEs. METHODS: Participants aged 6 years and older were tested for the following 19 allergen-specific IgE antibodies: the aeroallergens Alternaria, Aspergillus, Bermuda grass, birch, cat, cockroach, dog, dust mite (D. Pteronyssinus and D. farinae), mouse, oak, ragweed, rat, thistle, and rye grass; and the food allergens egg white, milk, peanut, and shrimp. A positive test was the lower limit of detection for the assay (0.35 kU/L). Analyses were conducted on participants with a complete panel of IgEs (N = 7268). Principal components analysis, factor analysis, and cluster analysis were used to reduce the panel of 19 allergens into groups of allergens. Groupings were explored independent of any disease associations. RESULTS: Multivariate statistical analysis revealed that the salient features among the 19 allergen-specific IgEs can be summarized into fewer groups. These clusters correspond to reported biological classifications as follows: 1) pollens; 2) mammals; 3) dust mite; 4) cockroach and shrimp; and 5) egg and milk. CONCLUSIONS: The 19 allergen-specific IgEs clustered into five groups that reflect the biological classification of the allergen sources. It is not known whether the clustering reflects cross-reactivity of the antibody assays or a propensity for persons to be sensitized to multiple allergens within a cluster. The clustering suggests that only a few selected tests are needed to classify the sensitivity of an individual.

SummaryBackground Asthma causes significant morbidity in children, and studies have demonstrated that environmental allergies contribute to increased asthma morbidity.Objective We investigated the differences between allergen skin tests and specific IgE (SIgE) and the role of IgG in regards to allergen exposure levels, and asthma morbidity in inner‐city children.Methods Five hundred and six serum samples from the National Cooperative Inner City Asthma Study (NCICAS) were evaluated for SIgE to cockroach (Blattella germanica), dust mite (Dermatophagoides farinae), and Alternaria as well as specific IgG (SIgG) and IgG4 to cockroach (B. germanica) and total IgE levels. Associations between sensitization to these allergens, exposures, and asthma morbidity were determined.Results Sensitization to environmental allergens and total IgE correlated with increased health care and medication use, but not with symptoms of wheeze. Sensitization with exposure to cockroach was associated with increased asthma morbidity, whereas dust mite sensitization was correlated with asthma morbidity independent of exposure. There was also a strong correlation between SIgE levels and skin test results, but the tests did not always agree. The relationship between SIgE and asthma morbidity is linear with no obvious cutoff value. Increased Bla g 1 in the home was a good predictor for sensitization; however, this relationship was not demonstrated for Der f 1. Cockroach SIgG correlated with increased health care use, however, there was no modifying effect of SIgG or SIgG4 on the association between cockroach SIgE and asthma morbidity.Conclusions SIgE levels and skin prick test results to environmental allergens can serve as markers of severe asthma for inner‐city children. Asthma morbidity increased in a linear manner with SIgE levels. IgG was not an important predictor or modifier of asthma morbidity.

RATIONALE: The Head-off Environmental Asthma in Louisiana (HEAL) Study is examining whether exposure to the increased levels of mold and other allergens in New Orleans post-Hurricane Katrina affected symptoms in children with asthma by gathering both environmental and clinical data.METHODS: 182 children ages 4-12 years with moderate-severe asthma living in New Orleans and the surrounding area were enrolled March 2007-March 2008. Prick skin testing was performed to dust mite mix (DM), cockroach mix (CR), cat, dog, rodents, and the primary molds Alternaria, Cladosporium, Penicillium, Aspergillus in addition to 10 other molds present in high concentrations after the flooding.RESULTS: In the post-Katrina population 159 of the 182 (87%) enrolled were sensitive to at least one allergen. In the atopic subgroup, DM sensitivity was present in 75.5% (120 /159), CR sensitivity in 58.5% and mold sensitivity to the 4 primary molds in 74.8% while mold sensitivity to at least one of the 14 species tested was present in 81.1%. In contrast, the results of the Inner-City Asthma Study (ICAS) with 937 atopic children with moderate to severe asthma enrolled in 7 U.S. cities revealed DM sensitivity to be 62%, CR 69%, and reactivity to at least one of the primary molds to be 50%.CONCLUSIONS: When compared to the results of ICAS, children enrolled in HEAL have increased reactivity to mold and dust mite but less sensitivity to cockroach. Ongoing environmental sampling from the homes of HEAL participants will help to clarify the differences between these study populations. RATIONALE: The Head-off Environmental Asthma in Louisiana (HEAL) Study is examining whether exposure to the increased levels of mold and other allergens in New Orleans post-Hurricane Katrina affected symptoms in children with asthma by gathering both environmental and clinical data. METHODS: 182 children ages 4-12 years with moderate-severe asthma living in New Orleans and the surrounding area were enrolled March 2007-March 2008. Prick skin testing was performed to dust mite mix (DM), cockroach mix (CR), cat, dog, rodents, and the primary molds Alternaria, Cladosporium, Penicillium, Aspergillus in addition to 10 other molds present in high concentrations after the flooding. RESULTS: In the post-Katrina population 159 of the 182 (87%) enrolled were sensitive to at least one allergen. In the atopic subgroup, DM sensitivity was present in 75.5% (120 /159), CR sensitivity in 58.5% and mold sensitivity to the 4 primary molds in 74.8% while mold sensitivity to at least one of the 14 species tested was present in 81.1%. In contrast, the results of the Inner-City Asthma Study (ICAS) with 937 atopic children with moderate to severe asthma enrolled in 7 U.S. cities revealed DM sensitivity to be 62%, CR 69%, and reactivity to at least one of the primary molds to be 50%. CONCLUSIONS: When compared to the results of ICAS, children enrolled in HEAL have increased reactivity to mold and dust mite but less sensitivity to cockroach. Ongoing environmental sampling from the homes of HEAL participants will help to clarify the differences between these study populations.

Background Cockroach allergy is an important cause of inner city asthma. To perform valid studies on the diagnosis and treatment of cockroach allergy, biological potencies of test extracts need to be established, and a surrogate in vitro test for biological potency should be chosen.Methods Sixty-two cockroach-allergic adult subjects were recruited for quantitative skin testing with three commercial German cockroach extracts. The intradermal D50 values were determined using linear interpolation, and the biologic potencies were determined from D50 data. The extracts were also analysed for relative potency, using a competition ELISA, and for specific allergen content, using a two-site ELISA.Results Estimates of each extract's D50 were analysable in 48-55 subjects, with D50s between 10.3 and 11.8. All three extracts were bioequivalent using pre-set criteria. The biological potencies of the extracts were 1738-8570 bioequivalent allergy units (BAU)/mL (geometric mean=3300), and these relative potencies were similar to those estimated by competition ELISA and specific allergen content. IgE against cockroach allergens were detected in sera from 34 subjects with analysable D50s, and 17 subjects had IgE directed against specific cockroach allergens. Although the presence of anti-Bla g 5 correlated with the subjects' skin test responses for 2/3 extracts, no single allergen was immunodominant. Antibody responses among the subjects were heterogeneous.Conclusions Although commercial cockroach extracts are relatively low in potency, immunotherapeutic doses should be achievable. Biological potency may be estimated using D50 testing, a combination of specific allergen determinations, or by an overall potency assay such as the competition ELISA.Capsule Summary The biological potency of three German cockroach allergen extracts, determined in an inner city population, was 1738-8570 BAU/mL. No one allergen was immunodominant, and surrogate in vitro testing methods were examined.