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Dust mite species and allergen concentrations in beds of individuals belonging to different urban socioeconomic groups in Brazil.

BACKGROUND: Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis dust mites are among the most important agents of hypersensitivity reactions in human beings. However, a role of other mites in the etiology of these reactions has not yet been excluded. OBJECTIVES: To investigate the nature of the dust mite fauna and the presence of Der p 1 (allergen 1 of Dermatophagoides pteronyssinus) and Blo t 5 (allergen 5 of Blomia tropicalis) on beds used by individuals with different socioeconomic backgrounds in Salvador, a major Brazilian city and to investigate possible associations of mite frequencies and allergen levels with (a) season of the year, (b) housing characteristics, (c) bed cleaning behaviors that could affect mite densities, and (d) allergy history. METHODS: Dust samples were collected from 459 beds of 101 residences from two groups with different socioeconomic levels (hereafter called wealthy and poor groups) in the city of Salvador, Brazil, for the identification of mite species and determination of Der p 1 and Blo t 5 levels. History of allergy was collected using the ISAAC phase I questionnaire. RESULTS: Eighty nine percent of the beds analyzed harbored at least one mite species. B. tropicalis was found in 71.8%, D. pteronyssinus in 39.9%, Cheyletus sp. in 33.9%, and Gohieria fusca in 21.1% of the beds. B. tropicalis was found with a similar frequency in beds of the two socioeconomic groups; D. pteronyssinus was found more frequently in the beds of the wealthy than of the poor group, whereas the reverse was observed with G. fusca. The concentrations of Der p 1 and Blo t 5 allergens exceeded the cut-off for sensitization of 2 microg/g of dust in 94.0% and 69.3% of the wealthy and poor group beds, respectively. No associations were found between history of allergy and mite species or between history of allergy and the concentrations of mite allergens. CONCLUSIONS: The observation of B. tropicalis and D. pteronyssinus as the most frequently found mites is consistent with previous reports from tropical regions. The higher frequency of G. fusca in beds of individuals from the poor group than those from the wealthy group could be a consequence of different bed cleaning behaviors between the two groups.

Allergens↗

Childhood asthma and indoor aeroallergens and endotoxin in Palestine: a case-control study.

This study was carried out to evaluate the relationship between wheezing or sensitization and concentrations of mites, cat and dog allergens, and bacterial endotoxin in Palestine. A nested case-control involved analysis of mattress and floor dust from a 110 children's houses with reported wheezing and without wheezing. We found no consistent associations between allergen levels and either wheeze or specific atopic sensitization. Furthermore, no clear associations between mattress endotoxin levels and wheeze or atopy were found. Endotoxin in floor dust was inversely associated with atopic sensitization and wheeze, statistically significant only for atopic wheeze. Finally, a nonsignificant inverse association was observed between living room endotoxin and atopy within the non-wheezing control group. In conclusion, although our study found mostly negative results, it does suggest that endotoxin on living room floors might protect against atopic wheeze. However, this finding should be interpreted with caution due the relatively small sample size of the study and requires further confirmation.

Air Pollutants↗

A longitudinal analysis of the efficacy of environmental interventions on asthma-related quality of life and symptoms among children in urban public housing.

In an environmental intervention study in public housing, we examined monthly Juniper Paediatric Asthma Quality of Life (QOL) Questionnaires for 51 children. Longitudinal analysis and spline models were used to identify time periods with significant improvements in QOL to inform judgments about causality. We found significant improvements in QOL, with moderate improvements before environmental interventions, increased rates of improvement immediately after, and reduced rates more than 5 months post-intervention. Effect modification analyses identified high-risk subpopulations and emphasized the importance of environmental, social, and economic conditions. Our results demonstrate the value of longitudinal techniques in evaluating the benefits of environmental interventions for asthma.

Adolescent↗

Co-administration of vaccination with DNA encoding T cell epitope on the Der p and BCG inhibited airway remodeling in a murine model of chronic asthma.

Therapeutic modalities of airway remodeling in asthma have proved to be unsuccessful regarding reversing the previously established chronic airway changes. Recently, the potential of plasmid DNA to inhibit the Th2 immune response has been demonstrated in animal models of asthma. Bacillus Calmette-Guerin (BCG) immunization also induced immunomodulation, which appeared to be reliant on the properties of the interferon-gamma that was produced. Mice were immunized with house dust mite extract (HDM). At the 3 week point, we injected BCG subcutaneously into mice on three successive weeks. One week after the BCG injection, we immunized mice with the DNA plasmid encoding for murine T-cell epitope on Dermatophagoide pteronyssinus 2 thrice weekly. At 9 weeks after immunization, we measured airway responsiveness. Twenty four hours later, we performed bronchoalveolar lavage and histological examinations. Co-administration of DNA vaccination and BCG resulted in a partial suppression of the overproduction of goblet cells and the thickness of the peribronchial smooth muscle in ongoing allergic responses. In the bronchoalveolar lavage fluid, the number of total cells and eosinophils was reduced, and regarding the change of cytokines, the concentration of IL-4 was also decreased, but interferon-gamma was increased in the co-administration group, opposed to the asthma group. These results suggest that co-administration of vaccination with the DNA encoding T-cell epitope and BCG are effective regarding ongoing allergic response and might constitute an ideal method for combating allergic disease in the future.

Animals↗

Effect of floorcovering construction on content and vertical distribution of house dust mite allergen, Der p I.

Domestic floorcoverings often contain appreciable quantities of particulate pollutants, such as house dust mite allergen, Der p I. Exposure to Der p I is a risk factor for the development of mite sensitization and asthma. We investigated whether carpet construction was related to the Der p I content in normal use, and its vertical distribution. We hoped to inform development of methods to remove such material. Along with one hard flooring surface, a range of carpets with differing pile conformations (loop vs. cut), pile heights, yarn twists, and pile densities were placed in houses for 13 months. The carpets were later sectioned to allow profiling of Der p I throughout the pile strata using monoclonal antibody, enzyme-linked immunosorbent assay. Not surprisingly, significantly lower amounts of Der p I were found on hard flooring than any of the carpets, which all contained similar amounts of mite allergen. For all carpets, the Der p I concentration per unit area was found to be inversely related to the distance from the carpet backing. We conclude that carpet construction is not a good predictor of Der p I content in the home. We also suggest that, as carpet construction likely influences ease of disturbance of material within the pile, methods to remove or denature particulate pollutants such as Der p I will be most effective if they are able to target the bulk of allergenic material, found toward the base of the pile.

Air Movements↗

Allergen sensitivity and asthma severity at an inner city asthma center.

The objective of this study was to examine the relationship of allergen sensitivity to asthma symptoms among inner-city asthmatics seen at our Brooklyn, NY, asthma center. We hypothesized that asthma severity would increase for adults and children with increased cockroach and dust mite allergen sensitivity. Data were gathered from retrospective chart review for all patients who were treated at the center with a diagnosis of asthma and had undergone skin-prick testing (SPT) for allergen sensitivity during 1998 (pediatric, n = 79; adult, n = 29). Asthma severity (determined by National Heart, Lung and Blood Institute [NHLBI] asthma severity class) was examined in relation to allergen sensitivity. Allergen sensitivity was measured by percent positive to skin-prick testing as well as by relative mean diameter of skin prick test wheals. For adults, mite sensitivity prevalence was 61% and cockroach sensitivity prevalence was 41%. For children, mite sensitivity prevalence was 49%; cockroach sensitivity prevalence was 42%. For adults, asthma severity correlated significantly with sensitivity to Cladosporium, tree, and grass as measured by percent positive skin tests and by increasing mean diameter of skin test wheals. There was a significant correlation with severity for adult dust mite sensitivity only as measured by increasing mean wheal diameter. Ragweed sensitivity showed a significant correlation with severity only as measured by percent positive skin tests. There was a significant positive association for adults between increasing asthma severity and total number of allergen sensitivities per subject. There was no significant correlation for children between asthma severity and total number of allergen sensitivities per subject. Among children, no specific allergen sensitization showed a significant positive association with asthma severity. By both measures of allergen sensitization, there was a significant negative association for children between Cladosporium and asthma severity. Among our inner-city asthmatic population significant correlation between mite sensitivity and asthma severity was found only in adults. No significant association was seen with cockroach. However, outdoor allergen sensitivity (Cladosporidium, tree, ragweed, and grass) significantly correlated with asthma for adults in this inner city population.

Adult↗

TH1 and TH2 cytokine production among asthmatic children after immunotherapy.

Allergen immunotherapy results in a number of changes in clinical and immunological parameters. To study the kinetic influence of immunotherapy on cytokine production, we evaluated the ratios of Th1/Th2 for patients receiving mite-extract immunotherapy with 3-month intervals. Changes in Th1/Th2 ratio were calculated based on the intracellular cytokine and surface CD4 staining of peripheral blood mononuclear cells (PBMC). No significantly different Th1/Th2 ratios were detected after immunotherapy, although ratios were lower for asthmatic children when compared with normal controls. Cytokine production was also determined on supernatants from mite- or mitogen-activated PBMC cells. A significantly increased production of all cytokines was detected from activated PBMC from patients after immunotherapy. Thus hyposensitization with mite extract for 1 year might improve the cytokine production capacity of asthma patients' PBMC.

Allergens↗

Steroid-naive adolescents with mild intermittent allergic asthma have airway hyperresponsiveness and elevated exhaled nitric oxide levels.

Although atopic asthma symptoms often seem to disappear around puberty, subjects in this age group may experience unexpected, often severe, asthma attacks. This may be related to persistence of untreated airway hyperresponsiveness/inflammation in a life period characterized by low perceptiveness of disease-related symptoms. This study was designed to evaluate the prevalence and the severity of bronchial hyperreactivity and the exhaled nitric oxide (FENO) levels in a group of steroid-naive asthmatic adolescents. Fifty-two patients with mild-intermittent asthma were studied, ages 12 to 16, sensitized to house dust mites; 22 age-matched controls, were also studied. Asthma patients showed FEV1, FEF25-75%, and FVC values not significantly different from controls, (p > 0.05, each comparison). By contrast, although none of the control subjects showed bronchial hyperreactivity, increased airway responsiveness to methacholine (MCh) was demonstrated in the majority of the patients and found to be severe in 36.5% (MCh PD20 > or = 400 microg or accumulative dose < or = 1220 microg) and moderate in 32.7% (MCh PD20 400-1400 microg or accumulative dose 1220-4620 microg). In addition, FENO concentrations were significantly higher in asthmatics, as compared with controls (20.4 +/- 5.3 ppb and 4.4 +/- 0.7 ppb, respectively; p < 0.01) and 83% of the patients had FENO levels higher than 8.9 ppb (i.e., > 2 standard deviations of the mean in control subjects). A positive, statistically significant correlation was found between FEF25-75% values and MCh PD20 (r = 0.358; p < 0.01) or MCh accumulative dose (r = 0.355; p < 0.05). No correlations were demonstrated between MCh responsiveness and FVC or FEV1 values or FENO levels and between FENO levels and pulmonary function parameters (p > 0.05). The high incidence of bronchial hyperresponsiveness to MCh and of airway inflammation (as demonstrated by the elevated FENO levels) in adolescents with mild asthma suggests the need for more accurate evaluation and, possibly, for early intervention with antiinflammatory drugs in a significant proportion of patients in this age group.

Adolescent↗

House dust mite allergen Der p 1 elevates the release of inflammatory cytokines and expression of adhesion molecules in co-culture of human eosinophils and bronchial epithelial cells.

House dust mite (HDM) is a common allergen of allergic asthma. Eosinophils are principal effector cells of allergic inflammation and their adhesion onto human bronchial epithelial cells is mediated by a CD18-intracellular adhesion molecule-1 (ICAM-1)-dependent interaction. We studied the effects of HDM Dermatophagoides pteronyssinus (Der p) 1 on the activation of eosinophils and bronchial epithelial BEAS-2B cells. Cytokines and adhesion molecules were measured using flow cytometry. Transcription factor nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) and signaling molecule p38 mitogen-activated protein kinase (MAPK) were analyzed using electromobility shift assay and western blot, respectively. Der p 1 protein was found to potently induce the release of IL-1beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha and granulocyte macrophage colony-stimulating factor from eosinophils. Such induction was further up-regulated for IL-6 and IL-10, and down-regulated for TNF-alpha and IL-1beta in eosinophil-BEAS-2B cells co-culture. Surface expression of CD18 and ICAM-1 on eosinophils was greatly increased by Der p 1; such inductive effect on ICAM-1 was also found to be more prominent on BEAS-2B cells from the co-culture than BEAS-2B cells alone. Der p 1 was found to activate NF-kappaB and AP-1 activity in eosinophils alone and in co-culture and BEAS-2B cells in co-culture. Moreover, Der p 1 could activate p38 MAPK in BEAS-2B cells and eosinophils alone and in co-culture. Selective inhibition of NF-kappaB, AP-1 and p38 MAPK resulted in differential suppression of the Der p 1-induced cytokine release and adhesion molecule expression. As an allergen, HDM could therefore induce the release of inflammatory cytokines and expression of adhesion molecules from the interaction of human eosinophils and bronchial epithelial cells.

Antigens, Dermatophagoides↗

Sex-dependent influence of LMAN1 on allergen-induced airway hyperresponsiveness.

Allergic asthma is a chronic inflammatory disease of the airways characterized by a type 2-high adaptive immune response towards common aeroantigens such as dust mite, pollen, and animal dander. Despite the advances made toward translation of various biologics into the clinic, the limited efficacy of these therapies in certain populations, combined with the ineligibility of some patients for treatment (clinically or economically), have led to the continued need for the development of more widely effective allergic asthma therapies. Our lab previously identified lectin mannose-binding 1 (LMAN1) as a novel receptor for house dust mite (HDM) and showed that in vitro, LMAN1 downregulated inflammatory NF-&#x3ba;B signaling in DCs in response to HDM. In this follow-up work, we investigated the in vivo relevance of LMAN1 by subjecting LMAN1 knockout (KO) mice and wild type (WT) littermate controls to a model of HDM-induced allergic asthma. Surprisingly, we discovered that loss of LMAN1 led to opposing effects on airway hyperresponsiveness (AHR), which were dependent on the sex of the mice. HDM-treated female LMAN1 KO mice showed increased AHR, while HDM-treated male KO mice showed decreased AHR, compared with their WT counterparts. We further identified the features of HDM-induced asthma which may account for the gender-biased effects of LMAN1 on lung function. This work not only highlights the complexity of the loss of LMAN1 in vivo but also suggests that such sex-dependent responses should be taken into consideration when pursuing LMAN1 as a therapeutic target for treatment of allergic asthma.

Animals↗

Domestic risk factors for wheeze in urban and rural Ethiopian children.

BACKGROUND: To identify which environmental exposures underpin the emergence of asthma epidemics, we need to study epidemics as they appear, as is now happening in the Jimma region of Ethiopia. We have previously studied risk factors for asthma in adults in Jimma and have now completed a survey of young children. AIM: To establish the prevalence of asthma in urban and rural children in Jimma, and to identify locally important risk factors. DESIGN: Cross-sectional survey. METHODS: All children aged 1-5 years living in Jimma town and three surrounding rural regions were identified. Data were collected using an interviewer-led questionnaire, and consenting children had skin prick tests to house dust mite and cockroach. RESULTS: We surveyed 7155 children, of whom 3623 (51%) were female and 4285 (60%) lived in the urban area. The prevalence of wheeze in the last year was 3.4%, and was lower in the rural area (OR 0.47; 95%CI 0.34-0.66). In the urban area, the main risk factors for wheeze were a longer duration of breastfeeding, use of kerosene, and environmental tobacco smoke, while living with animals was protective. In rural children, the main risk factors were a positive skin prick test and living with animals. DISCUSSION: The prevalence of wheeze in children in the Jimma region is low, particularly in rural children. In addition to having an impact on disease prevalence, place of residence also appears to modify the impact of environmental risk factors for wheeze.

Animals↗

Systemic administration of Bordetella pertussis enhances pulmonary sensitization to house dust mite in juvenile rats.

The incidence of allergies and asthma has increased significantly in the past few decades. The objectives of this study were to establish an allergy model in weanling rats to more closely reflect the developing immune system of children, and to determine whether systemic administration of inactivated Bordetella pertussis could enhance pulmonary and systemic immune responses to locally administered house dust mite antigen (HDM). Three-week old female Brown Norway rats were sensitized with 10 micro g HDM intratracheally or intraperitoneally, with or without a simultaneous injection of 10(8) whole killed B. pertussis organisms. Ten days later, all the rats were challenged with 5 micro g HDM via the trachea. Bronchial lymph nodes and bronchoalveolar lavage fluid (BAL) were collected 0, 2, and 4 days post-challenge. Coadministration of pertussis and intratracheal instillation of HDM enhanced HDM-specific lymphoproliferative responses and increased BAL levels of total protein, lactate dehydrogenase, HDM-specific IgE and IgG antibodies, and the number of eosinophils in BAL to the same extent as had occurred in the systemically immunized animals. The data show that intratracheal instillation of HDM induces a mild allergic sensitization in juvenile rats, and that ip injection with B. pertussis enhances this sensitization process to levels seen in animals injected with antigen and B pertussis together. These results suggest that simultaneous exposure to Th2-inducing vaccine components and allergenic proteins may be a risk factor for allergic sensitization and the development of asthma in susceptible individuals.

Animals↗

Chemokine RANTES promoter polymorphisms in allergic rhinitis.

OBJECTIVES/HYPOTHESIS: RANTES is one of the most widely studied of the chemokines linked to allergic diseases. Two polymorphisms of the RANTES promoter region (-403 G/A and -28 C/G) have been found. The authors investigated whether these RANTES promoter polymorphisms were associated with allergic rhinitis. STUDY DESIGN: Case-control study. METHODS: Blood samples for genetic analysis were obtained from 151 individuals with allergic rhinitis and from 278 healthy individuals without atopic disease. Polymerase chain reaction-based assays for detection of the -403 G/A and -28 C/G polymorphisms of the RANTES gene were used for genotyping. RESULTS: The frequencies of both the RANTES -403A and -28G alleles were significantly higher in patients with allergic rhinitis than in control subjects (P <.05 for both). CONCLUSION: The study results indicated that the -403 and -28 alleles in the RANTES promoter region belong to the predictor gene set for allergic rhinitis and could be used in genomic analysis.

Adult↗

The genetics of atopic dermatitis.

PURPOSE OF REVIEW: Atopic dermatitis is typified by itchy, inflamed skin. It is increasingly common in the developed world and is a major cause of morbidity in infants and young children. Most children with the disease have high levels of immunoglobulin E and many have concomitant asthma. The cause of the disease is unknown, but it is highly heritable. Identification of the genes and genetic variants underlying atopic dermatitis may lead to new treatments and better classification of children with the disease. RECENT FINDINGS: Preliminary genetic studies have identified genes or clusters of genes that are expressed in the outermost layer of the skin to be just as important as genes that may modify the atopic process. These genes may influence other diseases, including psoriasis. Genome screens in mouse models seem to indicate involvement of some of the equivalent chromosomal regions as for human disease. SUMMARY: The findings suggest that atopy in atopic dermatitis may be a secondary process, rather than the cause of the disease. The barrier function of the skin is seen not to be merely passive. Identification of the genes underlying atopic dermatitis is feasible and likely within a few years.

Allergens↗

New diagnostic classification of allergic skin disorders.

PURPOSE OF REVIEW: To highlight the importance of one common nomenclature for allergic skin disorders. RECENT FINDINGS: Diseases are best defined on the pathophysiological mechanisms underlying the symptoms. Although the mechanisms behind what is sometimes unfortunately referred to as 'atopic eczema' or 'atopic dermatitis' have been quite well understood for 30 years the present terms used are confusing. Over the years more than 20 different names have been used. SUMMARY: Doctors, scientists and patients in the field of allergy must use one and the same terminology for allergic diseases or the result will be confusion. Diagnosis, prevention, treatment, patient advice, environmental relations, and the search for genetic markers are examples of areas that will be hampered by conflicting results. Strong efforts should be invested into broadly implementing the European Academy of Allergology and Clinical Immunology (EAACI) revised nomenclature for allergy.

Allergens↗

Human ocular mast cells.

PURPOSE OF REVIEW: Seasonal allergic conjunctivitis is a common and clinically significant type I hypersensitivity response, in which the mast cell is considered to play a pivotal role in causing the signs and symptoms, including ocular itching, hyperaemia, lacrimation and chemosis. This review focuses on the biology of the human mast cell, particularly that of the human conjunctiva. RECENT FINDINGS: The ocular mast cell not only releases histamine and eicosanoids into the extravascular environment when activated, but also synthesizes the cytokines IL-4 and TNF-alpha. The number of IL-4 messenger RNA-positive mast cells found in the conjunctival submucosa increases threefold in seasonal allergic conjunctivitis 'in season' compared with 'out of season', suggesting a role in disease. Treatment of the eye with 2% nedocromil sodium eye drops twice a day for 2 weeks reduced the tear concentrations of both histamine and prostaglandin D(2) by more than 70% at 30 min after challenge (both <0.05) illustrating an effective mast cell stabilizing effect in the conjunctiva. SUMMARY: Mast cells are a heterogeneous family of cells that are pivotal in initiating the signs and symptoms of seasonal allergic conjunctivitis. The expression of cytokines also endows them with the ability to initiate the inflammatory cascade, resulting in eosinophil accumulation associated with vernal conjunctivitis. Drug modulation of mast cell activity, although reducing the acute symptoms of active disease, also reduces the cytokine stimulus for the development of chronic allergic inflammation.

Allergens↗

Hygiene hypothesis and endotoxin: what is the evidence?

PURPOSE OF REVIEW: The hygiene hypothesis has gained strong support over the past few years. Exposure to microbial products in early life could be an underlying factor in this hypothesis, but the mechanisms that lead from a less clean and more crowded environment to a lower prevalence of asthma and allergies are not known. Among the variety of potential microbial molecules that may confer protection against the development of asthma and allergies, endotoxin, a component of Gram-negative bacteria, has incited lively as well as controversial discussions. This review focuses on recent studies on endotoxin and its role in the context of the hygiene hypothesis. RECENT FINDINGS: Results from cross-sectional surveys, prospective cohorts, and experimental studies in vitro and in rodents suggest that exposure to house dust endotoxin in early life protects from atopic sensitization and IgE-mediated diseases, but is a risk factor for wheezing in infancy. SUMMARY: Numerous studies have supported the hygiene hypothesis, but whether endotoxin by itself confers the protection or whether it acts as a marker for another environmental exposure is still unclear. The challenge for the future will be to identify those factors that confer the protection proposed by the hygiene hypothesis, and to find strategies to modify the environment without causing harm to susceptible individuals.

Allergens↗

Engineered allergens for immunotherapy.

PURPOSE OF REVIEW: Specific immunotherapy is a clinically effective causative treatment for allergic conditions. However, the reagents used for immunotherapy are crude extracts prepared from natural sources with potential life-threatening anaphylactic side effects. Molecular cloning of allergens has made it feasible to design novel therapeutic approaches for improved and safer forms of allergen-specific immunotherapy. The purpose of this review is to examine recent advances made in the last 2 years in genetic engineering of allergens for specific immunotherapy. RECENT FINDINGS: Genetic engineering of allergen with nil or low IgE reactivity but retained T-cell reactivity offers a novel therapeutic approach to improving safety and efficacy of allergen-specific immunotherapy. Hypoallergenic forms of major allergens have been produced, with reduced IgE epitopes while preserving other characteristics of the molecule to induce a protective response. SUMMARY: Hypoallergenic forms of major allergens are potential candidates for allergen-specific immunotherapy in the future. These genetically engineered hypoallergens now need to be tested in clinical trials before being widely used. Safer and more efficacious vaccines would increase patient compliance leading to extensive use of immunotherapy.

Air Pollutants↗