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The pathogenesis of asthma has been partially linked to lung and gut microbiome. We utilized a steroid‐resistant chronic model of cockroach antigen‐induced (CRA) asthma with corticosteroid (fluticasone) treatment to examine lung and gut microbiome during disease. The pathophysiology assessment demonstrated that mucus and airway hyperresponsiveness were increased in the chronic CRA with no alteration in the fluticasone (Flut)‐treated group, demonstrating steroid resistance. Analysis of mRNA from lungs showed no decrease of MUC5AC or Gob5 in the Flut‐treated group. Furthermore, flow‐cytometry in lung tissue showed eosinophils and neutrophils were not significantly reduced in the Flut‐treated group compared to the chronic CRA group. When the microbiome profiles were assessed, data showed that only the Flut‐treated animals were significantly different in the gut microbiome. Finally, a functional analysis of cecal microbiome metabolites using PiCRUSt showed several biosynthetic pathways were significantly enriched in the Flut‐treated group, with tryptophan pathway verified by ELISA with increased kynurenine in homogenized cecum samples. While the implications of these data are unclear, they may suggest a significant impact of steroid treatment on future disease pathogenesis through microbiome and associated metabolite pathway changes. [ABSTRACT FROM AUTHOR]

Abstract The pathogenesis of asthma has been partially linked to lung and gut microbiome. We utilized a steroid‐resistant chronic model of cockroach antigen‐induced (CRA) asthma with corticosteroid (fluticasone) treatment to examine lung and gut microbiome during disease. The pathophysiology assessment demonstrated that mucus and airway hyperresponsiveness were increased in the chronic CRA with no alteration in the fluticasone (Flut)‐treated group, demonstrating steroid resistance. Analysis of mRNA from lungs showed no decrease of MUC5AC or Gob5 in the Flut‐treated group. Furthermore, flow‐cytometry in lung tissue showed eosinophils and neutrophils were not significantly reduced in the Flut‐treated group compared to the chronic CRA group. When the microbiome profiles were assessed, data showed that only the Flut‐treated animals were significantly different in the gut microbiome. Finally, a functional analysis of cecal microbiome metabolites using PiCRUSt showed several biosynthetic pathways were significantly enriched in the Flut‐treated group, with tryptophan pathway verified by ELISA with increased kynurenine in homogenized cecum samples. While the implications of these data are unclear, they may suggest a significant impact of steroid treatment on future disease pathogenesis through microbiome and associated metabolite pathway changes.

BackgroundThirdhand smoke (THS) represents the accumulation of secondhand smoke on indoor surfaces and in dust, which, over time, can become more toxic than secondhand smoke. Although it is well known that children of smokers are at increased risk for asthma or asthma exacerbation if the disease is already present, how exposure to THS can influence the development or exacerbation of asthma remains unknown.ObjectiveWe investigated whether epicutaneous exposure to an important component of THS, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), can influence asthma pathology in a mouse model elicited by means of repeated intranasal challenge with cockroach antigen (CRA).MethodsWild-type mice, α7 nicotinic acetylcholine receptor (nAChR)- or mast cell (MC)-deficient mice, and mice with MCs that lacked α7 nAChRs or were the host's sole source of α7 nAChRs were subjected to epicutaneous NNK exposure, intranasal CRA challenge, or both, and the severity of features of asthma pathology, including airway hyperreactivity, airway inflammation, and airway remodeling, was assessed.ResultsWe found that α7 nAChRs were required to observe adverse effects of epicutaneous NNK exposure on multiple features of CRA-induced asthma pathology. Moreover, MC expression of α7 nAChRs contributed significantly to the ability of epicutaneous NNK exposure to exacerbate airway hyperreactivity to methacholine, airway inflammation, and airway remodeling in this model.ConclusionOur results show that skin exposure to NNK, a component of THS, can exacerbate multiple features of a CRA-induced model of asthma in mice and define MCs as key contributors to these adverse effects of NNK.

Rationale: Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered as an important regulator for immune diseases. We have previously shown that AhR protects against allergic airway inflammation. The underlying mechanism, however, remains undetermined. Objectives: We sought to determine whether AhR specifically in type II alveolar epithelial cells (AT2) modulates allergic airway inflammation and its underlying mechanisms. Methods: The role of AhR in AT2 cells in airway inflammation was investigated in a mouse model of asthma with AhR conditional knockout mice in AT2 cells (Sftpc-Cre;AhRf/f). The effect of AhR on allergen-induced autophagy was examined by both in vivo and in vitro analyses. The involvement of autophagy in airway inflammation was analyzed by using autophagy inhibitor chloroquine. The AhR-regulated gene profiling in AT2 cells was also investigated by RNA sequencing (RNA-seq) analysis. Results: Sftpc-Cre;AhRf/f mice showed exacerbation of allergen-induced airway hyperresponsiveness and airway inflammation with elevated Th2 cytokines in bronchoalveolar lavage fluid (BALF). Notably, an increased allergen-induced autophagy was observed in the lung tissues of Sftpc-Cre;AhRf/f mice when compared with wild-type mice. Further analyses suggested a functional axis of AhR-TGF-ß1 that is critical in driving allergic airway inflammation through regulating allergen-induced cellular autophagy. Furthermore, inhibition of autophagy with autophagy inhibitor chloroquine significantly suppressed cockroach allergen-induced airway inflammation, Th2 cytokines in BALFs, and expression of autophagy-related genes LC3 and Atg5 in the lung tissues. In addition, RNA-seq analysis suggests that autophagy is one of the major pathways and that CALCOCO2/NDP52 and S1009 are major autophagy-associated genes in AT2 cells that may contribute to the AhR-mediated cockroach allergen-induced airway inflammation and, subsequently, allergic asthma. Conclusion: These results suggest that AhR in AT2 cells functions as a protective mechanism against allergic airway inflammation through controlling cell autophagy. [ABSTRACT FROM AUTHOR]

Abstract Background Nonpharmacologic interventions for asthma management rely on identification and mitigation of important asthma triggers. Cockroach exposure is strongly associated with asthma morbidity. It is also associated with stress, another risk factor for asthma. Despite high prevalence of both in vulnerable populations, the impact of joint exposure has not been examined. Methods Participants included 173 children with asthma in New Orleans, Louisiana. Cockroach exposure was based on visual inspection using standard protocols. Caregiver stress was measured using Cohen’s 4-item Perceived Stress Scale. Outcomes included unscheduled clinic or emergency department (ED) visits, hospitalization, and pulmonary function. Multivariable logistic regression was performed to assess independent effects of the exposure on the outcome and effect modification was examined in stratified analysis based on stress. Path analysis to explore the mediation effect by stress was performed using a probit link with parameters based on Bayes’ method with non-informative priors. Results Adjusting for stress and other covariates, cockroach exposure was associated with unscheduled clinic/ED visits (aOR = 6.2; 95% CI 1.8, 21.7). Positive associations were also found for hospitalization and FEV1

Macrophage polarization has been demonstrated to exert a vital role on asthma pathogenesis. Mesenchymal stem cells (MSC) have the capacity to modulate macrophage differentiation from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype. However, the impact of MSC-macrophage interactions on asthma development and underlying mechanisms responsible for this interaction remain largely unknown. The aim of this study was to investigate the role of AhR expressed on MSC in macrophage polarization in a cockroach extract (CRE)-induced asthma mouse model. The studies here revealed that MSC polarized macrophages from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype in this model. The mRNA levels of interleukin (IL)-6, IL-1β, and NOS2 as M1 markers were significantly decreased while those of select M2 markers such as Arg-1, FIZZ1, and YM-1 were significantly enhanced. It was also observed that aryl hydrocarbon receptor (AhR) signaling was significantly increased during asthma pathogenesis as demonstrated by enhanced mRNA expression of AhR, CYP1a1, and CYP1b1. It was also seen that the elevated AhR signaling was able to attenuate the onset of asthma. Use of an AhR antagonist (CH223191) resulted in significant inhibition of the AhR signaling and increases in M2 marker expression, but led to elevation of expression of M1 markers in the CRE-induced asthma model. Taken together, the current study showed that MSC can modulate macrophage polarization, in part, via activation of AhR signaling during CRE-induced asthma.

Background: Despite long-standing recognition in the significance of mucus overproduction in asthma, its etiology remains poorly understood. Muc5ac is a secretory mucin that has been associated with reduced pulmonary function and asthma exacerbations. Objectives: We sought to investigate the immunological pathway that controls Muc5ac expression and allergic airway inflammation in asthma. Methods: Cockroach allergen-induced Muc5ac expression and aryl hydrocarbon receptor (AhR) signaling activation was examined in the human bronchial epithelial cells (HBECs) and mouse model of asthma. AhR regulation of Muc5ac expression, mitochondrial ROS (Mito-ROS) generation, and NLRP3 inflammasome was determined by AhR knockdown, the antagonist CH223191, and AhR-/- mice. The role of NLRP3 inflammasome in Muc5ac expression and airway inflammation was also investigated. Results: Cockroach allergen induced Muc5ac overexpression in HBECs and airways of asthma mouse model. Increased expression of AhR and its downstream genes CYP1A1 and CYP1B1 was also observed. Mice with AhR deletion showed increased allergic airway inflammation and MUC5AC expression. Moreover, cockroach allergen induced epithelial NLRP3 inflammasome activation (e.g., NLRP3, Caspase-1, and IL-1β), which was enhanced by AhR knockdown or the antagonist CH223191. Furthermore, AhR deletion in HBECs led to enhanced ROS generation, particularly Mito-ROS, and inhibition of ROS or Mito-ROS subsequently suppressed the inflammasome activation. Importantly, inhibition of the inflammasome with MCC950, a NLRP3-specifc inhibitor, attenuated allergic airway inflammation and Muc5ac expression. IL-1β generated by the activated inflammasomes mediated cockroach allergen-induced Muc5ac expression in HBECs. Conclusions: These results reveal a previously unidentified functional axis of AhR-ROS-NLRP3 inflammasome in regulating Muc5ac expression and airway inflammation. [ABSTRACT FROM AUTHOR]

BackgroundDespite long-standing recognition in the significance of mucus overproduction in asthma, its etiology remains poorly understood. Muc5ac is a secretory mucin that has been associated with reduced pulmonary function and asthma exacerbations.ObjectivesWe sought to investigate the immunological pathway that controls Muc5ac expression and allergic airway inflammation in asthma.MethodsCockroach allergen-induced Muc5ac expression and aryl hydrocarbon receptor (AhR) signaling activation was examined in the human bronchial epithelial cells (HBECs) and mouse model of asthma. AhR regulation of Muc5ac expression, mitochondrial ROS (Mito-ROS) generation, and NLRP3 inflammasome was determined by AhR knockdown, the antagonist CH223191, and AhR-/- mice. The role of NLRP3 inflammasome in Muc5ac expression and airway inflammation was also investigated.ResultsCockroach allergen induced Muc5ac overexpression in HBECs and airways of asthma mouse model. Increased expression of AhR and its downstream genes CYP1A1 and CYP1B1 was also observed. Mice with AhR deletion showed increased allergic airway inflammation and MUC5AC expression. Moreover, cockroach allergen induced epithelial NLRP3 inflammasome activation (e.g., NLRP3, Caspase-1, and IL-1β), which was enhanced by AhR knockdown or the antagonist CH223191. Furthermore, AhR deletion in HBECs led to enhanced ROS generation, particularly Mito-ROS, and inhibition of ROS or Mito-ROS subsequently suppressed the inflammasome activation. Importantly, inhibition of the inflammasome with MCC950, a NLRP3-specifc inhibitor, attenuated allergic airway inflammation and Muc5ac expression. IL-1β generated by the activated inflammasomes mediated cockroach allergen-induced Muc5ac expression in HBECs.ConclusionsThese results reveal a previously unidentified functional axis of AhR-ROS-NLRP3 inflammasome in regulating Muc5ac expression and airway inflammation.

Glutathione-S transferases (GSTs) are part of a ubiquitous family of dimeric proteins that participate in detoxification reactions. It has been demonstrated that various GSTs induce allergic reactions in humans: those originating from house dust mites (HDM), cockroaches, and helminths being the best characterized. Evaluation of their allergenic activity suggests that they have a clinical impact. GST allergens belong to different classes: mu (Blo t 8, Der p 8, Der f 8, and Tyr p 8), sigma (Bla g 5 and Asc s 13), or delta (Per a 5). Also, IgE-binding molecules belonging to the pi-class have been discovered in helminths, but they are not officially recognized as allergens. In this review, we describe some aspects of the biology of GST, analyze their allergenic activity, and explore the structural aspects and clinical impact of their cross-reactivity.

Background: Nonpharmacologic interventions for asthma management rely on identification and mitigation of important asthma triggers. Cockroach exposure is strongly associated with asthma morbidity. It is also associated with stress, another risk factor for asthma. Despite high prevalence of both in vulnerable populations, the impact of joint exposure has not been examined.Methods: Participants included 173 children with asthma in New Orleans, Louisiana. Cockroach exposure was based on visual inspection using standard protocols. Caregiver stress was measured using Cohen's 4-item Perceived Stress Scale. Outcomes included unscheduled clinic or emergency department (ED) visits, hospitalization, and pulmonary function. Multivariable logistic regression was performed to assess independent effects of the exposure on the outcome and effect modification was examined in stratified analysis based on stress. Path analysis to explore the mediation effect by stress was performed using a probit link with parameters based on Bayes' method with non-informative priors.Results: Adjusting for stress and other covariates, cockroach exposure was associated with unscheduled clinic/ED visits (aOR = 6.2; 95% CI 1.8, 21.7). Positive associations were also found for hospitalization and FEV1 < 80%. High stress modified the relationship with unscheduled clinic/ED visits (high aOR = 7.7 95% CI 1.0, 60.2, versus normal aOR = 4.1 95% CI 0.8, 21.9). Path models identified direct and indirect effects (p = 0.05) indicating that a majority of the total effect on unscheduled clinic/ED visits is attributed directly to cockroach exposure.Conclusion: The strong association between cockroach exposure and asthma morbidity is not due to uncontrolled confounding by stress. The combination of cockroach exposure and high stress, common in urban homes, are modifiable factors associated with poor asthma outcomes. [ABSTRACT FROM AUTHOR]

Macrophage polarization has been demonstrated to exert a vital role on asthma pathogenesis. Mesenchymal stem cells (MSC) have the capacity to modulate macrophage differentiation from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype. However, the impact of MSC-macrophage interactions on asthma development and underlying mechanisms responsible for this interaction remain largely unknown. The aim of this study was to investigate the role of AhR expressed on MSC in macrophage polarization in a cockroach extract (CRE)-induced asthma mouse model. The studies here revealed that MSC polarized macrophages from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype in this model. The mRNA levels of interleukin (IL)-6, IL-1β, and NOS2 as M1 markers were significantly decreased while those of select M2 markers such as Arg-1, FIZZ1, and YM-1 were significantly enhanced. It was also observed that aryl hydrocarbon receptor (AhR) signaling was significantly increased during asthma pathogenesis as demonstrated by enhanced mRNA expression of AhR, CYP1a1, and CYP1b1. It was also seen that the elevated AhR signaling was able to attenuate the onset of asthma. Use of an AhR antagonist (CH223191) resulted in significant inhibition of the AhR signaling and increases in M2 marker expression, but led to elevation of expression of M1 markers in the CRE-induced asthma model. Taken together, the current study showed that MSC can modulate macrophage polarization, in part, via activation of AhR signaling during CRE-induced asthma. [ABSTRACT FROM AUTHOR]

Introduction Cockroach allergen exposure elicits cockroach sensitization and poses an increased risk for asthma. However, the major components in cockroach allergen and the mechanisms underlying the induction of cockroach allergen-induced allergy and asthma remain largely elusive. We sought to examine the role of cockroach-associated glycan in regulating human basophil function. Methods N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry. Binding of cockroach allergen to serum IgE from cockroach allergic subjects was determined by solid-phase binding immunoassays. Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined. Expression of C-type lectin receptors (CLRs) and their role in mediating glycan-uptake in the basophils was also investigated. Results MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc). Deglycosylated Bla g 2 showed reduced binding to IgE and was less capable of inducing histamine release from human basophils. In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects. An analysis of CLRs revealed the expression of DC-SIGN and DCIR, but not MRC1 and dectin-1, in human basophils. Neutralizing antibody to DCIR, but not DC-SIGN, significantly inhibited Bla g 2 uptake by human basophils. A dose-dependent bindings of cockroach allergen to DCIR was also observed. Conclusions These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function. [ABSTRACT FROM AUTHOR]

Highlights: [•] Bla g 4 is a major cockroach allergen that belongs to the lipocalin family. [•] It was determined that Bla g 4 binds tyramine and octopamine. [•] Structural analysis provides details for tyramine binding. [•] Most likely Bla g 4 and Per a 4 bind different ligands. [ABSTRACT FROM AUTHOR]

Rationale: Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered as an important regulator for immune diseases. We have previously shown that AhR protects against allergic airway inflammation. The underlying mechanism, however, remains undetermined., Objectives: We sought to determine whether AhR specifically in type II alveolar epithelial cells (AT2) modulates allergic airway inflammation and its underlying mechanisms., Methods: The role of AhR in AT2 cells in airway inflammation was investigated in a mouse model of asthma with AhR conditional knockout mice in AT2 cells ( Sftpc-Cre;AhR f/f ). The effect of AhR on allergen-induced autophagy was examined by both in vivo and in vitro analyses. The involvement of autophagy in airway inflammation was analyzed by using autophagy inhibitor chloroquine. The AhR-regulated gene profiling in AT2 cells was also investigated by RNA sequencing (RNA-seq) analysis., Results: Sftpc-Cre;AhR f/f mice showed exacerbation of allergen-induced airway hyperresponsiveness and airway inflammation with elevated Th2 cytokines in bronchoalveolar lavage fluid (BALF). Notably, an increased allergen-induced autophagy was observed in the lung tissues of Sftpc-Cre;AhR f/f mice when compared with wild-type mice. Further analyses suggested a functional axis of AhR-TGF-β1 that is critical in driving allergic airway inflammation through regulating allergen-induced cellular autophagy. Furthermore, inhibition of autophagy with autophagy inhibitor chloroquine significantly suppressed cockroach allergen-induced airway inflammation, Th2 cytokines in BALFs, and expression of autophagy-related genes LC3 and Atg5 in the lung tissues. In addition, RNA-seq analysis suggests that autophagy is one of the major pathways and that CALCOCO2/NDP52 and S1009 are major autophagy-associated genes in AT2 cells that may contribute to the AhR-mediated cockroach allergen-induced airway inflammation and, subsequently, allergic asthma., Conclusion: These results suggest that AhR in AT2 cells functions as a protective mechanism against allergic airway inflammation through controlling cell autophagy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhao, Zhang, Tu, Wan, Shen, Zhang, Trivedi and Gao.)

In the past, cockroach allergen exposure assessment mainly focused on settled dust in homes in low-income urban cities in the United States. That choice was not wrong; without measureable levels of cockroach allergen, it is difficult to show associations with any home characteristics, much less with health outcomes (e.g., allergy, asthma). However, recent studies in other suburban areas, schools, and other countries have elucidated the importance of cockroach allergen in these environments too. In addition, characterizing the underlying factors that give rise to cockroach allergen exposure (or protect against it) can lead to more targeted public health interventions. This review discusses different approaches to sampling indoor environments, interprets recent asthma and allergy studies, compares cockroach allergen levels from past studies with those of recent studies, and describes strategies for decreasing exposures. [ABSTRACT FROM AUTHOR]

Background: Compounds which activate the innate immune system, such as lipopolysaccharide, are significant components of ambient air, and extremely difficult to remove from the environment. It is currently unclear how prior inhalation of endotoxin affects allergen sensitization. We examined whether lung-specific endotoxin tolerance induction prior to sensitization can modulate the response to allergen. Methods: Endotoxin tolerance was induced by repeated intratracheal exposure to endotoxin. All mice were then sensitized and challenged by direct intratracheal instillation of cockroach allergen. Results: After allergen sensitization and challenge, endotoxin tolerant mice had significantly decreased airways hyperresponsiveness to methacholine challenge, which was confirmed by invasive lung function tests. Decreased goblet cell hyperplasia and mucus production were also found by histological assessment. Tolerant mice were protected from airway eosinophilia through the mechanism of reduced CCL11 and CCL24. Interestingly, endotoxin tolerant mice had only a modest reduction in cockroach-specific IgE; however, total IgE was significantly reduced. Conclusions: These data show that induction of endotoxin tolerance prior to sensitization protects against the hallmark features of asthma-like inflammation, and that transient modulation of innate immunity can have long-lasting effects on adaptive responses. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Bla g 2, one of the major cockroach allergens, induces a strong IgE response against conformational epitopes, and on reexposure, sensitized individuals often display symptoms of allergic rhinitis and asthma. The aim of the current study was to perform a test of the efficacy of a modified phage display screening, characterization of selected phages and an automated algorithm, EpiSearch, in locating an important conformational epitope. Methods: The monoclonal antibody 7C11, which partially inhibits the binding of patient IgE antibodies to Bla g 2, was used to screen a random peptide phage library. After 3 rounds of panning, 32 phage clones were isolated and the amino acid sequences of their peptides were determined. The relative affinity and specificity of the binding of these peptides to 7C11 were tested in ELISAs. The amino acid composition of these peptides was then matched with clusters of residues on the surface of the 3-dimensional (3D) structure of Bla g 2, using our EpiSearch algorithm. Results: The amino acid sequences of the peptides on selected phages differed at only one position, occupied by 1 of 2 negatively charged residues. The two 12-mer sequences bound to 7C11 with similar avidity and specificity. There was good concordance between the residues in the 3D clusters identified from our phage display/computational method with the co-crystal structural analysis. Conclusion: Conformational epitopes may be mapped through screening of clones from random peptide phage display libraries and EpiSearch. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Rationale: Basophils contribute to anaphylaxis and allergies. We examined the utility of assessing basophil-associated surface antigens (CD11b/CD63/CD123/CD203c/CD294) in characterizing and monitoring subjects with nut allergy. Methods: We used flow cytometry to analyze basophils at baseline (without any activation) and after ex vivo stimulation of whole blood by addition of nut or other allergens for 2, 10, and 30 min. We also evaluated whether basophil expression of CD11b/CD63/CD123/CD203c/CD294 was altered in subjects treated with anti-IgE monoclonal antibody (omalizumab) to reduce plasma levels of IgE. Results: We demonstrate that basophil CD203c levels are increased at baseline in subjects with nut allergy compared to healthy controls (13 subjects in each group, p < 0.0001). Furthermore, we confirm that significantly increased expression of CD203c occurs on subject basophils when stimulated with the allergen to which the subject is sensitive and can be detected rapidly (10 min of stimulation, n = 11, p < 0.0008). In 5 subjects with severe peanut allergy, basophil CD203c expression following stimulation with peanut allergen was significantly decreased (p < 0.05) after 4 and 8 weeks of omalizumab treatment but returned toward pretreatment levels after treatment cessation. Conclusions: Subjects with nut allergy show an increase of basophil CD203c levels at baseline and following rapid ex vivo stimulation with nut allergen. Both can be reduced by omalizumab therapy. These results highlight the potential of using basophil CD203c levels for baseline diagnosis and therapeutic monitoring in subjects with nut allergy. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The association between allergen skin sensitization and helminth infection has been debated for years. Here, we sought to estimate the prevalence of atopic sensitization of residents living in area endemic for lymphatic filariasis and intestinal helminths and to investigate the association between these different species of helminths with allergen skin test reactivity to allergens. Methods: Five hundred and eighty-three individuals living in an area endemic for Brugia malayi and for intestinal helminths were skin prick tested using 3 allergens. Microfilariae were enumerated by filtration of 1 ml nocturnally collected blood, and 442 stool samples were examined for the presence of intestinal helminth eggs. Results: The prevalence of skin prick test positivity to any allergen was 23.5% (to cockroach 20.6%, to house dust mite 6.2% and to grass pollen 1.2%). Individuals with B. malayi infection had a significantly reduced risk for atopic reactivity to cockroach (adjusted odds ratio 0.56, 95% CI 0.35-0.88). In the same population, no association was found between the presence of intestinal helminths and any skin test reactivity. Conclusions: In a general population, across all ages in a rural area of Indonesia, the prevalence of skin test reactivity to house dust mite is as low as in other non-affluent countries, and infection with B. malayi appears to reduce the risk of skin reactivity to cockroach. On the other hand, we found no association between infection with intestinal helminths and skin test reactivity to aeroallergens. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Many low-income housing units in the United States continue to have chronic German cockroach, Blattella germanica (L.), infestations and high prevalence of cockroach allergens despite the availability of highly effective cockroach control products. Several studies have demonstrated the greater effectiveness of integrated pest management (IPM) compared with routine chemical interventions in apartment buildings and the benefit of cockroach allergen reduction using IPM. Yet, there has been little information on the cost and benefit of community-wide cockroach IPM, which is critical for voluntary adoption of IPM programs. We evaluated a community-wide IPM program in two low-income apartment complexes in Gary, IN. The program included education of staff and residents, monthly monitoring, and nonchemical (laying sticky traps) and chemical treatment based on monitoring results. One complex of 191 apartments was treated with cockroach gel bait, boric acid dust, and sticky traps by state licensed entomologists from Purdue University (E-IPM group). The other complex of 251 apartments was treated by pest management professionals (PMPs) from a contractor (C-IPM group) following the same protocol as the E-IPM group. Purdue University researchers trained Gary Housing Authority (GHA) staff on cockroach biology and management and cockroach allergen reduction techniques. GHA staff educated all residents in the two complexes on cockroach control and allergen reduction through printed materials, demonstrations, or both. Purdue University entomologists conducted the initial and monthly monitoring in both complexes (laying six sticky traps per apartment and retrieving them the next day) with the assistance from GHA to evaluate program effectiveness, guide insecticide applications, and identify apartments with poor sanitation conditions, Dust samples were collected from kitchen floors of 72 cockroach-infested apartments at the beginning, and again at 6 and 12 mo to evaluate changes in cockroach allergen Bla g 1 concentration. E-IPM resulted in significantly faster cockroach trap count reduction than C-IPM. At 12 mo, the number of cockroach-infested apartments decreased by 74% in both treatment groups. Geometric mean cockroach trap counts decreased from 99.7 at baseline to 0.4 (99.6% reduction) by E-IPM and from 76.0 at baseline to 1.3 (98.3% reduction) by C-IPM. From the first quarter to the fourth quarter, cockroach bait use decreased by 88.5 and 92.7% for E-IPM and C-IPM group, respectively. From month 0 to month 12, geometric mean Bla g 1 concentrations decreased from 27.8 to 2.2 U per gram of dust (U/g) in the E-IPM group and from 5.8 to 2.4 U/g in the C-IPM group. Assuming salary rates at $60/h for PMPs and $19/h for housing authority staff, the mean monthly cockroach management (material and labor expenses) cost was $7.5 USD/apartment for both groups excluding education cost. The cost for subsequent years service is expected to be lower due to reduced cockroach infestations. The effectiveness of both IPM programs was affected by the lack of assistance from housing authority with periodic inspections of the apartments, lack of proper maintenance of the properties, and inadequate cooperation from residents. [ABSTRACT FROM AUTHOR]

Background Environmental exposures to cockroach allergen and endotoxin are recognized epidemiological risk factors for the early development of allergies and asthma in children. Because of this, it is important to examine the role of early-life concurrent inhalation exposures to cockroach allergen and endotoxin in the pathogenesis of allergic airways disease. Objective We examined the effects of repeated concomitant endotoxin and cockroach allergen inhalation on the pulmonary and systemic immune responses of newborn and juvenile mice. Methods C3H/HeBFeJ mice were exposed to inhaled endotoxin and cockroach allergen via intranasal instillation from day 2 to 21 after birth, and systemic and pulmonary responses were examined in serum, bronchoalveolar lavage fluid, and lung tissue. Results Cockroach allergen exposures induced pulmonary eosinophilic inflammation, total and allergen-specific IgE, IgG1, and IgG2a production, and alveolar remodelling. Co-exposures with endotoxin and cockroach allergen significantly increased serum IgE and IgG1, lung inflammation, and alveolar wall thickness, and decreased airspace volume density. Importantly, compared with exposures with individual substances, the responses to co-exposures were more than additive. Conclusions Repeated inhalation exposures of neonatal and juvenile mice to endotoxin and cockroach allergen increased the pulmonary inflammatory and systemic immune responses in a synergistic manner and enhanced alveolar remodelling in the developing lung. These data underscore the importance of evaluating the effect of multiple, concurrent environmental exposures, and of using an experimental model that incorporates clinically relevant timing and route of exposures. [ABSTRACT FROM AUTHOR]

Background The cockroach is a major source of indoor allergens, which cause perennial rhinitis and asthma. Per a 7 is one of the major allergens from the American cockroach, eliciting IgE reaction in over 50% of sera from allergic individuals. However, the actions of Per a 7 in the pathogenesis of allergic diseases remain poorly understood. Objective The aim of the study was to investigate the effects of Per a 7 on the expression of protease-activated receptors (PARs) on murine mast cells and the release of T-helper type 2 (Th2) cytokines from these cells. Methods Per a 7 gene was cloned and expressed in Escherichia coli. The purified recombinant Per a 7 (rPer a 7) was used to challenge murine mast cells P815 and the expression of PARs was determined by using real-time quantitative RT-PCR and flow cytometry. The release of IL-4 and IL-13 was detected with ELISA. Results rPer a 7 was solubly expressed in E. coli and the purified rPer a 7 reacted with 75% (six out of eight) of the sera from cockroach-allergic patients. Following stimulation of rPer a 7, the expression of PAR-1, PAR-2, PAR-3 and PAR-4 mRNAs on P815 cells increased by 8.7-, 6.8-, 14.4- and 8.8-fold, respectively, following 2- and 6-h incubation periods, and the expression of PAR-1, PAR-2 and PAR-4 proteins was enhanced following 16-h incubation. rPer a 7 provoked approximately up to a 4.8- and 2.3-fold increase in IL-4 and IL-13 release from P815 cells following 6- and 16-h incubation periods. Conclusion rPer a 7 induced up-regulation of PAR expression on P815 cells and provoked Th2 cytokines IL-4 and IL-13 secretion from these murine mast cells, which implicated that this major cockroach allergen is likely to contribute to the development of cockroach-related allergic disease. [ABSTRACT FROM AUTHOR]

Low-income housing often has multiple indoor health risks. Among them, pest infestation, pesticide use, and pest allergens are recognized as common risks which affect residents' health. Cockroach and rodent allergens are associated with morbidity and mortality of asthmatics. To characterize the levels of pest infestation, residents' attitudes toward pest control, and the relationships among cockroaches, mice, cockroach allergen level, asthma and allergy rate in public housing, we interviewed residents from 358 randomly selected apartments in Gary, Indiana and assessed the environmental conditions. Dust samples were collected from 101 apartment kitchen floors to analyze for cockroach allergen (Bla g 1 and Bla g 2) levels. Eighty one percent of the apartments were found infested by cockroaches, mice, ants, spiders, or flies. In the 101 apartments evaluated, 98% of the kitchen dust samples had detectable levels of Bla g 1 allergen (≥0.4 U/g), 52% had ≥2 U/g, and 33% had ≥8 U/g of Bla g 1. Among the 1,173 residents, 13% and 9% had physician-diagnosed asthma and allergy, respectively. Existence of diagnosed asthmatic was positively correlated with mouse infestations. [ABSTRACT FROM AUTHOR]

Background: We previously reported significant reductions in cockroach allergen concentrations in urban homes by reducing cockroach infestations. Objective: To determine the effectiveness of pest control performed by professional entomologists, compared with commercial companies, in reducing cockroach allergen. Methods: This 3-arm randomized controlled trial enrolled 60 cockroach-infested homes in North Carolina. Homes were randomly assigned to a control group or 1 of 2 treatment groups. Treatment 1 had insecticide baits placed by entomologists from North Carolina State University. Treatment 2 received pest control from a randomly assigned commercial company. Vacuumed dust sampling and cockroach trapping were conducted at 0, 6, and 12 months. Dust samples were analyzed by ELISA. Results: In treatment 1 homes, there were significant reductions in geometric mean trap counts compared with control and treatment 2 homes at 12 months. Relative to control, significant 12-month reductions in Bla g 1 were evident in treatment 1 homes at all sampled sites, except bedroom floor. From baseline to month 12, geometric mean Bla g 1 concentrations (U/g) decreased from 64.2 to 5.6 in kitchen, 10.6 to 1.1 in living room, 10.7 to 1.9 on bedroom floor, and 3.6 to 2.3 in bed. Treatment 2 homes showed no significant 12-month allergen reductions versus control. Conclusion: Reductions in Bla g 1 in cockroach-infested homes can be achieved by reducing infestations; however, the magnitude of allergen reduction is dependent on the thoroughness and effectiveness of cockroach eradication efforts. Clinical implications: Elimination of cockroaches is an effective method for reducing exposure to cockroach allergen. [Copyright &y& Elsevier]

The efficacy of residential interventions to reduce cockroach allergens in public housing developments was evaluated over months of follow-up. Repeated measurements were collected from 39 apartments, with longitudinal analyses used to evaluate changes over time. Bla g 1 kitchen concentrations were reduced 71% and bed concentrations 53% (86% and 70% for Bla g 2, respectively) by 6 months post-intervention, after which concentrations began to increase. Apartments with higher concentrations were usually in poorer condition and benefited most from pest management efforts. Intensive interventions can significantly reduce the allergen burden in public housing apartments, but intervention efforts must be sustained. [ABSTRACT FROM AUTHOR]

A highly active glutathione S-transferase was purified from adult German cockroaches, Blattella germanica. The purified enzyme appeared as a single band of 24 kDa by SDS/PAGE, and had a different electrophoretic mobility than, a previously identified Sigma class glutathione S-transferase (Bla g 5). Kinetic study of 1-chloro-2,4-dinitrobenzene conjugation revealed a high catalytic rate but common substrate-binding and cosubstrate-binding affinities, with Vmax, kcat, Km for 1-chloro-2,4-dinitrobenzene and Km for glutathione estimated to be 664 µmol·mg−1·min−1, 545 s−1, 0.33 mm and 0.76 mm, respectively. Interestingly, this enzyme possessed the highest activity for cumene hydroperoxide among insect glutathione S-transferases reported to date. Along with the ability to metabolize 1,1,1-trichloro-2,2-bis( p-chlorophenyl)ethane and 4-hydroxynonenal, this glutathione S-transferase may play a role in defense against insecticides as well as oxidative stress. On the basis of the amino acid sequences obtained from Edman degradation and MS analyses, a 987-nucleotide cDNA clone encoding a glutathione S-transferase ( BggstD1) was isolated. The longest ORF encoded a 24 614 Da protein consisting of 216 amino acid residues. The sequence had close similarities (∼ 45–60%) to that of Delta class glutathione S-transferases, but had only 14% identity to Bla g 5. The putative amino acid sequence contained matching peptide fragments of the purified glutathione S-transferase. ELISA showed that BgGSTD1 bound to serum IgE obtained from patients with cockroach allergy, indicating that the protein may be a cockroach allergen. [ABSTRACT FROM AUTHOR]

We characterized the prevalence of cockroach allergen exposure in a nationally representative sample of U.S. homes and assessed risk factors for elevated concentrations. DESIGN: We used data from the National Survey of Lead and Allergens in Housing, a population-based cross-sectional survey. PARTICIPANTS: Participants were residents of 831 U.S. homes in the survey. EVALUATIONS/MEASUREMENTS: We analyzed allergen, questionnaire, and observational data of 831 U.S. homes. RESULTS: Cockroach allergen (Bla g 1) concentrations exceed 2.0 U/g, a level associated with allergic sensitization, in 11% of U.S. living room floors and 13% of kitchen floors. Concentrations exceed 8.0 U/g, a level associated with asthma morbidity, in 3% of living room floors and 10% of kitchen floors. Elevated concentrations were observed in high-rise apartments, urban settings, pre-1940 constructions, and households with incomes < $20,000. Odds of having concentrations > 8.0 U/g were greatest when roach problems were reported or observed and increased with the number of cockroaches observed and with indications of recent cockroach activity. CONCLUSIONS: Household cockroach allergen exposure is characterized in a nationally representative context. The allergen is prevalent in many settings, at levels that may contribute to allergic sensitization and asthma morbidity. RELEVANCE TO CLINICAL OR PROFESSIONAL PRACTICE: Likelihood of exposure can be assessed by consideration of demographic and household determinants. [ABSTRACT FROM AUTHOR]

Background: With 63% of US children under 5 years of age in regular child care, day-care facilities could be an important source of exposure to indoor allergens. Objective: This study examined levels of 7 indoor allergens in 89 day-care facilities in 2 North Carolina counties. Methods: At each facility, a questionnaire was administered, observations were made, and vacuumed dust samples were collected from carpeted and noncarpeted areas of one room. Allergen concentrations were measured with antibody-based ELISAs. Results: Each allergen was detected in a majority of facilities (52% to 100%). Geometric mean concentrations were 5.19 μg/g for Alternaria alternata, 2.06 μg/g for Can f 1, 1.43 μg/g for Fel d 1, 0.21 U/g for Bla g 1, 0.20 μg/g for Der p 1, 0.10 μg/g for Der f 1, and 0.01 μg/g for Mus m 1. Concentrations for 5 of the 7 allergens were not statistically different from concentrations found in southern US homes sampled in the National Survey of Lead and Allergens in Housing. In rooms with carpet and hard-surfaced flooring, levels of A alternata, Can f 1, Der f 1, Der p 1, and Fel d 1 were statistically higher on carpet. Conclusions: In this survey of day-care facilities in North Carolina, detectable levels of indoor allergens were commonly found. For many young children and day-care staff, day-care facilities might be a source of clinically relevant exposures to indoor allergens. [Copyright &y& Elsevier]

Although allergen exposure can clearly aggravate the condition of sensitized patients with asthma, there is uncertainty and controversy about exactly which allergen avoidance interventions should be recommended to patients with asthma. Interventions that appear logical may fail to be clinically efficacious for several reasons. Although narrow interventions, such as allergen-impermeable mattress covers to reduce exposure to dust mite allergens, may offer little benefit if used alone, recent evidence suggests that a multifaceted, home-based environmental intervention focusing on multiple exposures may provide clinical benefits to patients with asthma. The role of allergen avoidance in infancy in the primary prevention of asthma is a subject of active investigation, but data remain too preliminary to make public health recommendations in this regard. [Copyright &y& Elsevier]

The German cockroach,Blattella germanica(Linnaeus) (Dictyoptera: Blattellidae), produces several potent human allergens, one of which,Blattella germanicaallergen 1 (Bla g 1), is produced in the midgut and excreted in faeces. We tested with descriptive and experimental approaches the hypothesis that Bla g 1 production is related to food intake in adult males and females of the German cockroach. Bla g 1 mRNA expression in the female midgut (assayed by real time quantitative polymerase chain reaction), her Bla g 1 content (assayed by enzyme-linked immunosorbent assay), and the female's faeces production and its Bla g 1 content tracked a cyclic pattern in relation to the gonadotrophic cycle. All four measures rose as food intake increased, declined before oviposition in relation to diminishing food intake, and remained low while the female carried an egg case for 20 days. After her first clutch of embryos hatched, the female resumed feeding, and faeces and Bla g 1 production increased concomitantly. Both Bla g 1 mRNA expression and Bla g 1 protein levels remained low in experimentally starved females. However, when starved females were allowed to feed, Bla g 1 production elevated and the gonadotrophic cycle resumed. Bla g 1 mRNA expression also increased six-fold in response to feeding compared to starved females. By contrast, there were no apparent cycles in the pattern of Bla g 1 production in males, reflecting their low and non-cyclic food intake. Our results therefore demonstrate that Bla g 1 production inB. germanicais modulated in relation to food intake. [ABSTRACT FROM AUTHOR]

Background: Asthma morbidity increases every year, especially among children, and exposure to high levels of indoor allergens is a very important factor. We evaluated the prevalence and exposure to cockroach (CR) allergen in asthmatic children in Poland, and also tested the hypothesis that asthma with allergy to CR is more severe than with allergy to other antigens. Methods: One hundred and sixty children with asthma were examined, had skin prick tests (SPT) with common and CR allergens, underwent spirometry, and provocation tests to histamine. Children with positive SPT to CR had measured specific IgE levels to this antigen and Bla g 2 concentrations were measured in their homes. Results: The most common allergen, was dust mite 51.3%, followed by pollen 48.8% and CR allergen 24.3%. In children with CR sensitivity, 13% had mild asthma, 26% moderate and 61% had severe asthma. Their levels for forced expiratory volume in one second (FEV 1 ), and the provocative concentration of histamine that caused a 20% fall in FEV 1 (PC 20 ), were statistically lower than in the group of children with other than CR allergies. Bla g 2 antigen was detected in 55.13% samples. The highest levels of Bla g 2 were found in old houses, without central heating, and in houses with lower income. Conclusion: In Polish children, CR allergen is a very important factor of sensitivity. Concentrations of Bla g 2 in homes are higher than previously reported in other European countries, and are strongly related to the houses' characteristics. Also, children with CR hypersensitivity have severe asthma more often than children with other allergies. [ABSTRACT FROM AUTHOR]

Increasing asthma prevalence is evident in many countries and childhood asthma has also become one of the most common chronic diseases in children. Exposure to indoor allergens has been be attributed to a significant increase in asthma occurrence. Meanwhile, allergen distribution varies widely among different countries. This brief investigation reports the distribution of common indoor allergens, such as mite (Dermatophagoides pteronyssinus, Der p 1 and Der p 2), cat (Felis domesticus, Fel d 1), and German cockroach allergens (Blattella germanica, Bla g 1) at different sites of asthmatic children in Taiwan. Approximately 40 asthmatic children''s homes participated in this study and the cohort was followed prospectively for approximately 6 months, starting in December until the following May. Dust samples were collected from each child''s mattress, and bedroom and living room floors. All samples were analyzed with monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA). Statistical difference of Der p 1 concentrations is observed among those on the mattress, bedroom and living room floor, except for in May. Seasonal variation in Der p 1 levels on the mattress and bedroom floor is also significant (P<0.025 and 0.001, respectively). Distributional variation seems to be significant for most allergens among sites within homes in most seasons. Therefore, if only one sample is to be taken, the month of May would be a more ideal choice of study period, and detailed sampling across sites appears to be necessary should the true environmental exposure of allergens be desired. [Copyright &y& Elsevier]