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PubMed2006

Early postnatal exposure to allergen and ozone leads to hyperinnervation of the pulmonary epithelium.

Airway injury in infant monkeys exposed to ozone and/or house dust mite allergen (HDMA) is associated with a loss of epithelial innervation. In this study, we evaluated for persistence/recovery of the altered epithelial innervation. Thirty-day-old rhesus monkeys were exposed to repeated episodes of HDMA and/or ozone from 1 to 6 months of age and subsequently allowed to recover for 6 months in the absence of further ozone exposure and/or minimal HDMA challenge (sufficient to maintain allergen sensitization). At 1 year of age, nerve density in intrapulmonary airways was immunohistochemically evaluated using antibodies directed against protein gene product 9.5. Hyperinnervation and irregular epithelial nerve distribution was observed in both HDMA- and ozone-exposed groups; most prominent alterations were observed in animals exposed to HDMA plus ozone. Therefore, while adaptive mechanisms exist that re-establish epithelial innervation following cessation or diminution of exposure to HDMA and/or ozone, the recovery is associated with persistent proliferative mechanisms that result in hyperinnervation of the airways.

Allergens↗
PubMed2006

The effect of home characteristics on dust antigen concentrations and loads in homes.

On-site home visits, consisting of a home inspection, dust sampling, and questionnaires were conducted in 777 homes belonging to an ongoing birth cohort study in Cincinnati, Ohio. Various home characteristics were investigated, and antigen levels (concentrations [microg/g] and loadings [microg/m(2)]; IU for cockroach allergen) in floor dust samples collected in child's primary activity room were analyzed by ELISA. Monoclonal antibodies were used for the analysis of cat, house dust mite, and cockroach allergens, and polyclonal antibodies for Alternaria and dog antigens. The relationship between the antigen levels and home characteristics was investigated through a generalized multiple regression model. More than half of the homes experienced mold/water damage. Cats and dogs were present in 19.7% and 31.1% of homes, respectively. More than 90% of homes had either carpet or area rug covering their floors. Among 777 homes, 87-92% of homes had measurable amount of Alternaria, cat, and dog allergen/antigen in house dust, whereas only 38% and 14% of homes had measurable levels of house dust mite and cockroach, respectively. Alternaria antigen level in house dust was not associated with visual mold/water damage, which was suspected to be one of the sources for this antigen in homes. Instead, the antigen level was high in samples taken in fall and in homes having dogs implicating that Alternaria antigen appears to be transported from outdoors to indoors. A high level was also measured in homes using a dehumidifier (these homes have experienced excessive humidity) and in-home venting of clothes dryer, which might be associated with microclimate affecting mold growth and spore release. The allergen/antigen level (both concentration and loading) of cat, dog and cockroach was significantly associated with the number of cats and dogs, or the appearance of cockroaches, respectively. High level of house dust mite allergen was measured in bedrooms and in homes using dehumidifier and no central forced air heating system. Having indoor plants was shown to reduce allergen levels. Carpeted floor was found to hold larger amount of antigens than non-carpeted floor. Antigen loading demonstrated more consistent and larger numbers of associations with home characteristics compared to antigen concentration. This study encompassed a wide range of home characteristics and various antigen types. Our findings provide information on home characteristics that can be used for allergen avoidance and in planning future exposure assessment studies.

Air Pollution, Indoor↗
PubMed2006

Structural and functional localization of airway effects from episodic exposure of infant monkeys to allergen and/or ozone.

Both allergen and ozone exposure increase asthma symptoms and airway responsiveness in children. Little is known about how these inhalants may differentially modify airway responsiveness in large proximal as compared to small distal airways. We evaluated whether bronchi and respiratory bronchioles from infant monkeys exposed episodically to allergen and/or ozone differentially develop intrinsic hyperresponsiveness to methacholine and whether eosinophils and/or pulmonary neuroendocrine cells play a role. Infant monkeys were exposed episodically for 5 months to: (1) filtered air, (2) aerosolized house dust mite allergen, (3) ozone 0.5 ppm, or (4) house dust mite allergen + ozone. Studying the function/structure relationship of the same lung slices, we evaluated methacholine airway responsiveness and histology of bronchi and respiratory bronchioles. In bronchi, intrinsic responsiveness was increased by allergen exposure, an effect reduced by bombesin antagonist. In respiratory bronchioles, intrinsic airway responsiveness was increased by allergen + ozone exposure. Eosinophils were increased by allergen and allergen + ozone exposure in bronchi and by allergen exposure in respiratory bronchioles. In both airways, exposure to allergen + ozone resulted in fewer tissue eosinophils than did allergen exposure alone. In bronchi, but not in respiratory bronchioles, the number of eosinophils and neuroendocrine cells correlated with airway responsiveness. We conclude that episodically exposing infant monkeys to house dust mite allergen with or without ozone increased intrinsic airway responsiveness to methacholine in bronchi differently than in respiratory bronchioles. In bronchi, eosinophils and neuroendocrine cells may play a role in the development of airway hyperresponsiveness.

Airway Resistance↗
PubMed2005

Peptide induces CD4(+)CD25+ and IL-10+ T cells and protection in airway allergy models.

The purpose of this study was to evaluate whether a single peptide containing a major T cell epitope might induce peripheral tolerance in a complex allergen model. C57BL/6 mice were sensitized by intraperitoneal injection of house dust mite extract (HDM), and exposed to antigen via trachea instillation. Der p 1 peptide was administered by i.v. before or after sensitization. Lung lavage fluids were analyzed for cellular infiltration. Respiratory exposure of sensitized mice to antigen results in airway inflammation and eosinophilia. Intravenous administration of a single peptide protected sensitized mice from these changes. Further, the emergence of antigen-specific CD25(+)CD4+ and IL-10 secreting cell populations in DO11.10 mice was demonstrated after peptide administration. Thus, intravenous delivery of a single peptide epitope is capable of inducing peripheral tolerance and protection in a complex allergy model, possibly through regulatory T cells and bystander suppression.

Adoptive Transfer↗
PubMed2004

Allergen-specific immunotherapy induces Th1 shift in dogs with atopic dermatitis.

Allergen-specific immunotherapy has been applied to canine atopic dermatitis. Despite the accumulated clinical evidence of its effect for atopic dogs, the basic immunologic mechanisms were not fully understood. In this study, the cytokine profile ex vivo in canine atopic dermatitis before and after allergen-specific immunotherapy was characterized using competitive reverse transcription-polymerase chain reaction (RT-PCR). Blood samples were collected from 10 dogs with atopic dermatitis and peripheral blood mononuclear cells were stimulated with house dust mite antigen. The levels of IFN-gamma and IL-4 mRNA were lower in atopic dogs compared with non-atopic controls. The ratio of IFN-gamma/IL-4 was low in atopic dogs indicating a cytokine profile polarized to Th2. The level of IFN-gamma after immunotherapy was significantly higher than that before (P < 0.05) whereas that of IL-4 mRNA was not changed. Consequently, the ratio of IFN-gamma/IL-4 after immunotherapy was significantly higher than that before immunotherapy (P < 0.05). These results indicate a Th2 cytokine bias is the dominant state in atopic dogs and allergen-specific immunotherapy causes a shift to wards a Th1 bias by enhancing IFN-gamma expression.

Animals↗
PubMed2005

Measurement of serum immunoglobulin E (IgE) specific for house dust mite antigens in normal cats and cats with allergic skin disease.

The purpose of this study was to determine whether cats with allergic skin disease have significant concentrations of serum Immunoglobulin E (IgE) specific for antigens derived from the house dust mites (HDM) Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus (DP). Enzyme-linked immunosorbent assays (ELISA) were developed for this purpose. Binding of serum allergen-specific IgE was detected via the use of biotinylated Fc-epsilon receptor alpha chain protein (FcvarepsilonRIalpha). Following optimisation of the assay, serum samples from 59 cats with allergic skin disease and 54 clinically normal cats were screened. Results were expressed as ELISA units per ml (EU/ml) compared to a standard curve. Serological findings were correlated with the clinical presentation of affected cats. Cats with symptoms of feline allergic skin disease were grouped as follows: self-induced alopecia without lesions (group 1), papulocrusting dermatitis (group 2), eosinophilic granuloma complex (group 3), papular/ulcerative dermatitis of head and neck/facial dermatitis (group 4), and a combination of symptoms (group 5). Control normal cats comprised the final group (group 6). The Kruskal-Wallis test was used for statistical analysis. There was no significant difference between groups for DF- and DP-specific IgE concentrations with a p-value of 0.875 and 0.705, respectively. Although the FcvarepsilonRIalpha-based ELISA was able to detect house dust mite-specific feline IgE, the presence of this allergen-specific IgE correlates poorly with the presence of clinical manifestations of allergic skin disease. The results of this study question the clinical relevance of house dust mite-specific IgE in feline allergic skin disease.

Animals↗
PubMed2003

Roxithromycin promotes lymphocyte apoptosis in Dermatophagoides-sensitive asthma patients.

A new macrolide, roxithromycin, may be an effective treatment for asthma. Lymphocyte apoptosis is impaired in patients with asthma, while spontaneous apoptosis increases during remission, and such changes may be involved in the onset and remission of mite-sensitive asthma. Lymphocyte apoptosis was evaluated by incubating cells from patients with asthma in the presence of roxithromycin. Low concentrations of roxithromycin (1-500 ng/ml) augmented the early, but not late, phase of apoptosis in Dermatophagoides farinae-stimulated peripheral blood mononuclear (PBM) cells, while high concentrations of roxithromycin (1 microg/ml; 6 microg/ml is the maximum serum level) augmented both the early and late phases of apoptosis. In both unstimulated and phytohemagglutinin-stimulated cells, roxithromycin did not significantly affect the induction of apoptosis. In cells from normal subjects, roxithromycin did not affect the induction of apoptosis. Other antibiotics, including cefazolin and ampicillin, did not cause significant induction of apoptosis. Fas ligand, but not Fas receptor, expression on D. farinae-stimulated cells was up-regulated after stimulation with 1 microg/ml roxithromycin, while Bcl-2 expression on both unstimulated and D. farinae-stimulated cells showed a decrease after the same treatment. Roxithromycin can induce apoptosis of D. farinae-activated lymphocytes in patients with D. farinae-sensitive asthma. Induction of the Fas/Fas ligand system and reduced Bcl-2 expression were involved in the promotion of apoptosis by roxithromycin treatment.

Adolescent↗
PubMed2003

Differences in airway-inflammation development by house dust mite and diesel exhaust inhalation among mouse strains.

Three mouse strains (BALB/c, ICR, and C3H/He) were injected intratracheally with house dust mites (Der f) four times at 2-week intervals during exposure to diesel exhaust (DE) or clean air for 8 weeks. Der f treatment caused eosinophilic inflammation and proliferation of goblet cells in the airways of the three strains. DE + Der f caused a further increase of eosinophils in BALB/c and ICR mice, but not in C3H/He mice. DE + Der f significantly increased interleukin (IL)-5; regulated on activation, normal T cell expressed, and presumably secreted (RANTES); eotaxin, monocyte chemotactic protein-1 (MCP-1); and macrophage-inflammatory protein-1 alpha (MIP-1 alpha) in all three strains. However, the protein of IL-5 decreased more in C3H/He mice treated with DE + Der f than in mice treated with Air + Der f. The levels of IL-5 in lung tissues corresponded to the pathological changes by Der f and/or DE treatment. The levels of MCP-1 and MIP-1 alpha in the three strains corresponded to the accumulation of lymphocytes in the airway. The adjuvant effect of DE on IgG1 production was observed in the ICR and C3H/He mice. These results suggest that the murine strain differences in the production of eosinophilic airway inflammation by DE + Der f is related to differences in local expression of IL-5, eotaxin, and IgG1 production. The enhancing effects of DE exposure may be mediated mainly by local IL-5.

Administration, Inhalation↗
PubMedDate not supplied

An immunoepidemiological approach to asthma: identification of in-vitro T-cell response patterns associated with different wheezing phenotypes in children.

BACKGROUND: Increasing evidence suggests that patterns of T-cell immunity to inhalant allergens in genetically diverse human populations are more heterogeneous than previously assumed, and that covert differences in expression patterns might underlie variations in airway disease phenotypes. We tested this proposition in a community sample of children. METHODS: We analysed data from 172 individuals who had been recruited antenatally to a longitudinal birth cohort study. Of the 194 birth cohort participants, data from the 147 probands (age range 8.6-13.5 years) who consented to blood collection were included along with data from 25 consenting siblings (mean age 11 years [range 7.4-17.4]). We ascertained clinical phenotypes related to asthma and allergy. We measured T-cell responses to allergens and mitogens, together with blood eosinophils and IgE/IgG antibodies, and assessed associations between these indices and clinical phenotypes. FINDINGS: Atopy was associated with allergen-specific T-helper (Th)2 responses dominated by interleukin 4, interleukin 5, interleukin 9, interleukin 13, whereas interleukin 10, tumour necrosis factor alpha, and interferon gamma responses were common to both atopics and non-atopics. The wheal size from skin prick with allergen was positively associated with in-vitro interleukin 5 and interferon gamma responses, and negatively associated with interleukin 10. Asthma, especially in atopics, was strongly associated with eosinophilia/interleukin 5, and bronchial hyper-responsiveness (BHR) was associated with eosinophilia plus polyclonal interferon gamma production. BHR in non-atopics was associated with elevated allergen-specific and polyclonal interleukin 10 production. INTERPRETATION: Parallel immunological and clinical profiling of children identified distinctive immune response patterns related to asthma and wheeze compared with BHR, in atopics non-atopics. Immunological hyper-responsiveness, including within the Th1 cytokine compartment, is identified as a hallmark of BHR. RELEVANCE TO PRACTICE: These findings highlight the heterogeneity of immune response patterns in asthmatic children, including those with seemingly homogeneous Th2-driven atopic asthma. Further elucidation of the covert relationships between wheezing phenotypes and underlying immunophenotypes in this age group will potentially lead to more effective treatments for what is an unexpectedly heterogeneous collection of disease subtypes.

Adolescent↗
PubMed2003

Enhanced expression of B7.2 (CD86) by percutaneous sensitization with house dust mite antigen.

House dust mite antigen is a well-known allergen in the pathogenesis of atopic dermatitis (AD), a chronic relapsing inflammatory skin disease. We evaluated the AD model mice sensitized with house dust mite antigen and observed a Th2-dominant immune response. In this experiment, BALB/c mice were sensitized percutaneously with house dust mite antigen three times with 7 days interval after skin barrier disruption. A remarkable infiltration of polymorphonuclear granulocytes and monocytes in the cutis was observed in mice treated with this antigen, high serum IgE levels and IL-4 mRNA expression in local lymph node cells was also observed. CD19(+) B cell numbers overturned to CD4(+) helper T cells. In these mice, there was significant increase of B7.2 (CD86) expression on CD19(+) B cells. These results indicate that house dust mite antigen sensitizes BALB/c mice and skews their Th1/Th2 balance toward Th2.

Administration, Cutaneous↗
PubMed2003

Chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen, Der p 1 for oral vaccination in mice.

Our previous studies indicated that intramuscular (i.m.) immunisation with full length Der p 1 cDNA induced significant humoral response to the left domain (approximately corresponding to amino acids 1-116) but not to the right domain (approximately corresponding to amino acids 117-222) of Der p 1 allergen. This study explored the use of chitosan-DNA nanoparticles for oral immunisation to induce immune responses specific to both the left and right domains of Der p 1. DNA constructs pDer p 1 (1-222) and pDer p 1 (114-222) were complexed with chitosan and delivered orally followed by an i.m. injection of pDer p 1 (1-222) 13 weeks later. Such approach has successfully primed Th1-skewed immune responses against both domains of Der p 1. This strategy could be further optimised for more efficacious gene vaccination for full length Der p 1.

Administration, Oral↗
PubMedDate not supplied

Pulmonary functions in atopic and nonatopic asthmatic children.

BACKGROUND: we examined how lung function and certain clinical and laboratory characteristics in asthmatic children were changed according to skin test positivity to aeroallergens. METHODS: a skin prick test was conducted using standardized extracts of 10 different allergens in 56 children with bronchial asthma, aged 5-15 years, in Dicle University Hospital. Lung function was measured by Microplus spirometer. RESULTS: among the 56 subjects, asthma was classified as mild in 16, moderate in 42 and severe in 3. At least one skin prick test was positive (monosensitized) in 35 subjects (62 %) and positive reactivity to two or more aeroallergens (polysensitized) was found in 17 subjects (30 %). Positive skin test reactions to aeroallergens were associated with a decrease (as percentage of the predicted decrease) in FEV1, FVC and PEF values. Significant differences were also found between prick test-positive and -negative asthmatics in duration of breastfeeding (8.5 5 months vs 15 7 months, respectively, p < 0.007), age at which cow's milk had been started (5.7 1.6 vs 10.5 5.4, p = 0.004); total serum IgE concentration (350 221 IU/ml vs 234 164 IU/ml, p = 0.02), age at onset of asthma symptoms (2.5 1.9 years vs 4.1 2.2 years) and number of asthma attacks per year (7.0 3.1 vs 5.2 3.5, p = 0.012). When one-way ANOVA and a post-Hoc test were used, asthma attacks were more frequent and severe and allergic conjunctivitis symptoms were more frequent in the polysensitized group than in the nonsensitized and monosensitized groups (p = 0.03). CONCLUSIONS: children with positive skin prick test results, especially those with combined sensitivity to dust mite, cat and dog, were at increase risk of more severe asthma.

Animals↗
PubMedDate not supplied

Influence in the quality of life of the respiratory patients by environmental control and the acaricide Frontac®.

The present prospective, open, observational study assessed the effect of the use of standard environmental control measures together with the application of an acaricide-containing aerosol of esbiol/benzyl benzoate/piperonyl butoxide/2-phenylphenol (Frontac) on several clinical and environmental parameters in patients suffering from perennial allergic rhinoconjunctivitis related to house dust mites (HDM). Fifty-five patients were enrolled and studied for one year. Both symptoms and the patients' quality of life (evaluated by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)) were assessed at several clinic visits. The amount of HDM antigen was semi-quantitatively estimated using the guanine test. We found a significant decrease (p < 0.001) in most nasal symptoms scores: sneezing, runny nose, stuffy nose and itching. The overall quality of life (QoL) score also showed a significant improvement during the study period; the mean score decrease found was 0.86 (CI 95 %, 0.54-1.17) (p < 0.001). Five of the seven domains included in the questionnaire decreased significantly: non-hayfever symptoms; practical problems; nasal symptoms; eye symptoms, and emotions. These QoL score decreases were found during the first 3 months and later remained stable at lower levels than at baseline. The content of guanine in dust samples decreased significantly from 2.17 0.75 to 1.43 0.68 (p < 0.001). No toxic adverse events were recorded. In conclusion, these results show an improvement in the quality of life and a clinical benefit of the long-term use of the new chemical acaricide tested, together with environmental measures, in the home of patients suffering from allergic respiratory pathology.

Acaricides↗
PubMedDate not supplied

Atopic dermatitis with mononuclear phagocytic activity deficiency.

Five patients with atopic dermatitis, three males and two females, aged 2 to 17 years, had positive reactions to air allergens (Dermatophagoides pteronyssinus and/or farinae). All the patients suffered from severe recurrent dermatophytosis that responded poorly to antifungal treatment. The results of immunologic evaluation by laboratory tests were normal, except for a decrease in the ingestion phase by mononuclear phagocytes. After diagnosis of immunodeficiency, ketoconazole shampoo was used prophylactically and at the very first signs of recurrence of dermatophytosis, systemic antifungal treatment was started, without concurrent use of macrolides and with monitoring of hepatic function. The fungal infections responded well to this treatment and the patients' quality of life markedly improved.

Administration, Cutaneous↗
PubMedDate not supplied

[Proliferative response of peripheral blood mononuclear cells to the recombinant allergen BtM of the Blomia tropicalis housedust mite].

Allergic diseases are triggered when individuals genetically predisposed to developing an allergy (atopy) are exposed to sensitizing allergens. These allergens are captured and processed by antigen-presenting cells (APC) which presents them to T lymphocytes. Some of these allergens have a significant influence on the development of this type of disease and cause most of the symptoms in allergic individuals around the world. They are found in the feces of house dust mites, which have diverse and varied origin in several species, for example the Blomia tropicalis (Bt) mite. In Cartagena (Colombia), this highly prevalent mite has been a central object of study by the Institute of Immunological Research of the University of Cartagena, where several of its allergens have been cloned, sequenced and expressed as recombinant allergens. Moreover, their capacity to bind to IgE and the frequency of this process has been studied. The aim of the present study was to analyze the lymphoproliferative response of peripheral blood mononuclear cells (PBMC) in healthy and allergic individuals to one of the recombinant allergens of B. tropicalis, BtM. This response was studied in PBMC from six patients with allergy to Bt (positive cutaneous test to Bt extract), using a cellular proliferation technique, with incorporation of 3H thymidine at days 3 and 6 days of culture, and at three different concentrations of BtM. Notable among the results was the high proliferation produced by cells from patient JF018 at 3 days of stimulus (41.7 IE), with the lowest concentration of protein (100 microg/mL). Moreover, in all the experiments this concentration was the cause of most of the cell proliferation. In addition, some response to control LAC012 against glutathione-S-transferase (GST) was induced. In conclusion, the results of the present study demonstrate that the recombinant allergen BtM is able to induce a cellular response in the PBMC of patients allergic to Bt. Moreover, it is able to induce a response similar to that produced by natural allergens, because its pattern of response is similar to that shown by cells stimulated with Bt extract. These results also show that a process of anergy can be produced in cells when excess antigen is present. In some individuals (both allergic and nonallergic), GST is able to cause a proliferative response, indicating its sensitizing potential in these individuals.

Allergens↗
PubMed2003

Control of environmental allergens as a therapeutic approach.

The first rule of environmental allergen control is that avoidance is appropriate for allergic patients with asthma. Although this rule is obvious to allergists, it frequently is not considered by families and physicians who are not trained in allergy. The next step in environmental avoidance is to determine the specific sensitivity of a patient. Clinically, practitioners have to address reduction of exposure to more than one allergen, and it is likely that the complexity of dealing with several treatment regimes decreases compliance.

Air Pollution, Indoor↗
PubMed2003

Biology, ecology, and prevalence of dust mites.

The house dust mites D. farinae, D. pteronyssinus, and E. maynei are sources of multiple potent allergens in the indoor environment. They are common inhabitants in homes worldwide. Many biologically significant studies have revealed how well adapted these mites are to the microhabitats in homes. Ambient RH is a key factor in determining where these mites are found. Many aspects of the biology of house dust mites are not understood. A greater understanding of the biology of dust mites may reveal new strategies for controlling dust mites and their allergens in homes.

Air Pollution, Indoor↗