Allergic Asthma (allergic + asthma)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Allergic Asthma

  • severe allergic asthma


  • Selected Abstracts


    Suppression of allergic airway inflammation in a mouse model by Der p2 recombined BCG

    IMMUNOLOGY, Issue 1pt2 2009
    Hai-Feng Ou-Yang
    Summary Allergic asthma is a chronic inflammatory disease mediated by T helper (Th)2 cell immune responses. Currently, immunotherapies based on both immune deviation and immune suppression, including the development of recombinant mycobacteria as immunoregulatory vaccines, are attractive treatment strategies for asthma. In our previous studies, we created a genetically recombinant form of bacille Calmette,Guerin (rBCG) that expressed Der p2 of house dust mites and established that it induced a shift from a Th2 response to a Th1 response in naive mice. However, it is unclear whether rBCG could suppress allergic airway inflammation in a mouse model. In this article we report that rBCG dramatically inhibited airway inflammation, eosinophilia, mucus production and mast cell degranulation in allergic mice. Analysis of interferon-, (IFN-,) and interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid (BALF) and lung tissue revealed that the suppression was associated with a shift from a Th2 response to a Th1 response. At the same time, rBCG induced a CD4+ CD25+ Foxp3+ T-cell subtype that could suppress the proliferation of Th2 effector cells in vitro in an antigen-specific manner. Moreover, suppression of CD4+ CD25+ T cells could be adoptively transferred. Thus, our results demonstrate that rBCG induces both generic and specific immune responses. The generic immune response is associated with a shift from a Th2 to a Th1 cytokine response, whereas the specific immune response against Der p2 appears to be related to the expansion of transforming growth factor-, (TGF-,)-producing CD4+ CD25+ Foxp3+ regulatory T cells. rBCG can suppress asthmatic airway inflammation through both immune deviation and immune suppression and may be a feasible, efficient immunotherapy for asthma. [source]


    Allergic asthma in patients with common variable immunodeficiency

    ALLERGY, Issue 4 2010
    R. C. Agondi
    To cite this article: Agondi RC, Barros MT, Rizzo LV, Kalil J, Giavina-Bianchi P. Allergic asthma in patients with common variable immunodeficiency. Allergy 2010; 65: 510,515. Abstract Background:, Many patients with common variable immunodeficiency (CVID) have a clinical history suggestive of allergic respiratory disease. However, in such individuals, the prevalence of asthma and the role of atopy have not been well established. The objective of this study was to evaluate pulmonary function and identify asthma in patients with CVID. We also investigated the role of IgE as a trigger of asthma in these patients. Methods:, Sixty-two patients diagnosed with CVID underwent spirometry, as well as skin prick testing and in vitro determination of serum-specific IgE levels for aeroallergens, together with bronchial provocation with histamine and allergen. Results:, The most common alteration identified through spirometry was obstructive lung disease, which was observed in 29 (47.5%) of the 62 patients evaluated. Eighteen (29.0%) of the 62 patients had a clinical history suggestive of allergic asthma. By the end of the study, asthma had been diagnosed in nine (14.5%) patients and atopy had been identified in six (9.7%). In addition, allergic asthma had been diagnosed in four patients (6.5% of the sample as a whole; 22.2% of the 18 patients with a clinical history suggestive of the diagnosis). Conclusion:, In this study, CVID patients testing negative for specific IgE antibodies and suspected of having allergic asthma presented a positive response to bronchial provocation tests with allergens. To our knowledge, this is the first such study. When CVID patients with a history suggestive of allergic asthma test negative on traditional tests, additional tests designed to identify allergic asthma might be conducted. [source]


    Allergen provocation increases TH2-cytokines and FOXP3 expression in the asthmatic lung

    ALLERGY, Issue 3 2010
    S. Thunberg
    To cite this article: Thunberg S, Gafvelin G, Nord M, Grönneberg R, Grunewald J, Eklund A, van Hage M. Allergen provocation increases TH2-cytokines and FOXP3 expression in the asthmatic lung. Allergy 2010; 65: 311,318. Abstract Background:, Allergic asthma is caused by allergen-specific IgE and T-helper cell (Th) type 2 responses towards airborne allergens. The objective of this study was to investigate local and systemic regulatory mechanisms in the early asthmatic response to bronchial allergen provocation. Methods:, Birch pollen-allergic patients with mild asthma (n = 13) and healthy nonallergic controls (n = 14) were subjected to bronchoalveolar lavage (BAL) and blood sampling. On patients BAL was performed twice: without preceding provocation (,before samples') and 24 h after bronchial provocation with birch pollen allergen. Lymphocytes in BAL and peripheral blood mononuclear cells (PBMCs) were phenotyped by multi-colour flow cytometry and cytokines measured by cytometric bead array. Proliferation and secreted cytokines were analysed in allergen-stimulated PBMCs, CD25+ depleted PBMCs and PBMCs with IL-10 neutralizing antibodies. Results:, The numbers of CD69+ and FOXP3+ lymphocytes were higher in BAL after compared with before allergen provocation in asthmatic patients. Moreover, allergen provocation increased expression of FOXP3 in CD4+CD25bright cells. The cytokine profile in BAL fluid from asthmatics revealed higher levels of IL-5, compared with the controls, and an increase in IL-5, IL-6, IL-9 and IL-10 after allergen provocation. Pollen allergen stimulated PBMC cultures from asthmatic patients produced elevated levels of IL-5 and IL-13 compared with the controls, which were not affected by depletion of CD25+ cells or IL-10 neutralization. Conclusion:, Despite an increase in CD4+CD25bright cells expressing high levels of FOXP3 in response to bronchial allergen provocation, asthmatic patients exhibit enhanced levels of Th2 cytokines in the lung, which may indicate an inability among infiltrating cells to suppress Th2 responses. [source]


    Both allergic and nonallergic asthma are associated with increased FENO levels, but only in never-smokers

    ALLERGY, Issue 1 2009
    A. Malinovschi
    Background:, Allergic asthma is consistently associated with increased FENO levels whereas divergence exists regarding the use of exhaled nitric oxide (NO) as marker of inflammation in nonallergic asthma and in asthmatic smokers. The aim of this study is to analyze the effect of having allergic or nonallergic asthma on exhaled nitric oxide levels, with special regard to smoking history. Methods:, Exhaled NO measurements were performed in 695 subjects from Turin (Italy), Gothenburg and Uppsala (both Sweden). Current asthma was defined as self-reported physician-diagnosed asthma with at least one asthma symptom or attack recorded during the last year. Allergic status was defined by using measurements of specific immunoglobulin E (IgE). Smoking history was questionnaire-assessed. Results:, Allergic asthma was associated with 91 (60, 128) % [mean (95% CI)] increase of FENO while no significant association was found for nonallergic asthma [6 (,17, 35) %] in univariate analysis, when compared to nonatopic healthy subjects. In a multivariate analysis for never-smokers, subjects with allergic asthma had 77 (27, 145) % higher FENO levels than atopic healthy subjects while subjects with nonallergic asthma had 97 (46, 166) % higher FENO levels than nonatopic healthy subjects. No significant asthma-related FENO increases were noted for ex- and current smokers in multivariate analysis. Conclusions:, Both allergic and nonallergic asthma are related to increased FENO levels, but only in never-smoking subjects. The limited value of FENO to detect subjects with asthma among ex- and current smokers suggests the predominance of a noneosinophilic inflammatory phenotype of asthma among ever-smokers. [source]


    T-cell activation in occupational asthma and rhinitis

    ALLERGY, Issue 2 2007
    E. Mamessier
    Background:, Allergic asthma and rhinitis are described as associated with a Th2 activation. However, recent works indicate that a Th1 activation can also be associated with these diseases, concomitantly to a defect in regulatory T (Treg) cell activation. Occupational asthma (OA) and occupational rhinitis (OR) are peculiar cases of these diseases in which the T-cell activation profile is largely unknown. Objective:, To characterize T-cell activation induced after a specific inhalation test (SIT) in OA and OR. Material and methods:, A total of 21 subjects with OA, 10 subjects with OR, 10 exposed nonallergic (ENA) subjects, and 14 healthy volunteers were included. The SIT with the incriminated substance was performed in patients and ENA subjects. Blood and induced sputum were obtained before and after SIT. T cells were analysed for CD69, CD25, IL-13, and IFN- , expression by flow cytometry. IL-4 and IFN- , were assayed by enzyme-linked immunosorbent assay (ELISA) in cell culture supernatants. Treg cells were identified as CD4+CD25+highCD45RO+CD69, T cells in peripheral blood. Results:, Baseline IFN- , production was decreased in OA and OR compared with controls. The SIT induced an increase in both Th1 and Th2 cells in blood and sputum from OA. In this group, the proportion of peripheral Treg cells decreased after SIT. Similar results were found in the CD8+ population. ELISA assays were concordant with flow cytometry. In OR, an attenuated activation profile was found, with an increase in the proportion of IL-13-producing T cells after SIT. By contrast, in ENA subjects, SIT induced Th2 activation, with an increase in Treg cells and a decrease in Th1 cells. Conclusions:, Our results demonstrate a gradient of T-cell activation from a tolerating profile in ENA subjects to an inflammatory profile in OA, with an intermediate stage in OR. [source]


    Pharmacology and immunological actions of a herbal medicine ASHMITM on allergic asthma

    PHYTOTHERAPY RESEARCH, Issue 7 2010
    Tengfei Zhang
    Abstract Allergic asthma is a chronic and progressive inflammatory disease for which there is no satisfactory treatment. Studies reported tolerability and efficacy of an anti-asthma herbal medicine intervention (ASHMI) for asthma patients, developed from traditional Chinese medicine. To investigate the pharmacological actions of ASHMI on early- and late-phase airway responses (EAR and LAR), Ovalbumin (OVA)-sensitized mice received 6 weeks of ASHMI treatment beginning 24,h following the first intratracheal OVA challenge. EAR were determined 30,min following the fourth challenge and LAR 48,h following the last challenge. ASHMI effects on cytokine secretion, murine tracheal ring contraction and human bronchial smooth muscle cell prostaglandin (PG) production were also determined. ASHMI abolished EAR, which was associated with significantly reduced histamine, leukotriene C4, and OVA-specific IgE levels, as well as LAR, which was associated with significantly reduced bronchoalveolar lavage fluid (BALF) eosinophils, decreased airway remodeling, and lower Th2 cytokine levels in BALF and splenocyte cultures. Furthermore, ASHMI inhibited contraction of murine tracheal rings and increased production of the potent smooth muscle relaxer PGI2. ASHMI abrogation of allergic airway responses is associated with broad effects on asthma pathological mechanisms. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Dendritic cells in asthma: a function beyond sensitization

    CLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2005
    L. S. Van Rijt
    Summary Allergic asthma is one of the most common chronic diseases in western society, characterized by variable airway obstruction, mucus hypersecretion and infiltration of the airway wall with T-helper type 2 (Th2) cells, eosinophils and mast cells. If we are to devise new causal therapies for this disease, it is important to elucidate how Th2 cells are activated and respond to intrinsically harmless allergens. Dendritic cells (DCs) are the most important antigen-presenting cells in the lung and are mainly recognized for their exceptional potential to generate a primary immune response and sensitization to aeroallergens. Much less attention has been paid to the role of DCs in established inflammation. Based on functional studies in a murine model for asthma, in this review article, we propose that DCs are essential for generating allergen-specific effector Th2 responses in ongoing inflammation in sensitized mice. A better understanding of the role of DCs in the maintenance of the inflammatory response to allergens in asthma should lead to new therapeutic approaches intervening at the top of the inflammatory cascade. [source]


    Contact dermatitis around a tracheostoma due to salbutamol sulfate and Aldecin®

    CONTACT DERMATITIS, Issue 2 2006
    Daisuke Tsuruta
    Contact dermatitis around a tracheostoma is quite rare. So far, there have been only 2 reports about this in medical literature. We, in this study, report herewith contact dermatitis in a 61-year-old Japanese man around a tracheostoma due to salbutamol sulfate and Aldecin®. The patient used inhaled Sultanol® and Aldecin® for the treatment for allergic asthma. On examination, it was found that there was lichenified, exudative erythema with pigmentation around the tracheostoma. Patch testing with 1% aq. Sultanol® and Aldecin® revealed a positive reaction. Furthermore, patch testing for salbutamol sulfate 1% pet. also showed positive reaction. Although the contact allergen of our patient has not been fully determined (beclomethasone or other ingredients), this must be the first reported case of double contact dermatitis around a tracheostoma from salbutamol and Aldecin®. [source]


    Interferon-,-dependent inhibition of late allergic airway responses and eosinophilia by CD8+,, T cells

    IMMUNOLOGY, Issue 2 2007
    Susumu Isogai
    Summary We have previously shown that CD8+,, T cells decrease late allergic airway responses, airway eosinophilia, T helper 2 cytokine expression and increase interferon-, (IFN-,) expression. We hypothesized that the effects of CD8+,, T cells were IFN-, mediated. Brown Norway rats were sensitized to ovalbumin on day 1. Cervical lymph node CD8+,, T cells from sensitized animals were treated with antisense oligodeoxynucleotide (5 µmol/l) to inhibit IFN-, synthesis or control oligodeoxynucleotide and 3·5 × 104 CD8+,, T cells were injected intraperitoneally into sensitized recipients on day 13. Rats were challenged with aerosolized ovalbumin on day 15 and lung resistance was monitored over an 8 hr period, after which bronchoalveolar lavage was performed. Control oligodeoxynucleotide treated ,, T cells decreased late airway responses and eosinophilia in bronchoalveolar lavage. There was a complete recovery of late airway responses and a partial recovery of airway eosinophilia in recipients of antisense oligodeoxynucleotide treated cells. Macrophage ingestion of eosinophils was frequent in rats administered ,,T cells but reduced in recipients of antisense oligodeoxynucleotide treated cells. These results indicate that CD8+,, T cells inhibit late airway responses and airway eosinophilia through the secretion of IFN-,. Defective or altered ,, T-cell function may account for some forms of allergic asthma. [source]


    Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell-mediated anti-tumour responses

    IMMUNOLOGY, Issue 2 2004
    Pallavur V. Sivakumar
    Summary Cytokines and their receptors represent key targets for therapeutic intervention. Ligands are being used to supplement cell numbers that become depleted as a result of disease (organ failure, infection) or subsequent disease treatments (i.e. chemotherapy). Conversely, the inhibition of target cell binding by cytokines is an established strategy for abrogating pathologic cellular activities common to many immunological diseases. Considerable effort in biomedical research is being focused on the cytokine families that play a dominant role in regulating immunity and then prioritizing each member for its therapeutic potential. Currently, the interleukin-2 (IL-2) family of cytokines is widely recognized for its central involvement in controlling lymphocyte function and is the most explored for medical utility. Collectively, these proteins (or their antagonists) are either marketed drugs or have received advanced testing for an impressive array of indications including cancer, infectious disease, transplantation, inflammation and allergic asthma. Here we review the current understanding of IL-21, the most recent member of this cytokine family to be discovered. As will be discussed, IL-21 shares many of the same attributes as its relatives in that it has broad immunoregulatory activity and can modulate both humoral and cell-mediated responses. Its ability to stimulate durable anti-tumour responses in mice defines one therapeutic indication that merits clinical development. [source]


    TAP1 gene AccI polymorphism is associated with atopic bronchial asthma

    JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2003
    Liang-Wen Hang
    Abstract Asthma is a hyperresponsive airway disease that may involve inflammation responses. A transporter associated with the antigen processing 1 gene (TAP1) is involved in antigen processing, and is therefore considered to play a role in the pathogenesis of bronchial asthma. The aim of this study was to test whether the polymorphisms of the TAP1 gene are a genetic marker for susceptibility to bronchial asthma. A normal control group comprised of 43 healthy people, and 116 patients with allergic asthma were examined in this study. The polymorphism was detected by polymerase chain reaction (PCR)-based restriction analysis. Associations between atopic bronchial asthma and TAP1 polymorphisms were evaluated. The results revealed no significant differences between normal individuals and asthmatics in regard to the TAP1 gene DpnII polymorphism (P=0.752). However, there was a significant difference between the control and asthma groups as regards the TAP1 gene AccI polymorphism (P=0.020). The odds ratio (OR) of GG homozygotes of the TAP1 AccI polymorphism was 229.8 compared with the AA homozygote group. The results show that the AccI polymorphism may be an indicator for atopic bronchial asthma. J. Clin. Lab. Anal. 17:57,60, 2003. © 2003 Wiley-Liss, Inc. [source]


    Early activation of coagulation after allergen challenge in patients with allergic asthma

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2009
    M. SCHOUTEN
    [source]


    Projections of the effects of climate change on allergic asthma: the contribution of aerobiology

    ALLERGY, Issue 9 2010
    L. Cecchi
    To cite this article: Cecchi L, D'Amato G, Ayres JG, Galan C, Forastiere F, Forsberg B, Gerritsen J, Nunes C, Behrendt H, Akdis C, Dahl R, Annesi-Maesano I. Projections of the effects of climate change on allergic asthma: the contribution of aerobiology. Allergy 2010; 65: 1073,1081. Abstract Climate change is unequivocal and represents a possible threat for patients affected by allergic conditions. It has already had an impact on living organisms, including plants and fungi with current scenarios projecting further effects by the end of the century. Over the last three decades, studies have shown changes in production, dispersion and allergen content of pollen and spores, which may be region- and species-specific. In addition, these changes may have been influenced by urban air pollutants interacting directly with pollen. Data suggest an increasing effect of aeroallergens on allergic patients over this period, which may also imply a greater likelihood of the development of an allergic respiratory disease in sensitized subjects and exacerbation of symptomatic patients. There are a number of limitations that make predictions uncertain, and further and specifically designed studies are needed to clarify current effects and future scenarios. We recommend: More stress on pollen/spore exposure in the diagnosis and treatment guidelines of respiratory and allergic diseases; collection of aerobiological data in a structured way at the European level; creation, promotion and support of multidisciplinary research teams in this area; lobbying the European Union and other funders to finance this research. [source]


    Allergic asthma in patients with common variable immunodeficiency

    ALLERGY, Issue 4 2010
    R. C. Agondi
    To cite this article: Agondi RC, Barros MT, Rizzo LV, Kalil J, Giavina-Bianchi P. Allergic asthma in patients with common variable immunodeficiency. Allergy 2010; 65: 510,515. Abstract Background:, Many patients with common variable immunodeficiency (CVID) have a clinical history suggestive of allergic respiratory disease. However, in such individuals, the prevalence of asthma and the role of atopy have not been well established. The objective of this study was to evaluate pulmonary function and identify asthma in patients with CVID. We also investigated the role of IgE as a trigger of asthma in these patients. Methods:, Sixty-two patients diagnosed with CVID underwent spirometry, as well as skin prick testing and in vitro determination of serum-specific IgE levels for aeroallergens, together with bronchial provocation with histamine and allergen. Results:, The most common alteration identified through spirometry was obstructive lung disease, which was observed in 29 (47.5%) of the 62 patients evaluated. Eighteen (29.0%) of the 62 patients had a clinical history suggestive of allergic asthma. By the end of the study, asthma had been diagnosed in nine (14.5%) patients and atopy had been identified in six (9.7%). In addition, allergic asthma had been diagnosed in four patients (6.5% of the sample as a whole; 22.2% of the 18 patients with a clinical history suggestive of the diagnosis). Conclusion:, In this study, CVID patients testing negative for specific IgE antibodies and suspected of having allergic asthma presented a positive response to bronchial provocation tests with allergens. To our knowledge, this is the first such study. When CVID patients with a history suggestive of allergic asthma test negative on traditional tests, additional tests designed to identify allergic asthma might be conducted. [source]


    After 6 years with Xolair; a 3-year withdrawal follow-up

    ALLERGY, Issue 1 2010
    A. Nopp
    Abstract Background:, This study reports the clinical and immunological state of patients 3 years after a 6-year period of Xolair treatment for severe allergic asthma. Methods:, The patient's cat allergen sensitivity, measured as CD-sens, IgE and IgE- and IgG4 antibodies, was analysed and compared with asthma severity evaluated from FEV1 and a questionnaire. Results:, Three years after treatment with Xolair was stopped, 12/18 patients reported improved or unchanged asthma compared with ongoing Xolair treatment. Most of the patients were in a stable clinical condition, 16/18 had not increased nightly asthma attacks and 14/18 little or no increase in medication. The CD-sens to cat was still significantly lower (P < 0.02) than untreated patients with allergic asthma and lower than expected from their serum IgE antibody levels. Conclusion:, Most of the patients in this study had, still 3 years after closing of 6 years Xolair treatment, a surprisingly mild and stable asthma. Interestingly, the observed, considerable, downregulation of basophil allergen sensitivity, CD-sens, most likely representing mast cell allergen sensitivity, contributed to the clinical results. [source]


    Effects of omalizumab on markers of inflammation in patients with allergic asthma

    ALLERGY, Issue 12 2009
    S. Holgate
    Asthma is a chronic inflammatory disease of the airways in which immunoglobulin E (IgE) plays a key role by activating a variety of inflammatory cells through interactions with Fc,RI and Fc,RII receptors. The role of IgE in allergic inflammation provided the rationale for developing omalizumab, a humanized monoclonal anti-IgE antibody, for patients with moderate-to-severe or severe allergic asthma. The reductions in circulating levels of IgE resulting from omalizumab treatment leads to reductions in Fc,RI expression on mast cells, basophils and dendritic cells. This combined effect results in attenuation of several markers of inflammation, including peripheral and bronchial tissue eosinophilia and levels of granulocyte macrophage colony stimulating factor, interleukin (IL)-2, IL-4, IL-5 and IL-13. By blocking IgE binding to its receptors and diminishing dendritic cell Fc,RI receptor expression, omalizumab may also reduce allergen presentation to T cells and the production of Th2 cytokines. The anti-inflammatory effects of omalizumab may, therefore, explain the reductions in asthma exacerbations and symptoms seen in clinical trials in patients with moderate-to-severe or severe, persistent, inadequately controlled allergic asthma. [source]


    The size of the disease relevant IgE antibody fraction in relation to ,total-IgE' predicts the efficacy of anti-IgE (Xolair®) treatment

    ALLERGY, Issue 10 2009
    S. G. O. Johansson
    Background:, Some patients with allergic asthma treated with anti-IgE (Xolair®) do not become symptom free. Better criteria for response assessment than allergy skin tests or IgE determination are needed. The impact of the size of the disease relevant allergen-specific IgE antibody fraction, i.e. the percentage of IgE antibody of total IgE, was evaluated in cat allergic patients treated with the recommended doses of Xolair®. Results were measured as changes in basophil allergen threshold sensitivity (CD-sens). Methods:, In a double-blind placebo controlled trial 20 patients with a high (>3.8%) and 18 with a low (<1%) percentage of IgE antibodies to cat were given Xolair® for 16 weeks and the change in CD-sens was compared to 11 and 10 patients, respectively, in each group receiving placebo. Results:, The CD-sens dropped significantly in both the high (P < 0.001) and low (P < 0.001) group on Xolair® but did not change significantly after placebo. For Xolair® -treated patients, at the end of the trial there was a highly significant (P < 0.001) difference in CD-sens between the high group, where no patients, and the low group, where 13/18 patients, had become negative. Conclusions:, The currently recommended doses of Xolair® very efficiently eliminate IgE antibodies if the IgE antibody fraction is <1% of total IgE but has not enough effect on allergen sensitivity if the fraction is >3,4%. Further studies will show if increased doses of Xolair® would help also these patients, who seem to represent about 1/3 of the patient population. [source]


    Blockade of CCR4 in a humanized model of asthma reveals a critical role for DC-derived CCL17 and CCL22 in attracting Th2 cells and inducing airway inflammation

    ALLERGY, Issue 7 2009
    F. Perros
    Background:, As Th2 type lymphocytes orchestrate the cardinal features of allergic asthma, inhibiting their recruitment to the lungs could be of therapeutic benefit. Although human Th2 cells express the CCR4 chemokine receptor and increased production of CCR4 ligands has been found in asthmatic airways, studies in animals have reached contradictory conclusions on whether blocking this pathway would be beneficial. Objective:, As a lack of efficacy might be due to differences between mouse and man, we readdressed this question using a humanized severe combined immunodeficiency model of asthma. Methods:, Mice received peripheral blood mononuclear cells from house dust mite (HDM) allergic asthmatic patients and then underwent bronchial challenge with HDM. Results:, This resulted in marked allergic inflammation and bronchial hyper-reactivity. Administration of CCR4 blocking antibody abolished the airway eosinophilia, goblet cell hyperplasia, IgE synthesis and bronchial hyperreactivity. In this chimeric system, human CD11c+ dendritic cells (DCs) were the predominant source of CCR4 ligands, suggesting that DC-derived chemokines attract Th2 cells. In separate experiments using human DCs, in vitro exposure to HDM of DCs from HDM allergic patients but not healthy controls caused CCL17 and CCL22 release that resulted in chemoattraction of polarized human Th2 cells in a CCR4-dependent way. Conclusions:, Taken together, our data provide proof of concept that CCR4 blockade inhibits the salient features of asthma and justify further clinical development of CCR4 antagonists for this disease. [source]


    Both allergic and nonallergic asthma are associated with increased FENO levels, but only in never-smokers

    ALLERGY, Issue 1 2009
    A. Malinovschi
    Background:, Allergic asthma is consistently associated with increased FENO levels whereas divergence exists regarding the use of exhaled nitric oxide (NO) as marker of inflammation in nonallergic asthma and in asthmatic smokers. The aim of this study is to analyze the effect of having allergic or nonallergic asthma on exhaled nitric oxide levels, with special regard to smoking history. Methods:, Exhaled NO measurements were performed in 695 subjects from Turin (Italy), Gothenburg and Uppsala (both Sweden). Current asthma was defined as self-reported physician-diagnosed asthma with at least one asthma symptom or attack recorded during the last year. Allergic status was defined by using measurements of specific immunoglobulin E (IgE). Smoking history was questionnaire-assessed. Results:, Allergic asthma was associated with 91 (60, 128) % [mean (95% CI)] increase of FENO while no significant association was found for nonallergic asthma [6 (,17, 35) %] in univariate analysis, when compared to nonatopic healthy subjects. In a multivariate analysis for never-smokers, subjects with allergic asthma had 77 (27, 145) % higher FENO levels than atopic healthy subjects while subjects with nonallergic asthma had 97 (46, 166) % higher FENO levels than nonatopic healthy subjects. No significant asthma-related FENO increases were noted for ex- and current smokers in multivariate analysis. Conclusions:, Both allergic and nonallergic asthma are related to increased FENO levels, but only in never-smoking subjects. The limited value of FENO to detect subjects with asthma among ex- and current smokers suggests the predominance of a noneosinophilic inflammatory phenotype of asthma among ever-smokers. [source]


    Omalizumab therapy: patients who achieve greatest benefit for their asthma experience greatest benefit for rhinitis

    ALLERGY, Issue 1 2009
    M. Humbert
    Background:, Asthma and rhinitis are considered components of a single IgE-mediated inflammatory disorder. However, despite being shown to often co-exist, they are typically treated as independent conditions. Omalizumab, an anti-IgE antibody, has proven effective in the treatment of both asthma and rhinitis. Aims:, To examine whether a response to omalizumab in terms of asthma control predicts a higher likelihood of rhinitis response in patients with concomitant allergic asthma and rhinitis. Methods:, This post hoc analysis was conducted on efficacy results from the SOLAR trial in which patients with moderate-to-severe asthma and rhinitis were randomized to receive omalizumab or placebo for 28 weeks. Patients were classified as asthma responders based on the physician's overall assessment (complete control or marked improvement in a five-level evaluation). Rhinitis responders were identified using the Rhinitis Quality of Life Questionnaire (RQLQ) questionnaire (, 1.0 point improvement in overall score). Results:, Data were available for 207 omalizumab-treated patients and 192 placebo patients. According to the physicians overall assessment, 123 (59.4%) of omalizumab-treated patients were asthma responders, with the likelihood of a rhinitis response significantly (P < 0.001) greater in these patients than in the placebo group. The odds ratio for rhinitis response in omalizumab-treated asthma responders vs nonresponders was 3.56 (95% CI: 1.94,6.54). Conclusions:, A response in terms of asthma following omalizumab therapy is associated with a significantly increased probability of improvement in rhinitis. [source]


    Nerve growth factor localization in the nasal mucosa of patients with persistent allergic rhinitis

    ALLERGY, Issue 1 2009
    M. Bresciani
    Background and objectives:, Nerve growth factor (NGF) and NGF receptors have been shown to be expressed by structural and infiltrating inflammatory cells in the human allergic bronchial mucosa and conjunctiva. In the nose, a positive immunostaining for NGF was recently reported in biopsies of subjects undergoing surgery for refractory nasal obstruction. This study was aimed at studying by immunohistochemistry NGF expression and localization in the nasal mucosa from subjects with moderate/severe persistent allergic rhinitis and natural allergen exposure. Methods:, Immunostaining for NGF, tryptase and eosinophil cationic protein was performed in human nasal turbinate sections of 25 patients affected by persistent allergic rhinitis and sensitization to Dermatophagoides pteronyssinus. Results:, NGF was consistently expressed in the epithelium and in the submucosa of allergic rhinitic subjects, preferentially localized in eosinophils and mast cells. A strong NGF immunostaining was found in mucous cells of the epithelial lining and in the submucosal glands. Conclusions:, As previously shown for allergic asthma and allergic conjunctivitis, NGF is also detectable in the nasal mucosa of patients with persistent allergic rhinitis. The preferential NGF localization in mucous cells of the epithelial lining and in the submucosal glands suggests a possible role for NGF in modulating secretion in allergic rhinitis and possibly other allergic diseases. [source]


    The functional insufficiency of human CD4+CD25high T-regulatory cells in allergic asthma is subjected to TNF-, modulation

    ALLERGY, Issue 1 2008
    Y.-L. Lin
    Background:, Natural CD4+CD25highFoxp3+ regulatory T (nTreg) cells are important in maintaining immunologic tolerance, but their role in the pathogenesis of allergic asthma is unclear. We studied the function of nTreg cells in allergic asthmatic children and assessed the factors which may relate to the functional insufficiency of nTreg cells. Methods:, The percentage of CD4+CD25high Treg cells, the expression of Foxp3, and the cell-induced suppressive activity of nTreg cells isolated from nonatopic controls, allergic asthmatics, and allergen-specific immunotherapy (AIT)-treated asthmatic patients were studied. Results:, Although the percentage of nTreg in peripheral blood mononuclear cells was increased, the expression of Foxp3 and its cell-induced suppressive activity were significantly lower in Dermatophagoides pteronyssinus (Der p)-sensitive asthmatic children when compared to nonatopic controls. In contrast, the expression of Foxp3 and the functional activity of nTreg cells were reversed in allergic asthmatics who received AIT. The addition of recombinant tumor necrosis factor (TNF)-, directly downregulated Foxp3 expression and abrogated the cell-induced suppressive function of Treg cells. The anti-TNF-, reagent, etanercept, restored the functional activity and Foxp3 expression of CD4+CD25high Treg derived from allergic asthmatics. Conclusions:, The functional insufficiency of nTreg cells in patients with allergic asthma may be related to the enhanced production of TNF-, and its effect on the Foxp3 expression. These results may explain, in part, the effectiveness of anti-TNF-, therapy in the treatment of allergic asthma. [source]


    Chemokine receptor antagonists: a novel therapeutic approach in allergic diseases

    ALLERGY, Issue 12 2004
    J. Elsner
    The aim of this review is to give an overview of the role of chemokines, particularly ligands of the CC chemokine receptor CCR3, in allergic diseases and to show the new concept in the treatment of allergies using chemokine receptor antagonists. Allergic diseases such as allergic asthma, allergic rhinitis and atopic dermatitis are characterized by a complex interaction of different cell types and mediators. Among this, Th2 cells, mast cells, basophils and eosinophils are found in the inflamed tissue due to the attraction of chemokines. Of all the known chemokine receptors, the chemokine receptor CCR3 seems to play the major role in allergic diseases which is supported by the detection of this receptor on the cell types mentioned above. Therefore, academic and industrial research focus on compounds to block this receptor. To date, certain chemokine receptor antagonists derived from peptides and small molecules exist to block the chemokine receptor CCR3. However, the in vivo data about these compounds and the mechanisms of receptor interaction are poorly understood, as yet. For the development of additional chemokine receptor antagonists, more details about the interaction between the ligands and their receptors are required. Therefore, additional studies will lead to the identification of novel CCR3 chemokine receptor antagonists, which can be therapeutically used in allergic asthma, allergic rhinitis, and atopic dermatitis. [source]


    Neurogenic mechanisms in bronchial inflammatory diseases

    ALLERGY, Issue 11 2004
    D. A. Groneberg
    Neurogenic inflammation encompasses the release of neuropeptides from airway nerves leading to inflammatory effects. This neurogenic inflammatory response of the airways can be initiated by exogenous irritants such as cigarette smoke or gases and is characterized by a bi-directional linkage between airway nerves and airway inflammation. The event of neurogenic inflammation may participate in the development and progression of chronic inflammatory airway diseases such as allergic asthma or chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying neurogenic inflammation are orchestrated by a large number of neuropeptides including tachykinins such as substance P and neurokinin A, or calcitonin gene-related peptide. Also, other biologically active peptides such as neuropeptide tyrosine, vasoactive intestinal polypeptide or endogenous opioids may modulate the inflammatory response and recently, novel tachykinins such as virokinin and hemokinins were identified. Whereas the different aspects of neurogenic inflammation have been studied in detail in laboratory animal models, only little is known about the role of airway neurogenic inflammation in human diseases. However, different functional properties of airway nerves may be used as targets for future therapeutic strategies and recent clinical data indicates that novel dual receptor antagonists may be relevant new drugs for bronchial asthma or COPD. [source]


    Cross-reactivity among fungal allergens: a clinically relevant phenomenon?

    MYCOSES, Issue 2 2009
    Reto Crameri
    Summary Atopic patients suffering from allergic asthma, allergic rhinitis, or atopic eczema often have detectable levels of serum IgE antibodies to fungi. Although the association between fungal sensitisation and different forms of allergic diseases, including allergic asthma and life-threatening allergic bronchopulmonary aspergillosis, is well established, the clinical relevance of cross-reactivity among different fungal species remains largely unknown. Recent progress in molecular cloning of fungal allergens and the availability of more than 40 completely sequenced fungal genomes facilitates characterisation, cloning, and production of highly pure recombinant allergens, identification of homologous and orthologous allergens widespread among the fungal kingdom, in silico prediction, and experimental in vitro and in vivo verification of cross-reactivity between homologous pan-allergens. These studies indicate that cross-reactivity is an important component of fungal sensitisation. [source]


    Apoptosis, airway inflammation and anti-asthma therapy: From immunobiology to clinical application

    PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 4 2008
    Fabrizio Spinozzi
    T lymphocyte apoptosis is essential for maintaining immune system homeostasis. Experimental evidence suggests apoptosis control mechanisms may be impaired in inflammatory conditions, particularly airway Th2-type allergic diseases. This review briefly examines the mucosal immune system homeostasis and common apoptotic pathways and discusses impaired apoptosis, allergy, airway inflammation, remodelling and fibrosis. Finally, the paper presents an update on pharmacological targeting of apoptosis to control airway inflammation in patients with allergic asthma. [source]


    Exhaled nitric oxide in asthmatic children and adolescents after nasal allergen challenge

    PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2005
    Christophe Pedroletti
    Epidemiological data suggest a comorbidity link between nasal and bronchial allergic disease. Exhaled nitric oxide (FENO) is a sensitive marker of bronchial inflammation and increases after bronchial allergen provocation. We studied FENO in 19 children and adolescents with allergic asthma and 10 controls before and 2, 6 and 24 h after a single nasal allergen challenge. The correlation between FENO and other markers of allergic inflammation, such as eosinophils in blood and eosinophil cationic protein (ECP) in serum and nasal lavage was also assessed. FENO remained unchanged 24 h post-challenge in both steroid and steroid-naïve patients. At 6 h post-challenge, FENO decreased in both asthmatics and controls. The asthmatic subjects showed a positive correlation between FENO and blood eosinophils before (r = 0.71, p = 0.001) and after the challenge, and between FENO and ECP in nasal lavage (r = 0.62, p = 0.02) 2 h after the challenge. Mean ECP in nasal lavage increased post-challenge but not significantly. We conclude that a single nasal allergen challenge does not augment bronchial inflammation although FENO, is related to blood eosinophil count and to the nasal inflammatory response. Our data do not support the theory of a direct transmission of the nasal inflammation to the lower airways. [source]


    A whisper from the silent lung zone

    PEDIATRIC PULMONOLOGY, Issue 8 2009
    Fatma Aljassim MD
    Abstract Multiple breath inert gas washout (MBW) is now regarded as "an insightful, sound, and useful tool to explore the lung and its response to injury in all of its compartments". We describe the important finding of pronounced intra-acinar airways response to indirect challenge testing, detected using MBW but missed by spirometry, in an adolescent with evidence of airway inflammation, and a background of severe respiratory syncytial virus (RSV) infection as an infant. These tests were performed as part of an 18-year follow up of a cohort with severe RSV infection (requiring hospitalization) in the first year of life, and has previously reported significantly higher rates of symptoms of allergic asthma and other features of atopic disease at 13 years in comparison to age matched controls. Small airway dysfunction and ventilation inhomogeneity have emerged as important features of early respiratory disease processes, and this case report provides further evidence supporting its important role in reactive airways disease. Pediatr Pulmonol. 2009; 44:829,832. © 2009 Wiley-Liss, Inc. [source]


    Pharmacology and immunological actions of a herbal medicine ASHMITM on allergic asthma

    PHYTOTHERAPY RESEARCH, Issue 7 2010
    Tengfei Zhang
    Abstract Allergic asthma is a chronic and progressive inflammatory disease for which there is no satisfactory treatment. Studies reported tolerability and efficacy of an anti-asthma herbal medicine intervention (ASHMI) for asthma patients, developed from traditional Chinese medicine. To investigate the pharmacological actions of ASHMI on early- and late-phase airway responses (EAR and LAR), Ovalbumin (OVA)-sensitized mice received 6 weeks of ASHMI treatment beginning 24,h following the first intratracheal OVA challenge. EAR were determined 30,min following the fourth challenge and LAR 48,h following the last challenge. ASHMI effects on cytokine secretion, murine tracheal ring contraction and human bronchial smooth muscle cell prostaglandin (PG) production were also determined. ASHMI abolished EAR, which was associated with significantly reduced histamine, leukotriene C4, and OVA-specific IgE levels, as well as LAR, which was associated with significantly reduced bronchoalveolar lavage fluid (BALF) eosinophils, decreased airway remodeling, and lower Th2 cytokine levels in BALF and splenocyte cultures. Furthermore, ASHMI inhibited contraction of murine tracheal rings and increased production of the potent smooth muscle relaxer PGI2. ASHMI abrogation of allergic airway responses is associated with broad effects on asthma pathological mechanisms. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Clinical evaluation of the Chinese herbal medicine formula STA-1 in the treatment of allergic asthma

    PHYTOTHERAPY RESEARCH, Issue 5 2006
    Tung-Ti Chang
    Abstract Although some formulae of traditional Chinese medicines (TCM) have been used for antiasthma treatment, few of them have had sufficient discussion on their efficacy, safety and mechanisms. In this study, the availability of the TCM formula STA-1 for the treatment of allergic asthma was investigated by conducting a double-blind, placebo-controlled and randomized trial. One hundred and twenty patients between the ages of 5 to 20 years with mild-to-moderate asthma were included. These patients were treated with either STA-1 or placebo in a dose of 80 g/kg/day and were administered twice daily for 6 months. The main outcome measures were a daily diary record of symptoms, supplementary bronchodilator and glucocorticoid treatment, changes of pulmonary function (forced expiratory volume in 1 s), changes of total and Dermatophagoides pteronyssinus (DP)-specific IgE and side effects. The results showed a statistically significant reduction of symptom scores, systemic steroid dose, total IgE and specific IgE in the STA-1 group. Furthermore, STA-1 also improved the pulmonary lung function FEV1 compared with the placebo group and only minimal side effects were shown. These results suggested that STA-1 is available for the treatment of mild-to-moderate chronic asthma. Copyright © 2006 John Wiley & Sons, Ltd. [source]