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Environmental exposures in early life appear to play an important role in the pathogenesis of childhood asthma, but the potentially modifiable exposures that lead to asthma remain uncertain.We sought to identify early-life environmental risk factors for childhood asthma in a birth cohort of high-risk inner-city children.We examined the relationship of prenatal and early-life environmental factors to the occurrence of asthma at 7 years of age among 442 children.Higher house dust concentrations of cockroach, mouse, and cat allergens in the first 3 years of life were associated with lower risk of asthma (for cockroach allergen: odds ratio per interquartile range increase in concentration, 0.55; 95% CI, 0.36-0.86; P .01). House dust microbiome analysis using 16S ribosomal RNA sequencing identified 202 and 171 bacterial taxa that were significantly (false discovery rate 0.05) more or less abundant, respectively, in the homes of children with asthma. A majority of these bacteria were significantly correlated with 1 of more allergen concentrations. Other factors associated significantly positively with asthma included umbilical cord plasma cotinine concentration (odds ratio per geometric SD increase in concentration, 1.76; 95% CI, 1.00-3.09; P = .048) and maternal stress and depression scores.Among high-risk inner-city children, higher indoor levels of pet or pest allergens in infancy were associated with lower risk of asthma. The abundance of a number of bacterial taxa in house dust was associated with increased or decreased asthma risk. Prenatal tobacco smoke exposure and higher maternal stress and depression scores in early life were associated with increased asthma risk.

BACKGROUND: Cockroach allergens are an important cause of IgE-mediated sensitization in inner-city asthmatics. However, cockroach extracts used for diagnosis and immunotherapy are not standardized. OBJECTIVE: To determine the allergen content of non-standardized German cockroach extracts and the levels of sensitization to an expanded set of cockroach allergens as determinants of in vitro extract potency for IgE reactivity. METHODS: Twelve German cockroach extracts were compared for allergen content and for potency of IgE reactivity. Bla g 1, Bla g 2 and Bla g 5 were measured by immunoassays. IgE antibody levels to eight purified recombinant allergens from groups 1, 2, 4, 5, 6, 7, 9 and 11 were measured by ImmunoCAP. IgE antibody binding inhibition assays were performed to assess extract in vitro potencies (IC30) relative to an arbitrarily selected reference extract in five cockroach allergic subjects. RESULTS: Allergen levels were highly variable. Three new major allergens (groups 6, 9 and 11), were identified among highly cockroach-sensitized subjects (CAP-class ≥ 3). Sensitization profiles were unique per subject, without immunodominant allergens. The sum of IgE to eight allergen components showed a good correlation with cockroach-specific IgE (r = 0.88; p < 0.001). In vitro potencies varied among different extracts per subject, and among subjects for each extract. CONCLUSIONS: The in vitro potency of German cockroach extracts for IgE reactivity depends on allergen content and allergen-specific IgE titers of the cockroach-allergic subject. These factors are relevant for selection of potent extracts to be used for immunotherapy and for the design and interpretation of data from immunotherapy trials.

Background Exposure to cockroaches is an important asthma trigger, particularly for children with asthma living in inner cities. Integrated pest management is the recommended approach to cockroach abatement; however, it is costly and difficult to implement. The impact of reducing cockroach exposure on asthma outcomes is not known. Objective We sought to test the use of a single intervention, insecticidal bait, to reduce cockroach exposure in the home of children with asthma in New Orleans and to examine the impact of cockroach reduction on asthma outcomes. Methods One hundred two children aged 5 to 17 years with moderate to severe asthma were enrolled in a 12-month randomized controlled trial testing the use of insecticidal bait on cockroach counts and asthma morbidity. Homes were visited 6 times and asthma symptoms were assessed every 2 months. Results After adjustment, intervention homes had significantly fewer cockroaches than did control homes (mean change in cockroaches trapped, 13.14; 95% CI, 6.88-19.39; P P = .03; 1.17, 95% CI, 0.11-2.24, P = .03, respectively) and a higher proportion of children with FEV 1 of less than 80% predicted (odds ratio, 5.74; 95% CI, 1.60-20.57; P = .01) compared with children living in intervention homes. Conclusions Previous research has demonstrated improvement in asthma health outcomes using multifaceted interventions. The strategic placement of insecticidal bait, which is inexpensive, has low toxicity, and is widely available, resulted in sustained cockroach elimination over 12 months and was associated with improved asthma outcomes. This single intervention may be an alternative to multifaceted interventions currently recommended to improve asthma morbidity.

Background Modifiers of symptom severity in patients with allergic rhinoconjunctivitis (AR) are imprecisely characterized. The hygiene hypothesis implicates childhood microbial exposure as a protective factor. Cockroach sensitization (C+) might be a proxy for microbial exposure. Objective We sought to determine whether C+ assayed by means of skin prick tests influenced AR symptom severity in controlled and natural settings. Methods Total symptom scores (TSSs) were recorded by 21 participants with house dust mite allergy (M+) in the natural setting and during repeated exposures of 3 hours per day to house dust mite allergen in an allergen challenge chamber (ACC). In M+ participants the peripheral blood and nasal cells were assayed for T-cell activation and transcriptomic profiles (by using RNA sequencing), respectively. Participants allergic to mountain cedar (n = 21), oak (n = 34), and ragweed (n = 23) recorded TSSs during separate out-of-season exposures to these pollens (any pollen sensitization [P+]) in the ACC; a subset recorded TSSs in the pollination seasons. Results The hierarchy of TSSs (highest to lowest) among M+ participants tracked the following skin prick test sensitization statuses: M+P+C− > M+P+C+ > M+P−C− > M+P−C+. In nasal cells and peripheral blood the immune/inflammatory responses were rapidly resolved in M+P+C+ compared with M+P+C− participants. Among those allergic to pollen, C+ was associated with a lower TSS during pollen challenges and the pollination season. After aggregated analysis of all 4 ACC studies, C+ status was associated with a 2.8-fold greater likelihood of a lower TSS compared with C− status (odds ratio, 2.78; 95% CI, 1.18-6.67; P = .02). Conclusions C+ status is associated with mitigation of AR symptom severity in adults with AR.

Background Studies have demonstrated that IgE-binding cross-reactive epitopes between shrimp, cockroach, and house dust mite tropomyosins can account for the presence of detectable IgE to shrimp in patients with cockroach and dust mite allergies. Objective We investigated the correlation between IgE-mediated sensitization to shrimp, cockroach, and dust mite in relation to allergen exposure in inner-city children. Methods Five hundred four serum samples from the National Cooperative Inner-City Asthma Study were evaluated for specific IgE to shrimp, and the results were compared with specific IgE to cockroach (Blattella germanica) and dust mite (Dermatophagoides farinae). Associations between IgE sensitization to these allergens and environmental exposures were determined. Results There was a strong positive correlation between shrimp, cockroach, and dust mite IgE levels. High exposure to cockroach (B germanica) in the home, particularly in the bedroom and television room, was significantly correlated with higher shrimp and cockroach IgE levels. In contrast, high exposure to dust mite in the home was highly correlated with IgE levels to D farinae but not with shrimp IgE levels. There is a synergistic relationship between cockroach IgE levels and exposure in predicting shrimp IgE levels. Conclusions For children with evidence of IgE-mediated sensitization to cockroach and shrimp, having high exposure to cockroach in the home can contribute to higher shrimp IgE levels, which might not correlate with clinical reactivity. Further patient evaluations with clinical histories of shrimp exposure and reactions, as well as oral food challenges, would have to be performed to confirm these findings.

Background Mannose receptor (MRC1/CD206) has been suggested to mediate allergic sensitization and asthma to multiple glycoallergens, including cockroach allergens. Objective We sought to determine the existence of a protective mechanism through which MRC1 limits allergic inflammation through its intronic miR-511-3p. Methods We examined MRC1-mediated cockroach allergen uptake by lung macrophages and lung inflammation using C57BL/6 wild-type (WT) and Mrc1 −/− mice. The role of miR-511-3p in macrophage polarization and cockroach allergen–induced lung inflammation in mice transfected with adeno-associated virus (AAV)–miR-511-3p (AAV–cytomegalovirus–miR-511-3p–enhanced green fluorescent protein) was analyzed. Gene profiling of macrophages with or without miR-511-3p overexpression was also performed. Results Mrc1 −/− lung macrophages showed a significant reduction in cockroach allergen uptake compared with WT mice, and Mrc1 −/− mice had an exacerbated lung inflammation with increased levels of cockroach allergen–specific IgE and T H 2/T H 17 cytokines in a cockroach allergen–induced mouse model compared with WT mice. Macrophages from Mrc1 −/− mice showed significantly reduced levels of miR-511-3 and an M1 phenotype, whereas overexpression of miR-511-3p rendered macrophages to exhibit a M2 phenotype. Furthermore, mice transfected with AAV–miR-511-3p showed a significant reduction in cockroach allergen–induced inflammation. Profiling of macrophages with or without miR-511-3p overexpression identified 729 differentially expressed genes, wherein expression of prostaglandin D 2 synthase (Ptgds) and its product PGD 2 were significantly downregulated by miR-511-3p. Ptgds showed a robust binding to miR-511-3p, which might contribute to the protective effect of miR-511-3p. Plasma levels of miR-511-3p were significantly lower in human asthmatic patients compared with nonasthmatic subjects. Conclusion These studies support a critical but previously unrecognized role of MRC1 and miR-511-3p in protection against allergen-induced lung inflammation.

The specificity of serum antibody responses to different cockroach allergens has not been studied.We sought to quantitate serum IgE and IgG antibodies to a panel of purified cockroach allergens among cockroach-sensitized subjects.IgE antibodies to recombinant cockroach allergens (rBla g 1, rBla g 2, rBla g 4, rBla g 5, and rPer a 7) were measured in sera containing IgE antibodies to Blattella germanica extract (n = 118) by using a streptavidin CAP assay and a multiplex flow cytometric assay. Specific IgG antibodies were determined by using radioimmunoprecipitation techniques.Specific IgE antibodies measured by means of CAP assay and multiplex assay were strongly correlated ( r = 0.8, P.001). The sum of IgE antibodies (in international units per milliliter) against all 5 allergens equated to IgE antibodies to cockroach extract. Although the prevalence of IgE antibodies was highest for rBla g 2 (54.4%) and rBla g 5 (37.4%), patterns of IgE antibody binding were unique to each subject. Surprisingly, only 16% of cockroach-sensitized subjects with IgE antibodies to house dust mite exhibited IgE antibody binding to cockroach tropomyosin (rPer a 7). Specific IgE antibodies were associated with increased IgG antibody levels, although detection of IgG in the absence of IgE was not uncommon.The techniques described offer a new approach for defining the hierarchy of purified allergens. IgE antibodies directed against 5 allergens constitute the majority of the IgE antibody repertoire for cockroach. Such distinct patterns of IgE-IgG responsiveness to different cockroach allergens highlight the complexity of B-cell responses to environmental allergens.

The past year has seen a welcome increase in the number of articles published in the Journal on environmental and occupational disorders. Some of the major themes have been risk factors for allergic sensitization, the measurement and containment of domestic allergens (especially cockroach but also house dust mite), and risk factors for occupational allergy and asthma. Some important articles were also presented on mechanisms of occupational and environmental asthma.

Background We have shown that serine proteases in German cockroach extract increase TNF-α–induced expression of IL-8 in human bronchial epithelial cells. The mechanism by which cockroach proteases regulate cytokine expression is unknown; however, protease-activated receptors (PARs) might play a role. Objective We sought to determine the role of PARs and extracellular-signal-regulated kinase (ERK) in cockroach-induced regulation of IL-8 expression. Methods 16HBE14o- human bronchial epithelial cells were treated with the specific PAR-1 and PAR-2 agonists, TFRIFD and SLIGKV, respectively. IL-8 transcription was assessed by transiently transfecting cells with a luciferase-tagged IL-8 promoter construct, and in some cases, dominant-negative expression vectors. To block PAR cleavage, antibodies against the cleavage region of PAR-1 and PAR-2 were used. ERK phosphorylation was determined by Western blot. Results Although both PAR-1 and PAR-2 were endogenously expressed in 16HBE14o- cells, selective activation of PAR-2 but not PAR-1 mimicked the effect of cockroach extract on IL-8 expression. Using a blocking antibody against cleavage of PAR-2 but not PAR-1 attenuated cockroach-extract-induced responses, suggesting that cockroach proteases cleave PAR-2. Treatment of cells with cockroach extract and SLIGKV each increased phosphorylation of ERK. Chemical or genetic inhibition of Ras and mitogen-activated protein kinase/ERK (MEK), upstream activators of ERK, each attenuated cockroach- and PAR-2–induced IL-8 transcription. Conclusion Cockroach proteases and PAR-2 activation synergistically increase TNF-α–induced IL-8 transcription via activation of ERK. These data suggest an important role for PAR-2 and ERK activation in the regulation of cytokine expression in airway epithelium in response to cockroach proteases.

Background: Clinically relevant reductions in exposure to cockroach allergen, an important risk factor for asthma in inner-city households, have proven difficult to achieve in intervention trials. Objective: This study investigated a method for the abatement of cockroach allergen in low-income, urban homes. The goal was to reduce mean Bla g 1 concentrations below the previously proposed thresholds for allergic sensitization and asthma morbidity. Methods: A prerandomized, nonmasked trial with 16 intervention and 15 control homes was conducted. Study inclusion was based on 50 to 500 cockroaches trapped in a 3-day period. The interventions consisted of occupant education, placement of insecticide bait, and professional cleaning. Vacuumed dust and multiple swab samples were collected at 0, 1, 2, 4, and 6 months in intervention homes and at 0 and 6 months in control homes. Room maps containing cockroach and allergen data were used to guide and monitor the interventions. Results: From 0 to 6 months among intervention homes, geometric mean Bla g 1 concentrations (U/g dust) decreased from 633 to 24 on kitchen floors (96% reduction), from 25 to 4.3 on living room floors/sofas (83% reduction), from 46 to 7.3 on bedroom floors (84% reduction), and from 6.1 to 1.0 in bedroom beds (84% reduction). These reductions, with the exception of that on the bedroom floor ( P = .06), were statistically significant relative to changes in control homes. Conclusions: Substantial reductions in cockroach allergen levels can be achieved in inner-city homes. In this study, allergen levels were reduced below the sensitization threshold (2 U/g) in beds, arguably the most relevant site for exposure, and below the asthma morbidity threshold (8 U/g) on bedroom floors and living room floors/sofas. The level on kitchen floors, although reduced 96%, remained above the asthma morbidity threshold. Future studies will test the intervention's effectiveness in asthma prevention trials. (J Allergy Clin Immunol 2003;112:339-45.)

Public places, including schools, have been identified as sources of exposure to allergens derived from mites, cockroach, cat, and dog and to endotoxin.The purposes of this study were to assess and compare exposure to allergens and endotoxin in 4 types of public child-care facilities in Brazil and to investigate whether the presence of children and the performance of cleaning procedures could have an influence on allergen and endotoxin levels.We have analyzed dust from bedding, floors, chairs, and tables of daycare centers (DCs), preschools, kindergartens, and elementary schools (ESs). Major allergens from mites, cockroach, cat, and dog were quantitated by means of ELISA, and endotoxin content was determined by using the Limulus Amebocyte Lysate assay.Group 1 mite allergens were greater than 2 microg/g in 67% of DC and preschool samples and in 8.9% and 2.2% of kindergarten and ES samples, respectively. The presence of bedding in DCs and preschools accounted for increased levels of mite allergens in these settings. Levels of Bla g 1 were higher in ES floors compared with those found in DC and preschool floors. Low levels (1 microg/g) of Fel d 1 e Can f 1 were found in most samples. Levels of endotoxin in DCs and preschools were 3 times higher than in ESs.DCs and schools in Brazil should be considered as important sources of exposure to dust mites and cockroach allergens and to endotoxin. Recommendations for mite allergen avoidance should include appropriate care of bedding in DCs and preschools.

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 μg/g; median, 1.60 μg/g; bedroom: range, 0-294 μg/g; median, 0.52 μg/g; television-living room: range, 0-203 μg/g; median, 0.57 μg/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. (J Allergy Clin Immunol 2000;106:1070-4.)

Background: Cockroach allergen is recognized as a causal factor for asthma. However, airborne cockroach allergen has not been detected in undisturbed conditions, and therefore the behavior and properties of airborne cockroach allergen have been poorly characterized. A new aeroallergen sampling method and sensitive system of immunoassay have been used to examine cockroach allergen exposure. Objective: Our purpose was to measure and characterize airborne cockroach allergens during normal domestic exposure in the homes of Sydney, Australia. Methods: Air sampling with Institute of Occupational Medicine, Edinburgh (IOM) samplers was performed in the living rooms of 10 houses during low- and no-disturbance environments. In addition, inhaled particles were collected by each home occupant during low domestic exposure with use of intra-nasal samplers that impact particles onto an adhesive surface. The particles collected on the IOMs and the intra-nasal samplers were immunostained with Bla g 1 monoclonal antibodies. Particle size, morphologic characteristics, and the relative Bla g 1 content of particles were estimated. Reservoir dust samples from the kitchen, living room, and bedroom were assayed by an ELISA. Two forms of repeatability of IOM air sampling were examined. The first measure tested the repeatability of 2 IOM samples collected simultaneously in the same room during low- and no-disturbance activities. The second measure examined the repeatability of IOM sampling over time on 10 consecutive days. Results: Bla g 1 was detected in reservoir dust samples taken from all homes (geometric mean 1.5 U/g, range 0.2-9.4 U/g). Inhaled particles containing Bla g 1 were detected during 1 hour of intra-nasal sampling in 8 of 10 homes during low disturbance. Cockroach particles were detected on all of the IOM samples collected for both 4-hour low-disturbance and overnight no-disturbance sampling environments. Particles containing Bla g 1 collected with the IOM samplers during low disturbance ranged in size from 3 to 350 μm. These particles are amorphous and irregular in shape, and a majority of the large particles were described as flakes (flat, transparent particles) and fibers (threadlike). A relationship was demonstrated between the allergen content of cockroach particles and their particle size. The larger particles elute more Bla g 1. The coefficient of repeatability for measurements made during low and no disturbance was 3.62 and 2.09, respectively. For measurements repeated over time at the same site, the coefficient of repeatability was 2.61. This represents the fold range within which 95% of pairs of measurements made at an interval of 1 day would be expected to lie. Conclusions: Airborne cockroach allergen is present in both undisturbed and low-disturbance environments in homes with relatively low reservoir levels of Bla g 1. In agreement with previous reports, airborne particles containing cockroach allergen (Bla g 1) are mainly associated with particles >10 μm. These particles are amorphous and irregular in shape and can be described as flakes and fibers. (J Allergy Clin Immunol 1999;104:672-80.)

Background: Cockroaches produce several proteins that induce IgE antibody responses. Although cockroaches are abundant in warm and humid areas, sensitization to cockroach allergens has not been investigated in Brazil. Objective: The aims of this study were to investigate the frequency of cockroach allergy among patients with asthma, rhinitis, or both in Brazil and to identify American cockroach allergens. Methods: Skin tests using cockroach extracts were performed on children and young adults with asthma, rhinitis, or both. A Periplaneta americana complementary (c)DNA library was screened by using IgE antibodies from Brazilian patients allergic to cockroaches. Reactivity of an mAb directed to Dermatophagoides pteronyssinus tropomyosin against cockroach tissue was examined by immunofluorescence. Results: Cockroach allergy was present in 55% and 79% of the patients, as determined by using skin prick tests alone or combined prick and intradermal tests, respectively. Five cDNA clones reacted with IgE antibody and contained the same sequence. A representative clone (1300 bp), pa12, coded for a protein that reacted with 50% of the sera from patients allergic to cockroaches on plaque immunoassay and showed a high degree of homology to tropomyosins, particularly those from invertebrates. P americana tropomyosin showed 80%, 81%, and 82% sequence identity to tropomyosins from D pteronyssinus, D farinae, and shrimp, respectively, which have been previously defined as important allergens. An mAb directed against D pteronyssinus tropomyosin, which also recognizes shrimp tropomyosin, showed binding to cockroach striated muscle. Conclusion: Our results support the recommendation that cockroach extracts should be routinely used for the evaluation of patients with asthma, rhinitis, or both in Brazil. The identification of P americana tropomyosin as an important allergen will make it possible to investigate cross-reactivity among cockroaches, mites, and food derived from invertebrates. (J Allergy Clin Immunol 1999;104:329-37.)

Background: The prevalence of asthma in the northernmost region of Sweden has been estimated at 6% to 8% in spite of the very dry climate. The causes of the increase in asthma are not clear, but conditions are unfavorable for dust mite growth, and domestic animals are thought to be the primary source of indoor allergens. Objectives: We sought to investigate the relationship between asthma, exposure, and sensitization in Northern Sweden, with a focus on the role of schools. Methods: Serum was collected from 110 asthmatic children, 55 children with symptoms of asthma but no established diagnosis, and 63 control children (age, 7 and 8 years). Total IgE and specific IgE to 7 allergens were measured. Dust samples were collected from the classrooms of 7- and 8-year-old children in 22 schools from Kiruna and Lulea, Sweden. For comparison, dust was also collected from 24 homes in Kiruna and 2 schools in Virginia in the United States. Results: Serum IgE antibody assays on 165 children with respiratory symptoms confirmed that there was a high degree of sensitization to cat, dog, and birch in Northern Sweden. Cat and dog allergens were present in almost all of the school samples in Sweden. By contrast, dust mite and cockroach allergens were generally unmeasurable. The highest levels of cat and dog allergens were found in samples from desks and chairs. Cat and dog allergen levels in the schools were comparable with but higher than those in the homes without pets. The schools in Virginia had similar allergen levels, except that samples from this humid region also had significant mite allergen. Conclusions: In this climate the primary sensitization associated with asthma is to cat dander and dog dander but also to birch pollen. Mite and cockroach allergens were not present in the dust samples, and sensitization to these allergens was not significant. The schools appear to be a major site of exposure to cat and dog allergens. These results are relevant both to an understanding of the reasons for the increase in asthma in this region and to any proposal to reduce exposure to allergens. (J Allergy Clin Immunol 1999;103:1018-24.)

Background: Sensitization to allergens produced by German and American cockroaches is strongly associated with the cause of asthma. Most of the cockroach allergens identified to date have been species specific. Objective: The aim of this study was to identify and sequence cross-reactive cockroach allergens. Methods: A Periplaneta americana cDNA library was screened with IgE antibody from patients in the United States who were allergic to cockroach and who were sensitized to Blattella germanica . Results: A cDNA clone was isolated that contained an 870-bp sequence with a 695-bp open reading frame, encoding a 231 amino acid protein, molecular weight 26.2 kd. Plaque immunoassays using anti-Bla g 1 and anti-Per a 1 mAbs and a panel of human IgE antibodies showed that the protein expressed by these clones was Per a 1. Sequence homology searches showed that Per a 1 was homologous to 5 previously reported, but unidentified, sequences from B germanica and P americana . These sequences encoded proteins with multiple molecular sizes containing approximately 100 amino acid repeats. The Per a 1 sequence also showed 31% identity to a mosquito precursor protein, ANG12, which may be involved in digestion. The Per a 1 cDNA was expressed in Pichia pastoris to produce purified recombinant allergen (yield, 14 mg/L). Conclusion: The results define the molecular structure and antigenic relationships between a new family of cross-reactive "Group 1" allergens produced by both P americana and B germanica . These recombinant allergens and specific mAbs will provide tools to improve the diagnosis and treatment of allergic diseases caused by cockroaches. (J Allergy Clin Immunol 1999;103:859-64.)

Cockroach allergen is important in asthma. Practical methods to reduce exposure are needed.We sought to evaluate the effectiveness of house cleaning and professional extermination on lowering cockroach antigen levels in inner-city dwellings.As part of the National Cooperative Inner-City Asthma Study intervention, 265 of 331 families with asthmatic children who had positive skin test responses to cockroach allergen consented to a professional home extermination with 2 applications of a cockroach insecticide (Abamectin, Avert) combined with directed education on cockroach allergen removal. On a random subset of 48 homes undergoing cockroach extermination in the intervention group, Bla g 1 was measured in settled dust from the kitchen, bedroom, and TV/living room. The first sample was collected 1 week before extermination, with additional samples after the exterminations at approximately 2, 6, and 12 months after the first sample. Self-reported problems with cockroaches were collected at baseline and after 12 months of follow-up in both the intervention and control group.The geometric mean kitchen level of Bla g 1 decreased at 2 months (33.6 U/g) relative to preextermination levels (68.7 U/g, P.05). The percent of kitchens with over 8 U/g of Bla g 1 followed a similar pattern, but only the decrease from preextermination to 6-month levels was significant (86.8% vs 64.3%, P.05). By the 12-month visit, the allergen burden had returned to or exceeded baseline levels. Except for an increase in the bedroom at 2 months (8.9 U/g vs 11.1 U/g, P.05), no other significant change was seen. Only about 50% of the families followed the cleaning instructions; no greater effect was found in these homes. Self-reported problems with cockroaches showed no difference between the intervention and control group after 1 year of follow-up.Despite a significant, but short-lived, decrease the cockroach allergen burden remained well above levels previously found to be clinically significant.

Background: Although cross-reactivity between mollusks and other crustaceans in shrimp-sensitive subjects has been reported, the mechanism of this allergenic cross-reactivity has not been studied in detail. Objective: To investigate this cross-reactivity in vitro, we have taken advantage of a complementary DNA that expresses tropomyosin, the immunodominant shrimp allergen. Methods: Serum IgE from nine patients with known anaphylaxis to shrimp and five normal volunteers were analyzed by immunoblotting against 13 distinct crustaceans and mollusks. As additional antigens, muscle preparations were isolated from grasshopper, cockroach, fruit fly, chicken, and mouse. Results: Sera from all patients, but not control subjects, reacted specifically with a 38 kd protein in all crustaceans and mollusks studied. In addition, 8 of 9 sera from patients, but from none of the normal control subjects, recognized proteins of various other molecular weights among the mollusk extracts studied. The 38 kd protein was identified as tropomyosin and was shown to share immunodominant epitopes among all species of crustaceans and mollusks tested by specific absorption studies. Moreover, sera from all nine subjects with shrimp allergy demonstrated IgE reactivities against grasshopper, cockroach, and fruit fly but not chicken or murine muscle. Conclusion: The allergic epitopes on tropomyosin are conserved among invertebrates including not only shellfish but also insects. This latter observation suggests that persons sensitive to shrimp should undergo further study for potential cross-reactive inhalant or ingested insect sensitivity. (J ALLERGY CLIN IMMUNOL 1996;98:954-61.)

Previous studies have established that atopic individuals living in cockroach-infested housing become sensitized to cockroach aeroallergens and produce IgE antibodies to a variety of proteins. We describe the isolation of a complementary DNA clone from an expression library, constructed with messenger RNA from German (Blattella germanica) cockroaches, which encodes a major allergen involved in mediating cockroach hypersensitivity. Approximately 0.2% of the clones from a lambda ZAP XR cDNA library bound IgE from a patient with cockroach sensitivity. A randomly selected subset of these clones revealed that they were either different isolates of the same gene or members of a closely related gene family. One of the largest clones (a 4 kb insert) from this subset, Bla g Bd90K hybridized to a single mRNA of approximately the same size. DNA sequence analysis showed that this gene consisted of seven 576 bp tandem repeats with a short unique region at either end. No significant sequence homologies were found between the cockroach clone and any other gene reported in the GenBank database. Serum from 17 of 22 (77%) patients with cockroach hypersensitivity identified IgE-binding recombinant protein expressed from clone Bla g Bd90K in Escherichia coli XL-Blue cells as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis/immunoblot analysis. This recombinant protein migrates with a molecular weight (90 kd) apparently similar to one identified in whole body extracts. We have identified and isolated a cDNA that encodes a major cockroach allergen (Bla g Bd90K) present in German cockroaches.

BACKGROUND: The domestic cockroach has been identified as an important source of indoor aeroallergens worldwide in both temperate and tropical climates. Because cockroach populations are highest in crowded urban areas, some have suggested that the increased asthma morbidity and mortality rates in inner cities could be related in part to cockroach allergen exposure. We have examined cockroach allergen exposure in the homes of children with asthma in both urban and suburban locations and have related the rates of exposure and sensitization to socioeconomic, racial, and demographic factors. OBJECTIVE: The study was designed to determine the independent contribution of race, socioeconomic status, and place of residence to the risk of cockroach allergen exposure and sensitization in children with asthma. METHODS: Eighty-seven children with moderate to severe allergic asthma, aged 5 to 17 years, participating in a prospective trial of immunotherapy, were evaluated. Extracted dust samples from three home locations were analyzed by using two-site monoclonal immunoassays for major cockroach allergens (Bla g 1 and Bla g 2). A puncture skin test with a mixed cockroach allergen extract was performed in 81 of the 87 subjects. RESULTS: In the 87 homes evaluated, 26% of the bedroom dust samples had detectable levels of cockroach allergen. In homes with detectable bedroom cockroach allergen levels, mean Bla g 1 and Bla g 2 concentrations in urban and suburban homes were similar. Over 80% of children with bedroom Bla g 1 or Bla g 2 of 1 U/gm or greater demonstrated skin sensitivity to cockroach allergen. The rate of cockroach sensitization was directly related to the level of bedroom exposure. African-American race was the only factor that was independently associated with cockroach allergen exposure ( p = 0.05). Lower socioeconomic status, age greater than 11 years, cockroach exposure, and African-American race were all independently associated with cockroach allergen sensitization on the basis of stepwise multiple linear regression analysis. CONCLUSIONS: African-American race and low socioeconomic status were both independent, significant risk factors for cockroach allergen sensitization in children with atopic asthma. Cockroach allergen is detectable throughout the house, including the critical bedroom environment. (J ALLERGY CLIN IMMUNOL 1996;97:1393-1401.)

A sandwich ELISA was developed to measure the concentration of cockroach allergen in the environment. The assay was based on a monospecific rabbit antibody preparation reactive with determinants shared by the important allergens. Per a I and Bla g I, from American and German cockroaches. The sensitivity was 0.2 ng Lowry protein of Per a I equivalents per milliliter, corresponding to 1 ng of Per a I equivalents per gram of dust ( Per a I eq/gm). The assay did not react with noncockroach-allergen sources. Dust samples from 73 households in a cockroach-infested area were assayed. The concentration in these samples varied from below detection to 200,000 ng of Per a eq/gm of dust. Three commercial cockroach-allergen extracts all contained the allergen. The assay will be valuable for studies of the clinically relevant cockroach-allergen exposure levels and for assessment of efficacy of allergen-avoidance measures. Furthermore, the assay could be used for sanitary documentation in bakeries, restaurants, etc.

Aqueous whole body extracts from two major domiciliary cockroaches, the American, Periplaneta americana , and the German, Blattella germanica were analyzed in crossed immunoelectrophoresis and immunoblotting. Forty-five antigens were found in P. americana and 29 in B. germanica . IgE-binding antigens were identified by crossed radioimmunoelectrophoresis with sera from 30 cockroach-allergic patients. Seven and three precipitates from P. americana and B. germanica bound significant amounts of IgE. A cross-reactive, apparently homologous allergen, from P. americana and B. germanica bound IgE from 100% and 70%, respectively, of the patients. These important allergens were tentatively named Per a I and Bla g I. The allergens were purified by sequential ion exchange, gel filtration, and isoelectric focusing. Both allergens had a molecular size of 33 to 37 kd in Sephadex G-75 gel filtration, and 28 kd in high-performance liquid chromatography gel filtration. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a minor band at approximately 25 kd, and most of the protein at 6 kd. The isoelectric point of both allergens was found be to 3.5. In amino acid analysis, the allergens were highly similar. Skin test revealed the allergens to be important in vivo sensitizing agents. The allergens may be used for environmental assays for cockroach exposure in the homes of allergic subjects.

Background Cockroach allergy is a key contributor to asthma morbidity in children living in urban environments. Objective We sought to document immune responses to cockroach allergen and provide direction for the development of immunotherapy for cockroach allergy. Methods Four pilot studies were conducted: (1) an open-label study to assess the safety of cockroach sublingual immunotherapy (SLIT) in adults and children; (2) a randomized, double-blind biomarker study of cockroach SLIT versus placebo in adults; (3) a randomized, double-blind biomarker study of 2 doses of cockroach SLIT versus placebo in children; and (4) an open-label safety and biomarker study of cockroach subcutaneous immunotherapy (SCIT) in adults. Results The adult SLIT trial (n = 54; age, 18-54 years) found a significantly greater increase in cockroach-specific IgE levels between the active and placebo groups (geometric mean ratio, 1.92; P 4 levels in actively treated subjects ( P = .09) but no evidence of functional blocking antibody response. The pediatric SLIT trial (n = 99; age, 5-17 years) found significant differences in IgE, IgG, and IgG 4 responses between both active groups and the placebo group but no consistent differences between the high- and low-dose groups. In the SCIT study the treatment resulted in significant changes from baseline in cockroach IgE, IgG 4 , and blocking antibody levels. The safety profile of cockroach immunotherapy was reassuring in all studies. Conclusions The administration of cockroach allergen by means of SCIT is immunologically more active than SLIT, especially with regard to IgG 4 levels and blocking antibody responses. No safety concerns were raised in any age group. These pilot studies suggest that immunotherapy with cockroach allergen is more likely to be effective with SCIT.

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 FEV 1 /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.

Background Sensitization to cockroach is one of the strongest identified risk factors for greater asthma morbidity in low-income urban communities; however, the timing of exposures relevant to the development of sensitization has not been elucidated fully. Furthermore, exposure to combustion byproducts, including polycyclic aromatic hydrocarbons (PAHs), can augment the development of allergic sensitization. Objective We sought to test the hypotheses that domestic cockroach allergen measured prenatally would predict cockroach sensitization in early childhood and that this association would be greater for children exposed to higher PAH concentrations. Methods Dominican and African American pregnant women living in New York City were enrolled. In the third trimester expectant mothers wore personal air samplers for measurement of 8 nonvolatile PAHs and the semivolatile PAH pyrene, and dust was collected from homes for allergen measurement. Glutathione-S-transferase μ 1 (GSTM1) gene polymorphisms were measured in children. Allergen-specific IgE levels were measured from the children at ages 2, 3, 5, and 7 years. Results Bla g 2 in prenatal kitchen dust predicted cockroach sensitization at the ages of 5 to 7 years (adjusted relative risk [RR], 1.15; P = .001; n = 349). The association was observed only among children with greater than (RR, 1.22; P = .001) but not less than (RR, 1.07; P = .24) the median sum of 8 nonvolatile PAH levels. The association was most pronounced among children with higher PAH levels and null for the GSTM1 gene (RR, 1.54; P = .001). Conclusions Prenatal exposure to cockroach allergen was associated with a greater risk of allergic sensitization. This risk was increased by exposure to nonvolatile PAHs, with children null for the GSTM1 mutation particularly vulnerable.