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Sample records for allergic asthmatic airway

  1. Pentraxin 3 (PTX3 expression in allergic asthmatic airways: role in airway smooth muscle migration and chemokine production.

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    Jingbo Zhang

    Full Text Available Pentraxin 3 (PTX3 is a soluble pattern recognition receptor with non-redundant functions in inflammation and innate immunity. PTX3 is produced by immune and structural cells. However, very little is known about the expression of PTX3 and its role in allergic asthma.We sought to determine the PTX3 expression in asthmatic airways and its function in human airway smooth muscle cells (HASMC. In vivo PTX3 expression in bronchial biopsies of mild, moderate and severe asthmatics was analyzed by immunohistochemistry. PTX3 mRNA and protein were measured by real-time RT-PCR and ELISA, respectively. Proliferation and migration were examined using (3H-thymidine incorporation, cell count and Boyden chamber assays.PTX3 immunoreactivity was increased in bronchial tissues of allergic asthmatics compared to healthy controls, and mainly localized in the smooth muscle bundle. PTX3 protein was expressed constitutively by HASMC and was significantly up-regulated by TNF, and IL-1β but not by Th2 (IL-4, IL-9, IL-13, Th1 (IFN-γ, or Th-17 (IL-17 cytokines. In vitro, HASMC released significantly higher levels of PTX3 at the baseline and upon TNF stimulation compared to airway epithelial cells (EC. Moreover, PTX3 induced CCL11/eotaxin-1 release whilst inhibited the fibroblast growth factor-2 (FGF-2-driven HASMC chemotactic activity.Our data provide the first evidence that PTX3 expression is increased in asthmatic airways. HASMC can both produce and respond to PTX3. PTX3 is a potent inhibitor of HASMC migration induced by FGF-2 and can upregulate CCL11/eotaxin-1 release. These results raise the possibility that PTX3 may play a dual role in allergic asthma.

  2. Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice.

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    Zhang, Ning; Deng, Changwen; Zhang, Xingxing; Zhang, Jingxi; Bai, Chong

    2018-01-01

    Asthma is a worldwide common chronic airway disease that cannot be cured and results in the huge burden in public health. Oxidative stress was considered an important mechanism in the pathogenesis of asthma. Hydrogen gas been demonstrated to function as a novel antioxidant and exert therapeutic antioxidant activity in a number of diseases and the function of this nontoxic gas in asthma was unclear. The purpose of the study aims to examine the effect of inhalation hydrogen gas on the pathophysiology of a mouse model of asthma. A murine model of ovalbumin (OVA)-induced allergic airway inflammation was used in this study. Briefly, Mice were sensitized to ovalbumin and received inhalation of 67% high concentration of hydrogen gas for 60 min once a day for 7 consecutive days after OVA or PBS challenge respectively. Lung function was assessed in the apparatus with 4 channels of biological signal system. Morphology and goblet cell hyperplasia were stained by H/E and Periodic acid-Schiff staining. Cytologic classification in the bronchial alveolar lavage fluid (BALF) was analyzed by Wright Giemsa staining. Serum, BALF and lung tissue were collected for biochemical assay. One-way analysis of variance (ANOVA) was used to determine statistical significance between groups. Multiple comparisons were made by Bonferroni's Multiple Comparison Test by using GraphPad Prism 5 software. Inhalation of hydrogen gas abrogated ovalbumin-induced the increase in lung resistance. Concomitantly, the asthmatic mice showed severe inflammatory infiltration and goblet cell hyperplasia which were reversed by hydrogen gas inhalation. Hydrogen gas inhalation reduced significantly the number of total cells, eosinophils and lymphocytes in BALF. Increased level of IL-4, IL-13, TNF-α and CXCL15 in the BALF and IL-4 in the serum were decreased significantly after inhalation. Hydrogen gas inhalation markedly upregulated the activity of decreased superoxide dismutase and significantly attenuated the

  3. Uncoordinated production of Laminin-5 chains in airways epithelium of allergic asthmatics

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    Virtanen Ismo

    2005-09-01

    Full Text Available Abstract Background Laminins are a group of proteins largely responsible for the anchorage of cells to basement membranes. We hypothesized that altered Laminin chain production in the bronchial mucosa might explain the phenomenon of epithelial cell shedding in asthma. The aim was to characterize the presence of Laminin chains in the SEBM and epithelium in allergic and non-allergic asthmatics. Patients and methods Biopsies were taken from the bronchi of 11 patients with allergic and 9 patients with non-allergic asthma and from 7 controls and stained with antibodies against the Laminin (ln chains alpha1-alpha5, beta1-beta2 and gamma1-gamma2. Results Lns-2,-5 and -10 were the main Laminins of SEBM. The layer of ln-10 was thicker in the two asthmatic groups while an increased thickness of lns-2 and -5 was only seen in allergic asthmatics. The ln gamma2-chain, which is only found in ln 5, was exclusively expressed in epithelial cells in association with epithelial injury and in the columnar epithelium of allergic asthmatics. Conclusion The uncoordinated production of chains of ln-5 in allergic asthma could have a bearing on the poor epithelial cell anchorage in these patients.

  4. Targeted inhibition of Six1 attenuates allergic airway inflammation and remodeling in asthmatic mice.

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    Yang, Zhao-Chuan; Yi, Ming-Ji; Shan, Yan-Chun; Wang, Chong; Ran, Ni; Jin, Li-Ying; Fu, Peng; Feng, Xue-Ying; Xu, Lei; Qu, Zheng-Hai

    2016-12-01

    Asthma is an inflammatory disease of the airways, characterized by lung eosinophilia, mucus hypersecretion by goblet cells and airway hyperresponsiveness to inhaled allergens. The purpose of this study was to evaluate the effects of Six1 on airway inflammation and remodeling and the underlying mechanisms in a murine model of chronic asthma. Female BALB/c mice were randomly divided into four groups: phosphate-buffered saline control, ovalbumin (OVA)-induced asthma group, OVA+siNC and OVA+siSix1. In this mice model, Six1 expression level was significantly elevated in OVA-induced asthma of mice. Additionally, downregulation of Six1 dramatically decreased OVA-challenged inflammation, infiltration, and mucus production. Moreover, silencing of Six1 resulted in decreased levels of immunoglobulin E and inflammatory mediators and reduced inflammatory cell accumulation, as well as inhibiting the expression of important mediators including matrix metalloproteinase MMP-2 and MMP-9, which is related to airway remodeling. Further analysis indicated that silencing of Six1 can significantly inhibit NF-kB pathway activation in the lungs. .In conclusion, these findings indicated that the downregulation of Six1 effectively inhibited airway inflammation and reversed airway remodeling, which suggest that Six1 represents a promising therapeutic strategy for human allergic asthma. Copyright © 2016. Published by Elsevier Masson SAS.

  5. Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function

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    Bunn Janice Y

    2010-03-01

    Full Text Available Abstract Background Asthma is a chronic inflammatory disease of the airway that is characterized by a Th2-type of immune response with increasing evidence for involvement of Th17 cells. The role of IL-6 in promoting effector T cell subsets suggest that IL-6 may play a functional role in asthma. Classically IL-6 has been viewed as an inflammatory marker, along with TNFα and IL-1β, rather than as regulatory cytokine. Objective To investigate the potential relationship between IL-6 and other proinflammatory cytokines, Th2/Th17 cytokines and lung function in allergic asthma, and thus evaluate the potential role of IL-6 in this disease. Methods Cytokine levels in induced sputum and lung function were measured in 16 healthy control and 18 mild-moderate allergic asthmatic subjects. Results The levels of the proinflammatory biomarkers TNFα and IL-1β were not different between the control and asthmatic group. In contrast, IL-6 levels were specifically elevated in asthmatic subjects compared with healthy controls (p S = 0.53, p Conclusions In mild-moderate asthma, IL-6 dissociates from other proinflammatory biomarkers, but correlates with IL-13 levels. Furthermore, IL-6 may contribute to impaired lung function in allergic asthma.

  6. Chitotriosidase inhibits allergic asthmatic airways via regulation of TGF-β expression and Foxp3+ Treg cells.

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    Hong, J Y; Kim, M; Sol, I S; Kim, K W; Lee, C-M; Elias, J A; Sohn, M H; Lee, C G

    2018-02-08

    Chitotriosidase (chitinase 1, Chit1), a major true chitinase in humans, is induced in childhood asthma and has been implicated in the pathogenesis of a variety of inflammatory and tissue remodeling responses. However, the role and the mechanisms that underlie these contributions to the diseases have not been defined. We hypothesized that Chit1 plays a significant role in the pathogenesis of allergic asthma. Wild-type and Chit1-deficient mice and cells in culture were used to define the roles of Chit1 in models of allergic adaptive Th2 inflammation. In addition, the levels of sputum Chit1 were evaluated in pediatric asthma patients and compared to control. The levels of sputum Chit1 were significantly increased in the patients with childhood asthma. Mice with Chit1 null mutation demonstrated enhanced allergic Th2 inflammatory and cytokine and IgE responses to OVA or house dust mite allergen sensitization and challenge. However, the expression levels of TGF-β1 were significantly decreased with a diminished number of Foxp3 + regulatory T cells (Treg) in the lungs of Chit1 -/- mice compared to WT controls. In vitro, the absence of Chit1 significantly reduced TGF-β-stimulated conversion of CD4 + CD25 - naïve T cells to CD4 + Foxp3 + Treg cells, suggesting Chit1 is required for optimal effect of TGF-β1 in Treg cell differentiation. Chit1 plays a protective role in the pathogenesis of allergic inflammation and asthmatic airway responses via regulation of TGF-β expression and Foxp3 + Treg cells. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  7. Relationship between airway pathophysiology and airway inflammation in older asthmatics

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    Porsbjerg, Celeste M; Gibson, Peter G; Pretto, Jeffrey J

    2013-01-01

    , neutrophil airway inflammation increases airway closure during bronchoconstriction, while eosinophil airway inflammation increases airway hyperresponsiveness (AHR). METHODS: Asthmatic subjects (n = 26), aged ≥55 years (68% female), were studied, and AHR to 4.5% saline challenge was measured by the response...... or eNO. CONCLUSIONS: In older patients with asthma, airway inflammatory cells are linked to abnormal airway physiology. Eosinophilic airway inflammation is associated with AHR while neutrophilic inflammation may be an important determinant of airflow limitation at rest and airway closure during......BACKGROUND AND OBJECTIVE: Asthma-related morbidity is greater in older compared with younger asthmatics. Airway closure is also greater in older asthmatics, an observation that may be explained by differences in airway inflammation. We hypothesized that in older adult patients with asthma...

  8. Allergic Fungal Airway Disease.

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    Rick, E M; Woolnough, K; Pashley, C H; Wardlaw, A J

    Fungi are ubiquitous and form their own kingdom. Up to 80 genera of fungi have been linked to type I allergic disease, and yet, commercial reagents to test for sensitization are available for relatively few species. In terms of asthma, it is important to distinguish between species unable to grow at body temperature and those that can (thermotolerant) and thereby have the potential to colonize the respiratory tract. The former, which include the commonly studied Alternaria and Cladosporium genera, can act as aeroallergens whose clinical effects are predictably related to exposure levels. In contrast, thermotolerant species, which include fungi from the Candida, Aspergillus, and Penicillium genera, can cause a persistent allergenic stimulus independent of their airborne concentrations. Moreover, their ability to germinate in the airways provides a more diverse allergenic stimulus, and may result in noninvasive infection, which enhances inflammation. The close association between IgE sensitization to thermotolerant filamentous fungi and fixed airflow obstruction, bronchiectasis, and lung fibrosis suggests a much more tissue-damaging process than that seen with aeroallergens. This review provides an overview of fungal allergens and the patterns of clinical disease associated with exposure. It clarifies the various terminologies associated with fungal allergy in asthma and makes the case for a new term (allergic fungal airway disease) to include all people with asthma at risk of developing lung damage as a result of their fungal allergy. Lastly, it discusses the management of fungirelated asthma.

  9. Functional phenotype of airway myocytes from asthmatic airways

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    Wright, David B.; Trian, Thomas; Siddiqui, Sana; Pascoe, Chris D.; Ojo, Oluwaseun O.; Johnson, Jill R.; Dekkers, Bart G. J.; Dakshinamurti, Shyamala; Bagchi, Rushita; Burgess, Janette K.; Kanabar, Varsha

    In asthma, the airway smooth muscle (ASM) cell plays a central role in disease pathogenesis through cellular changes which may impact on its microenvironment and alter ASM response and function. The answer to the long debated question of what makes a 'healthy' ASM cell become 'asthmatic' still

  10. Tripterygium polyglycosid attenuates the established airway inflammation in asthmatic mice.

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    Chen, Chang-Gui; Wang, Hui-Ying; Dai, Yu; Wang, Jiao-Li; Xu, Wei-Hua

    2013-04-01

    To investigate the effect of Tripterygium polyglycosid on establishing airway eosinophil infiltration and related airway hyperresponsiveness of asthmatic mice. A mature murine asthmatic model was made with ovabulmin sensitized and challenged C57BL/6 mice. Forty mice were divided into four groups with 10 mice in each group: mice sensitized and challenged with saline (WS group), mice sensitized and challenged with ovalbumin (WO group), mice sensitized and challenged with ovalbumin and treated with Tripterygium polyglycosid (TP group) and Dexamethasone (DXM group). The mice were intraperitoneally injected with 20 μg chicken ovabulmin emulsified in injected alum on days 0 and 14, then were challenged with an aerosol generated from 1% ovabulmin on days 24, 25 and 26. Tripterygium polyglycosid was injected intraperitoneally at 50 mg/kg on days 25, 26 and 27 after ovabulmin challenge. Dexamethasone was administrated to mice at 2 mg/kg on day 21, 23 before ovabulmin challenge. The airway hyperresponsiveness, mucus production, eosinophils in parabronchial area and bronchoalveolar lavage fluid and the level of interleukin-5, granulo-macrophage clone stimulating factor in bronchoalveolar lavage fluid were measured as indexes of inflammation. Tripterygium polyglycosid treatment after ovabulmin challenge completely inhibited eosinophil infiltration in bronchoalveolar lavage fluid [(0.63 ± 0.34)× 10(4) vs. (75.0 ± 14.8)× 10(4), Pbronchoalveolar lavage fluid (28.8 ± 2.8 pg/mL vs. 7.5 ± 3.5 pg/mL, Pbronchoalveolar lavage fluid didn't change with drugs intervention. The administration of Tripterygium polyglycosid could inhibit the established airway inflammation and reduce the airway hyperresponsiveness of allergic asthmatic mice. It provides a possible alternative therapeutic for asthma.

  11. Effect of inhaled dust mite allergen on regional particle deposition and mucociliary clearance in allergic asthmatics**

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    Background Acute exacerbations in allergic asthmatics may lead to impaired ability to clear mucus from the airways, a key factor in asthma morbidity. Objective The purpose of this study was to determine the effect of inhaled house dust mite challenge on the regional deposition of...

  12. Anti-inflammatory effects of embelin in A549 cells and human asthmatic airway epithelial tissues.

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    Lee, In-Seung; Cho, Dong-Hyuk; Kim, Ki-Suk; Kim, Kang-Hoon; Park, Jiyoung; Kim, Yumi; Jung, Ji Hoon; Kim, Kwanil; Jung, Hee-Jae; Jang, Hyeung-Jin

    2018-02-01

    Allergic asthma is the most common type in asthma, which is defined as a chronic inflammatory disease of the lung. In this study, we investigated whether embelin (Emb), the major component of Ardisia japonica BL. (AJB), exhibits anti-inflammatory effects on allergic asthma via inhibition of NF-κB activity using A549 cells and asthmatic airway epithelial tissues. Inflammation was induced in A549 cells, a human airway epithelial cell line, by IL-1β (10 ng/ml) treatment for 4 h. The effects of Emb on NF-κB activity and COX-2 protein expression in inflamed airway epithelial cells and human asthmatic airway epithelial tissues were analyzed via western blot. The secretion levels of NF-κB-mediated cytokines/chemokines, including IL-4, 6, 9, 13, TNF-α and eotaxin, were measured by a multiplex assay. Emb significantly blocked NF-κB activity in IL-1β-treated A549 cells and human asthmatic airway epithelial tissues. COX-2 expression was also reduced in both IL-1β-treated A549 cells and asthmatic tissues Emb application. Emb significantly reduced the secretion of IL-4, IL-6 and eotaxin in human asthmatic airway epithelial tissues by inhibiting activity of NF-κB. The results of this study suggest that Emb may be used as an anti-inflammatory agent via inhibition of NF-κB and related cytokines.

  13. Role of tachykinin NK2-receptor activation in the allergen-induced late asthmatic reaction, airway hyperreactivity and airway inflammatory cell influx in conscious, unrestrained guinea-pigs

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    Schuiling, M; Zuidhof, A.B; Meurs, Herman; Zaagsma, Hans

    1 In a guinea-pig model of allergic asthma, we investigated the involvement of the tachykinin NK2 receptors in allergen-induced early (EAR) and late (LAR) asthmatic reactions, airway hyperreactivity (AHR) after these reactions and inflammatory cell influx in the airways, using the selective

  14. Role of tachykinin NK1 and NK2 receptors in allergen-induced early and late asthmatic reactions, airway hyperresponsiveness, and airway inflammation in conscious, unrestrained guinea pigs

    NARCIS (Netherlands)

    Schuiling, M; Zuidhof, A.B; Zaagsma, Hans; Meurs, Herman

    Using a guinea pig model of allergic asthma, we investigated the effects of the inhaled, highly selective nonpeptide tachykinin NK1 and NK2 receptor antagonists SR 140333 and SR 48968, respectively, on allergen-induced early (EAR) and late (LAR) asthmatic reactions, airway hyperreactivity (AHR)

  15. Sputum RNA signature in allergic asthmatics following allergen bronchoprovocation test

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    Rob G.J.A. Zuiker

    2016-07-01

    Full Text Available Background: Inhaled allergen challenge is a validated disease model of allergic asthma offering useful pharmacodynamic assessment of pharmacotherapeutic effects in a limited number of subjects. Objectives: To evaluate whether an RNA signature can be identified from induced sputum following an inhaled allergen challenge, whether a RNA signature could be modulated by limited doses of inhaled fluticasone, and whether these gene expression profiles would correlate with the clinical endpoints measured in this study. Methods: Thirteen non-smoking, allergic subjects with mild-to-moderate asthma participated in a randomised, placebo-controlled, 2-period cross-over study following a single-blind placebo run-in period. Each period consisted of three consecutive days, separated by a wash-out period of at least 3 weeks. Subjects randomly received inhaled fluticasone ((FP MDI; 500 mcg BID×5 doses in total or placebo. On day 2, house dust mite extract was inhaled and airway response was measured by FEV1 at predefined time points until 7 h post-allergen. Sputum was induced by NaCl 4.5%, processed and analysed at 24 h pre-allergen and 7 and 24 h post-allergen. RNA was isolated from eligible sputum cell pellets (<80% squamous of 500 cells, amplified according to NuGEN technology, and profiled on Affymetrix arrays. Gene expression changes from baseline and fluticasone treatment effects were evaluated using a mixed effects ANCOVA model at 7 and at 24 h post-allergen challenge. Results: Inhaled allergen-induced statistically significant gene expression changes in sputum, which were effectively blunted by fluticasone (adjusted p<0.025. Forty-seven RNA signatures were selected from these responses for correlation analyses and further validation. This included Th2 mRNA levels for cytokines, chemokines, high-affinity IgE receptor FCER1A, histamine receptor HRH4, and enzymes and receptors in the arachidonic pathway. Individual messengers from the 47 RNA signatures

  16. Allergic Non-Asthmatic Adults Have Regional Pulmonary Responses to Segmental Allergen Challenge.

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    Vanessa J Kelly

    Full Text Available Allergic non-asthmatic (ANA adults experience upper airway symptoms of allergic disease such as rhinorrhea, congestion and sneezing without symptoms of asthma. The aim of this study was to utilize PET-CT functional imaging to determine whether allergen challenge elicits a pulmonary response in ANA subjects or whether their allergic disease is truly isolated to the upper airways.In 6 ANA subjects, bronchoalveolar lavages (BAL were performed at baseline and 24h after instillation of an allergen and a diluent in separate lung lobes. After instillation (10h, functional imaging was performed to quantify and compare regional perfusion, ventilation, fractional gas content (Fgas, and glucose uptake rate (Ki between the baseline, diluent and allergen lobes. BAL cell counts were also compared.In ANA subjects, compared to the baseline and diluent lobes, perfusion and ventilation were significantly lower in the allergen lobe (median [inter-quartile range], baseline vs. diluent vs. allergen: Mean-normalized perfusion; 0.87 [0.85-0.97] vs. 0.90 [0.86-0.98] vs. 0.59 [0.55-0.67]; p<0.05. Mean-normalized ventilation 0.89 [0.88-0.98] vs. 0.95 [0.89-1.02] vs. 0.63 [0.52-0.67], p<0.05. In contrast, no significant differences were found in Fgas between baseline, diluent and allergen lobes or in Ki. Total cell counts, eosinophil and neutrophil cell counts (cells/ml BAL were significantly greater in the allergen lobe compared to the baseline lobe (all P<0.05.Despite having no clinical symptoms of a lower airway allergic response (cough and wheeze allergic non-asthmatic subjects have a pulmonary response to allergen exposure which manifests as reduced ventilation and perfusion.

  17. An ovine tracheal explant culture model for allergic airway inflammation

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    Abeynaike Latasha

    2010-08-01

    Full Text Available Abstract Background The airway epithelium is thought to play an important role in the pathogenesis of asthmatic disease. However, much of our understanding of airway epithelial cell function in asthma has been derived from in vitro studies that may not accurately reflect the interactive cellular and molecular pathways active between different tissue constituents in vivo. Methods Using a sheep model of allergic asthma, tracheal explants from normal sheep and allergic sheep exposed to house dust mite (HDM allergen were established to investigate airway mucosal responses ex vivo. Explants were cultured for up to 48 h and tissues were stained to identify apoptotic cells, goblet cells, mast cells and eosinophils. The release of cytokines (IL-1α, IL-6 and TNF-α by cultured tracheal explants, was assessed by ELISA. Results The general morphology and epithelial structure of the tracheal explants was well maintained in culture although evidence of advanced apoptosis within the mucosal layer was noted after culture for 48 h. The number of alcian blue/PAS positive mucus-secreting cells within the epithelial layer was reduced in all cultured explants compared with pre-cultured (0 h explants, but the loss of staining was most evident in allergic tissues. Mast cell and eosinophil numbers were elevated in the allergic tracheal tissues compared to naïve controls, and in the allergic tissues there was a significant decline in mast cells after 24 h culture in the presence or absence of HDM allergen. IL-6 was released by allergic tracheal explants in culture but was undetected in cultured control explants. Conclusions Sheep tracheal explants maintain characteristics of the airway mucosa that may not be replicated when studying isolated cell populations in vitro. There were key differences identified in explants from allergic compared to control airways and in their responses in culture for 24 h. Importantly, this study establishes the potential for the

  18. Expression of activated Fc gamma RII discriminates between multiple granulocyte-priming phenotypes in peripheral blood of allergic asthmatic subjects.

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    Kanters, Deon; ten Hove, Willem; Luijk, Bart; van Aalst, Corneli; Schweizer, René C; Lammers, Jan-Willem J; Leufkens, Hubert G M; Raaijmakers, Jan A M; Bracke, Madelon; Koenderman, Leo

    2007-11-01

    Allergic asthma is associated with chronic airway and systemic immune responses. Systemic responses include priming of peripheral blood eosinophils, which is enhanced after allergen challenge. In a subpopulation of asthmatic subjects, neutrophils are associated with bronchial inflammation. We sought to monitor systemic granulocyte priming in allergic asthmatic subjects as a consequence of chronic and acute inflammatory signals initiated by allergen challenge. Blood was taken at baseline and 6 to 24 hours after allergen challenge in asthmatic subjects with and without late asthmatic responses. Systemic granulocyte priming was studied by using expression of cellular markers, such as alpha-chain of Mac-1 (alpha m)/CD11b, L-selectin/CD62L, and an activation epitope present on Fc gamma RII/CD32 recognized by monoclonal phage antibody A17. Eosinophils of asthmatic subjects have a primed phenotype identified by cell-surface markers. Neutrophils of these patients were subtly primed, which was only identified after activation with N-formyl-methionyl-leucyl-phenylalanine. After allergen challenge, an acute increase in eosinophil priming characterized by enhanced expression of activated Fc gamma RII was found in patients experiencing a late asthmatic response and not in patients with a single early asthmatic response. In contrast, expression of alpha m/CD11b and L-selectin on granulocytes was not different between control and asthmatic subjects and was not affected by allergen challenge. Interestingly, expression of both adhesion molecules was positively correlated, and alpha m expression on eosinophils and neutrophils correlated positively with bronchial hyperresponsiveness. Different phases, phenotypes, or both of allergic asthma are associated with distinct priming profiles of inflammatory cells in peripheral blood. Insight in differences of systemic innate responses will lead to better definition of asthma subtypes and to better designs of new therapeutic options.

  19. FoxO1 regulates allergic asthmatic inflammation through regulating polarization of the macrophage inflammatory phenotype

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    Chung, Sangwoon; Lee, Tae Jin; Reader, Brenda F.; Kim, Ji Young; Lee, Yong Gyu; Park, Gye Young; Karpurapu, Manjula; Ballinger, Megan N.; Qian, Feng; Rusu, Luiza; Chung, Hae Young; Unterman, Terry G.; Croce, Carlo M.; Christman, John W.

    2016-01-01

    Inflammatory monocyte and tissue macrophages influence the initiation, progression, and resolution of type 2 immune responses, and alveolar macrophages are the most prevalent immune-effector cells in the lung. While we were characterizing the M1- or M2-like macrophages in type 2 allergic inflammation, we discovered that FoxO1 is highly expressed in alternatively activated macrophages. Although several studies have been focused on the fundamental role of FoxOs in hematopoietic and immune cells, the exact role that FoxO1 plays in allergic asthmatic inflammation in activated macrophages has not been investigated. Growing evidences indicate that FoxO1 acts as an upstream regulator of IRF4 and could have a role in a specific inflammatory phenotype of macrophages. Therefore, we hypothesized that IRF4 expression regulated by FoxO1 in alveolar macrophages is required for established type 2 immune mediates allergic lung inflammation. Our data indicate that targeted deletion of FoxO1 using FoxO1-selective inhibitor AS1842856 and genetic ablation of FoxO1 in macrophages significantly decreases IRF4 and various M2 macrophage-associated genes, suggesting a mechanism that involves FoxO1-IRF4 signaling in alveolar macrophages that works to polarize macrophages toward established type 2 immune responses. In response to the challenge of DRA (dust mite, ragweed, and Aspergillus) allergens, macrophage specific FoxO1 overexpression is associated with an accentuation of asthmatic lung inflammation, whereas pharmacologic inhibition of FoxO1 by AS1842856 attenuates the development of asthmatic lung inflammation. Thus, our study identifies a role for FoxO1-IRF4 signaling in the development of alternatively activated alveolar macrophages that contribute to type 2 allergic airway inflammation. PMID:27007158

  20. Eosinophilic airway inflammation in asthmatic patients is associated with an altered airway microbiome

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    Sverrild, Asger; Kiilerich, Pia; Brejnrod, Asker Daniel

    2017-01-01

    of eosinophilic airway inflammation correlates with variations in the microbiome across asthmatic patients, whereas neutrophilic airway inflammation does not. This warrants further investigation on molecular pathways involved in both patients with eosinophilic and those with noneosinophilic asthma.......BACKGROUND: Asthmatic patients have higher microbiome diversity and an altered composition, with more Proteobacteria and less Bacteroidetes compared with healthy control subjects. Studies comparing airway inflammation and the airway microbiome are sparse, especially in subjects not receiving anti......-inflammatory treatment. OBJECTIVE: We sought to describe the relationship between the airway microbiome and patterns of airway inflammation in steroid-free patients with asthma and healthy control subjects. METHODS: Bronchoalveolar lavage fluid was collected from 23 steroid-free nonsmoking patients with asthma and 10...

  1. Impacts of allergic airway inflammation on lung pathology in a mouse model of influenza A virus infection.

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    Kawaguchi, Akira; Suzuki, Tadaki; Ohara, Yuki; Takahashi, Kenta; Sato, Yuko; Ainai, Akira; Nagata, Noriyo; Tashiro, Masato; Hasegawa, Hideki

    2017-01-01

    Influenza A virus is the respiratory pathogen responsible for influenza. Infection by the 2009 pandemic influenza A (H1N1) virus caused severe lower airway inflammation and pneumonia. Asthma is a chronic inflammatory disorder of the airways that affects the entire brachial tree, and was one of the commonest underlying medical conditions among patients hospitalized with the 2009 pandemic influenza virus infection. Although respiratory virus infections are the major causes of asthma exacerbation, the mechanism by which influenza exacerbates asthma is poorly understood. Animal models of disease comorbidity are crucial to understanding host-pathogen interactions and elucidating complex pathologies. Existing murine models of influenza virus infection in asthmatics show that asthmatic mice are highly resistant to influenza virus infection, which contradicts clinical observations in humans. Here, we developed a murine model of influenza virus/asthma comorbidity using NC/Nga mice, which are highly sensitive to allergic reactions such as atopic dermatitis and allergic airway inflammation. This model was then used to examine the impact of allergic airway inflammation on lung pathology in the 2009 pandemic influenza virus infected mice. The results showed that induction of acute allergic airway inflammation in pre-existing influenza virus infection had additive effects on exacerbation of lung pathology, which mirrors findings in human epidemiological studies. In contrast, pre-existing allergic airway inflammation protected from subsequent influenza virus infection, which was compatible with those of previous murine models of influenza virus infection in asthmatic mice. These variable outcomes of this murine model indicate that the temporal relation between allergic airway inflammation and influenza virus infection might play a critical role in asthma and influenza comorbidity. Thus, this murine model will further our understanding of how influenza virus infection affects an

  2. Silibinin attenuates allergic airway inflammation in mice

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    Choi, Yun Ho [Department of Anatomy, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Jin, Guang Yu [Department of Radiology, Yanbian University Hospital, YanJi 133002 (China); Guo, Hui Shu [Centralab, The First Affiliated Hospital of Dalian Medical University, Dalian 116011 (China); Piao, Hong Mei [Department of Respiratory Medicine, Yanbian University Hospital, YanJi 133000 (China); Li, Liang chang; Li, Guang Zhao [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China); Lin, Zhen Hua [Department of Pathology, Yanbian University School of Basic Medical Sciences, YanJi 133000 (China); Yan, Guang Hai, E-mail: ghyan@ybu.edu.cn [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  3. Role of L-arginine in the deficiency of nitric oxide and airway hyperreactivity after the allergen-induced early asthmatic reaction in guinea-pigs

    NARCIS (Netherlands)

    de Boer, J; Duyvendak, M; Schuurman, F.E; Pouw, F.M W; Zaagsma, Hans; Meurs, Herman

    1999-01-01

    1 Using a guinea-pig model of allergic asthma, we investigated the role of L-arginine limitation in the allergen-induced deficiency of nitric oxide (NO) and airway hyperreactivity (AHR) after the early asthmatic reaction, by examining the effects of various concentrations of the NO synthase (NOS)

  4. Effects of Pranlukast Hydrate on Airway Hyperresponsiveness in Non-Asthmatic Patients with Japanese Cedar Pollinosis

    Directory of Open Access Journals (Sweden)

    Hironori Sagara

    2009-01-01

    Conclusions: The results indicate that pranlukast hydrate inhibits airway hyperresponsiveness in non-asthmatic patients with Japanese cedar pollinosis. In turn, this suggests that cysteinyl leukotrienes have a role in increased airway responsiveness.

  5. Allergic asthmatics show divergent lipid mediator profiles from healthy controls both at baseline and following birch pollen provocation.

    Directory of Open Access Journals (Sweden)

    Susanna L Lundström

    Full Text Available Asthma is a respiratory tract disorder characterized by airway hyper-reactivity and chronic inflammation. Allergic asthma is associated with the production of allergen-specific IgE and expansion of allergen-specific T-cell populations. Progression of allergic inflammation is driven by T-helper type 2 (Th2 mediators and is associated with alterations in the levels of lipid mediators.Responses of the respiratory system to birch allergen provocation in allergic asthmatics were investigated. Eicosanoids and other oxylipins were quantified in the bronchoalveolar lumen to provide a measure of shifts in lipid mediators associated with allergen challenge in allergic asthmatics.Eighty-seven lipid mediators representing the cyclooxygenase (COX, lipoxygenase (LOX and cytochrome P450 (CYP metabolic pathways were screened via LC-MS/MS following off-line extraction of bronchoalveolar lavage fluid (BALF. Multivariate statistics using OPLS were employed to interrogate acquired oxylipin data in combination with immunological markers.Thirty-two oxylipins were quantified, with baseline asthmatics possessing a different oxylipin profile relative to healthy individuals that became more distinct following allergen provocation. The most prominent differences included 15-LOX-derived ω-3 and ω-6 oxylipins. Shared-and-Unique-Structures (SUS-plot modeling showed a correlation (R(2 = 0.7 between OPLS models for baseline asthmatics (R(2Y[cum] = 0.87, Q(2[cum] = 0.51 and allergen-provoked asthmatics (R(2Y[cum] = 0.95, Q(2[cum] = 0.73, with the majority of quantified lipid mediators and cytokines contributing equally to both groups. Unique structures for allergen provocation included leukotrienes (LTB(4 and 6-trans-LTB(4, CYP-derivatives of linoleic acid (epoxides/diols, and IL-10.Differences in asthmatic relative to healthy profiles suggest a role for 15-LOX products of both ω-6 and ω-3 origin in allergic inflammation. Prominent differences at baseline levels indicate

  6. Allergic Asthmatics Show Divergent Lipid Mediator Profiles from Healthy Controls Both at Baseline and following Birch Pollen Provocation

    Science.gov (United States)

    Lundström, Susanna L.; Yang, Jun; Källberg, Henrik J.; Thunberg, Sarah; Gafvelin, Guro; Haeggström, Jesper Z.; Grönneberg, Reidar; Grunewald, Johan; van Hage, Marianne; Hammock, Bruce D.; Eklund, Anders; Wheelock, Åsa M.; Wheelock, Craig E.

    2012-01-01

    Background Asthma is a respiratory tract disorder characterized by airway hyper-reactivity and chronic inflammation. Allergic asthma is associated with the production of allergen-specific IgE and expansion of allergen-specific T-cell populations. Progression of allergic inflammation is driven by T-helper type 2 (Th2) mediators and is associated with alterations in the levels of lipid mediators. Objectives Responses of the respiratory system to birch allergen provocation in allergic asthmatics were investigated. Eicosanoids and other oxylipins were quantified in the bronchoalveolar lumen to provide a measure of shifts in lipid mediators associated with allergen challenge in allergic asthmatics. Methods Eighty-seven lipid mediators representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened via LC-MS/MS following off-line extraction of bronchoalveolar lavage fluid (BALF). Multivariate statistics using OPLS were employed to interrogate acquired oxylipin data in combination with immunological markers. Results Thirty-two oxylipins were quantified, with baseline asthmatics possessing a different oxylipin profile relative to healthy individuals that became more distinct following allergen provocation. The most prominent differences included 15-LOX-derived ω-3 and ω-6 oxylipins. Shared-and-Unique-Structures (SUS)-plot modeling showed a correlation (R2 = 0.7) between OPLS models for baseline asthmatics (R2Y[cum] = 0.87, Q2[cum] = 0.51) and allergen-provoked asthmatics (R2Y[cum] = 0.95, Q2[cum] = 0.73), with the majority of quantified lipid mediators and cytokines contributing equally to both groups. Unique structures for allergen provocation included leukotrienes (LTB4 and 6-trans-LTB4), CYP-derivatives of linoleic acid (epoxides/diols), and IL-10. Conclusions Differences in asthmatic relative to healthy profiles suggest a role for 15-LOX products of both ω-6 and ω-3 origin in allergic

  7. The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics.

    Directory of Open Access Journals (Sweden)

    Sonia R Rosner

    Full Text Available Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM cells to stretch, but underlying molecular mechanisms-and their failure in asthma-remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma.

  8. Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors

    NARCIS (Netherlands)

    Burgess, J. K.; Ketheson, A.; Faiz, A.; Rempel, K. A. Limbert; Oliver, B. G.; Ward, J. P. T.; Halayko, A. J.

    2018-01-01

    Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness

  9. The active contribution of Toll-like receptors to allergic airway inflammation.

    Science.gov (United States)

    Chen, Keqiang; Xiang, Yi; Yao, Xiaohong; Liu, Ying; Gong, Wanghua; Yoshimura, Teizo; Wang, Ji Ming

    2011-10-01

    Epithelia lining the respiratory tract represent a major portal of entry for microorganisms and allergens and are equipped with innate and adaptive immune signaling receptors for host protection. These include Toll-like receptors (TLRs) that recognize microbial components and evoke diverse responses in cells of the respiratory system. TLR stimulation by microorganism-derived molecules activates antigen presenting cells, control T helper (Th) 1, Th2, and Th17 immune cell differentiation, cytokine production by mast cells, and activation of eosinophils. It is clear that TLR are involved in the pathophysiology of allergic airway diseases such as asthma. Dendritic cells (DCs), a kind of antigen presenting cells, which play a key role in the induction of allergic airway inflammation, are privileged targets for pathogen associated molecular patterns (PAMPs). During the allergic responses, engagement of TLRs on DCs determines the Th2 polarization of the T cells. TLR signaling in mast cells increases the release of IL-5, and TLR activation of airway epithelial cells forces the generation of proallergic Th2 type of cytokines. Although these responses aim to protect the host, they may also result in inflammatory tissue damage in the airway. Under certain conditions, stimulation of TLRs, in particular, TLR9, may reduce Th2-dependent allergic inflammation by induction of Th1 responses. Therefore, understanding the complex regulatory roles of TLRs in the pathogenesis of allergic airway inflammation should facilitate the development of preventive and therapeutic measures for asthmatic patients. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Preexposure to ozone blocks the antigen-induced late asthmatic response of the canine peripheral airways

    Energy Technology Data Exchange (ETDEWEB)

    Turner, C.R.; Kleeberger, S.R.; Spannhake, E.W. (Johns Hopkins Medical Institutions, Baltimore, MD (USA))

    1989-01-01

    The influence of exposure of the airways to ozone on acute allergic responsiveness has been investigated in several species. Little is known, however, about the effect of this environmental pollutant on the late asthmatic response (LAR) in animals in which it is exhibited. The purpose of this study was to evaluate this effect in the canine peripheral airways and to assess the potential role of mast cells in modulating the effect. A series of experiments on seven mongrel dogs demonstrated that the numbers of mast cells at the base of the epithelial region of small subsegmental airways exposed to 1 ppm ozone for 5 min were significantly (p less than .01) increased 3 h following exposure compared to air exposed or nonexposed control airways. In a second series of experiments performed on eight additional mongrel dogs with inherent sensitivity to Ascaris suum antigen, antigen aerosol was administered to the sublobar segment 3 h following ozone preexposure when mast cell numbers were presumed to be increased. These experiments were performed to determine whether ozone preexposure could enhance the late-phase response to antigen by virtue of acutely increasing the number of mast cells available to bind the antigen. Four of the eight dogs tested displayed a late-phase response to antigen following air-sham preexposure. In these four dogs, simultaneous ozone preexposure of a contralateral lobe completely blocked the late-phase response to antigen. These results indicate that the consequences of a single exposure to ozone persist beyond its effects on acute antigen-induced bronchoconstriction and extend to the complex processes involved with the late response. This attenuating effect of ozone is seen under conditions where mast-cell numbers in the airways are increased above baseline levels.

  11. Matrine suppresses airway inflammation by downregulating SOCS3 expression via inhibition of NF-κB signaling in airway epithelial cells and asthmatic mice

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Daqing [Department of Respiration, Xi’an Children’s Hospital, Xi’an 710003 (China); Wang, Jing [Department of Neonatology, Xi’an Children’s Hospital, Xi’an 710003 (China); Yang, Niandi [Outpatient Department, School of Aerospace Engineering, Air Force Engineering University, Xi’an 710038 (China); Ma, Haixin, E-mail: drhaixinma@163.com [Department of Quality Control, Xi’an Children’s Hospital, Xi’an 710003 (China)

    2016-08-12

    Matrine has been demonstrated to attenuate allergic airway inflammation. Elevated suppressor of cytokine signaling 3 (SOCS3) was correlated with the severity of asthma. The aim of this study was to investigate the effect of matrine on SOCS3 expression in airway inflammation. In this study, we found that matrine significantly inhibited OVA-induced AHR, inflammatory cell infiltration, goblet cell differentiation, and mucous production in a dose-dependent manner in mice. Matrine also abrogated the level of interleukin (IL)-4 and IL-13, but enhanced interferon (IFN)-γ expression, both in BALF and in lung homogenates. Furthermore, matrine impeded TNF-α-induced the expression of IL-6 and adhesion molecules in airway epithelial cells (BEAS-2B and MLE-12). Additionally, we found that matrine inhibited SOCS3 expression, both in asthmatic mice and TNF-α-stimulated epithelial cells via suppression of the NF-κB signaling pathway by using pcDNA3.1-SOCS3 plasmid, SOCS3 siRNA, or nuclear factor kappa-B (NF-κB) inhibitor PDTC. Conclusions: Matrine suppresses airway inflammation by downregulating SOCS3 expression via inhibition of NF-κB signaling in airway epithelial cells and asthmatic mice. - Highlights: • Matrine attenuates asthmatic symptoms and regulates Th1/Th2 balance in vivo. • Matrine suppresses inflammation responses in vitro. • Matrine decreases SOCS3 expression both in vivo and in vitro. • Matrine inhibits SOCS3 expression by suppressing NF-κB signaling.

  12. Asthmatic airways obstruction assessment based on detailed analysis of respiratory sound spectra

    NARCIS (Netherlands)

    Oud, M.; Dooijes, E. H.; van der Zee, J. S.

    2000-01-01

    This paper concerns the analysis of adventitious sounds produced by individual asthmatic patients, and relates the sounds to the degree of airways obstruction at the moment of sound recording. In this study, airways obstruction is represented by a parameter commonly used in clinical tests, the

  13. Wogonin Induces Eosinophil Apoptosis and Attenuates Allergic Airway Inflammation

    Science.gov (United States)

    Dorward, David A.; Sharma, Sidharth; Rennie, Jillian; Felton, Jennifer M.; Alessandri, Ana L.; Duffin, Rodger; Schwarze, Jurgen; Haslett, Christopher; Rossi, Adriano G.

    2015-01-01

    Rationale: Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites. Objectives: To investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate eosinophil-dominant allergic inflammation in vivo in mice. Methods: Human and mouse eosinophil apoptosis in response to wogonin was investigated by cellular morphology, flow cytometry, mitochondrial membrane permeability, and pharmacological caspase inhibition. Allergic lung inflammation was modeled in mice sensitized and challenged with ovalbumin. Bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation, mucus production, and inflammatory mediator production. Airway hyperresponsiveness to aerosolized methacholine was measured. Measurements and Main Results: Wogonin induced time- and concentration-dependent human and mouse eosinophil apoptosis in vitro. Wogonin-induced eosinophil apoptosis occurred with activation of caspase-3 and was inhibited by pharmacological caspase inhibition. Wogonin administration attenuated allergic airway inflammation in vivo with reductions in BAL and interstitial eosinophil numbers, increased eosinophil apoptosis, reduced airway mucus production, and attenuated airway hyperresponsiveness. This wogonin-induced reduction in allergic airway inflammation was prevented by concurrent caspase inhibition in vivo. Conclusions: Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans. PMID:25629436

  14. NEUROTROPHIN MEDIATION OF ALLERGIC AIRWAYS RESPONSES TO INHALED DIESEL PARTICLES IN MICE

    Science.gov (United States)

    Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airway hyper-responsiveness. Diesel exhaust particulates (DEP) associated with the combustion of diesel fuel exacerbate many of these allergic airways respons...

  15. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro-Filho, Jaime [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Moraes de Carvalho, Katharinne Ingrid [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Mendes, Diego da [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Melo, Christianne Bandeira [Laboratório de Inflamação, Instituto Biofisica Carlos Chagas Filho, UFRJ, Rio de Janeiro (Brazil); Martins, Marco Aurélio [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Dias, Celidarque da [Laboratório de Fitoquímica, Departamento de Ciências Farmacêuticas, UFPB, João Pessoa, Paraíba (Brazil); Piuvezam, Márcia Regina, E-mail: mrpiuvezam@ltf.ufpb.br [Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); and others

    2013-11-15

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

  16. Impact of Aspergillus fumigatus in allergic airway diseases

    Directory of Open Access Journals (Sweden)

    Chaudhary Neelkamal

    2011-06-01

    Full Text Available Abstract For decades, fungi have been recognized as associated with asthma and other reactive airway diseases. In contrast to type I-mediated allergies caused by pollen, fungi cause a large number of allergic diseases such as allergic bronchopulmonary mycoses, rhinitis, allergic sinusitis and hypersensitivity pneumonitis. Amongst the fungi, Aspergillus fumigatus is the most prevalent cause of severe pulmonary allergic disease, including allergic bronchopulmonary aspergillosis (ABPA, known to be associated with chronic lung injury and deterioration in pulmonary function in people with chronic asthma and cystic fibrosis (CF. The goal of this review is to discuss new understandings of host-pathogen interactions in the genesis of allergic airway diseases caused by A. fumigatus. Host and pathogen related factors that participate in triggering the inflammatory cycle leading to pulmonary exacerbations in ABPA are discussed.

  17. Upper and lower airway pathology in young children with allergic- and non-allergic rhinitis

    DEFF Research Database (Denmark)

    Chawes, Bo

    2011-01-01

    and epidemiological surveys have suggested a close connection between upper and lower airway diseases expressed as the "united airways concept". Furthermore, an association between upper and lower airway diseases also seems to exist in non-atopic individuals. Nevertheless, the nature of this association is poorly...... understood and there is a paucity of data objectivizing this association in young children. The aim of this thesis was to describe pathology in the upper and lower airways in young children from the COPSAC birth cohort with investigator-diagnosed allergic- and non-allergic rhinitis. Nasal congestion is a key...... airway patency end-points derived from paper I to examine whether upper and lower airway patency are associated. Upper airway patency was assessed by acoustic rhinometry before and after intranasal α-agonist and lower airway patency by spirometry before and after inhaled β2-agonist. Upper and lower...

  18. [Allergic inflamation of the lower airways in patients with allergic rhinitis].

    Science.gov (United States)

    Stefanović, Lj; Balaban, J; Stosović, R; Mitrović, N; Djurasinović, M; Tanurdzić, S

    1994-01-01

    Reporting two of our cases we wanted to point to a great dilemma related to the final diagnosis. Recently, such cases have been more frewuently seen, since in all patients with allergic rhinitis conditions of the lower airways is examined before the administration of the specific immunotherapy. Therefore, we may see patients who are still free of pulmonary sings, despite of positive specific and/or non specific bronchoprovocative tests. The presented cases with evidenced allergic rhinitis are probably in the phase of development of allergic bronchial asthma, the phase of "allergic inflammation" of the lower airways, not clinically manifested yet.

  19. PTEN gene silencing contributes to airway remodeling and induces airway smooth muscle cell proliferation in mice with allergic asthma.

    Science.gov (United States)

    Wen, Xin; Yan, Jing; Han, Xin-Rui; Zheng, Gui-Hong; Tang, Ran; Liu, Li-Fang; Wu, Dong-Mei; Lu, Jun; Zheng, Yuan-Lin

    2018-01-01

    Allergic asthma is a complex genetic disorder that involves interactions between genetic and environmental factors. Usage of PTEN may be a good therapeutic strategy for the management of allergic inflammation. Thus, the present study aims to explore the effects of phosphatase and tensin homolog ( PTEN ) gene silencing on airway remodeling and proliferation of airway smooth muscle cells (ASMCs) in a mouse model of allergic asthma. A total of 56 healthy female BABL/c mice (weighing between 16 to 22 grams) were selected and were assigned on random into ovalbumin (OVA; mice were stimulated with OVA to induce allergic asthma), OVA + si-PTEN, normal saline (NS; mice were treated with normal saline) and NS + si-PTEN groups. Masson staining was employed in order to observe lung tissue sections. Immunohistochemical staining was used to detect the expression of α-SMA + . Gene silencing was conducted in the NS + si-PTEN and OVA + si-PTEN groups. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were used to detect the mRNA and protein expressions of PTEN in ASMCs of each group. CCK-8 assay and flow cytometry were performed to determine the cell proliferation rate and cell cycle. Airway remodeling and changes of smooth muscle layer were found in allergic asthmatic mice with thick airway walls. The expression of alpha smooth muscle actin (α-SMA + ) was significantly higher in ASMCs of the OVA, OVA + si-PTEN and NS + si-PTEN groups compared with ASMCs of the NS group. The mRNA and protein expressions of PTEN reduced in the OVA, OVA + si-PTEN and NS + si-PTEN groups. The rate of ASMCs proliferation in OVA, OVA + si-PTEN and NS + si-PTEN groups were significantly higher than the NS group. The proportion of ASMCs in S and G2 stages increased, while the number of cells in the G1 stage decreased after PTEN gene silencing. These results demonstrated that PTEN gene silencing might promote proliferation of ASMCs and airway remodeling in a

  20. Innate Immune Responses to Engineered Nanomaterials During Allergic Airway Inflammation

    Science.gov (United States)

    Shipkowski, Kelly Anne

    disease would modulate the innate immune response to MWCNTs. We hypothesized that Th2 cytokines and the allergic asthmatic microenvironment would alter MWCNT-induced inflammasome activation and IL- 1beta secretion both in vitro and in vivo. In vitro, THP-1 cells, a human monocytic cell line, were differentiated into macrophages and exposed to MWCNTs and or recombinant Th2 cytokines, specifically IL-4 and/or IL-13. Exposure of THP-1 cells to MWCNTs alone caused dose-dependent secretion of IL-1beta, while co-exposure to IL-4 and/or IL-13 suppressed MWCNT-induced IL-1beta. Further analysis determined that IL-4 and IL-13 were phosphorylating the protein signal transducer and activator of transcription 6 (STAT6) and subsequently inhibiting inflammasome activation and function through suppression of caspase-1, a cysteine protease responsible for cleavage of pro-IL-1beta into an active, secretable form. In vivo, wild-type C57BL6 mice were sensitized intranasally with HDM allergen and exposed to MWCNTs via oropharyngeal aspiration. Treatment with MWCNTs alone induced secretion of IL-1beta in the bronchoalveolar lavage fluid (BALF) one day post-exposure, while sensitization with HDM prior to MWCNT exposure suppressed MWCNT-induced IL-1beta. Immunohistochemical (IHC) analysis of lung sections from exposed animals showed that HDM sensitization inhibited MWCNT-induced pro-casapse-1 protein expression, responsible for inflammasome activation, in the airway epithelium and macrophages. MWCNT exposure combined with HDM sensitization increased inflammatory cell infiltration and subsequent acute lung inflammation and chronic fibrosis. Analysis of the systemic effects of MWCNT exposure during allergic airway sensitization showed that MWCNTs and/or HDM allergen upregulated STAT3 mRNA expression in the lungs, liver, and spleen of exposed animals, and at the same induced mixed T helper (Th) responses in the different tissues. Collectively, these data suggest that the allergic microenvironment

  1. L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction

    NARCIS (Netherlands)

    Maarsingh, H.; Bossenga, B. E.; Bos, I. S. T.; Volders, H. H.; Zaagsma, J.; Meurs, H.

    Peroxynitrite has been shown to be crucially involved in airway hyperresponsiveness (AHR) after the late asthmatic reaction (LAR). Peroxynitrite production may result from simultaneous synthesis of nitric oxide (NO) and superoxide by inducible NO-synthase (iNOS) at low L-arginine concentrations.

  2. Upper and lower airway pathology in young children with allergic- and non-allergic rhinitis

    DEFF Research Database (Denmark)

    Chawes, Bo

    2011-01-01

    understood and there is a paucity of data objectivizing this association in young children. The aim of this thesis was to describe pathology in the upper and lower airways in young children from the COPSAC birth cohort with investigator-diagnosed allergic- and non-allergic rhinitis. Nasal congestion is a key...... nasal eosinophilia albeit less than children with allergic rhinitis. These findings suggest different pathology in allergic- and non-allergic rhinitis which may have important clinical implications for early pharmacological treatment of rhinitis in young children. In paper II, we utilized the nasal...

  3. Association between allergic rhinitis and hospital resource use among asthmatic children in Norway

    DEFF Research Database (Denmark)

    Sazonov Kocevar, V; Thomas, J; Jonsson, L

    2005-01-01

    BACKGROUND: Preliminary evidence suggests that inadequately controlled allergic rhinitis in asthmatic patients can contribute towards increased asthma exacerbations and poorer symptom control, which may increase medical resource use. The objective of this study was therefore to assess the effect...... of concomitant allergic rhinitis on asthma-related hospital resource utilization among children below 15 years of age with asthma in Norway. METHODS: A population-based retrospective cohort study of children (aged 0-14 years) with asthma was conducted using data from a patient-specific public national database...

  4. Fungal glycan interactions with epithelial cells in allergic airway disease.

    Science.gov (United States)

    Roy, René M; Klein, Bruce S

    2013-08-01

    Human exposure to fungi results in a wide range of health outcomes, from invasive disease or allergy to immune tolerance. Inhaled fungi contact airway epithelial cells as an early event, and this host:fungal interaction can shape the eventual immunological outcome. Emerging evidence points to exposure to fungal cell wall carbohydrates in the development of allergic airway disease. Herein, we describe determinants of fungal allergenicity, and review the responses of airway epithelial cells to fungal carbohydrates. A greater understanding of the recognition of and response to fungal carbohydrates by airway epithelial cells may lead to the development of targeted therapies that ameliorate allergic airway disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma.

    Science.gov (United States)

    Yarova, Polina L; Stewart, Alecia L; Sathish, Venkatachalem; Britt, Rodney D; Thompson, Michael A; P Lowe, Alexander P; Freeman, Michelle; Aravamudan, Bharathi; Kita, Hirohito; Brennan, Sarah C; Schepelmann, Martin; Davies, Thomas; Yung, Sun; Cholisoh, Zakky; Kidd, Emma J; Ford, William R; Broadley, Kenneth J; Rietdorf, Katja; Chang, Wenhan; Bin Khayat, Mohd E; Ward, Donald T; Corrigan, Christopher J; T Ward, Jeremy P; Kemp, Paul J; Pabelick, Christina M; Prakash, Y S; Riccardi, Daniela

    2015-04-22

    Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyperreactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics. Copyright © 2015, American Association for the Advancement of Science.

  6. Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors.

    Science.gov (United States)

    Burgess, J K; Ketheson, A; Faiz, A; Limbert Rempel, K A; Oliver, B G; Ward, J P T; Halayko, A J

    2018-01-16

    Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness of hTERT immortalisation of human ASM cells as a research tool. Specifically we compared proliferative capacity, inflammatory mediator release and extracellular matrix (ECM) production in hTERT immortalised and parent primary ASM cells from asthmatic and non-asthmatic donors. Our studies revealed no significant differences in proliferation, IL-6 and eotaxin-1 production, or CTGF synthesis between donor-matched parent and hTERT immortalised ASM cell lines. However, deposition of ECM proteins fibronectin and fibulin-1 was significantly lower in immortalised ASM cells compared to corresponding primary cells. Notably, previously reported differences in proliferation and inflammatory mediator release between asthmatic and non-asthmatic ASM cells were retained, but excessive ECM protein deposition in asthmatic ASM cells was lost in hTERT ASM cells. This study shows that hTERT immortalised ASM cells mirror primary ASM cells in proliferation and inflammatory profile characteristics. Moreover, we demonstrate both strengths and weaknesses of this immortalised cell model as a representation of primary ASM cells for future asthma pathophysiological research.

  7. Upper and lower airway pathology in young children with allergic- and non-allergic rhinitis.

    Science.gov (United States)

    Chawes, Bo L K

    2011-05-01

    Allergic- and non-allergic rhinitis are very common diseases in childhood in industrialized countries. Although these conditions are widely trivialized by both parents and physicians they induce a major impact on quality of life for the affected children and a substantial drainage of health care resources. Unfortunately, diagnostic specificity is hampered by nonspecific symptom history and lack of reliable diagnostic tests which may explain why the pathology behind such diagnoses is poorly understood. Improved understanding of the pathophysiology of allergic- and non-allergic rhinitis in young children may contribute to the discovery of new mechanisms involved in pathogenesis and help direct future research to develop correctly timed preventive measures as well as adequate monitoring and treatment of children with rhinitis. Asthma is a common comorbidity in subjects with allergic rhinitis and epidemiological surveys have suggested a close connection between upper and lower airway diseases expressed as the "united airways concept". Furthermore, an association between upper and lower airway diseases also seems to exist in non-atopic individuals. Nevertheless, the nature of this association is poorly understood and there is a paucity of data objectivizing this association in young children. The aim of this thesis was to describe pathology in the upper and lower airways in young children from the COPSAC birth cohort with investigator-diagnosed allergic- and non-allergic rhinitis. Nasal congestion is a key symptom in both allergic- and non-allergic rhinitis, and eosinophilic inflammation is a hallmark of the allergic diseases. In paper I, we studied nasal eosinophilia and nasal airway patency assessed by acoustic rhinometry in children with allergic rhinitis, non-allergic rhinitis and healthy controls. Allergic rhinitis was significantly associated with nasal eosinophilia and irreversible nasal airway obstruction suggesting chronic inflammation and structural remodeling

  8. Prolonged ozone exposure in an allergic airway disease model: Adaptation of airway responsiveness and airway remodeling

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    Park Chang-Soo

    2006-02-01

    Full Text Available Abstract Background Short-term exposure to high concentrations of ozone has been shown to increase airway hyper-responsiveness (AHR. Because the changes in AHR and airway inflammation and structure after chronic ozone exposure need to be determined, the goal of this study was to investigate these effects in a murine model of allergic airway disease. Methods We exposed BALB/c mice to 2 ppm ozone for 4, 8, and 12 weeks. We measured the enhanced pause (Penh to methacholine and performed cell differentials in bronchoalveolar lavage fluid. We quantified the levels of IL-4 and IFN-γ in the supernatants of the bronchoalveolar lavage fluids using enzyme immunoassays, and examined the airway architecture under light and electron microscopy. Results The groups exposed to ozone for 4, 8, and 12 weeks demonstrated decreased Penh at methacholine concentrations of 12.5, 25, and 50 mg/ml, with a dose-response curve to the right of that for the filtered-air group. Neutrophils and eosinophils increased in the group exposed to ozone for 4 weeks compared to those in the filtered-air group. The ratio of IL-4 to INF-γ increased significantly after exposure to ozone for 8 and 12 weeks compared to the ratio for the filtered-air group. The numbers of goblet cells, myofibroblasts, and smooth muscle cells showed time-dependent increases in lung tissue sections from the groups exposed to ozone for 4, 8, and 12 weeks. Conclusion These findings demonstrate that the increase in AHR associated with the allergic airway does not persist during chronic ozone exposure, indicating that airway remodeling and adaptation following repeated exposure to air pollutants can provide protection against AHR.

  9. Innate immunity as the orchestrator of allergic airway inflammation and resolution in asthma.

    Science.gov (United States)

    Thiriou, Despoina; Morianos, Ioannis; Xanthou, Georgina; Samitas, Konstantinos

    2017-07-01

    The respiratory system is constantly in direct contact with the environment and, has therefore, developed strong innate and adaptive immune responses to combat pathogens. Unlike adaptive immunity which is mounted later in the course of the immune response and is naive at the outset, innate immunity provides the first line of defense against microbial agents, while also promoting resolution of inflammation. In the airways, innate immune effector cells mainly consist of eosinophils, neutrophils, mast cells, basophils, macrophages/monocytes, dendritic cells and innate lymphoid cells, which attack pathogens directly or indirectly through the release of inflammatory cytokines and antimicrobial peptides, and coordinate T and B cell-mediated adaptive immunity. Airway epithelial cells are also critically involved in shaping both the innate and adaptive arms of the immune response. Chronic allergic airway inflammation and linked asthmatic disease is often considered a result of aberrant activation of type 2 T helper cells (Th2) towards innocuous environmental allergens; however, innate immune cells are increasingly recognized as key players responsible for the initiation and the perpetuation of allergic responses. Moreover, innate cells participate in immune response regulation through the release of anti-inflammatory mediators, and guide tissue repair and the maintenance of airway homeostasis. The scope of this review is to outline existing knowledge on innate immune responses involved in allergic airway inflammation, highlight current gaps in our understanding of the underlying molecular and cellular mechanisms and discuss the potential use of innate effector cells in new therapeutic avenues. Copyright © 2017. Published by Elsevier B.V.

  10. Prostaglandin E2 and Transforming Growth Factor-β Play a Critical Role in Suppression of Allergic Airway Inflammation by Adipose-Derived Stem Cells.

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    Kyu-Sup Cho

    Full Text Available The role of soluble factors in the suppression of allergic airway inflammation by adipose-derived stem cells (ASCs remains to be elucidated. Moreover, the major soluble factors responsible for the immunomodulatory effects of ASCs in allergic airway diseases have not been well documented. We evaluated the effects of ASCs on allergic inflammation in asthmatic mice treated with a prostaglandin E2 (PGE2 inhibitor or transforming growth factor-β (TGF-β neutralizing antibodies.Asthmatic mice were injected intraperitoneally with a PGE2 inhibitor or TGF-β neutralizing antibodies at approximately the same time as ASCs injection and were compared with non-treated controls. In asthmatic mice, ASCs significantly reduced airway hyperresponsiveness, the number of total inflammatory cells and eosinophils in the bronchoalveolar lavage fluid (BALF, eosinophilic inflammation, goblet cell hyperplasia, and serum total and allergen-specific IgE and IgG1. ASCs significantly inhibited Th2 cytokines, such as interleukin (IL-4, IL-5, and IL-13, and enhanced the Th1 cytokine (Interferon-γ and regulatory cytokines (IL-10 and TGF-β in the BALF and lung draining lymph nodes (LLNs. ASCs engraftment caused significant increases in the regulatory T cell (Treg and IL-10+ T cell populations in LLNs. However, blocking PGE2 or TGF-β eliminated the immunosuppressive effect of ASCs in allergic airway inflammation.ASCs are capable of secreting PGE2 and TGF-β, which may play a role in inducing Treg expansion. Furthermore, treatment with a PGE2 inhibitor or TGF-β neutralizing antibodies eliminated the beneficial effect of ASCs treatment in asthmatic mice, suggesting that PGE2 and TGF-β are the major soluble factors responsible for suppressing allergic airway inflammation.

  11. Effects of Corni fructus on ovalbumin-induced airway inflammation and airway hyper-responsiveness in a mouse model of allergic asthma

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    Kim Seung-Hyung

    2012-03-01

    Full Text Available Abstract Background Allergic asthma is a chronic inflammatory lung disease that is characterized by airway hyperresponsiveness (AHR to allergens, airway oedema, increased mucus secretion, excess production of T helper-2 (Th2 cytokines, and eosinophil accumulation in the lungs. Corni fructus (CF is a fruit of Cornus officinalis Sieb. Et. Zucc. (Cornaceae and has been used in traditional Korean medicine as an anti-inflammatory, analgesic, and diuretic agent. To investigate the anti-asthmatic effects of CF and their underlying mechanism, we examined the influence of CF on the development of pulmonary eosinophilic inflammation and airway hyperresponsiveness in a mouse model of allergic asthma. Methods In this study, BALB/c mice were systemically sensitized to ovalbumin (OVA by intraperitoneal (i.p., intratracheal (i.t. injections and intranasal (i.n. inhalation of OVA. We investigated the effect of CF on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, and OVA-specific immunoglobulin E (IgE production. Results The CF-treated groups showed suppressed eosinophil infiltration, allergic airway inflammation, and AHR via reduced production of interleuin (IL -5, IL-13, and OVA-specific IgE. Conclusions Our data suggest that the therapeutic effects of CF in asthma are mediated by reduced production of Th2 cytokines (IL-5, eotaxin, and OVA-specific IgE and reduced eosinophil infiltration.

  12. Upper and lower airway pathology in young children with allergic- and non-allergic rhinitis

    DEFF Research Database (Denmark)

    Chawes, Bo Lk

    2011-01-01

    Allergic- and non-allergic rhinitis are very common diseases in childhood in industrialized countries. Although these conditions are widely trivialized by both parents and physicians they induce a major impact on quality of life for the affected children and a substantial drainage of health care...... resources. Unfortunately, diagnostic specificity is hampered by nonspecific symptom history and lack of reliable diagnostic tests which may explain why the pathology behind such diagnoses is poorly understood. Improved understanding of the pathophysiology of allergic- and non-allergic rhinitis in young...... airway patencies were strongly associated and independent of body size, rhinitis and asthma. The association was consistent for both baseline values and for decongested nasal airway patency and post-ß2 FEV1. Blood and nasal eosinophilia were also associated with nasal airway obstruction. This suggests...

  13. Probiotics as Additives on Therapy in Allergic Airway Diseases: A Systematic Review of Benefits and Risks

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    Rashmi Ranjan Das

    2013-01-01

    Full Text Available Background. We conducted a systematic review to find out the role of probiotics in treatment of allergic airway diseases.  Methods. A comprehensive search of the major electronic databases was done till March 2013. Trials comparing the effect of probiotics versus placebo were included. A predefined set of outcome measures were assessed. Continuous data were expressed as standardized mean difference with 95% CI. Dichotomous data were expressed as odds ratio with 95% CI. P value < 0.05 was considered as significant. Results. A total of 12 studies were included. Probiotic intake was associated with a significantly improved quality of life score in patients with allergic rhinitis (SMD −1.9 (95% CI −3.62, −0.19; P = 0.03, though there was a high degree of heterogeneity. No improvement in quality of life score was noted in asthmatics. Probiotic intake also improved the following parameters: longer time free from episodes of asthma and rhinitis and decrease in the number of episodes of rhinitis per year. Adverse events were not significant. Conclusion. As the current evidence was generated from few trials with high degree of heterogeneity, routine use of probiotics as an additive on therapy in subjects with allergic airway diseases cannot be recommended.

  14. Nebulized perflubron and carbon dioxide rapidly dilate constricted airways in an ovine model of allergic asthma.

    Science.gov (United States)

    El Mays, Tamer Y; Choudhury, Parichita; Leigh, Richard; Koumoundouros, Emmanuel; Van der Velden, Joanne; Shrestha, Grishma; Pieron, Cora A; Dennis, John H; Green, Francis Hy; Snibson, Ken J

    2014-09-16

    The low toxicity of perfluorocarbons (PFCs), their high affinity for respiratory gases and their compatibility with lung surfactant have made them useful candidates for treating respiratory diseases such as adult respiratory distress syndrome. We report results for treating acute allergic and non-allergic bronchoconstriction in sheep using S-1226 (a gas mixture containing carbon dioxide and small volumes of nebulized perflubron). The carbon dioxide, which is highly soluble in perflubron, was used to relax airway smooth muscle. Sheep previously sensitized to house dust mite (HDM) were challenged with HDM aerosols to induce early asthmatic responses. At the maximal responses (characterised by an increase in lung resistance), the sheep were either not treated or treated with one of the following; nebulized S-1226 (perflubron + 12% CO2), nebulized perflubron + medical air, 12% CO2, salbutamol or medical air. Lung resistance was monitored for up to 20 minutes after cessation of treatment. Treatment with S-1226 for 2 minutes following HDM challenge resulted in a more rapid, more profound and more prolonged decline in lung resistance compared with the other treatment interventions. Video bronchoscopy showed an immediate and complete (within 5 seconds) re-opening of MCh-constricted airways following treatment with S-1226. S-1226 is a potent and rapid formulation for re-opening constricted airways. Its mechanism(s) of action are unknown. The formulation has potential as a rescue treatment for acute severe asthma.

  15. Multiple bronchoceles in a non-asthmatic patient with allergic bronchopulmonary aspergillosis.

    Science.gov (United States)

    Amin, Muhammad Umar; Mahmood, Rabia

    2008-09-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction due to a fungus, Aspergillus fumigatus. It is typically seen in patients with long-standing asthma. Our patient was a non-asthmatic 18 years old male who presented with chronic cough for 2 years. Peripheral blood eosinophilia and elevated scrum IgE were observed. His x-ray chest revealed v-shaped opacity in the left upper lobe close to the hilum. High resolution computed tomographic scan of the chest revealed multiple dilated bronchi filled with mucous (bronchoceles) and central bronchiectasis (CB) involving main segmental bronchi. Central bronchiectasis (CB) was typical of ABPA but bronchocele formation was a rare manifestation of the disease. The patient was managed with oral prednisolone and was relieved of his symptoms. Occurrence of ABPA in non-asthmatics is very rare and deserves reporting.

  16. Secretoglobin Superfamily Protein SCGB3A2 Alleviates House Dust Mite-Induced Allergic Airway Inflammation in Mice.

    Science.gov (United States)

    Yoneda, Mitsuhiro; Xu, Lei; Kajiyama, Hiroaki; Kawabe, Shuko; Paiz, Jorge; Ward, Jerrold M; Kimura, Shioko

    2016-01-01

    Secretoglobin (SCGB) 3A2, a novel, lung-enriched, cytokine-like, secreted protein of small molecular weight, was demonstrated to exhibit various biological functions including anti-inflammatory, antifibrotic and growth-factor activities. Anti-inflammatory activity was uncovered using the ovalbumin-induced allergic airway inflammation model. However, further validation of this activity using knockout mice in a different allergic inflammation model is necessary in order to establish the antiallergic inflammatory role for this protein. Scgb3a2-null (Scgb3a2-/-) mice were subjected to nasal inhalation of Dermatophagoides pteronyssinus extract for 5 days/week for 5 consecutive weeks; control mice received nasal inhalation of saline as a comparator. Airway inflammation was assessed by histological analysis, the number of inflammatory cells and various Th2-type cytokine levels in the lungs and bronchoalveolar lavage fluids by qRT-PCR and ELISA, respectively. Exacerbated inflammation was found in the airway of Scgb3a2-/- mice subjected to house dust mite (HDM)-induced allergic airway inflammation compared with saline-treated control groups. All the inflammation end points were increased in the Scgb3a2-/- mice. The Ccr4 and Ccl17 mRNA levels were higher in HDM-treated lungs of Scgb3a2-/- mice than wild-type mice or saline-treated Scgb3a2-/- mice, whereas no changes were observed for Ccr3 and Ccl11 mRNA levels. These results demonstrate that SCGB3A2 has an anti-inflammatory activity in the HDM-induced allergic airway inflammation model, in which SCGB3A2 may modulate the CCR4-CCL17 pathway. SCGB3A2 may provide a useful tool to treat allergic airway inflammation, and further studies on the levels and function of SCGB3A2 in asthmatic patients are warranted. © 2016 S. Karger AG, Basel.

  17. Effect of ozone exposure on maximal airway narrowing in non-asthmatic and asthmatic subjects

    NARCIS (Netherlands)

    Hiltermann, T J; Stolk, J; Hiemstra, P S; Fokkens, P H; Rombout, P J; Sont, J K; Sterk, P J; Dijkman, J H

    1995-01-01

    1. Ozone is a major constituent of air pollution in the summer. Epidemiological studies have demonstrated that there is an increase in hospital admissions for respiratory diseases 1 day after peak levels of ambient ozone. This may be due to an increase in the responsiveness of the airways to

  18. Arginine homeostasis in allergic asthma

    NARCIS (Netherlands)

    Maarsingh, Harm; Zaagsma, Johan; Meurs, Herman

    2008-01-01

    Allergic asthma is a chronic disease characterized by early and late asthmatic reactions, airway hyperresponsiveness, airway inflammation and airway remodelling. Changes in L-arginine homeostasis may contribute to all these features of asthma by decreased nitric oxide (NO) production and increased

  19. Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

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    Aihua Hu

    Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

  20. A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice

    International Nuclear Information System (INIS)

    Ismail, Norazren; Jambari, Nuzul Nurahya; Zareen, Seema; Akhtar, Mohamad Nadeem; Shaari, Khozirah; Zamri-Saad, Mohamad; Tham, Chau Ling; Sulaiman, Mohd Roslan; Lajis, Nordin Hj; Israf, Daud Ahmad

    2012-01-01

    Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5–10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2 mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2 mg/kg with no effect at the lowest dose of 0.2 mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics. -- Highlights: ► Safer and effective anti-asthmatic drugs are in great demand. ► tHGA is a new 5-LO/cysLT inhibitor that inhibits allergic asthma in mice. ► tHGA is a natural compound that can be synthesized. ► Doses as low as 2 mg/kg alleviate lung pathology in experimental asthma. ► tHGA is a potential drug lead for the treatment of allergic asthma.

  1. β2-Agonist induced cAMP is decreased in asthmatic airway smooth muscle due to increased PDE4D

    NARCIS (Netherlands)

    Trian, Thomas; Burgess, Janette K; Niimi, Kyoko; Moir, Lyn M; Ge, Qi; Berger, Patrick; Liggett, Stephen B; Black, Judith L; Oliver, Brian G

    2011-01-01

    BACKGROUND AND OBJECTIVE: Asthma is associated with airway narrowing in response to bronchoconstricting stimuli and increased airway smooth muscle (ASM) mass. In addition, some studies have suggested impaired β-agonist induced ASM relaxation in asthmatics, but the mechanism is not known. OBJECTIVE:

  2. Mucosal exposure to cockroach extract induces allergic sensitization and allergic airway inflammation

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    Arizmendi Narcy G

    2011-12-01

    Full Text Available Abstract Background Allergic sensitization to aeroallergens develops in response to mucosal exposure to these allergens. Allergic sensitization may lead to the development of asthma, which is characterized by chronic airway inflammation. The objective of this study is to describe in detail a model of mucosal exposure to cockroach allergens in the absence of an exogenous adjuvant. Methods Cockroach extract (CE was administered to mice intranasally (i.n. daily for 5 days, and 5 days later mice were challenged with CE for 4 consecutive days. A second group received CE i.n. for 3 weeks. Airway hyperresponsiveness (AHR was assessed 24 h after the last allergen exposure. Allergic airway inflammation was assessed by BAL and lung histology 48 h after the last allergen exposure. Antigen-specific antibodies were assessed in serum. Lungs were excised from mice from measurement of cytokines and chemokines in whole lung lysate. Results Mucosal exposure of Balb/c mice to cockroach extract induced airway eosinophilic inflammation, AHR and cockroach-specific IgG1; however, AHR to methacholine was absent in the long term group. Lung histology showed patchy, multicentric damage with inflammatory infiltrates at the airways in both groups. Lungs from mice from the short term group showed increased IL-4, CCL11, CXCL1 and CCL2 protein levels. IL4 and CXCL1 were also increased in the BAL of cockroach-sensitized mice in the short-term protocol. Conclusions Mucosal exposure to cockroach extract in the absence of adjuvant induces allergic airway sensitization characterized by AHR, the presence of Th2 cytokines in the lung and eosinophils in the airways.

  3. Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.

    Science.gov (United States)

    Bossi, R; Banfi, P; Filipazzi, V; Castelli, C; Braga, P C

    1994-04-01

    The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p < or = 0.05] in comparison to no effect for placebo. Similarly, in airway responsiveness to specific allergen, active treatment antagonized the bronchoconstrictor effect of grass pollen by 83% and of various allergens (dermatophagoides and grass pollen) by 72%, i.e. AR of 0.17 (95% confidence interval 0.045-0.65; p < 0.01) and of 0.28 (95% confidence interval 0.07-1.04; p < 0.05), respectively. No antagonist effect was evident with placebo at all times. Besides inhibiting cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release.

  4. Airway hyperresponsiveness and quality of life in Western red cedar asthmatics removed from exposure.

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    Jian-Qing He

    Full Text Available OBJECTIVES: Most western red cedar asthmatics (WRCA continue to have symptoms even after removal from exposure. Consequently, health-related quality of life (HRQL is often impaired. The objective of this study was to evaluate the relationship between two measures of AHR and HRQL scores in those with WRCA. METHODS: HRQL was determined by the short form 36 (SF-36 in 46 male, non-smoking individuals with WRCA removed from exposure to western red cedar, on average, 15 years earlier. The relationships between the SF-36 total score and its eight domains with 2 indices from methacholine-stimulated airway hyperresponsiveness (the provocative concentration of methacholine causing a 20% fall in FEV(1 [PC(20] and bronchial reactivity index [BRI] were analyzed by the Pearson correlation and multiple linear regression. RESULTS: PC(20 was significantly correlated with the SF-36 total score and its two domains of bodily pain and general health (r = 0.34, 0.40, 0.40, p = 0.023, 0.006, 0.006, respectively. BRI was significantly correlated with bodily pain and general health (r = -0.35, -0.42, p = 0.017, 0.004, respectively; correlations remain significant after adjusting for age, ethnicity, years since diagnosis, years since last exposure and use of inhaled corticosteroid. BRI and other measures of airway responsiveness were not associated with inhaled corticosteroids use. CONCLUSIONS: In Western red cedar asthmatics removed from exposure, measures of airway responsiveness are associated with HRQL.

  5. Airway hyperresponsiveness and quality of life in Western red cedar asthmatics removed from exposure.

    Science.gov (United States)

    He, Jian-Qing; Chan-Yeung, Moira; Carlsten, Chris

    2012-01-01

    Most western red cedar asthmatics (WRCA) continue to have symptoms even after removal from exposure. Consequently, health-related quality of life (HRQL) is often impaired. The objective of this study was to evaluate the relationship between two measures of AHR and HRQL scores in those with WRCA. HRQL was determined by the short form 36 (SF-36) in 46 male, non-smoking individuals with WRCA removed from exposure to western red cedar, on average, 15 years earlier. The relationships between the SF-36 total score and its eight domains with 2 indices from methacholine-stimulated airway hyperresponsiveness (the provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)] and bronchial reactivity index [BRI]) were analyzed by the Pearson correlation and multiple linear regression. PC(20) was significantly correlated with the SF-36 total score and its two domains of bodily pain and general health (r = 0.34, 0.40, 0.40, p = 0.023, 0.006, 0.006, respectively). BRI was significantly correlated with bodily pain and general health (r = -0.35, -0.42, p = 0.017, 0.004, respectively); correlations remain significant after adjusting for age, ethnicity, years since diagnosis, years since last exposure and use of inhaled corticosteroid. BRI and other measures of airway responsiveness were not associated with inhaled corticosteroids use. In Western red cedar asthmatics removed from exposure, measures of airway responsiveness are associated with HRQL.

  6. Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement

    Science.gov (United States)

    Alrashdan, Yazan A.; Alkhouri, Hatem; Chen, Emily; Lalor, Daniel J.; Poniris, Maree; Henness, Sheridan; Brightling, Christopher E.; Burgess, Janette K.; Armour, Carol L.; Ammit, Alaina J.

    2012-01-01

    CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix). CXCL10 mRNA and protein, JNK, NF-κB p65 phosphorylation, and Iκ-Bα protein degradation were assessed using real-time PCR, ELISA, and immunoblotting, respectively. Cytomix, IL-1β, and TNF-α induced CXCL10 mRNA expression more rapidly in asthmatic than nonasthmatic ASM cells. IL-1β and/or TNF-α combined with IFN-γ synergistically increased asthmatic ASM cell CXCL10 release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but cytomix-induced release was least affected, with only JNK and NF-κB inhibitors halving it. Notably, JNK phosphorylation was markedly less in asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect CXCL10 mRNA stability or Iκ-Bα degradation. Together, the JNK and NF-κB inhibitors completely inhibited their CXCL10 release. We concluded that, in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and CXCL10 gene expression was more rapid following cytomix stimulation. However, in both, JNK activation did not regulate early events leading to NF-κB activation. Thus JNK and NF-κB provide independent therapeutic targets for limiting CXCL10 production and mast cell migration to the ASM in asthma. PMID:22387292

  7. Quantitative computed tomography–derived clusters: Redefining airway remodeling in asthmatic patients☆

    Science.gov (United States)

    Gupta, Sumit; Hartley, Ruth; Khan, Umair T.; Singapuri, Amisha; Hargadon, Beverly; Monteiro, William; Pavord, Ian D.; Sousa, Ana R.; Marshall, Richard P.; Subramanian, Deepak; Parr, David; Entwisle, James J.; Siddiqui, Salman; Raj, Vimal; Brightling, Christopher E.

    2014-01-01

    Background Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)–assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms. Objectives The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes. Methods Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT-based asthma phenotypes. Results Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm3 [SD, 112.6 mm3], 259.0 mm3 [SD, 53.3 mm3], 366.4 mm3 [SD, 195.3 mm3], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects. Conclusions Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies. PMID:24238646

  8. Beta-escin has potent anti-allergic efficacy and reduces allergic airway inflammation

    Directory of Open Access Journals (Sweden)

    Unger Hermann

    2010-05-01

    Full Text Available Abstract Background Type I hypersensitivity is characterized by the overreaction of the immune system against otherwise innocuous substances. It manifests as allergic rhinitis, allergic conjunctivitis, allergic asthma or atopic dermatitis if mast cells are activated in the respective organs. In case of systemic mast cell activation, life-threatening anaphylaxis may occur. Currently, type I hypersensitivities are treated either with glucocorticoids, anti-histamines, or mast cell stabilizers. Although these drugs exert a strong anti-allergic effect, their long-term use may be problematic due to their side-effects. Results In the course of a routine in vitro screening process, we identified beta-escin as a potentially anti-allergic compound. Here we tested beta-escin in two mouse models to confirm this anti-allergic effect in vivo. In a model of the early phase of allergic reactions, the murine passive cutaneous anaphylaxis model, beta-escin inhibited the effects of mast cell activation and degranulation in the skin and dose-dependently prevented the extravasation of fluids into the tissue. Beta-escin also significantly inhibited the late response after antigen challenge in a lung allergy model with ovalbumin-sensitized mice. Allergic airway inflammation was suppressed, which was exemplified by the reduction of leucocytes, eosinophils, IL-5 and IL-13 in the bronchoalveolar lavage fluid. Histopathological examinations further confirmed the reduced inflammation of the lung tissue. In both models, the inhibitory effect of beta-escin was comparable to the benchmark dexamethasone. Conclusions We demonstrated in two independent murine models of type I hypersensitivity that beta-escin has potent anti-allergic properties. These results and the excellent safety profile of beta-escin suggest a therapeutic potential of this compound for a novel treatment of allergic diseases.

  9. Beta-escin has potent anti-allergic efficacy and reduces allergic airway inflammation.

    Science.gov (United States)

    Lindner, Ines; Meier, Christiane; Url, Angelika; Unger, Hermann; Grassauer, Andreas; Prieschl-Grassauer, Eva; Doerfler, Petra

    2010-05-21

    Type I hypersensitivity is characterized by the overreaction of the immune system against otherwise innocuous substances. It manifests as allergic rhinitis, allergic conjunctivitis, allergic asthma or atopic dermatitis if mast cells are activated in the respective organs. In case of systemic mast cell activation, life-threatening anaphylaxis may occur. Currently, type I hypersensitivities are treated either with glucocorticoids, anti-histamines, or mast cell stabilizers. Although these drugs exert a strong anti-allergic effect, their long-term use may be problematic due to their side-effects. In the course of a routine in vitro screening process, we identified beta-escin as a potentially anti-allergic compound. Here we tested beta-escin in two mouse models to confirm this anti-allergic effect in vivo. In a model of the early phase of allergic reactions, the murine passive cutaneous anaphylaxis model, beta-escin inhibited the effects of mast cell activation and degranulation in the skin and dose-dependently prevented the extravasation of fluids into the tissue. Beta-escin also significantly inhibited the late response after antigen challenge in a lung allergy model with ovalbumin-sensitized mice. Allergic airway inflammation was suppressed, which was exemplified by the reduction of leucocytes, eosinophils, IL-5 and IL-13 in the bronchoalveolar lavage fluid. Histopathological examinations further confirmed the reduced inflammation of the lung tissue. In both models, the inhibitory effect of beta-escin was comparable to the benchmark dexamethasone. We demonstrated in two independent murine models of type I hypersensitivity that beta-escin has potent anti-allergic properties. These results and the excellent safety profile of beta-escin suggest a therapeutic potential of this compound for a novel treatment of allergic diseases.

  10. Divergent effects of urban particulate air pollution on allergic airway responses in experimental asthma: a comparison of field exposure studies.

    Science.gov (United States)

    Wagner, James G; Morishita, Masako; Keeler, Gerald J; Harkema, Jack R

    2012-07-06

    Increases in ambient particulate matter of aerodynamic diameter of 2.5 μm (PM2.5) are associated with asthma morbidity and mortality. The overall objective of this study was to test the hypothesis that PM2.5 derived from two distinct urban U.S. communities would induce variable responses to aggravate airway symptoms during experimental asthma. We used a mobile laboratory to conduct community-based inhalation exposures to laboratory rats with ovalbumin-induced allergic airways disease. In Grand Rapids exposures were conducted within 60 m of a major roadway, whereas the Detroit was located in an industrial area more than 400 m from roadways. Immediately after nasal allergen challenge, Brown Norway rats were exposed by whole body inhalation to either concentrated air particles (CAPs) or filtered air for 8 h (7:00 AM - 3:00 PM). Both ambient and concentrated PM2.5 was assessed for mass, size fractionation, and major component analyses, and trace element content. Sixteen hours after exposures, bronchoalveolar lavage fluid (BALF) and lung lobes were collected and evaluated for airway inflammatory and mucus responses. Similar CAPs mass concentrations were generated in Detroit (542 μg/m3) and Grand Rapids (519 μg/m3). Exposure to CAPs at either site had no effects in lungs of non-allergic rats. In contrast, asthmatic rats had 200% increases in airway mucus and had more BALF neutrophils (250% increase), eosinophils (90%), and total protein (300%) compared to controls. Exposure to Detroit CAPs enhanced all allergic inflammatory endpoints by 30-100%, whereas inhalation of Grand Rapids CAPs suppressed all allergic responses by 50%. Detroit CAPs were characterized by high sulfate, smaller sized particles and were derived from local combustion sources. Conversely Grand Rapids CAPs were derived primarily from motor vehicle sources. Despite inhalation exposure to the same mass concentration of urban PM2.5, disparate health effects can be elicited in the airways of

  11. Divergent effects of urban particulate air pollution on allergic airway responses in experimental asthma: a comparison of field exposure studies

    Directory of Open Access Journals (Sweden)

    Wagner James G

    2012-07-01

    Full Text Available Abstract Background Increases in ambient particulate matter of aerodynamic diameter of 2.5 μm (PM2.5 are associated with asthma morbidity and mortality. The overall objective of this study was to test the hypothesis that PM2.5 derived from two distinct urban U.S. communities would induce variable responses to aggravate airway symptoms during experimental asthma. Methods We used a mobile laboratory to conduct community-based inhalation exposures to laboratory rats with ovalbumin-induced allergic airways disease. In Grand Rapids exposures were conducted within 60 m of a major roadway, whereas the Detroit was located in an industrial area more than 400 m from roadways. Immediately after nasal allergen challenge, Brown Norway rats were exposed by whole body inhalation to either concentrated air particles (CAPs or filtered air for 8 h (7:00 AM - 3:00 PM. Both ambient and concentrated PM2.5 was assessed for mass, size fractionation, and major component analyses, and trace element content. Sixteen hours after exposures, bronchoalveolar lavage fluid (BALF and lung lobes were collected and evaluated for airway inflammatory and mucus responses. Results Similar CAPs mass concentrations were generated in Detroit (542 μg/m3 and Grand Rapids (519 μg/m3. Exposure to CAPs at either site had no effects in lungs of non-allergic rats. In contrast, asthmatic rats had 200% increases in airway mucus and had more BALF neutrophils (250% increase, eosinophils (90%, and total protein (300% compared to controls. Exposure to Detroit CAPs enhanced all allergic inflammatory endpoints by 30-100%, whereas inhalation of Grand Rapids CAPs suppressed all allergic responses by 50%. Detroit CAPs were characterized by high sulfate, smaller sized particles and were derived from local combustion sources. Conversely Grand Rapids CAPs were derived primarily from motor vehicle sources. Conclusions Despite inhalation exposure to the same mass concentration of urban PM2

  12. Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor.

    Directory of Open Access Journals (Sweden)

    Konstantinos Samitas

    Full Text Available B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive.A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF and their receptors (CD127 and BAFFR, BCMA, TACI, respectively were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein and in vitro (colony forming cell assay. Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL of asthmatic patients and healthy controls.Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4 and co-stimulation (CD40, CD86 and are resistant to apoptosis (Bax. Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics.Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation.

  13. Involvement of galectin-9 in guinea pig allergic airway inflammation.

    Science.gov (United States)

    Yamamoto, Hitomi; Kashio, Yumiko; Shoji, Hiroki; Shinonaga, Rika; Yoshimura, Teizo; Nishi, Nozomu; Nabe, Takeshi; Nakamura, Takanori; Kohno, Shigekatsu; Hirashima, Mitsuomi

    2007-01-01

    There is little information about the involvement of galectin-9 (Gal-9) in allergic inflammation. Thus, we investigated the role of Gal-9 in asthma model guinea pigs. Airway resistance (R(aw)) was measured using a double-flow plethysmograph system. Gal-9 expression in the lung was assessed by Western blot and immunohistochemistry. Eosinophil chemotactic activity was evaluated in a chamber containing a polyvinylpyrolidone-free membrane. Cell apoptosis was analyzed on a flowcytometry with propidium iodide. In cloning guinea pig Gal-9 we identified three isoforms that differ only in the length of their linker peptides, just as with human Gal-9. Guinea pig Gal-9 was found to be a chemoattractant for eosinophils and to promote induction of apoptosis in sensitized but not non-sensitized T lymphocytes. In allergic airway hypersensitivity model, a low level of Gal-9 expression was observed in the nonsensitized/nonchallenged group, but upregulation was detected at 7 h after challenge and sustained up to 24 h. Such upregulation correlated with elevation of eosinophil peroxidase activity but not with increased R(aw). The present results provide evidence that Gal-9 is not involved in airway hypersensitivity, but is partly involved in prolonged eosinophil accumulation in the lung.

  14. Abnormalities of the airways and lung parenchyma in asthmatics: CT observations in 50 patients and inter- and intraobserver variability

    International Nuclear Information System (INIS)

    Grenier, P.; Mourey-Gerosa, I.; Benali, K.; Brauner, M.W.; Leung, A.N.; Lenoir, S..; Cordeau, M.P.; Mazoyer, B.

    1996-01-01

    The purpose of the study was to evaluate the CT abnormalities of airways and lung parenchyma in asthmatic patients and to assess inter- and intraobserver variability for these abnormalities. The CT scans of 50 asthmatic patients and 10 healthy volunteers were assessed independently by four independent chest radiologists who were masked with respect to the clinical informations. Bronchiectasis involving mostly subsegmental and destal bronchi was noted in 28.5% of the asthmatic subjects and none of the non-asthmatics. Bronchial wall thickening, small centrilobular opacities and decreased lung attenuation were observed in 82%, 21% and 31% of asthmatic patients respectively, compared with 7%, 5% and 7% of healthy subjects. The intra- and interobserver agreements for these four CT abnormalities were measured by the kappa statistic and ranged from 0.60 to 0.79 and from 0.40 to 0.64, respectively. It is concluded that asthmatic patients may exhibit bronchial wall thickening, bronchiectasis and morphological abnormalities suggestive of distal airways disease that can be assessed on CT scans with a clinically acceptable observer variability. (orig.)

  15. Identification of airway mucosal type 2 inflammation by using clinical biomarkers in asthmatic patients.

    Science.gov (United States)

    Silkoff, Philip E; Laviolette, Michel; Singh, Dave; FitzGerald, J Mark; Kelsen, Steven; Backer, Vibeke; Porsbjerg, Celeste M; Girodet, Pierre-Olivier; Berger, Patrick; Kline, Joel N; Chupp, Geoffrey; Susulic, Vedrana S; Barnathan, Elliot S; Baribaud, Frédéric; Loza, Matthew J

    2017-09-01

    The Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study profiled patients with mild, moderate, and severe asthma and nonatopic healthy control subjects. We explored this data set to define type 2 inflammation based on airway mucosal IL-13-driven gene expression and how this related to clinically accessible biomarkers. IL-13-driven gene expression was evaluated in several human cell lines. We then defined type 2 status in 25 healthy subjects, 28 patients with mild asthma, 29 patients with moderate asthma, and 26 patients with severe asthma based on airway mucosal expression of (1) CCL26 (the most differentially expressed gene), (2) periostin, or (3) a multigene IL-13 in vitro signature (IVS). Clinically accessible biomarkers included fraction of exhaled nitric oxide (Feno) values, blood eosinophil (bEOS) counts, serum CCL26 expression, and serum CCL17 expression. Expression of airway mucosal CCL26, periostin, and IL-13-IVS all facilitated segregation of subjects into type 2-high and type 2-low asthmatic groups, but in the ADEPT study population CCL26 expression was optimal. All subjects with high airway mucosal CCL26 expression and moderate-to-severe asthma had Feno values (≥35 ppb) and/or high bEOS counts (≥300 cells/mm 3 ) compared with a minority (36%) of subjects with low airway mucosal CCL26 expression. A combination of Feno values, bEOS counts, and serum CCL17 and CCL26 expression had 100% positive predictive value and 87% negative predictive value for airway mucosal CCL26-high status. Clinical variables did not differ between subjects with type 2-high and type 2-low status. Eosinophilic inflammation was associated with but not limited to airway mucosal type 2 gene expression. A panel of clinical biomarkers accurately classified type 2 status based on airway mucosal CCL26, periostin, or IL-13-IVS gene expression. Use of Feno values, bEOS counts, and serum marker levels (eg, CCL26 and CCL17) in combination might allow patient

  16. Alterations of the murine gut microbiome in allergic airway disease are independent of surfactant protein D

    DEFF Research Database (Denmark)

    Barfod, Kenneth Klingenberg; Roggenbuck, Michael; Al-Shuweli, Suzan

    2017-01-01

    with the lack of SP-D protein and presence of allergic airway disease in the widely used SP-D-deficient mouse model. Results We describe here for the first time the lung and gut microbiota of the SP-D mouse model with OVA induced allergic airway disease. After the challenge animals were killed and fecal samples...

  17. Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways

    Energy Technology Data Exchange (ETDEWEB)

    Denner, Darcy R.; Sangwan, Naseer; Becker, Julia B.; Hogarth, D. Kyle; Oldham, Justin; Castillo, Jamee; Sperling, Anne I.; Solway, Julian; Naureckas, Edward T.; Gilbert, Jack A.; White, Steven R.

    2016-05-01

    The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear. OBJECTIVES: We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia. METHODS: DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencing was used to compare the relative abundance of bacterial genera with clinical characteristics. RESULTS: Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus, Pseudomonas, and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella, Streptococcus, and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils. CONCLUSION: The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. [Serum levels of ANP signaling in different degree of allergic asthmatics and its role in the pathogenesis of
allergic asthma].

    Science.gov (United States)

    Yu, Yuanyuan; Zeng, Jinrong; Sun, Yabing; Wei, Jianghong; Huang, Jianwei; Ma, Libing

    2016-07-01

    To investigate the relationship between the severity of allergic asthma and the levels of atrial natriuretic peptide (ANP), and to analyze the potential role of ANP signaling in the pathogenesis of asthma.
 We recruited 96 subjects, including 23 healthy volunteers, 25 stable allergic asthmatics, 21 mild allergic asthmatics and 27 moderate allergic asthmatics, from the Affiliated Hospital of Guilin Medical University. ANP, IFN-γ and IL-4 levels in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expressions of natriuretic peptide receptor A (NPRA), transcription factor T-bet and GATA3 were measured by RT-PCR and Western blot.
 The levels of ANP in serum and the expressions of NPRA mRNA and protein in the peripheral blood mononuclear cell (PBMC) from the mild asthma group or the moderate group were elevated compared with those in the stable asthma group or the mild group, respectively (P<0.05). Consistently, expressions of GATA3 and levels of IL-4 showed the same tendency (P<0.05). In addition, levels of ANP in serum were positively correlated with the severity of asthma, whereas negatively correlated with the ratio of T-bet/GATA3 and IFN-γ/IL-4 (r=-0.85, P<0.05; r=-0.88, P<0.05, respectively).
 Levels of ANP signaling in serum were significantly increased with the severity of allergic asthma, suggesting a close relation with the pathogenesis of asthma; ANP signaling may play a role in the pathogenesis of allergic asthma through inducing the Th2-type immune response.

  19. Dietary Compound Kaempferol Inhibits Airway Thickening Induced by Allergic Reaction in a Bovine Serum Albumin-Induced Model of Asthma.

    Science.gov (United States)

    Shin, Daekeun; Park, Sin-Hye; Choi, Yean-Jung; Kim, Yun-Ho; Antika, Lucia Dwi; Habibah, Nurina Umy; Kang, Min-Kyung; Kang, Young-Hee

    2015-12-16

    Asthma is characterized by aberrant airways including epithelial thickening, goblet cell hyperplasia, and smooth muscle hypertrophy within the airway wall. The current study examined whether kaempferol inhibited mast cell degranulation and prostaglandin (PG) release leading to the development of aberrant airways, using an in vitro model of dinitrophenylated bovine serum albumin (DNP-BSA)-sensitized rat basophilic leukemia (RBL-2H3) mast cells and an in vivo model of BSA-challenged asthmatic mice. Nontoxic kaempferol at 10-20 μM suppressed β-hexosaminidase release and cyclooxygenase 2 (COX2)-mediated production of prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α) in sensitized mast cells. Oral administration of ≤20 mg/kg kaempferol blocked bovine serum albumin (BSA) inhalation-induced epithelial cell excrescence and smooth muscle hypertrophy by attenuating the induction of COX2 and the formation of PGD2 and PGF2α, together with reducing the anti-α-smooth muscle actin (α-SMA) expression in mouse airways. Kaempferol deterred the antigen-induced mast cell activation of cytosolic phospholipase A2 (cPLA2) responsive to protein kinase Cμ (PKCμ) and extracellular signal-regulated kinase (ERK). Furthermore, the antigen-challenged activation of Syk-phospholipase Cγ (PLCγ) pathway was dampened in kaempferol-supplemented mast cells. These results demonstrated that kaempferol inhibited airway wall thickening through disturbing Syk-PLCγ signaling and PKCμ-ERK-cPLA2-COX2 signaling in antigen-exposed mast cells. Thus, kaempferol may be a potent anti-allergic compound targeting allergic asthma typical of airway hyperplasia and hypertrophy.

  20. Aggravation of Allergic Airway Inflammation by Cigarette Smoke in Mice Is CD44-Dependent.

    Directory of Open Access Journals (Sweden)

    Smitha Kumar

    Full Text Available Although epidemiological studies reveal that cigarette smoke (CS facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation.Wild type (WT and CD44 knock-out (KO mice were exposed simultaneously to house dust mite (HDM extract and CS. Inflammatory cells, hyaluronic acid (HA and osteopontin (OPN levels were measured in bronchoalveolar lavage fluid (BALF. Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures.In WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice.We demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics.

  1. LF-15 & T7, synthetic peptides derived from tumstatin, attenuate aspects of airway remodelling in a murine model of chronic OVA-induced allergic airway disease.

    Directory of Open Access Journals (Sweden)

    Karryn T Grafton

    Full Text Available BACKGROUND: Tumstatin is a segment of the collagen-IV protein that is markedly reduced in the airways of asthmatics. Tumstatin can play an important role in the development of airway remodelling associated with asthma due to its anti-angiogenic properties. This study assessed the anti-angiogenic properties of smaller peptides derived from tumstatin, which contain the interface tumstatin uses to interact with the αVβ3 integrin. METHODS: Primary human lung endothelial cells were exposed to the LF-15, T3 and T7 tumstatin-derived peptides and assessed for cell viability and tube formation in vitro. The impact of the anti-angiogenic properties on airways hyperresponsiveness (AHR was then examined using a murine model of chronic OVA-induced allergic airways disease. RESULTS: The LF-15 and T7 peptides significantly reduced endothelial cell viability and attenuated tube formation in vitro. Mice exposed to OVA+ LF-15 or OVA+T7 also had reduced total lung vascularity and AHR was attenuated compared to mice exposed to OVA alone. T3 peptides reduced cell viability but had no effect on any other parameters. CONCLUSION: The LF-15 and T7 peptides may be appropriate candidates for use as novel pharmacotherapies due to their small size and anti-angiogenic properties observed in vitro and in vivo.

  2. Quantitative computed tomography-derived clusters: redefining airway remodeling in asthmatic patients.

    Science.gov (United States)

    Gupta, Sumit; Hartley, Ruth; Khan, Umair T; Singapuri, Amisha; Hargadon, Beverly; Monteiro, William; Pavord, Ian D; Sousa, Ana R; Marshall, Richard P; Subramanian, Deepak; Parr, David; Entwisle, James J; Siddiqui, Salman; Raj, Vimal; Brightling, Christopher E

    2014-03-01

    Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)-assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms. The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes. Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT-based asthma phenotypes. Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm(3) [SD, 112.6 mm(3)], 259.0 mm(3) [SD, 53.3 mm(3)], 366.4 mm(3) [SD, 195.3 mm(3)], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects. Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies. Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved.

  3. Allergic fungal airway disease: pathophysiologic and diagnostic considerations.

    Science.gov (United States)

    Woolnough, Kerry; Fairs, Abbie; Pashley, Catherine H; Wardlaw, Andrew J

    2015-01-01

    Fungal spores are ubiquitously present in indoor and outdoor air. A number can act as aeroallergens in Immunoglobulin E (IgE)-sensitized individuals and some thermotolerant fungi germinate in the lung where they can cause a combined allergic and infective stimulus leading to a number of clinical presentations characterized by evidence of lung damage. We discuss which biomarkers are useful in helping to guide diagnosis, prognosis and treatment of allergic fungal airway disease (AFAD). Diagnostic biomarkers, such as specific IgEs and fungal culture, for AFAD are limited by sensitivity, although this may be improved with novel agents such as specific IgEs to fungal components and quantitative PCR. Total IgE and hypereosinophilia are nonspecific and do not clearly relate to disease activity. High attenuation mucus and proximal bronchiectasis are specific, albeit insensitive markers of AFAD. Biomarkers that predict prognosis and treatment response are yet to be defined. This review summarizes the fungi involved and the current debate regarding the diagnostic criteria to define fungal-associated lung disease. We advocate the phasing out of the term allergic bronchopulmonary aspergillosis and the use of a more inclusive term such as AFAD, together with a more liberal set of criteria based largely on IgE sensitization to thermotolerant fungi, which identifies those patients at risk of developing lung damage.

  4. Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle relaxation in allergic asthma

    Directory of Open Access Journals (Sweden)

    Zaagsma Johan

    2006-01-01

    Full Text Available Abstract Background Using guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO production – due to competition with neuronal NO-synthase (nNOS for the common substrate, L-arginine. Furthermore, in a guinea pig model of allergic asthma, airway arginase activity is markedly increased after the early asthmatic reaction (EAR, leading to deficiency of agonist-induced, epithelium-derived NO and subsequent airway hyperreactivity. In this study, we investigated whether increased arginase activity after the EAR affects iNANC nerve-derived NO production and airway smooth muscle relaxation. Methods Electrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5 – 16 Hz-induced relaxation was measured in tracheal open-ring preparations precontracted to 30% with histamine in the presence of 1 μM atropine and 3 μM indomethacin. The contribution of NO to EFS-induced relaxation was assessed by the nonselective NOS inhibitor Nω-nitro-L-arginine (L-NNA, 100 μM, while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA, 10 μM. Furthermore, the role of substrate availability to nNOS was measured in the presence of exogenous L-arginine (5.0 mM. Results At 6 h after ovalbumin-challenge (after the EAR, EFS-induced relaxation (ranging from 3.2 ± 1.1% at 0.5 Hz to 58.5 ± 2.2% at 16 Hz was significantly decreased compared to unchallenged controls (7.1 ± 0.8% to 75.8 ± 0.7%; P P P Conclusion The results clearly demonstrate that increased arginase activity after the allergen-induced EAR contributes to a deficiency of iNANC nerve-derived NO and decreased airway smooth muscle relaxation, presumably via increased substrate competition with nNOS.

  5. Role of ROCK2 in CD4+cells in allergic airways responses in mice.

    Science.gov (United States)

    Kasahara, D I; Mathews, J A; Ninin, F M C; Wurmbrand, A P; Liao, J K; Shore, S A

    2017-02-01

    Rho kinases (ROCKs) contribute to allergic airways disease. ROCKs also play a role in lymphocyte proliferation and migration. To determine the role of ROCK2 acting within CD4 + cells in allergic airways responses. ROCK2-haploinsufficient (ROCK2 +/- ) and wild-type mice were sensitized with ovalbumin (OVA). ROCK2 +/- mice then received either CD4 + cells from ROCK2-sufficient OVA TCR transgenic (OT-II) mice or saline i.v. 48 h before challenge with aerosolized OVA. Wild-type mice received saline before challenge. Allergic airways responses were measured 48 h after the last challenge. Allergic airways responses were also assessed in mice lacking ROCK2 only in CD4 + cells (ROCK2 CD 4Cre mice) vs. control (CD4-Cre and ROCK2 flox/flox ) mice. OVA-induced increases in bronchoalveolar lavage lymphocytes, eosinophils, IL-13, IL-5, and eotaxin were reduced in ROCK2 +/- vs. wild-type mice, as were airway hyperresponsiveness and mucous hypersecretion. In ROCK2 +/- mice, adoptive transfer with CD4 + cells from OT-II mice restored effects of OVA on lymphocytes, eosinophils, IL-13, IL-5, and mucous hypersecretion to wild-type levels, whereas eotaxin and airway hyperresponsiveness were not affected. ROCK2 inhibitors reduced IL-13-induced release of eotaxin from airway smooth muscle (ASM), similar to effects of these inhibitors on ASM contractility. Despite the ability of adoptive transfer to restore allergic airways inflammation in ROCK2-insufficient mice, allergic inflammation was not different in ROCK2 CD 4Cre vs. control mice. ROCK2 contributes to allergic airways responses likely via effects within ASM cells and within non-lymphocyte cells involved in lymphocyte activation and migration into the airways. © 2016 John Wiley & Sons Ltd.

  6. Inhibition of protein kinase C delta attenuates allergic airway inflammation through suppression of PI3K/Akt/mTOR/HIF-1 alpha/VEGF pathway.

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    Yun Ho Choi

    Full Text Available Vascular endothelial growth factor (VEGF is supposed to contribute to the pathogenesis of allergic airway disease. VEGF expression is regulated by a variety of stimuli such as nitric oxide, growth factors, and hypoxia-inducible factor-1 alpha (HIF-1α. Recently, inhibition of the mammalian target of rapamycin (mTOR has been shown to alleviate cardinal asthmatic features, including airway hyperresponsiveness, eosinophilic inflammation, and increased vascular permeability in asthma models. Based on these observations, we have investigated whether mTOR is associated with HIF-1α-mediated VEGF expression in allergic asthma. In studies with the mTOR inhibitor rapamycin, we have elucidated the stimulatory role of a mTOR-HIF-1α-VEGF axis in allergic response. Next, the mechanisms by which mTOR is activated to modulate this response have been evaluated. mTOR is known to be regulated by phosphoinositide 3-kinase (PI3K/Akt or protein kinase C-delta (PKC δ in various cell types. Consistent with these, our results have revealed that suppression of PKC δ by rottlerin leads to the inhibition of PI3K/Akt activity and the subsequent blockade of a mTOR-HIF-1α-VEGF module, thereby attenuating typical asthmatic attack in a murine model. Thus, the present data indicate that PKC δ is necessary for the modulation of the PI3K/Akt/mTOR signaling cascade, resulting in a tight regulation of HIF-1α activity and VEGF expression. In conclusion, PKC δ may represent a valuable target for innovative therapeutic treatment of allergic airway disease.

  7. Cold air challenge for measuring airway reactivity in children: lack of a late asthmatic reaction.

    Science.gov (United States)

    Varga, E M; Eber, E; Zach, M S

    1990-01-01

    Cold air challenge (CACh) for measuring airway reactivity uses respiratory heat or water loss as a bronchoconstrictor stimulus; this stimulus is also important for the development of exercise-induced asthma, for which late asthmatic reactions (LARs) have been described. At 1200 hr on day 1, 22 children with asthma started to record their peak expiratory flow rate (PEFR) in 3 hr intervals until 0900 hr on day 2. At 1000 hr, they underwent a standardized 4 min CACh. Children then inhaled salbutamol and continued to record PEFR until 0900 hr on day 3. As a bronchodilator effect, PEFR measurements were significantly higher 2, 5, and 8 hr after CACh, but subsequently did not differ significantly from pre-CACh values. At 5 hr after CACh, individual values ranged from 95 to 137% of the corresponding pre-CACh measurements, at 8 hr from 94 to 150%, and at 11 hr from 80 to 121%. This random sample of children with asthma demonstrated no LAR after CACh.

  8. Alterations of the murine gut microbiome in allergic airway disease are independent of surfactant protein D

    Directory of Open Access Journals (Sweden)

    Kenneth K. Barfod

    2017-03-01

    Conclusions: Our results show that the composition of the microbiota is not influenced by the SP-D deficient genotype under naïve or OVA induced airway disease. However, OVA sensitization and pulmonary challenge did alter the gut microbiota, supporting a bidirectional lung-gut crosstalk. Future mechanistic investigations of the influence of induced allergic airway disease on gut microbiota are warranted.

  9. IL-18 Does not Increase Allergic Airway Disease in Mice When Produced by BCG

    Directory of Open Access Journals (Sweden)

    L. Amniai

    2007-01-01

    These data show that IL-18 did not increase allergic airway responses in the context of the mycobacterial infection, and suggest that BCG-IL-18 and BCG are able to prevent the development of local Th2 responses and therefore inhibit allergen-induced airway responses even after restimulation.

  10. CITRIC-ACID COUGH THRESHOLD AND AIRWAY RESPONSIVENESS IN ASTHMATIC-PATIENTS AND SMOKERS WITH CHRONIC AIR-FLOW OBSTRUCTION

    NARCIS (Netherlands)

    AUFFARTH, B; DEMONCHY, JGR; VANDERMARK, TW; POSTMA, DS; KOETER, GH

    The relation between citric acid cough threshold and airway hyperresponsiveness was investigated in 11 non-smoking patients with allergic asthma (mean FEV1 94% predicted) and 25 non-atopic smokers with chronic airflow obstruction (mean FEV1 65% predicted). Cough threshold was determined on two

  11. Bakery flour dust exposure causes non-allergic inflammation and enhances allergic airway inflammation in mice.

    Science.gov (United States)

    Marraccini, P; Brass, D M; Hollingsworth, J W; Maruoka, S; Garantziotis, S; Schwartz, D A

    2008-09-01

    Baker's asthma is one of the most commonly reported occupational lung diseases in countries where fresh bread is baked daily in large quantities, and is characterized by rhinitis, bronchial hyperresponsiveness, and reversible airflow obstruction. Epidemiological studies have identified pre-existing atopy as an important risk factor for developing baker's asthma, yet the aetiology and pathogenesis of baker's asthma remain poorly understood. We sought to develop a mouse model of baker's asthma that could be used to characterize the development and progression of baker's asthma. We were unable to sensitize mice to bakery flour dust or flour dust extract. We assessed total inflammatory cells, cellular differential, total serum IgE and the pro-inflammatory cytokine response to oropharyngeally instilled bakery flour dust or flour dust extract by itself or in the context of ovalbumin (OVA) sensitization and challenge. Both bakery flour dust and flour dust extract consistently elicited a neutrophilic inflammation in a Toll-like receptor 4-independent manner; suggesting that endotoxin is not playing a role in the inflammatory response to flour dust. Moreover, bakery flour dust and dust extract significantly enhance the inflammatory response in OVA-sensitized and challenged mice. Bakery flour dust and flour dust extract are strongly pro-inflammatory and can cause non-allergic airway inflammation and can enhance allergen-mediated airway inflammation.

  12. Acanthamoeba protease activity promotes allergic airway inflammation via protease-activated receptor 2.

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    Mi Kyung Park

    Full Text Available Acanthamoeba is a free-living amoeba commonly present in the environment and often found in human airway cavities. Acanthamoeba possesses strong proteases that can elicit allergic airway inflammation. To our knowledge, the aeroallergenicity of Acanthamoeba has not been reported. We repeatedly inoculated mice with Acanthamoeba trophozoites or excretory-secretory (ES proteins intra-nasally and evaluated symptoms and airway immune responses. Acanthamoeba trophozoites or ES proteins elicited immune responses in mice that resembled allergic airway inflammation. ES proteins had strong protease activity and activated the expression of several chemokine genes (CCL11, CCL17, CCL22, TSLP, and IL-25 in mouse lung epithelial cells. The serine protease inhibitor phenyl-methane-sulfonyl fluoride (PMSF inhibited ES protein activity. ES proteins also stimulated dendritic cells and enhanced the differentiation of naive T cells into IL-4-secreting T cells. After repeated inoculation of the protease-activated receptor 2 knockout mouse with ES proteins, airway inflammation and Th2 immune responses were markedly reduced, but not to basal levels. Furthermore, asthma patients had higher Acanthamoeba-specific IgE titers than healthy controls and we found Acanthamoeba specific antigen from house dust in typical living room. Our findings suggest that Acanthamoeba elicits allergic airway symptoms in mice via a protease allergen. In addition, it is possible that Acanthamoeba may be one of the triggers human airway allergic disease.

  13. Acanthamoeba Protease Activity Promotes Allergic Airway Inflammation via Protease-Activated Receptor 2

    Science.gov (United States)

    Park, Mi Kyung; Cho, Min Kyoung; Kang, Shin Ae; Park, Hye-Kyung; Kim, Dong-Hee; Yu, Hak Sun

    2014-01-01

    Acanthamoeba is a free-living amoeba commonly present in the environment and often found in human airway cavities. Acanthamoeba possesses strong proteases that can elicit allergic airway inflammation. To our knowledge, the aeroallergenicity of Acanthamoeba has not been reported. We repeatedly inoculated mice with Acanthamoeba trophozoites or excretory-secretory (ES) proteins intra-nasally and evaluated symptoms and airway immune responses. Acanthamoeba trophozoites or ES proteins elicited immune responses in mice that resembled allergic airway inflammation. ES proteins had strong protease activity and activated the expression of several chemokine genes (CCL11, CCL17, CCL22, TSLP, and IL-25) in mouse lung epithelial cells. The serine protease inhibitor phenyl-methane-sulfonyl fluoride (PMSF) inhibited ES protein activity. ES proteins also stimulated dendritic cells and enhanced the differentiation of naive T cells into IL-4-secreting T cells. After repeated inoculation of the protease-activated receptor 2 knockout mouse with ES proteins, airway inflammation and Th2 immune responses were markedly reduced, but not to basal levels. Furthermore, asthma patients had higher Acanthamoeba-specific IgE titers than healthy controls and we found Acanthamoeba specific antigen from house dust in typical living room. Our findings suggest that Acanthamoeba elicits allergic airway symptoms in mice via a protease allergen. In addition, it is possible that Acanthamoeba may be one of the triggers human airway allergic disease. PMID:24658532

  14. Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children.

    Directory of Open Access Journals (Sweden)

    Michael Fayon

    Full Text Available Many asthmatic patients exhibit uncontrolled asthma despite high-dose inhaled corticosteroids (ICS. Airway epithelial cells (AEC have distinct activation profiles that can influence ICS response.A pilot study to identify gene expression markers of AEC dysfunction and markers of corticosteroid sensitivity in asthmatic and non-asthmatic control children, for comparison with published reports in adults.AEC were obtained by nasal brushings and primary submerged cultures, and incubated in control conditions or in the presence of 10 ng/ml TNFalpha, 10-8M dexamethasone, or both. RT-PCR-based expression of FKBP51 (a steroid hormone receptor signalling regulator, NF-kB, IL-6, LIF (an IL-6 family neurotrophic cytokine, serpinB2 (which inhibits plasminogen activation and promotes fibrin deposition and porin (a marker of mitochondrial mass were determined.6 patients without asthma (median age 11yr; min-max: 7-13, 8 with controlled asthma (11yr, 7-13; median daily fluticasone dose = 100 μg, and 4 with uncontrolled asthma (12yr, 7-14; 1000 μg fluticasone daily were included. Baseline expression of LIF mRNA was significantly increased in uncontrolled vs controlled asthmatic children. TNFalpha significantly increased LIF expression in uncontrolled asthma. A similar trend was observed regarding IL-6. Dexamethasone significantly upregulated FKBP51 expression in all groups but the response was blunted in asthmatic children. No significant upregulation was identified regarding NF-kB, serpinB2 and porin.LIF and FKBP51 expression in epithelial cells were the most interesting markers of AEC dysfunction/response to corticosteroid treatment.

  15. A potential role for P2X7R in allergic airway inflammation in mice and humans.

    Science.gov (United States)

    Müller, Tobias; Vieira, Rodolfo Paula; Grimm, Melanie; Dürk, Thorsten; Cicko, Sanja; Zeiser, Robert; Jakob, Thilo; Martin, Stefan F; Blumenthal, Britta; Sorichter, Stephan; Ferrari, Davide; Di Virgillio, Francesco; Idzko, Marco

    2011-04-01

    P2X₇R deficiency is associated with a less severe outcome in acute and chronic inflammatory disorders. Recently, we demonstrated that extracellular adenosine triphosphate is involved in the pathogenesis of asthma by modulating the function of dendritic cells (DCs). However, the role of the purinergic receptor subtype P2X₇ is unknown. To elucidate the role of P2X₇R in allergic airway inflammation (AAI) in vitro and in vivo, P2X₇R expression was measured in lung tissue and immune cells of mice or in humans with allergic asthma. By using a specific P2X₇R-antagonist and P2X₇R-deficient animals, the role of this receptor in acute and chronic experimental asthma was explored. P2X₇R was found to be up-regulated during acute and chronic asthmatic airway inflammation in mice and humans. In vivo experiments revealed the functional relevance of this finding because selective P2X₇R inhibition or P2X₇R deficiency was associated with reduced features of acute and chronic asthma in the ovalbumin-alum or HDM model of AAI. Experiments with bone marrow chimeras emphasized that P2X₇R expression on hematopoietic cells is responsible for the proasthmatic effects of P2X₇R signaling. In the DC-driven model of AAI, P2X₇R-deficient DCs showed a reduced capacity to induce Th2 immunity in vivo. Up-regulation of P2X₇R on BAL macrophages and blood eosinophils could be observed in patients with chronic asthma. Our data suggest that targeting P2X₇R on hematopoietic cells (e.g., DCs or eosinophils) might be a new therapeutic option for the treatment of asthma.

  16. Kalanchoe pinnata inhibits mast cell activation and prevents allergic airway disease.

    Science.gov (United States)

    Cruz, E A; Reuter, S; Martin, H; Dehzad, N; Muzitano, M F; Costa, S S; Rossi-Bergmann, B; Buhl, R; Stassen, M; Taube, C

    2012-01-15

    Aqueous extract of Kalanchoe pinnata (Kp) have been found effective in models to reduce acute anaphylactic reactions. In the present study, we investigate the effect of Kp and the flavonoid quercetin (QE) and quercitrin (QI) on mast cell activation in vitro and in a model of allergic airway disease in vivo. Treatment with Kp and QE in vitro inhibited degranulation and cytokine production of bone marrow-derived mast cells following IgE/FcɛRI crosslinking, whereas treatment with QI had no effect. Similarly, in vivo treatment with Kp and QE decreased development of airway hyperresponsiveness, airway inflammation, goblet cell metaplasia and production of IL-5, IL-13 and TNF. In contrast, treatment with QI had no effect on these parameters. These findings demonstrate that treatment with Kp or QE is effective in treatment of allergic airway disease, providing new insights to the immunomodulatory functions of this plant. Copyright © 2011 Elsevier GmbH. All rights reserved.

  17. Polyopes affinis alleviates airway inflammation in a murine model of ...

    Indian Academy of Sciences (India)

    The successive intraperitoneal administration of P. affinis ethanolic extracts before the last airway OVA-challenge resulted in a significant inhibition of all asthmatic reactions. These data suggest that P. affinis ethanolic extracts possess therapeutic potential for the treatment of pulmonary allergic disorders such as allergic ...

  18. In Utero Cigarette Smoke Affects Allergic Airway Disease But Does Not Alter the Lung Methylome.

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    Kenneth R Eyring

    Full Text Available Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. In a house dust mite (HDM model of allergic airway disease, we measured airway hyperresponsiveness (AHR and airway inflammation between mice exposed prenatally to cigarette smoke (CS or filtered air (FA. DNA methylation and gene expression were then measured in lung tissue. We demonstrate that HDM-treated CS mice develop a more severe allergic airway disease compared to HDM-treated FA mice including increased AHR and airway inflammation. While DNA methylation changes between the two HDM-treated groups failed to reach genome-wide significance, 99 DMRs had an uncorrected p-value < 0.001. 6 of these 99 DMRs were selected for validation, based on the immune function of adjacent genes, and only 2 of the 6 DMRs confirmed the bisulfite sequencing data. Additionally, genes near these 6 DMRs (Lif, Il27ra, Tle4, Ptk7, Nfatc2, and Runx3 are differentially expressed between HDM-treated CS mice and HDM-treated FA mice. Our findings confirm that prenatal exposure to cigarette smoke is sufficient to modify allergic airway disease; however, it is unlikely that specific methylation changes account for the exposure-response relationship. These findings highlight the important role in utero cigarette smoke exposure plays in the development of allergic airway disease.

  19. Inhibition of allergic airway responses by heparin derived oligosaccharides: identification of a tetrasaccharide sequence

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    Ahmed Tahir

    2012-01-01

    Full Text Available Abstract Background Previous studies showed that heparin's anti-allergic activity is molecular weight dependent and resides in oligosaccharide fractions of Objective To investigate the structural sequence of heparin's anti-allergic domain, we used nitrous acid depolymerization of porcine heparin to prepare an oligosaccharide, and then fractionated it into disaccharide, tetrasaccharide, hexasaccharide, and octasaccharide fractions. The anti-allergic activity of each oligosaccharide fraction was tested in allergic sheep. Methods Allergic sheep without (acute responder and with late airway responses (LAR; dual responder were challenged with Ascaris suum antigen with and without inhaled oligosaccharide pretreatment and the effects on specific lung resistance and airway hyperresponsiveness (AHR to carbachol determined. Additional inflammatory cell recruitment studies were performed in immunized ovalbumin-challenged BALB/C mice with and without treatment. Results The inhaled tetrasaccharide fraction was the minimal effective chain length to show anti-allergic activity. This fraction showed activity in both groups of sheep; it was also effective in inhibiting LAR and AHR, when administered after the antigen challenge. Tetrasaccharide failed to modify the bronchoconstrictor responses to airway smooth muscle agonists (histamine, carbachol and LTD4, and had no effect on antigen-induced histamine release in bronchoalveolar lavage fluid in sheep. In mice, inhaled tetrasaccharide also attenuated the ovalbumin-induced peribronchial inflammatory response and eosinophil influx in the bronchoalveolar lavage fluid. Chemical analysis identified the active structure to be a pentasulfated tetrasaccharide ([IdoU2S (1→4GlcNS6S (1→4 IdoU2S (1→4 AMan-6S] which lacked anti-coagulant activity. Conclusions These results demonstrate that heparin tetrasaccharide possesses potent anti-allergic and anti-inflammatory properties, and that the domains responsible for anti-allergic

  20. Early sensitisation and development of allergic airway disease - risk factors and predictors

    DEFF Research Database (Denmark)

    Halken, Susanne

    2003-01-01

    The development and phenotypic expression of allergic airway disease depends on a complex interaction between genetic and several environmental factors, such as exposure to food, inhalant allergens and non-specific adjuvant factors (e.g. tobacco smoke, air pollution and infections). The first...

  1. Selective depletion of Foxp3+ Treg during sensitization phase aggravates experimental allergic airway inflammation.

    Science.gov (United States)

    Baru, Abdul Mannan; Hartl, Andrea; Lahl, Katharina; Krishnaswamy, Jayendra Kumar; Fehrenbach, Heinz; Yildirim, Ali O; Garn, Holger; Renz, Harald; Behrens, Georg M N; Sparwasser, Tim

    2010-08-01

    Recent studies highlight the role of Treg in preventing unnecessary responses to allergens and maintaining functional immune tolerance in the lung. We investigated the role of Treg during the sensitization phase in a murine model of experimental allergic airway inflammation by selectively depleting the Treg population in vivo. DEpletion of REGulatory T cells (DEREG) mice were depleted of Treg by diphtheria toxin injection. Allergic airway inflammation was induced using OVA as a model allergen. Pathology was assessed by scoring for differential cellular infiltration in bronchoalveolar lavage, IgE and IgG1 levels in serum, cytokine secretion analysis of lymphocytes from lung draining lymph nodes and lung histology. Use of DEREG mice allowed us for the first time to track and specifically deplete both CD25(+) and CD25(-) Foxp3(+) Treg, and to analyze their significance in limiting pathology in allergic airway inflammation. We observed that depletion of Treg during the priming phase of an active immune response led to a dramatic exacerbation of allergic airway inflammation in mice, suggesting an essential role played by Treg in regulating immune responses against allergens as early as the sensitization phase via maintenance of functional tolerance.

  2. Allergic sensitization enhances the contribution of Rho-kinase to airway smooth muscle contraction

    NARCIS (Netherlands)

    Schaafsma, D.; Gosens, Reinout; Bos, I.S.T.; Meurs, Herman; Zaagsma, Hans; Nelemans, Herman

    2004-01-01

    1 Repeated allergen challenge has been shown to increase the role of Rho-kinase in airway smooth muscle (ASM) contraction. We considered the possibility that active allergic sensitization by itself, that is, without subsequent allergen exposure, could be sufficient to enhance Rho-kinase-mediated ASM

  3. Prophylactic Supplementation of Bifidobacterium longum 51A Protects Mice from Ovariectomy-Induced Exacerbated Allergic Airway Inflammation and Airway Hyperresponsiveness

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    Eduardo Mendes

    2017-09-01

    Full Text Available Asthma is a chronic inflammatory disease that affects more females than males after puberty, and its symptoms and severity in women change during menstruation and menopause. Recently, evidence has demonstrated that interactions among the microbiota, female sex hormones, and immunity are associated with the development of autoimmune diseases. However, no studies have investigated if therapeutic gut microbiota modulation strategies could affect asthma exacerbation during menstruation and menopause. Here we aimed to examine the preventive effects of a probiotic, Bifidobacterium longum 51A, on airway inflammation exacerbation in allergic ovariectomized mice. We first evaluated the gut microbiota composition and diversity in mice 10 days after ovariectomy. Next, we examined whether re-exposure of ovariectomized allergic mice to antigen (ovalbumin would lead to exacerbation of lung inflammation. Finally, we evaluated the preventive and treatment effect of B. longum 51A on lung inflammation and airway hyperresponsiveness. Our results showed that whereas ovariectomy caused no alterations in the gut microbiota composition and diversity in this animal model, 10 days after ovariectomy, preventive use administration of B. longum 51A, rather than its use after surgery was capable of attenuate the exacerbated lung inflammation and hyperresponsiveness in ovariectomized allergic mice. This prophylactic effect of B. longum 51A involves acetate production, which led to increased fecal acetate levels and, consequently, increased Treg cells in ovariectomized allergic mice.

  4. 25-Hydroxyvitamin D, IL-31, and IL-33 in Children with Allergic Disease of the Airways

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    Anna Bonanno

    2014-01-01

    Full Text Available Low vitamin D is involved in allergic asthma and rhinitis. IL-31 and IL-33 correlate with Th2-associated cytokines in allergic disease. We investigated whether low vitamin D is linked with circulating IL-31 and IL-33 in children with allergic disease of the airways. 25-Hydroxyvitamin D [25(OH Vit D], IL-31, and IL-33 plasma levels were measured in 28 controls (HC, 11 allergic rhinitis (AR patients, and 35 allergic asthma with rhinitis (AAR patients. We found significant lower levels of 25(OH Vit D in AR and in AAR than in HC. IL-31 and IL-33 plasma levels significantly increased in AAR than HC. IL-31 and IL-33 positively correlated in AR and AAR. 25(OH Vit D deficient AAR had higher levels of blood eosinophils, exacerbations, disease duration, and total IgE than patients with insufficient or sufficient 25(OH Vit D. In AAR 25(OH Vit D levels inversely correlated with total allergen sIgE score and total atopy index. IL-31 and IL-33 did not correlate with 25(OH Vit D in AR and AAR. In conclusion, low levels of 25(OH Vit D might represent a risk factor for the development of concomitant asthma and rhinitis in children with allergic disease of the airways independently of IL-31/IL-33 Th2 activity.

  5. FINE PARTICLE MATTER ASSOCIATED WITH AIRWAY NEUTROPHILIA IN A SUBPOPULATION OF ADULT ASTHMATICS

    Science.gov (United States)

    Asthmatic adults are a heterogeneous group that is sensitive to the mass concentration of ambient particulate matter (PM). However, it is not clear which components of PM are responsible for these effects, nor are the mechanisms understood. We evaluated whether increases in ambi...

  6. Treatment of nocturnal airway obstruction improves daytime cognitive performance in asthmatics

    NARCIS (Netherlands)

    Weersink, EJM; vanZomeren, EH; Koeter, GH; Postma, DS

    1997-01-01

    It has been shown that asthmatics have nocturnal symptoms associated with impaired cognitive performance. We explored more carefully different therapeutic approaches on this performance in relation to lung function in 46 atopics with mild to moderate asthma and with a circadian variation in peak

  7. Pulmonary ORMDL3 is critical for induction of Alternaria-induced allergic airways disease.

    Science.gov (United States)

    Löser, Stephan; Gregory, Lisa G; Zhang, Youming; Schaefer, Katrein; Walker, Simone A; Buckley, James; Denney, Laura; Dean, Charlotte H; Cookson, William O C; Moffatt, Miriam F; Lloyd, Clare M

    2017-05-01

    Genome-wide association studies have identified the ORM (yeast)-like protein isoform 3 (ORMDL3) gene locus on human chromosome 17q to be a highly significant risk factor for childhood-onset asthma. We sought to investigate in vivo the functional role of ORMDL3 in disease inception. An Ormdl3-deficient mouse was generated and the role of ORMDL3 in the generation of allergic airways disease to the fungal aeroallergen Alternaria alternata was determined. An adeno-associated viral vector was also used to reconstitute ORMDL3 expression in airway epithelial cells of Ormdl3 knockout mice. Ormdl3 knockout mice were found to be protected from developing allergic airways disease and showed a marked decrease in pathophysiology, including lung function and airway eosinophilia induced by Alternaria. Alternaria is a potent inducer of cellular stress and the unfolded protein response, and ORMDL3 was found to play a critical role in driving the activating transcription factor 6-mediated arm of this response through Xbp1 and downstream activation of the endoplasmic reticulum-associated degradation pathway. In addition, ORMDL3 mediated uric acid release, another marker of cellular stress. In the knockout mice, reconstitution of Ormdl3 transcript levels specifically in the bronchial epithelium resulted in reinstatement of susceptibility to fungal allergen-induced allergic airways disease. This study demonstrates that ORMDL3, an asthma susceptibility gene identified by genome-wide association studies, contributes to key pathways that promote changes in airway physiology during allergic immune responses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. The Effects of Proresolution of Ellagic Acid in an Experimental Model of Allergic Airway Inflammation

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    Claudiney de Freitas Alves

    2013-01-01

    Full Text Available Asthma is a disease of airway inflammation characterized by airway hyperresponsiveness, eosinophilic inflammation, and hypersecretion of mucus. Ellagic acid, a compound derived from medicinal plants and fruits, has shown anti-inflammatory activity in several experimental disease models. We used the classical experimental model, in BALB/c mice, of sensibilization with ovalbumin to determine the effect of ellagic acid (10 mg/kg; oral route in the resolution of allergic airways response. Dexamethasone (1 mg/kg; subcutaneous route was used as a positive control. The control group consisted of nonimmunized mice that received challenge with ovalbumin. Ellagic acid and dexamethasone or vehicle (water were administered before or after intranasal allergen challenge. Ellagic acid accelerated the resolution of airways inflammation by decreasing total leukocytes and eosinophils numbers in the bronchoalveolar lavage fluid (BALF, the mucus production and lung inflammation in part by reducing IL-5 concentration, eosinophil peroxidase (EPO activity, and P-selectin expression, but not activator protein 1 (AP-1 and nuclear factor kappa B (NF-κB pathways. In addition, ellagic acid enhanced alveolar macrophage phagocytosis of IgG-OVA-coated beads ex vivo, a new proresolving mechanism for the clearance of allergen from the airways. Together, these findings identify ellagic acid as a potential therapeutic agent for accelerating the resolution of allergic airways inflammation.

  9. The who, where, and when of IgE in allergic airway disease.

    Science.gov (United States)

    Dullaers, Melissa; De Bruyne, Ruth; Ramadani, Faruk; Gould, Hannah J; Gevaert, Philippe; Lambrecht, Bart N

    2012-03-01

    Allergic asthma and allergic rhinitis/conjunctivitis are characterized by a T(H)2-dominated immune response associated with increased serum IgE levels in response to inhaled allergens. Because IgE is a key player in the induction and maintenance of allergic inflammation, it represents a prime target for therapeutic intervention. However, our understanding of IgE biology remains fragmentary. This article puts together our current knowledge on IgE in allergic airway diseases with a special focus on the identity of IgE-secreting cells ("who"), their location ("where"), and the circumstances in which they are induced ("when"). We further consider the therapeutic implications of the insights gained. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  10. Upper and lower airway pathology in young children with allergic- and non-allergic rhinitis

    DEFF Research Database (Denmark)

    Chawes, Bo Lk

    2011-01-01

    Allergic- and non-allergic rhinitis are very common diseases in childhood in industrialized countries. Although these conditions are widely trivialized by both parents and physicians they induce a major impact on quality of life for the affected children and a substantial drainage of health care...... resources. Unfortunately, diagnostic specificity is hampered by nonspecific symptom history and lack of reliable diagnostic tests which may explain why the pathology behind such diagnoses is poorly understood. Improved understanding of the pathophysiology of allergic- and non-allergic rhinitis in young...... children may contribute to the discovery of new mechanisms involved in pathogenesis and help direct future research to develop correctly timed preventive measures as well as adequate monitoring and treatment of children with rhinitis. Asthma is a common comorbidity in subjects with allergic rhinitis...

  11. Exogenous stimuli and circadian peak expiratory flow variation in allergic asthmatic children

    NARCIS (Netherlands)

    Postma, DS; VanderHeide, S; DeReus, DM; Koeter, GH; VanAalderen, WMC; Meijer, G.

    The influence of exogenous factors in the home on the circadian variation of airway obstruction has not been fully assessed in children with asthma. The aim of the present study was to investigate the contribution of exogenous stimuli to the degree of peak expiratory flow (PEF) variability during 24

  12. Imperatorin inhibits allergic airway inflammatory reaction and mucin ...

    African Journals Online (AJOL)

    Furthermore, MUC5AC in lung tissues was significantly down-regulated by treatment with IPT (20, 40 and 80 mg/kg, p < 0.01) in a dose-dependent fashion. Conclusion: The results show that IPT exerts notable therapeutic effects on allergic asthma in rats via suppression of IgE, histamine, inflammatory cells and cytokines, ...

  13. Imperatorin inhibits allergic airway inflammatory reaction and mucin ...

    African Journals Online (AJOL)

    Purpose: To study the therapeutic effects of imperatorin (IPT) on allergic asthma induced by ovalbumin in rats. Methods: Asthma was established in rats by injection of ovalbumin (OVA), and IPT (20, 40 and 80 mg/kg) was administered orally for 21 days. Inflammatory cells and cytokines were determined in the.

  14. Role of nitric oxide in the airway response to exercise in healthy and asthmatic subjects

    NARCIS (Netherlands)

    de Gouw, H. W.; Marshall-Partridge, S. J.; van der Veen, H.; van den Aardweg, J. G.; Hiemstra, P. S.; Sterk, P. J.

    2001-01-01

    A role of nitric oxide (NO) has been suggested in the airway response to exercise. However, it is unclear whether NO may act as a protective or a stimulatory factor. Therefore, we examined the role of NO in the airway response to exercise by using N-monomethyl-L-arginine (L-NMMA, an NO synthase

  15. TNF is required for TLR ligand–mediated but not protease-mediated allergic airway inflammation

    Science.gov (United States)

    Whitehead, Gregory S.; Thomas, Seddon Y.; Shalaby, Karim H.; Nakano, Keiko; Moran, Timothy P.; Ward, James M.; Flake, Gordon P.; Cook, Donald N.

    2017-01-01

    Asthma is associated with exposure to a wide variety of allergens and adjuvants. The extent to which overlap exists between the cellular and molecular mechanisms triggered by these various agents is poorly understood, but it might explain the differential responsiveness of patients to specific therapies. In particular, it is unclear why some, but not all, patients benefit from blockade of TNF. Here, we characterized signaling pathways triggered by distinct types of adjuvants during allergic sensitization. Mice sensitized to an innocuous protein using TLR ligands or house dust extracts as adjuvants developed mixed eosinophilic and neutrophilic airway inflammation and airway hyperresponsiveness (AHR) following allergen challenge, whereas mice sensitized using proteases as adjuvants developed predominantly eosinophilic inflammation and AHR. TLR ligands, but not proteases, induced TNF during allergic sensitization. TNF signaled through airway epithelial cells to reprogram them and promote Th2, but not Th17, development in lymph nodes. TNF was also required during the allergen challenge phase for neutrophilic and eosinophilic inflammation. In contrast, TNF was dispensable for allergic airway disease in a protease-mediated model of asthma. These findings might help to explain why TNF blockade improves lung function in only some patients with asthma. PMID:28758900

  16. Allergic rhinitis and asthma: inflammation in a one-airway condition

    Directory of Open Access Journals (Sweden)

    Haahtela Tari

    2006-11-01

    Full Text Available Abstract Background Allergic rhinitis and asthma are conditions of airway inflammation that often coexist. Discussion In susceptible individuals, exposure of the nose and lungs to allergen elicits early phase and late phase responses. Contact with antigen by mast cells results in their degranulation, the release of selected mediators, and the subsequent recruitment of other inflammatory cell phenotypes. Additional proinflammatory mediators are released, including histamine, prostaglandins, cysteinyl leukotrienes, proteases, and a variety of cytokines, chemokines, and growth factors. Nasal biopsies in allergic rhinitis demonstrate accumulations of mast cells, eosinophils, and basophils in the epithelium and accumulations of eosinophils in the deeper subepithelium (that is, lamina propria. Examination of bronchial tissue, even in mild asthma, shows lymphocytic inflammation enriched by eosinophils. In severe asthma, the predominant pattern of inflammation changes, with increases in the numbers of neutrophils and, in many, an extension of the changes to involve smaller airways (that is, bronchioli. Structural alterations (that is, remodeling of bronchi in mild asthma include epithelial fragility and thickening of its reticular basement membrane. With increasing severity of asthma there may be increases in airway smooth muscle mass, vascularity, interstitial collagen, and mucus-secreting glands. Remodeling in the nose is less extensive than that of the lower airways, but the epithelial reticular basement membrane may be slightly but significantly thickened. Conclusion Inflammation is a key feature of both allergic rhinitis and asthma. There are therefore potential benefits for application of anti-inflammatory strategies that target both these anatomic sites.

  17. Immunotherapy in allergic rhinitis and lower airway outcomes.

    Science.gov (United States)

    Cardona, V; Luengo, O; Labrador-Horrillo, M

    2017-01-01

    Allergic rhinitis and asthma constitute two clinical expressions of a single-condition, respiratory allergy. Allergen immunotherapy (AIT) is a form of treatment specifically aimed at modifying the response to sensitizing allergens. The inherent potential benefit of AIT is the simultaneous treatment of all clinical expressions of respiratory allergy. Current data support the effectiveness of subcutaneous and sublingual immunotherapy in rhinitis. Studies also provide proof for a beneficial effect in allergic asthma. Even more, substantial evidence points to the preventive effect on the progression from rhinitis to asthma. Despite the current knowledge on the basic mechanisms underlying the immunological effect of AIT is vast, the specific mechanisms for the preventive effect of primary sensitization or new sensitizations are poorly understood. This review aimed to provide a critical overview of the current knowledge on the effectiveness of AIT and its potential role in secondary prevention of respiratory allergy progression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Ventilation and Perfusion Lung Scintigraphy of Allergen-Induced Airway Responses in Atopic Asthmatic Subjects

    Directory of Open Access Journals (Sweden)

    Krishnan Parameswaran

    2007-01-01

    Full Text Available BACKGROUND: Both ventilation (V and perfusion (Q of the lungs are altered in asthma, but their relationships with allergen-induced airway responses and gas exchange are not well described.

  19. Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner

    Science.gov (United States)

    Dulek, Daniel E.; Newcomb, Dawn C.; Goleniewska, Kasia; Cephus, Jaqueline; Zhou, Weisong; Reiss, Sara; Toki, Shinji; Ye, Fei; Zaynagetdinov, Rinat; Sherrill, Taylor P.; Blackwell, Timothy S.; Moore, Martin L.; Boyd, Kelli L.; Kolls, Jay K.

    2014-01-01

    The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity. PMID:24958709

  20. Ambient air pollution, lung function, and airway responsiveness in asthmatic children.

    Science.gov (United States)

    Ierodiakonou, Despo; Zanobetti, Antonella; Coull, Brent A; Melly, Steve; Postma, Dirkje S; Boezen, H Marike; Vonk, Judith M; Williams, Paul V; Shapiro, Gail G; McKone, Edward F; Hallstrand, Teal S; Koenig, Jane Q; Schildcrout, Jonathan S; Lumley, Thomas; Fuhlbrigge, Anne N; Koutrakis, Petros; Schwartz, Joel; Weiss, Scott T; Gold, Diane R

    2016-02-01

    Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthmatic patients are lacking. We sought to investigate pollution effects in a longitudinal asthma study and effect modification by controller medications. We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide, and sulfur dioxide concentrations in 1003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to ZIP/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and forced vital capacity (FVC) percent predicted, FEV1/FVC ratio, and PC20, adjusting for seasonality and confounders. Same-day and 1-week average CO concentrations were negatively associated with postbronchodilator percent predicted FEV1 (change per interquartile range, -0.33 [95% CI, -0.49 to -0.16] and -0.41 [95% CI, -0.62 to -0.21], respectively) and FVC (-0.19 [95% CI, -0.25 to -0.07] and -0.25 [95% CI, -0.43 to -0.07], respectively). Longer-term 4-month CO averages were negatively associated with prebronchodilator percent predicted FEV1 and FVC (-0.36 [95% CI, -0.62 to -0.10] and -0.21 [95% CI, -0.42 to -0.01], respectively). Four-month averaged CO and ozone concentrations were negatively associated with FEV1/FVC ratio (P Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications might not protect but rather worsens the effects of CO on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Acute exposure to realistic acid fog: effects on respiratory function and airway responsiveness in asthmatics.

    Science.gov (United States)

    Leduc, D; Fally, S; De Vuyst, P; Wollast, R; Yernault, J C

    1995-11-01

    Naturally occurring fogs in industrialized cities are contaminated by acidic air pollutants. In Brussels, Belgium, the pH of polluted fogwater may be as low as 3 with osmolarity as low as 30 mOsm. In order to explore short-term respiratory effects of a realistic acid-polluted fog, we collected samples of acid fog in Brussels, Belgium, which is a densely populated and industrialized city, we defined characteristics of this fog and exposed asthmatic volunteers at rest through a face mask to fogs with physical and chemical characteristics similar to those of natural fogs assessed in this urban area. Fogwater was sampled using a screen collector where droplets are collected by inertial impaction and chemical content of fogwater was assessed by measurement of conductivity, pH, visible colorimetry, high pressure liquid chromatography, and atomic absorption spectrophotometry over a period of one year. The fogwater composition was dominated by NH4+ and SO4- ions. First we evaluated the possible effect of fog acidity alone. For this purpose 14 subjects with asthma were exposed at rest for 1 hr [mass median aerodynamic diameter to a large-particle (MMAD), 9 microns] aerosol with H2SO4 concentration of 500 micrograms/m3 (pH 2.5) and osmolarity of 300 mOsm. We did not observe significant change in pulmonary function or bronchial responsiveness to metacholine. In the second part of the work, 10 asthmatic subjects were exposed to acid fog (MMAD, 7 microns) containing sulfate and ammonium ions (major ions recovered in naturally occurring fogs) with pH 3.5 and osmolarity 30 mOsm. Again, pulmonary function and bronchial reactivity were not modified after inhalation of this fog. It was concluded that short-term exposure to acid fog reproducing acidity and hypoosmolarity of natural polluted fogs does not induce bronchoconstriction and does not change bronchial responsiveness in asthmatics.

  2. Inhibition of aldose reductase prevents experimental allergic airway inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Umesh C S Yadav

    2009-08-01

    Full Text Available The bronchial asthma, a clinical complication of persistent inflammation of the airway and subsequent airway hyper-responsiveness, is a leading cause of morbidity and mortality in critically ill patients. Several studies have shown that oxidative stress plays a key role in initiation as well as amplification of inflammation in airways. However, still there are no good anti-oxidant strategies available for therapeutic intervention in asthma pathogenesis. Most recent studies suggest that polyol pathway enzyme, aldose reductase (AR, contributes to the pathogenesis of oxidative stress-induced inflammation by affecting the NF-kappaB-dependent expression of cytokines and chemokines and therefore inhibitors of AR could be anti-inflammatory. Since inhibitors of AR have already gone through phase-III clinical studies for diabetic complications and found to be safe, our hypothesis is that AR inhibitors could be novel therapeutic drugs for the prevention and treatment of asthma. Hence, we investigated the efficacy of AR inhibition in the prevention of allergic responses to a common natural airborne allergen, ragweed pollen that leads to airway inflammation and hyper-responsiveness in a murine model of asthma.Primary Human Small Airway Epithelial Cells (SAEC were used to investigate the in vitro effects of AR inhibition on ragweed pollen extract (RWE-induced cytotoxic and inflammatory signals. Our results indicate that inhibition of AR prevents RWE -induced apoptotic cell death as measured by annexin-v staining, increase in the activation of NF-kappaB and expression of inflammatory markers such as inducible nitric oxide synthase (iNOS, cycloxygenase (COX-2, Prostaglandin (PG E(2, IL-6 and IL-8. Further, BALB/c mice were sensitized with endotoxin-free RWE in the absence and presence of AR inhibitor and followed by evaluation of perivascular and peribronchial inflammation, mucin production, eosinophils infiltration and airway hyperresponsiveness. Our results

  3. The spectrum of allergic fungal diseases of the upper and lower airways.

    Science.gov (United States)

    Rodrigues, Jonathan; Caruthers, Carrie; Azmeh, Roua; Dykewicz, Mark S; Slavin, Raymond G; Knutsen, Alan P

    2016-01-01

    Fungi cause a wide spectrum of fungal diseases of the upper and lower airways. There are three main phyla involved in allergic fungal disease: (1) Ascomycota (2) Basidiomycota (3) Zygomycota. Allergic fungal rhinosinusitis (AFRS) causes chronic rhinosinusitis symptoms and is caused predominantly by Aspergillus fumigatus in India and Bipolaris in the United States. The recommended treatment approach for AFRS is surgical intervention and systemic steroids. Allergic bronchopulmonary aspergillosis (APBA) is most commonly diagnosed in patients with asthma or cystic fibrosis. Long term systemic steroids are the mainstay treatment option for ABPA with the addition of an antifungal medication. Fungal sensitization or exposure increases a patient's risk of developing severe asthma and has been termed severe asthma associated with fungal sensitivity (SAFS). Investigating for triggers and causes of a patient's asthma should be sought to decrease worsening progression of the disease.

  4. IMAGE-BASED IN VIVO QUANTITATIVE ASSESSMENT OF HUMAN AIRWAY OPENING AND CONTRACTILITY BY FIBER OPTICAL NASOPHARYNGOSCOPY IN HEALTHY AND ASTHMATIC SUBJECTS

    Directory of Open Access Journals (Sweden)

    LINHONG DENG

    2013-04-01

    Full Text Available Assessment of human airway lumen opening is important in diagnosing and understanding the mechanisms of airway dysfunctions such as the excessive airway narrowing in asthma and chronic obstructive pulmonary disease (COPD. Although there are indirect methods to evaluate the airway calibre, direct in vivo measurement of the airway calibre has not been commonly available. With recent advent of the flexible fiber optical nasopharyngoscope with video recording it has become possible to directly visualize the passages of upper and lower airways. However, quantitative analysis of the recorded video images has been technically challenging. Here, we describe an automatic image processing and analysis method that allows for batch analysis of the images recorded during the endoscopic procedure, thus facilitates image-based quantification of the airway opening. Video images of the airway lumen of volunteer subject were acquired using a fiber optical nasopharyngoscope, and subsequently processed using Gaussian smoothing filter, threshold segmentation, differentiation, and Canny image edge detection, respectively. Thus the area of the open airway lumen was identified and computed using a predetermined converter of the image scale to true dimension of the imaged object. With this method we measured the opening/narrowing of the glottis during tidal breathing with or without making "Hee" sound or cough. We also used this method to measure the opening/narrowing of the primary bronchus of either healthy or asthmatic subjects in response to histamine and/or albuterol treatment, which also provided an indicator of the airway contractility. Our results demonstrate that the image-based method accurately quantified the area change waveform of either the glottis or the bronchus as observed by using the optical nasopharygoscope. Importantly, the opening/narrowing of the airway lumen generally correlated with the airflow and resistance of the airways, and could

  5. Cigarette smoke differentially affects IL-13-induced gene expression in human airway epithelial cells

    NARCIS (Netherlands)

    Mertens, Tinne C J; van der Does, Anne M; Kistemaker, Loes E; Ninaber, Dennis K; Taube, Christian; Hiemstra, Pieter S

    Allergic airways inflammation in asthma is characterized by an airway epithelial gene signature composed of POSTN, CLCA1, and SERPINB2 This Th2 gene signature is proposed as a tool to classify patients with asthma into Th2-high and Th2-low phenotypes. However, many asthmatics smoke and the effects

  6. Ionotropic and Metabotropic Proton-Sensing Receptors Involved in Airway Inflammation in Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Haruka Aoki

    2014-01-01

    Full Text Available An acidic microenvironment has been shown to evoke a variety of airway responses, including cough, bronchoconstriction, airway hyperresponsiveness (AHR, infiltration of inflammatory cells in the lung, and stimulation of mucus hyperproduction. Except for the participation of transient receptor potential vanilloid-1 (TRPV1 and acid-sensing ion channels (ASICs in severe acidic pH (of less than 6.0-induced cough and bronchoconstriction through sensory neurons, the molecular mechanisms underlying extracellular acidic pH-induced actions in the airways have not been fully understood. Recent studies have revealed that ovarian cancer G protein-coupled receptor 1 (OGR1-family G protein-coupled receptors, which sense pH of more than 6.0, are expressed in structural cells, such as airway smooth muscle cells and epithelial cells, and in inflammatory and immune cells, such as eosinophils and dendritic cells. They function in a variety of airway responses related to the pathophysiology of inflammatory diseases, including allergic asthma. In the present review, we discuss the roles of ionotropic TRPV1 and ASICs and metabotropic OGR1-family G protein-coupled receptors in the airway inflammation and AHR in asthma and respiratory diseases.

  7. Allergic airway disease in Italian bakers and pastry makers.

    Science.gov (United States)

    De Zotti, R; Larese, F; Bovenzi, M; Negro, C; Molinari, S

    1994-08-01

    A survey was carried out on respiratory symptoms and skin prick test response to common allergens (atopy), storage mites, and occupational allergens among 226 bakers and pastry makers from 105 small businesses in northern Italy. Atopy was present in 54 workers (23.4%); 40 workers (17.7%) were skin positive to at least one storage mite, 27 (11.9%) to wheat flour and 17 (7.5%) to alpha-amylase. Work related asthma was reported by 11 (4.9%) workers and rhinoconjunctivitis by 31 (17.7%); 22 workers (10.2%) complained of chronic bronchitis. The distribution of skin prick test results among bakers and among 119 white collar workers did not indicate (by logistic analysis) an increased risk for bakers to skin sensitisation to common allergens, storage mite, or to a group of five flours. Sensitisation to wheat flour, on the other hand, was present only among exposed workers. Skin sensitisation to occupational allergens was significantly associated with atopy (p < 0.001), smoking habit (p = 0.015), and work seniority (p = 0.027). The risk of work related symptoms was associated with sensitisation to wheat or alpha-amylase, and with atopy, but not with sensitisation to storage mites, work seniority, or smoking habit. The results of the study indicate that there is still a significant risk of allergic respiratory disease among Italian bakers. Not only wheat allergens, but also alpha-amylase must be considered as causative agents, although sensitisation to storage mites is not important in the occupational allergic response. Atopy must be regarded as an important predisposing factor for skin sensitisation to occupational allergens and for the onset of symptoms at work. The data confirm that for effective prevention, greater care should be taken not only in limiting environmental exposure, but also in identifying susceptible people.

  8. Reduction of tumstatin in asthmatic airways contributes to angiogenesis, inflammation, and hyperresponsiveness

    NARCIS (Netherlands)

    Burgess, Janette K; Boustany, Sarah; Moir, Lyn M; Weckmann, Markus; Lau, Justine Y; Grafton, Karryn; Baraket, Melissa; Hansbro, Philip M; Hansbro, Nicole G; Foster, Paul S; Black, Judith L; Oliver, Brian G

    2010-01-01

    RATIONALE: Angiogenesis is a prominent feature of remodeling in asthma. Many proangiogenic factors are up-regulated in asthma, but little is known about levels of endogenous antiangiogenic agents. Collagen IV is decreased in the airway basement membrane in asthma. It has six alpha chains, of which

  9. Anti-IgE treatment, airway inflammation and remodelling in severe allergic asthma: current knowledge and future perspectives

    Directory of Open Access Journals (Sweden)

    Konstantinos Samitas

    2015-12-01

    Full Text Available Asthma is a disorder of the airways involving various inflammatory cells and mediators and characterised by bronchial hyperresponsiveness, chronic inflammation and structural alterations in the airways, also known as remodelling. IgE is an important mediator of allergic reactions and has a central role in allergic asthma pathophysiology, as it is implicated in both the early and late phase allergic response. Moreover, clinical and mechanistic evidence has lately emerged, implicating IgE in the development of airway remodelling. The use of monoclonal antibodies targeting IgE, such as omalizumab, has proven very effective in improving respiratory symptoms and quality of life, while reducing asthma exacerbations, emergency room visits and the use of systemic corticosteroids in allergic severe asthma. These effects are believed to be mainly mediated by omalizumab's inhibitory effect on the initiation and further propagation of the allergic inflammation cascade. However, there is evidence to suggest that anti-IgE treatment remains effective long after it has been discontinued. In part, these findings could be attributed to the possible ameliorating effects of anti-IgE treatment on airway remodelling. In this review, we discuss recent findings supporting the notion that anti-IgE treatment modulates the complex immune responses that manifest clinically as asthma and ameliorates airway remodelling changes often observed in allergic severe asthma phenotypes.

  10. Endocrine disruptors found in food contaminants enhance allergic sensitization through an oxidative stress that promotes the development of allergic airway inflammation

    International Nuclear Information System (INIS)

    Kato, Takuma; Tada-Oikawa, Saeko; Wang, Linan; Murata, Mariko; Kuribayashi, Kagemasa

    2013-01-01

    In the past few decades, there has been a significant increase in incidence of allergic diseases. The hygiene hypothesis may provide some clues to explain this rising trend, but it may also be attributable to other environmental factors that exert a proallergic adjuvant effects. However, there is limited information on the risks of developing allergic asthma and related diseases through the ingestion of environmental chemicals found in food contaminants. In the present study, we have shown that oral administration of tributyltin, used as a model environmental chemical, induced oxidative-stress status in the bronchial lymph node, mesenteric lymph node and spleen, but not in the lung, where the initial step of allergic asthma pathogenesis takes place. Mice exposed to tributyltin exhibited heightened Th2 immunity to the allergen with more severe airway inflammation. Tributyltin also induced Treg cells apoptosis preferentially over non-Treg cells. All these effects of tributyltin exposure were canceled by the administration of glutathione monoethyl ester. Meanwhile, tributyltin did not affect airway inflammation of mice transferred with allergen-specific Th2 cells. Collectively, these results suggest that tributyltin exerts its pathological effect during the sensitization phase through oxidative stress that enhances the development of allergic diseases. The current study dissects the pathogenic role of oxidative stress induced by oral exposure to an environmental chemical during the sensitization phase of allergic airway inflammation and would be important for developing therapeutics for prevention of allergic diseases. - Highlights: • Oral exposure to TBT exacerbates airway inflammation. • TBT induces oxidative stress in secondary lymphoid organs, but not in the lung. • TBT preferentially induces regulatory T cell apoptosis over non-Treg cells. • TBT does not enhance pre-existing airway inflammation in sensitized mice. • Chemicals in food contaminants

  11. Endocrine disruptors found in food contaminants enhance allergic sensitization through an oxidative stress that promotes the development of allergic airway inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Takuma, E-mail: katotaku@doc.medic.mie-u.ac.jp [Department of Cellular and Molecular Immunology, Mie University Graduate School of Medicine (Japan); Tada-Oikawa, Saeko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine (Japan); Wang, Linan [Department of Cellular and Molecular Immunology, Mie University Graduate School of Medicine (Japan); Murata, Mariko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine (Japan); Kuribayashi, Kagemasa [Department of Cellular and Molecular Immunology, Mie University Graduate School of Medicine (Japan)

    2013-11-15

    In the past few decades, there has been a significant increase in incidence of allergic diseases. The hygiene hypothesis may provide some clues to explain this rising trend, but it may also be attributable to other environmental factors that exert a proallergic adjuvant effects. However, there is limited information on the risks of developing allergic asthma and related diseases through the ingestion of environmental chemicals found in food contaminants. In the present study, we have shown that oral administration of tributyltin, used as a model environmental chemical, induced oxidative-stress status in the bronchial lymph node, mesenteric lymph node and spleen, but not in the lung, where the initial step of allergic asthma pathogenesis takes place. Mice exposed to tributyltin exhibited heightened Th2 immunity to the allergen with more severe airway inflammation. Tributyltin also induced Treg cells apoptosis preferentially over non-Treg cells. All these effects of tributyltin exposure were canceled by the administration of glutathione monoethyl ester. Meanwhile, tributyltin did not affect airway inflammation of mice transferred with allergen-specific Th2 cells. Collectively, these results suggest that tributyltin exerts its pathological effect during the sensitization phase through oxidative stress that enhances the development of allergic diseases. The current study dissects the pathogenic role of oxidative stress induced by oral exposure to an environmental chemical during the sensitization phase of allergic airway inflammation and would be important for developing therapeutics for prevention of allergic diseases. - Highlights: • Oral exposure to TBT exacerbates airway inflammation. • TBT induces oxidative stress in secondary lymphoid organs, but not in the lung. • TBT preferentially induces regulatory T cell apoptosis over non-Treg cells. • TBT does not enhance pre-existing airway inflammation in sensitized mice. • Chemicals in food contaminants

  12. D-tryptophan from probiotic bacteria influences the gut microbiome and allergic airway disease.

    Science.gov (United States)

    Kepert, Inge; Fonseca, Juliano; Müller, Constanze; Milger, Katrin; Hochwind, Kerstin; Kostric, Matea; Fedoseeva, Maria; Ohnmacht, Caspar; Dehmel, Stefan; Nathan, Petra; Bartel, Sabine; Eickelberg, Oliver; Schloter, Michael; Hartmann, Anton; Schmitt-Kopplin, Philippe; Krauss-Etschmann, Susanne

    2017-05-01

    Chronic immune diseases, such as asthma, are highly prevalent. Currently available pharmaceuticals improve symptoms but cannot cure the disease. This prompted demands for alternatives to pharmaceuticals, such as probiotics, for the prevention of allergic disease. However, clinical trials have produced inconsistent results. This is at least partly explained by the highly complex crosstalk among probiotic bacteria, the host's microbiota, and immune cells. The identification of a bioactive substance from probiotic bacteria could circumvent this difficulty. We sought to identify and characterize a bioactive probiotic metabolite for potential prevention of allergic airway disease. Probiotic supernatants were screened for their ability to concordantly decrease the constitutive CCL17 secretion of a human Hodgkin lymphoma cell line and prevent upregulation of costimulatory molecules of LPS-stimulated human dendritic cells. Supernatants from 13 of 37 tested probiotic strains showed immunoactivity. Bioassay-guided chromatographic fractionation of 2 supernatants according to polarity, followed by total ion chromatography and mass spectrometry, yielded C 11 H 12 N 2 O 2 as the molecular formula of a bioactive substance. Proton nuclear magnetic resonance and enantiomeric separation identified D-tryptophan. In contrast, L-tryptophan and 11 other D-amino acids were inactive. Feeding D-tryptophan to mice before experimental asthma induction increased numbers of lung and gut regulatory T cells, decreased lung T H 2 responses, and ameliorated allergic airway inflammation and hyperresponsiveness. Allergic airway inflammation reduced gut microbial diversity, which was increased by D-tryptophan. D-tryptophan is a newly identified product from probiotic bacteria. Our findings support the concept that defined bacterial products can be exploited in novel preventative strategies for chronic immune diseases. Copyright © 2016. Published by Elsevier Inc.

  13. Airway function indicators and blood indicators in children with dust mite allergic rhinitis after sublingual immunotherapy

    Directory of Open Access Journals (Sweden)

    Hua Xiang

    2016-07-01

    Full Text Available Objective: To evaluate the airway function indicators and blood indicators in children with dust mite allergic rhinitis after sublingual immunotherapy. Methods: A total of 68 children with dust mite allergic rhinitis treated in our hospital from November, 2012 to October, 2015 were selected as the research subjects and randomly divided into observation group 34 cases and control group 34 cases. The control group received clinical routine therapy for allergic rhinitis, the observation group received sublingual immunotherapy, and then differences in basic lung function indicator values, small airway function indicator values and levels of serum inflammatory factors as well as serum ECP, TARC, Eotaxin-2 and VCAM were compared between two groups after treatment. Results: The FVC, FEV1, PEF and FEV1/FVC values of the observation group after treatment were higher than those of the control group (P<0.05; the MMEF, MEF50% and MEF25% values of the observation group were higher than those of the control group, and the proportion of AHR was lower than that of the control group (P<0.05; the serum IL-4, IL-9, IL-12, IL-13 and IL-16 levels of the observation group after treatment were lower than those of the control group, and the IL-10 and IL-12 levels are higher than those of the control group (P<0.05; the serum ECP, TARC, Eotaxin-2 and VCAM levels of the observation group children after treatment were lower than those of the control group (P<0.05. Conclusions: Sublingual immunotherapy for children with dust mite allergic rhinitis can optimize the airway function, reduce the systemic inflammatory response and eventually improve the children’s overall state, and it’s has positive clinical significance.

  14. Citrus tachibana Leaves Ethanol Extract Alleviates Airway Inflammation by the Modulation of Th1/Th2 Imbalance via Inhibiting NF-κB Signaling and Histamine Secretion in a Mouse Model of Allergic Asthma.

    Science.gov (United States)

    Bui, Thi Tho; Piao, Chun Hua; Kim, Soo Mi; Song, Chang Ho; Shin, Hee Soon; Lee, Chang-Hyun; Chai, Ok Hee

    2017-07-01

    Asthma is a chronic inflammatory disease of bronchial airway, which is characterized by chronic airway inflammation, airway edema, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration in the lungs. In this study, the therapeutic effect and the underlying mechanism of Citrus tachibana leaves ethanol extract (CTLE) in the ovalbumin (OVA)-induced allergic asthma and compound 48/80-induced anaphylaxis were investigated. Oral administration of CTLE inhibited OVA-induced asthmatic response by reducing airway inflammation, OVA-specific IgE and IgG1 levels, and increasing OVA-specific IgG2a levels. CTLE restored Th1/Th2 balance through an increase in Th2 cytokines tumor necrosis factor-α, interleukin (IL)-4, and IL-6 and decreases in Th1 cytokines interferon-γ and IL-12. Furthermore, CTLE inhibited the total level of NF-κB and the phosphorylation of IκB-α and NF-κB by OVA. In addition, CTLE dose-dependently inhibited compound 48/80-induced anaphylaxis via blocking histamine secretion from mast cells. The anti-inflammatory mechanism of CTLE may involve the modulation of Th1/Th2 imbalance via inhibiting the NF-κB signaling and histamine secretion. Taken together, we suggest that CTLE could be used as a therapeutic agent for patients with Th2-mediated or histamine-mediated allergic asthma.

  15. Receptor for advanced glycation end products and its ligand high-mobility group box-1 mediate allergic airway sensitization and airway inflammation.

    Science.gov (United States)

    Ullah, Md Ashik; Loh, Zhixuan; Gan, Wan Jun; Zhang, Vivian; Yang, Huan; Li, Jian Hua; Yamamoto, Yasuhiko; Schmidt, Ann Marie; Armour, Carol L; Hughes, J Margaret; Phipps, Simon; Sukkar, Maria B

    2014-08-01

    The receptor for advanced glycation end products (RAGE) shares common ligands and signaling pathways with TLR4, a key mediator of house dust mite (Dermatophagoides pteronyssinus) (HDM) sensitization. We hypothesized that RAGE and its ligand high-mobility group box-1 (HMGB1) cooperate with TLR4 to mediate HDM sensitization. To determine the requirement for HMGB1 and RAGE, and their relationship with TLR4, in airway sensitization. TLR4(-/-), RAGE(-/-), and RAGE-TLR4(-/-) mice were intranasally exposed to HDM or cockroach (Blatella germanica) extracts, and features of allergic inflammation were measured during the sensitization or challenge phase. Anti-HMGB1 antibody and the IL-1 receptor antagonist Anakinra were used to inhibit HMGB1 and the IL-1 receptor, respectively. The magnitude of allergic airway inflammation in response to either HDM or cockroach sensitization and/or challenge was significantly reduced in the absence of RAGE but not further diminished in the absence of both RAGE and TLR4. HDM sensitization induced the release of HMGB1 from the airway epithelium in a biphasic manner, which corresponded to the sequential activation of TLR4 then RAGE. Release of HMGB1 in response to cockroach sensitization also was RAGE dependent. Significantly, HMGB1 release occurred downstream of TLR4-induced IL-1α, and upstream of IL-25 and IL-33 production. Adoptive transfer of HDM-pulsed RAGE(+/+)dendritic cells to RAGE(-/-) mice recapitulated the allergic responses after HDM challenge. Immunoneutralization of HMGB1 attenuated HDM-induced allergic airway inflammation. The HMGB1-RAGE axis mediates allergic airway sensitization and airway inflammation. Activation of this axis in response to different allergens acts to amplify the allergic inflammatory response, which exposes it as an attractive target for therapeutic intervention. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  16. Eosinophilic rhinitis accompanies the development of lower airway inflammation and hyper-reactivity in sensitized mice exposed to aerosolized allergen

    NARCIS (Netherlands)

    Hellings, P. W.; Hessel, E. M.; van den Oord, J. J.; Kasran, A.; van Hecke, P.; Ceuppens, J. L.

    2001-01-01

    Allergic rhinitis is a risk factor for the development of asthma. About 80% of asthmatic patients also have rhinitis. However, the pattern of induction of allergic rhinitis and asthma remains unclear. The purpose of this study was to investigate the development of upper airway inflammation in mice

  17. Air Pollution and Allergic Airway Diseases: Social Determinantsand Sustainability in the Control and Prevention.

    Science.gov (United States)

    Paramesh, H

    2018-04-01

    Air pollution, global warming and climate change are the major contributing factors in causing the increase prevalence of allergic airway diseases like asthma and allergic rhinitis and they will be the defining issues for health system in the twenty-first century. Asthma is an early onset non-communicable environmental disease with global epidemic and contributes a greatest psycho socio economic burden. Nearly 8 million global deaths are from air pollution. Over one billion population are the sufferers during 2015 and will increase to 4 billion by 2050. Air pollution not only triggers the asthma episodes but also changes the genetic pattern in initiating the disease process. Over the years our concept of management of allergic airway disease has changed from control of symptoms to prevention of the disease. To achieve this we need positive development on clean air policies with standard norms, tracking progress, monitoring and evaluation, partnership and conventions with local and global authorities. We do have challenges to overcome like rapid urbanization, lack of multisectorial policy making, lack of finance for research and development and lack of monitoring exposure to health burden from air pollution. We need to prioritize our strategy by sustainable, safe, human settlement, cities, sustainable energy, industrialization, and research. The measures to be adopted are highlighted in this review article. With effective measures by all stake holders we can reduce air pollution and prevent the global warming by 2030, along with 194 countries as adopted by WHO in May 2015.

  18. Toxoplasma gondii infection induces suppression in a mouse model of allergic airway inflammation.

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    Ignacio M Fenoy

    Full Text Available Allergic asthma is an inflammatory disorder characterized by infiltration of the airway wall with inflammatory cells driven mostly by activation of Th2-lymphocytes, eosinophils and mast cells. There is a link between increased allergy and a reduction of some infections in Western countries. Epidemiological data also show that respiratory allergy is less frequent in people exposed to orofecal and foodborne microbes such as Toxoplasma gondii. We previously showed that both acute and chronic parasite T. gondii infection substantially blocked development of airway inflammation in adult BALB/c mice. Based on the high levels of IFN-γ along with the reduction of Th2 phenotype, we hypothesized that the protective effect might be related to the strong Th1 immune response elicited against the parasite. However, other mechanisms could also be implicated. The possibility that regulatory T cells inhibit allergic diseases has received growing support from both animal and human studies. Here we investigated the cellular mechanisms involved in T. gondii induced protection against allergy. Our results show for the first time that thoracic lymph node cells from mice sensitized during chronic T. gondii infection have suppressor activity. Suppression was detected both in vitro, on allergen specific T cell proliferation and in vivo, on allergic lung inflammation after adoptive transference from infected/sensitized mice to previously sensitized animals. This ability was found to be contact-independent and correlated with high levels of TGF-β and CD4(+FoxP3(+ cells.

  19. [Analysis of clinical features and allergic status of asthmatic patients with positive serum mycosis-specific IgE].

    Science.gov (United States)

    Mou, Yan; Ye, Ling; Gong, Ying; Zhang, Zhi-feng; Jin, Mei-ling

    2013-08-01

    To improve understanding of the clinical characteristics and diagnosis of allergic bronchopulmonary mycosis (ABPM). We retrospectively analyzed the clinical data, including clinical symptoms, laboratory tests, pulmonary function tests and chest CT imaging of 95 asthmatic patients with positive serum mycosis-specific IgE from January 2010 to September 2012 in Zhongshan Hospital Affiliated to Fudan University. Of the 95 patients, 59 cases met the diagnostic criteria of ABPM. There were 34 males and 25 females, with a mean age of (53 ± 4) years and a duration of asthma for (21 ± 4) years. Thirty-six cases showed mycosis hypersensitivity (MH). There were 10 males and 26 females, with a mean age of (46 ± 6) years and a duration of asthma for (16 ± 5) years. Clinical symptoms such as wheeze (52 vs 21, χ(2) = 11.159, P = 0.001), cough (54 vs 27, χ(2) = 4.859, P = 0.030) and expectoration (43 vs 9, χ(2) = 25.731, P = 0.000) were more common in the ABPM group compared to the MH group.In the ABPM group, 58 were A. fumigatus-specific IgE antibody positive, 34 Penicillium-specific IgE antibody positive and 1 only Penicillium-specific IgE antibody positive.While in the MH group, 15 were A.fumigatus-specific IgE antibody positive, 24 Penicillium-specific IgE antibody positive and 17 only Penicillium-specific IgE antibody positive.In the ABPM group, the percentage of positive fumigatus-specific IgE antibody was higher (58 vs 15, χ(2) = 24.500, P = 0.000), while the percentages of dermatophagoides pteronyssinus(21 vs 20, χ(2) = 3.632, P = 0.045) and Dermatophagoides farinae(17 vs 21, χ(2) = 8.118, P = 0.004) were lower. Total serum IgE [(4395 ± 1437) IU/ml vs (276 ± 133) IU/ml, T = 4.384, P = 0.000], peripheral eosinophil percentage[(12.56 ± 1.20)% vs (1.30 ± 0.15)%, t = 8.175, P = 0.000] and count [(2.09 ± 0.43)×10(9)/L vs (0.19 ± 0.04)×10(9)/L, t = 7.032, P = 0.000] were higher in the ABPM group as compared to the MH group.FEV1% slightly declined in the ABPM

  20. Protective effect of soybean oil- or fish oil-rich diets on allergic airway inflammation

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    Navarro-Xavier RA

    2016-05-01

    Full Text Available Roberta Araujo Navarro-Xavier,1 Karina Vieira de Barros,1 Iracema Senna de Andrade,1 Zaira Palomino,2 Dulce Elena Casarini,2 Vera Lucia Flor Silveira3 1Departamento de Fisiologia, 2Departamento de Medicina, 3Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, São Paulo, Brazil Background: The increased prevalence of asthma and allergic diseases in westernized societies has been associated with increased intake of diets rich in n-6 fatty acids (FAs and poor in n-3 FAs. This study aimed to analyze the prophylactic effects of treatment with a soybean oil-rich diet (rich in n-6 or fish oil (rich in n-3 in an allergic airway inflammation model on lung inflammation score, leukocyte migration, T-helper cell (Th-2 (interleukin [IL]-4, IL-5 and Th1 (interferon [IFN]-γ, tumor necrosis factor-α cytokines, lipoxin A4, nitric oxide, bradykinin, and corticosterone levels in bronchoalveolar lavage (BAL or lungs. Methods: Male Wistar rats fed with soybean oil- or fish oil-rich diet or standard rat chow were sensitized twice with ovalbumin–alumen and challenged twice with ovalbumin aerosol. The BAL and lungs were examined 24 hours later. Results: Both diets, rich in n-6 or n-3 FAs, impaired the allergic lung inflammation and reduced leukocyte migration, eosinophil and neutrophil percentages, and IL-4/IL-5/bradykinin levels in BAL and/or lungs, as well as increased the nitric oxide levels in BAL. The soybean oil-rich diet additionally increased the levels of lipoxin A4 and corticosterone in the lungs. Conclusion: Data presented demonstrated that the n-6 FA-rich diet had protective effect upon allergic airway inflammation and was as anti-inflammatory as the n-3 FA-rich diet, although through different mechanisms, suggesting that both diets could be considered as complementary therapy or a prophylactic alternative for allergic airway inflammation. Keywords: asthma, nitric oxide, n-6 fatty acids, n-3 fatty acids, cytokines

  1. Associations of airway inflammation and responsiveness markers in non asthmatic subjects at start of apprenticeship

    Science.gov (United States)

    2010-01-01

    Background Bronchial Hyperresponsiveness (BHR) is considered a hallmark of asthma. Other methods are helpful in epidemiological respiratory health studies including Fractional Exhaled Nitric Oxide (FENO) and Eosinophils Percentage (EP) in nasal lavage fluid measuring markers for airway inflammation along with the Forced Oscillatory Technique measuring Airway resistance (AR). Can their outcomes discriminate profiles of respiratory health in healthy subjects starting apprenticeship in occupations with a risk of asthma? Methods Rhinoconjunctivitis, asthma-like symptoms, FEV1 and AR post-Methacholine Bronchial Challenge (MBC) test results, FENO measurements and EP were all investigated in apprentice bakers, pastry-makers and hairdressers not suffering from asthma. Multiple Correspondence Analysis (MCA) was simultaneously conducted in relation to these groups and this generated a synthetic partition (EI). Associations between groups of subjects based on BHR and EI respectively, as well as risk factors, symptoms and investigations were also assessed. Results Among the 441 apprentice subjects, 45 (10%) declared rhinoconjunctivitis-like symptoms, 18 (4%) declared asthma-like symptoms and 26 (6%) suffered from BHR. The mean increase in AR post-MBC test was 21% (sd = 20.8%). The median of FENO values was 12.6 ppb (2.6-132 range). Twenty-six subjects (6.7%) had EP exceeding 14%. BHR was associated with atopy (p < 0.01) and highest FENO values (p = 0.09). EI identified 39 subjects with eosinophilic inflammation (highest values of FENO and eosinophils), which was associated with BHR and atopy. Conclusions Are any of the identified markers predictive of increased inflammatory responsiveness or of development of symptoms caused by occupational exposures? Analysis of population follow-up will attempt to answer this question. PMID:20604945

  2. Salmonella enterica serovar Typhimurium infection-induced CD11b+ Gr1+ cells ameliorate allergic airway inflammation.

    Science.gov (United States)

    Ganesh, Venkateswaran; Baru, Abdul Mannan; Hesse, Christina; Friedrich, Christin; Glage, Silke; Gohmert, Melanie; Jänke, Christine; Sparwasser, Tim

    2014-03-01

    Allergies are mainly characterized as an unrestrained Th2-biased immune response. Epidemiological data associate protection from allergic diseases with the exposure to certain infectious agents during early stages of life. Modulation of the immune response by pathogens has been considered to be a major factor influencing this protection. Recent evidence indicates that immunoregulatory mechanisms induced upon infection ameliorate allergic disorders. A longitudinal study has demonstrated reduced frequency and incidence of asthma in children who reported a prior infection with Salmonella. Experimental studies involving Salmonella enterica serovar Typhimurium-infected murine models have confirmed protection from induced allergic airway inflammation; however, the underlying cause leading to this amelioration remains incompletely defined. In this study, we aimed to delineate the regulatory function of Salmonella Typhimurium infection in the amelioration of allergic airway inflammation in mice. We observed a significant increase in CD11b+ Gr1+ myeloid cell populations in mice after infection with S. Typhimurium. Using in vitro and in vivo studies, we confirmed that these myeloid cells reduce airway inflammation by influencing Th2 cells. Further characterization showed that the CD11b+ Gr1+ myeloid cells exhibited their inhibitory effect by altering GATA-3 expression and interleukin-4 (IL-4) production by Th2 cells. These results indicate that the expansion of myeloid cells upon S. Typhimurium infection could potentially play a significant role in curtailing allergic airway inflammation. These findings signify the contribution of myeloid cells in preventing Th2-mediated diseases and suggest their possible application as therapeutics.

  3. Chlamydia pneumoniae infection induced allergic airway sensitization is controlled by regulatory T-cells and plasmacytoid dendritic cells.

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    Timothy R Crother

    Full Text Available Chlamydia pneumoniae (CP is associated with induction and exacerbation of asthma. CP infection can induce allergic airway sensitization in mice in a dose- and time-dependent manner. Allergen exposure 5 days after a low dose (mild-moderate, but not a high dose (severe CP infection induces antigen sensitization in mice. Innate immune signals play a critical role in controlling CP infection induced allergic airway sensitization, however these mechanisms have not been fully elucidated. Wild-type, TLR2-/-, and TLR4-/- mice were infected intranasally (i.n. with a low dose of CP, followed by i.n. exposure to human serum albumin (HSA and challenged with HSA 2 weeks later. Airway inflammation, immunoglobulins, eosinophils, and goblet cells were measured. Low dose CP infection induced allergic sensitization in TLR2-/- mice, but not in TLR4-/- mice, due to differential Treg responses in these genotypes. TLR2-/- mice had reduced numbers of Tregs in the lung during CP infection while TLR4-/- mice had increased numbers. High dose CP infection resulted in an increase in Tregs and pDCs in lungs, which prevented antigen sensitization in WT mice. Depletion of Tregs or pDCs resulted in allergic airway sensitization. We conclude that Tregs and pDCs are critical determinants regulating CP infection-induced allergic sensitization. Furthermore, TLR2 and TLR4 signaling during CP infection may play a regulatory role through the modulation of Tregs.

  4. Polygonum multiflorum Decreases Airway Allergic Symptoms in a Murine Model of Asthma.

    Science.gov (United States)

    Lee, Chen-Chen; Lee, Yueh-Lun; Wang, Chien-N; Tsai, Hsing-Chuan; Chiu, Chun-Lung; Liu, Leroy F; Lin, Hung-Yun; Wu, Reen

    2016-01-01

    The root of Polygonum multiflorum (also called He-Shou-Wu in Chinese) is a common herb and medicinal food in Asia used for its anti-aging properties. Our study investigated the therapeutic potential of an extract of the root of Polygonum multiflorum (PME) in allergic asthma by using a mouse model. Feeding of 0.5 and 1 mg/mouse PME inhibited ovalbumin (OVA)-induced allergic asthma symptoms, including airway inflammation, mucus production, and airway hyper-responsiveness (AHR), in a dose-dependent manner. To discern PME's mechanism of action, we examined the profile and cytokine production of inflammatory cells in bronchial alveolar lavage fluid (BALF). We found that eosinophils, the main inflammatory cell infiltrate in the lung of OVA-immunized mice, significantly decreased after PME treatment. Th2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13, eotaxin, and the proinflammatory cytokine tumor necrosis factor (TNF)-[Formula: see text], decreased in PME-treated mice. Elevated mRNA expression of Th2 transcription factor GATA-3 in the lung tissue was also inhibited after oral feeding of PME in OVA-immunized mice. Thus, we conclude that PME produces anti-asthma activity through the inhibition of Th2 cell activation.

  5. BLUNTING AIRWAYS EOSINOPHILIC INFLAMMATION RESULTS IN A DECREASED AIRWAY NEUTROPHIL RESPONSE TO INHALED LPS IN ATOPIC ASTHMATICS A ROLE FOR CD-14

    Science.gov (United States)

    Recent data demonstrate that atopic inflammation might enhance airway responses to inhaled LPS in individuals with atopic asthma by increasing CD14 expression on airway macrophages. We sought to determine whether blunting airway eosinophilic inflammation decreases CD14 expressio...

  6. The transcription factor Etv5 controls TH17 cell development and allergic airway inflammation.

    Science.gov (United States)

    Pham, Duy; Sehra, Sarita; Sun, Xin; Kaplan, Mark H

    2014-07-01

    The differentiation of TH17 cells, which promote pulmonary inflammation, requires the cooperation of a network of transcription factors. We sought to define the role of Etv5, an Ets-family transcription factor, in TH17 cell development and function. TH17 development was examined in primary mouse T cells wherein Etv5 expression was altered by retroviral transduction, small interfering RNA targeting a specific gene, and mice with a conditional deletion of Etv5 in T cells. The direct function of Etv5 on the Il17 locus was tested with chromatin immunoprecipitation and reporter assays. The house dust mite-induced allergic inflammation model was used to test the requirement for Etv5-dependent TH17 functions in vivo. We identify Etv5 as a signal transducer and activator of transcription 3-induced positive regulator of TH17 development. Etv5 controls TH17 differentiation by directly promoting Il17a and Il17f expression. Etv5 recruits histone-modifying enzymes to the Il17a-Il17f locus, resulting in increased active histone marks and decreased repressive histone marks. In a model of allergic airway inflammation, mice with Etv5-deficient T cells have reduced airway inflammation and IL-17A/F production in the lung and bronchoalveolar lavage fluid compared with wild-type mice, without changes in TH2 cytokine production. These data define signal transducer and activator of transcription 3-dependent feed-forward control of TH17 cytokine production and a novel role for Etv5 in promoting T cell-dependent airway inflammation. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  7. Gelam honey attenuates ovalbumin-induced airway inflammation in a mice model of allergic asthma

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    Nur Salme Suhana Shamshuddin

    2018-01-01

    Full Text Available Allergic asthma is a chronic inflammatory disorder of the pulmonary airways. Gelam honey has been proven to possess anti-inflammatory property with great potential to treat an inflammatory condition. However, the effect of ingestion of Gelam honey on allergic asthma has never been studied. This study aimed to investigate the efficacy of Gelam honey on the histopathological changes in the lungs of a mice model of allergic asthma. Forty-two Balb/c mice were divided into seven groups: control, I, II, III, IV, V and VI group. All groups except the control were sensitized and challenged with ovalbumin. Mice in groups I, II, III, IV, and V were given honey at a dose of 10% (v/v, 40% (v/v and 80% (v/v, dexamethasone 3 mg/kg, and phosphate buffered saline (vehicle respectively, orally once a day for 5 days of the challenged period. Mice were sacrificed 24 h after the last OVA challenged and the lungs were evaluated for histopathological changes by light microscopy. All histopathological parameters such as epithelium thickness, the number of mast cell and mucus expression in Group III significantly improved when compared to Group VI except for subepithelial smooth muscle thickness (p < 0.05. In comparing Group III and IV, all the improvements in histopathological parameters were similar. Also, Gelam honey showed a significant (p < 0.05 reduction in inflammatory cell infiltration and beta-hexosaminidase level in bronchoalveolar lavage fluid. In conclusion, we demonstrated that administration of high concentration of Gelam honey alleviates the histopathological changes of mice model of allergic asthma.

  8. Gelam honey attenuates ovalbumin-induced airway inflammation in a mice model of allergic asthma.

    Science.gov (United States)

    Shamshuddin, Nur Salme Suhana; Mohd Zohdi, Rozaini

    2018-01-01

    Allergic asthma is a chronic inflammatory disorder of the pulmonary airways. Gelam honey has been proven to possess anti-inflammatory property with great potential to treat an inflammatory condition. However, the effect of ingestion of Gelam honey on allergic asthma has never been studied. This study aimed to investigate the efficacy of Gelam honey on the histopathological changes in the lungs of a mice model of allergic asthma. Forty-two Balb/c mice were divided into seven groups: control, I, II, III, IV, V and VI group. All groups except the control were sensitized and challenged with ovalbumin. Mice in groups I, II, III, IV, and V were given honey at a dose of 10% (v/v), 40% (v/v) and 80% (v/v), dexamethasone 3 mg/kg, and phosphate buffered saline (vehicle) respectively, orally once a day for 5 days of the challenged period. Mice were sacrificed 24 h after the last OVA challenged and the lungs were evaluated for histopathological changes by light microscopy. All histopathological parameters such as epithelium thickness, the number of mast cell and mucus expression in Group III significantly improved when compared to Group VI except for subepithelial smooth muscle thickness (p < 0.05). In comparing Group III and IV, all the improvements in histopathological parameters were similar. Also, Gelam honey showed a significant (p < 0.05) reduction in inflammatory cell infiltration and beta-hexosaminidase level in bronchoalveolar lavage fluid. In conclusion, we demonstrated that administration of high concentration of Gelam honey alleviates the histopathological changes of mice model of allergic asthma.

  9. A GM-CSF/IL-33 pathway facilitates allergic airway responses to sub-threshold house dust mite exposure.

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    Alba Llop-Guevara

    Full Text Available Allergic asthma is a chronic immune-inflammatory disease of the airways. Despite aeroallergen exposure being universal, allergic asthma affects only a fraction of individuals. This is likely related, at least in part, to the extent of allergen exposure. Regarding house dust mite (HDM, we previously identified the threshold required to elicit allergic responses in BALB/c mice. Here, we investigated the impact of an initial immune perturbation on the response to sub-threshold HDM exposure. We show that transient GM-CSF expression in the lung facilitated robust eosinophilic inflammation, long-lasting antigen-specific Th2 responses, mucus production and airway hyperresponsiveness. This was associated with increased IL-33 levels and activated CD11b(+ DCs expressing OX40L. GM-CSF-driven allergic responses were significantly blunted in IL-33-deficient mice. IL-33 was localized on alveolar type II cells and in vitro stimulation of human epithelial cells with GM-CSF enhanced intracellular IL-33 independently of IL-1α. Likewise, GM-CSF administration in vivo resulted in increased levels of IL-33 but not IL-1α. These findings suggest that exposures to environmental agents associated with GM-CSF production, including airway infections and pollutants, may decrease the threshold of allergen responsiveness and, hence, increase the susceptibility to develop allergic asthma through a GM-CSF/IL-33/OX40L pathway.

  10. Does unrestrained single-chamber plethysmography provide a valid assessment of airway responsiveness in allergic BALB/c mice?

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    Chen Guoqin

    2009-07-01

    Full Text Available Abstract Background Unrestrained plethysmography has been used to monitor bronchoconstriction because of its ease of use and ability to measure airway responsiveness in conscious animals. However, its reliability remains controversial. Objective To investigate if unrestrained plethysmography could provide a valid interpretation of airway responsiveness in allergic BALB/c mice. Methods Ovalbumin sensitized BALB/c mice were randomized to receive either a single-dose Ovalbumin challenge (OVA-1D group or a three-dose Ovalbumin challenge (OVA-3D group. The OVA-1D group was further divided into OVA-1D-I (measured invasively, using lung resistance as the index of responsiveness and OVA-1D-N group (measured non-invasively, using Penh as the index of responsiveness. Similarly the OVA-3D group was divided into OVA-3D-I and OVA-3D-N groups based on the above methods. The control groups were sensitized and challenged with normal saline. Bronchial alveolar lavage fluid was taken and airway histopathology was evaluated for airway inflammation. Nasal responsiveness was tested with histamine challenge. Results Compared with controls, a significant increase in airway responsiveness was shown in the OVA-1D-N group (P Conclusion Penh can not be used as a surrogate for airway resistance. The invasive measurement is specific to lower airway. Penh measurement (done as a screening procedure, must be confirmed by a direct invasive measurement specific to lower airway in evaluating lower airway responsiveness.

  11. Maternal allergic contact dermatitis causes increased asthma risk in offspring.

    Science.gov (United States)

    Lim, Robert H; Arredouani, Mohamed S; Fedulov, Alexey; Kobzik, Lester; Hubeau, Cedric

    2007-07-27

    Offspring of asthmatic mothers have increased risk of developing asthma, based on human epidemiologic data and experimental animal models. The objective of this study was to determine whether maternal allergy at non-pulmonary sites can increase asthma risk in offspring. BALB/c female mice received 2 topical applications of vehicle, dinitrochlorobenzene, or toluene diisocyanate before mating with untreated males. Dinitrochlorobenzene is a skin-sensitizer only and known to induce a Th1 response, while toluene diisocyanate is both a skin and respiratory sensitizer that causes a Th2 response. Both cause allergic contact dermatitis. Offspring underwent an intentionally suboptimal protocol of allergen sensitization and aerosol challenge, followed by evaluation of airway hyperresponsiveness, allergic airway inflammation, and cytokine production. Mothers were tested for allergic airway disease, evidence of dermatitis, cellularity of the draining lymph nodes, and systemic cytokine levels. The role of interleukin-4 was also explored using interleukin-4 deficient mice. Offspring of toluene diisocyanate but not dinitrochlorobenzene-treated mothers developed an asthmatic phenotype following allergen sensitization and challenge, seen as increased Penh values, airway inflammation, bronchoalveolar lavage total cell counts and eosinophilia, and Th2 cytokine imbalance in the lung. Toluene diisocyanate treated interleukin-4 deficient mothers were able to transfer asthma risk to offspring. Mothers in both experimental groups developed allergic contact dermatitis, but not allergic airway disease. Maternal non-respiratory allergy (Th2-skewed dermatitis caused by toluene diisocyanate) can result in the maternal transmission of asthma risk in mice.

  12. Maternal allergic contact dermatitis causes increased asthma risk in offspring

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    Kobzik Lester

    2007-07-01

    Full Text Available Abstract Background Offspring of asthmatic mothers have increased risk of developing asthma, based on human epidemiologic data and experimental animal models. The objective of this study was to determine whether maternal allergy at non-pulmonary sites can increase asthma risk in offspring. Methods BALB/c female mice received 2 topical applications of vehicle, dinitrochlorobenzene, or toluene diisocyanate before mating with untreated males. Dinitrochlorobenzene is a skin-sensitizer only and known to induce a Th1 response, while toluene diisocyanate is both a skin and respiratory sensitizer that causes a Th2 response. Both cause allergic contact dermatitis. Offspring underwent an intentionally suboptimal protocol of allergen sensitization and aerosol challenge, followed by evaluation of airway hyperresponsiveness, allergic airway inflammation, and cytokine production. Mothers were tested for allergic airway disease, evidence of dermatitis, cellularity of the draining lymph nodes, and systemic cytokine levels. The role of interleukin-4 was also explored using interleukin-4 deficient mice. Results Offspring of toluene diisocyanate but not dinitrochlorobenzene-treated mothers developed an asthmatic phenotype following allergen sensitization and challenge, seen as increased Penh values, airway inflammation, bronchoalveolar lavage total cell counts and eosinophilia, and Th2 cytokine imbalance in the lung. Toluene diisocyanate treated interleukin-4 deficient mothers were able to transfer asthma risk to offspring. Mothers in both experimental groups developed allergic contact dermatitis, but not allergic airway disease. Conclusion Maternal non-respiratory allergy (Th2-skewed dermatitis caused by toluene diisocyanate can result in the maternal transmission of asthma risk in mice.

  13. Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

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    Chen-Chen Lee

    2015-01-01

    Full Text Available This study investigated the immunomodulatory effects of ferulic acid (FA on antigen-presenting dendritic cells (DCs in vitro and its antiallergic effects against ovalbumin- (OVA- induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS stimulation induced a high level of interleukin- (IL- 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF- α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4, MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13, and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN- γ production in bronchoalveolar lavage fluid (BALF and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model.

  14. Components of Streptococcus pneumoniae suppress allergic airways disease and NKT cells by inducing regulatory T cells.

    Science.gov (United States)

    Thorburn, Alison N; Foster, Paul S; Gibson, Peter G; Hansbro, Philip M

    2012-05-01

    Asthma is an allergic airways disease (AAD) caused by dysregulated immune responses and characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). NKT cells have been shown to contribute to AHR in some mouse models. Conversely, regulatory T cells (Tregs) control aberrant immune responses and maintain homeostasis. Recent evidence suggests that Streptococcus pneumoniae induces Tregs that have potential to be harnessed therapeutically for asthma. In this study, mouse models of AAD were used to identify the S. pneumoniae components that have suppressive properties, and the mechanisms underlying suppression were investigated. We tested the suppressive capacity of type-3-polysaccharide (T3P), isolated cell walls, pneumolysoid (Ply) and CpG. When coadministered, T3P + Ply suppressed the development of: eosinophilic inflammation, Th2 cytokine release, mucus hypersecretion, and AHR. Importantly, T3P + Ply also attenuated features of AAD when administered during established disease. We show that NKT cells contributed to the development of AAD and also were suppressed by T3P + Ply treatment. Furthermore, adoptive transfer of NKT cells induced AHR, which also could be reversed by T3P + Ply. T3P + Ply-induced Tregs were essential for the suppression of NKT cells and AAD, which was demonstrated by Treg depletion. Collectively, our results show that the S. pneumoniae components T3P + Ply suppress AAD through the induction of Tregs that blocked the activity of NKT cells. These data suggest that S. pneumoniae components may have potential as a therapeutic strategy for the suppression of allergic asthma through the induction of Tregs and suppression of NKT cells.

  15. Microfibrillar-associated protein 4 modulates airway smooth muscle cell phenotype in experimental asthma

    DEFF Research Database (Denmark)

    Pilecki, Bartosz; Schlosser, Anders; Wulf-Johansson, Helle

    2015-01-01

    . In the current study we investigated the role of MFAP4 in experimental allergic asthma. METHODS: MFAP4-deficient mice were subjected to alum/ovalbumin and house dust mite induced models of allergic airway disease. In addition, human healthy and asthmatic primary bronchial smooth muscle cell cultures were used...... to evaluate MFAP4-dependent airway smooth muscle responses. RESULTS: MFAP4 deficiency attenuated classical hallmarks of asthma, such as eosinophilic inflammation, eotaxin production, airway remodelling and hyperresponsiveness. In wild-type mice, serum MFAP4 was increased after disease development...... and correlated with local eotaxin levels. MFAP4 was expressed in human bronchial smooth muscle cells and its expression was upregulated in asthmatic cells. Regarding the underlying mechanism, we showed that MFAP4 interacted with integrin αvβ5 and promoted asthmatic bronchial smooth muscle cell proliferation...

  16. Early effects of continuous positive airway pressure in a rodent model of allergic rhinitis.

    Science.gov (United States)

    Vilaseca, I; Lehrer-Coriat, E; Torres, M; Aguilar, F; Almendros, I; Martínez-Vidal, B M; Farré, R; Montserrat, J M

    Continuous positive airway pressure (CPAP) is the most commonly used treatment in obstructive sleep apnea. In a previous rat model study, we demonstrated that nasal CPAP induces early rhinitis expressed by nasal neutrophil extravasation. Here we hypothesized that nasal CPAP would worsen nasal inflammation on a previously inflamed mucosa. The objective of this study was to evaluate the early nasal CPAP effects of allergic rhinitis (AR) in a rodent model. Twenty Sprague-Dawley rats were sensitized with intraperitoneal ovalbumin (OVA). Nasal inflammation was induced by the administration of intranasal OVA during consecutive days. The same procedure was performed in 20 control rats treated with saline solution. The allergic (AR) and non-allergic (NAR) rats were then randomized to nasal CPAP at 10 cm H 2 O for five hours or to sham CPAP. The degree of nasal inflammation was assessed by evaluating the percentage of neutrophils, eosinophils, basophils, and lymphocytes in the nasal mucosa. An unpaired Mann-Whitney test was used to analyze differences between groups. The greatest inflammation was observed in the group of AR without CPAP (1.24% ± 0.94%), followed by NAR with CPAP (0.64% ± 0.30%), AR with CPAP (0.64% ± 0.40%), and NAR without CPAP (0.21% ± 0.29%). Administration of nasal CPAP or allergy sensitization can produce, individually, neutrophil extravasation on the nasal mucosa of a rat model. The application of both stimuli is not responsible for increased inflammation. Therefore, this study suggests that rhinitis is not a major limitation for CPAP administration. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Inhibition of pan neurotrophin receptor p75 attenuates diesel particulate-induced enhancement of allergic airway responses in C57/B16J mice.

    Science.gov (United States)

    Farraj, Aimen K; Haykal-Coates, Najwa; Ledbetter, Allen D; Evansky, Paul A; Gavett, Stephen H

    2006-06-01

    Recent investigations have linked neurotrophins, including nerve growth factor (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF), to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance in allergic mice. Diesel exhaust particle (DEP) exposure has been linked to asthma exacerbation in many cities with vehicular traffic congestion. We tested the hypothesis that DEP-induced enhancement of the hallmark features of allergic airway disease in a murine model is dependent on the function of the pan neurotrophin receptor p75. Ovalbumin (OVA)-sensitized C57B1/6J mice were intranasally instilled with an antibody against the p75 receptor or saline alone 1 h before OVA challenge. The mice were then exposed nose-only to the PM2.5 fraction of SRM2975 DEP or air alone for 5 h beginning 1 h after OVA challenge. Two days later, air-exposed OVA-allergic mice developed a small but insignificant increase in methacholine-induced airflow obstruction relative to air-exposed, vehicle-sensitized mice. DEP-exposed OVA-allergic mice had a significantly greater degree of airway obstruction than all other groups. Instillation of anti-p75 significantly attenuated the DEP-induced increase in airway obstruction in OVA-allergic mice to levels similar to non-sensitized mice. The DEP-induced exacerbation of allergic airway responses may, in part, be mediated by neurotrophins.

  18. Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma

    Directory of Open Access Journals (Sweden)

    Jelena Skuljec

    2017-09-01

    Full Text Available Cellular therapy with chimeric antigen receptor (CAR-redirected cytotoxic T cells has shown impressive efficacy in the treatment of hematologic malignancies. We explored a regulatory T cell (Treg-based therapy in the treatment of allergic airway inflammation, a model for asthma, which is characterized by an airway hyper-reactivity (AHR and a chronic, T helper-2 (Th2 cell-dominated immune response to allergen. To restore the immune balance in the lung, we redirected Tregs by a CAR toward lung epithelia in mice upon experimentally induced allergic asthma, closely mimicking the clinical situation. Adoptively transferred CAR Tregs accumulated in the lung and in tracheobronchial lymph nodes, reduced AHR and diminished eosinophilic airway inflammation, indicated by lower cell numbers in the bronchoalveolar lavage fluid and decreased cell infiltrates in the lung. CAR Treg cells furthermore prevented excessive pulmonary mucus production as well as increase in allergen-specific IgE and Th2 cytokine levels in exposed animals. CAR Tregs were more efficient in controlling asthma than non-modified Tregs, indicating the pivotal role of specific Treg cell activation in the affected organ. Data demonstrate that lung targeting CAR Treg cells ameliorate key features of experimental airway inflammation, paving the way for cell therapy of severe allergic asthma.

  19. Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study.

    Science.gov (United States)

    Carlsten, Chris; Blomberg, Anders; Pui, Mandy; Sandstrom, Thomas; Wong, Sze Wing; Alexis, Neil; Hirota, Jeremy

    2016-01-01

    Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood. To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects. 18 blinded atopic volunteers were exposed to filtered air or 300 µg PM(2.5)/m(3) of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points. Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells. Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust. NCT01792232. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. Toll-like receptor-2 agonist-allergen coupling efficiently redirects Th2 cell responses and inhibits allergic airway eosinophilia.

    Science.gov (United States)

    Krishnaswamy, Jayendra Kumar; Jirmo, Adan Chari; Baru, Abdul Mannan; Ebensen, Thomas; Guzmán, Carlos A; Sparwasser, Tim; Behrens, Georg M N

    2012-12-01

    Toll-like receptor (TLR) agonists beneficially modulate allergic airway inflammation. However, the efficiency of TLR agonists varies considerably, and their exact cellular mechanisms (especially of TLR 2/6 agonists) are incompletely understood. We investigated at a cellular level whether the administration of the pharmacologically improved TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPP) conjugated to antigenic peptide (BPP-OVA) could divert an existing Th2 response and influence airway eosinophilia. The effects of BPP-OVA on airway inflammation were assessed in a classic murine sensitization/challenge model and an adoptive transfer model, which involved the adoptive transfer of in vitro differentiated ovalbumin (OVA)-specific Th2 cells. Functional T-cell stimulation by lung dendritic cells (DCs) was determined both in vitro and in vivo, combined with a cytokine secretion analysis. A single mucosal application of BPP-OVA efficiently delivered antigen, led to TLR2-mediated DC activation, and resulted in OVA-specific T-cell proliferation via lung DCs in vivo. In alternative models of allergic airway disease, a single administration of BPP-OVA before OVA challenge (but not BPP alone) significantly reduced airway eosinophilia, most likely through altered antigen-specific T-cell stimulation via DCs. Analyses of adoptively transferred Th2-biased cells after BPP-OVA administration in vivo suggested that BPP-OVA guides antigen-specific Th2 cells to produce significantly higher amounts of IFN-γ upon allergen challenge. In conclusion, our data show for the first time that a single mucosal administration of a TLR 2/6 agonist-allergen conjugate can provoke IFN-γ responses in Th2-biased cells and alleviate allergic airway inflammation.

  1. Mediators on human airway smooth muscle.

    Science.gov (United States)

    Armour, C; Johnson, P; Anticevich, S; Ammit, A; McKay, K; Hughes, M; Black, J

    1997-01-01

    1. Bronchial hyperresponsiveness in asthma may be due to several abnormalities, but must include alterations in the airway smooth muscle responsiveness and/or volume. 2. Increased responsiveness of airway smooth muscle in vitro can be induced by certain inflammatory cell products and by induction of sensitization (atopy). 3. Increased airway smooth muscle growth can also be induced by inflammatory cell products and atopic serum. 4. Mast cell numbers are increased in the airways of asthmatics and, in our studies, in airway smooth muscle that is sensitized and hyperresponsive. 5. We propose that there is a relationship between mast cells and airway smooth muscle cells which, once an allergic process has been initiated, results in the development of critical features in the lungs in asthma.

  2. Schistosoma mansoni-mediated suppression of allergic airway inflammation requires patency and Foxp3+ Treg cells.

    Directory of Open Access Journals (Sweden)

    Laura E Layland

    Full Text Available The continual rise of asthma in industrialised countries stands in strong contrast to the situation in developing lands. According to the modified Hygiene Hypothesis, helminths play a major role in suppressing bystander immune responses to allergens, and both epidemiological and experimental studies suggest that the tropical parasitic trematode Schistosoma mansoni elicits such effects. The focus of this study was to investigate which developmental stages of schistosome infection confer suppression of allergic airway inflammation (AAI using ovalbumin (OVA as a model allergen. Moreover, we assessed the functional role and localization of infection-induced CD4(+Foxp3(+ regulatory T cells (Treg in mediating such suppressive effects. Therefore, AAI was elicited using OVA/adjuvant sensitizations with subsequent OVA aerosolic challenge and was induced during various stages of infection, as well as after successful anti-helminthic treatment with praziquantel. The role of Treg was determined by specifically depleting Treg in a genetically modified mouse model (DEREG during schistosome infection. Alterations in AAI were determined by cell infiltration levels into the bronchial system, OVA-specific IgE and Th2 type responses, airway hyper-sensitivity and lung pathology. Our results demonstrate that schistosome infection leads to a suppression of OVA-induced AAI when mice are challenged during the patent phase of infection: production of eggs by fecund female worms. Moreover, this ameliorating effect does not persist after anti-helminthic treatment, and depletion of Treg reverts suppression, resulting in aggravated AAI responses. This is most likely due to a delayed reconstitution of Treg in infected-depleted animals which have strong ongoing immune responses. In summary, we conclude that schistosome-mediated suppression of AAI requires the presence of viable eggs and infection-driven Treg cells. These data provide evidence that helminth derived products

  3. Effect of an intranasal conrticosteroid on exercide induced bronchocostriction in asthmatic children

    NARCIS (Netherlands)

    Kersten, E.T.; Leeuwen, J.C. van; Brand, P.L.; Duiverman, E.J.; de Jongh, Franciscus H.C.; Thio, B.J.; Driessen, J.M.

    2012-01-01

    Rationale: Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children. Methods: This was a

  4. Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

    International Nuclear Information System (INIS)

    Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

    2012-01-01

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

  5. Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Chiara Murgia

    2011-10-01

    Full Text Available The apical cytoplasm of airway epithelium (AE contains abundant labile zinc (Zn ions that are involved in the protection of AE from oxidants and inhaled noxious substances. A major question is how dietary Zn traffics to this compartment. In rat airways, in vivo selenite autometallographic (Se-AMG-electron microscopy revealed labile Zn-selenium nanocrystals in structures resembling secretory vesicles in the apical cytoplasm. This observation was consistent with the starry-sky Zinquin fluorescence staining of labile Zn ions confined to the same region. The vesicular Zn transporter ZnT4 was likewise prominent in both the apical and basal parts of the epithelium both in rodent and human AE, although the apical pools were more obvious. Expression of ZnT4 mRNA was unaffected by changes in the extracellular Zn concentration. However, levels increased 3-fold during growth of cells in air liquid interface cultures and decreased sharply in the presence of retinoic acid. When comparing nasal versus bronchial human AE cells, there were significant positive correlations between levels of ZnT4 from the same subject, suggesting that nasal brushings may allow monitoring of airway Zn transporter expression. Finally, there were marked losses of both basally-located ZnT4 protein and labile Zn in the bronchial epithelium of mice with allergic airway inflammation. This study is the first to describe co-localization of zinc vesicles with the specific zinc transporter ZnT4 in airway epithelium and loss of ZnT4 protein in inflamed airways. Direct evidence that ZnT4 regulates Zn levels in the epithelium still needs to be provided. We speculate that ZnT4 is an important regulator of zinc ion accumulation in secretory apical vesicles and that the loss of labile Zn and ZnT4 in airway inflammation contributes to AE vulnerability in diseases such as asthma.

  6. FeNO for detecting lower airway involvement in patients with allergic rhinitis

    Science.gov (United States)

    Zhu, Zheng; Xie, Yanqing; Guan, Weijie; Gao, Yi; Xia, Shu; Zhong, Nanshan; Zheng, Jinping

    2016-01-01

    Allergic rhinitis (AR) is a risk factor for asthma development. The value of fractional exhaled nitric oxide (FeNO) in detecting lower airway involvement in the progress of AR-asthma march has not been evaluated. The aim of the present study was to investigate the value of FeNO in assessing lower airway inflammation and predicting bronchial hyperresponsiveness (BHR) in AR with or without asthma. FeNO and eosinophil count in induced sputum, and a methacholine bronchial provocation test were performed in 93 subjects, including: 45 AR patients (AR group); 20 patients with AR and asthma (AR with asthma group); and 28 normal controls (control group). The AR group was divided into two sub-groups: AR with asymptomatic BHR group and AR without BHR group. Correlation between FeNO and eosinophil count was assessed. Receiver operating characteristic (ROC) curve was applied to evaluate the predictive and diagnostic value of FeNO in detecting BHR. The values of FeNO in the AR and AR with asthma groups were higher [29.5 (22.0) ppb and 61.5 (33.0) ppb] compared with the normal control group (16.0 (10.0) ppb), where the values in brackets indicate the interquartile range of the values. The percentages of eosinophils in induced sputum were 2.43±3.56, 7.36±4.98 and 18.58±11.26% in the control, AR and AR with asthma groups, respectively. For the diagnosis of BHR, the area under the curve (AUC) was 0.910 (95%CI 0.836, 0.984), with the sensitivity and specificity 0.846 and 0.817 when the cut-off value takes 31.5 ppb. For diagnosis of asthma, the AUC was 0.873 (95%CI 0.753, 0.992) with sensitivity 0.857 and specificity 0.847 when taking the cut-off value to be 38.0 ppb. The value of FeNO was well correlated with eosinophil count in the sputum. The measurement of FeNO is an effective method in detecting lower airway involvement in AR developing to asthma. PMID:27703499

  7. Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin-Induced Allergic Airway Inflammation in a Mouse Model.

    Science.gov (United States)

    Zhang, Zhiyu; Shi, Lei; Pang, Wenhui; Liu, Wenwen; Li, Jianfeng; Wang, Haibo; Shi, Guanggang

    2016-01-01

    Recently, academic studies suggest that global growth of airway allergic disease has a close association with dietary changes including reduced consumption of fiber. Therefore, appropriate dietary fiber supplementation might be potential to prevent airway allergic disease (AAD). We investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms. The control mice and AAD model mice fed with 4% standard-fiber chow, while low-fiber group of mice fed with a 1.75% low-fiber chow. The two fiber-intervened groups including mice, apart from a standard-fiber diet, were also intragastric (i.g.) administrated daily with poorly fermentable cellulose or readily fermentable pectin (0.4% of daily body weight), respectively. All animals except normal mice were sensitized and challenged with ovalbumin (OVA) to induce airway allergic inflammation. Hallmarks of AAD were examined by histological analysis and ELISA. The variation in intestinal bacterial composition was assessed by qualitative analysis of 16S ribosomal DNA (rDNA) content in fecal samples using real-time PCR. Low-fiber diet aggravated inflammatory response in ovalbumin-induced allergic mice, whereas dietary fiber intake significantly suppressed the allergic responses, attenuated allergic symptoms of nasal rubbing and sneezing, decreased the pathology of eosinophil infiltration and goblet cell metaplasia in the nasal mucosa and lung, inhibited serum OVA-specific IgE levels, and lowered the levels of Th2 cytokines in NALF and BALF, but, increased Th1 (IFN-γ) cytokines. Additionally, dietary fiber intake also increased the proportion of Bacteroidetes and Actinobacteria, and decreased Firmicutes and Proteobacteria. Levels of probiotic bacteria, such as Lactobacillus and Bifidobacterium, were upgraded significantly. Long-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper fiber supplementation promotes effectively the

  8. Immunomodulatory Effects of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03, Alone and in Combination, on Peripheral Blood Mononuclear Cells of Allergic Asthmatics.

    Science.gov (United States)

    Drago, Lorenzo; De Vecchi, Elena; Gabrieli, Arianna; De Grandi, Roberta; Toscano, Marco

    2015-07-01

    The aim of this study was to evaluate probiotic characteristics of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03 alone and in combination and their immunomodulatory activity in asthmatic subjects. Subjects affected by allergic asthma were recruited. Initially, LS01 and BR03 were analyzed for their growth compatibility by a broth compatibility assay. To study the antimicrobial activity of probiotic strains, an agar diffusion assay was performed. Finally, cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with LS01 and BR03 was determined by means of specific quantitative enzyme-linked immunosorbent assay (ELISA). The growth of some clinical pathogens were slightly inhibited by LS01 and LS01-BR03 co-culture supernatant not neutralized to pH 6.5, while only the growth of E. coli and S. aureus was inhibited by the supernatant of LS01 and LS01-BR03 neutralized to pH 6.5. Furthermore, LS01 and BR03 combination was able to decrease the secretion of proinflammatory cytokines by PBMCs, leading to an intense increase in IL-10 production. L. salivarius LS01 and B. breve BR03 showed promising probiotic properties and beneficial immunomodulatory activity that are increased when the 2 strains are used in combination in the same formulation.

  9. THE USE OF SUPEROXIDE DISMUTASE IN ACCELERATING SYMPTOM RELIEF IN ASTHMATIC AND HOUSE DUST MITE ALLERGIC CHILDREN RECEIVING HOUSE DUST MITE IMMUNOTHERAPY: DOUBLE BLIND RANDOMIZED CONTROLLED CLINICAL TRIAL

    Directory of Open Access Journals (Sweden)

    Anang Endaryanto

    2015-09-01

    Full Text Available Objective: To evaluate the efficacy of superoxide dismutase (SOD in lung function (FEV1 reversibility and respiratory symptoms (drug scores, symptoms scores in asthmatic and house dust mite allergic children receiving house dust mites immunotherapy. Methods: Forty subjects aged 6–17 years old with asthma, tested positive for house dust mite allergy on skin prick test, and received immunotherapy were enrolled in this study. All subjects completed clinical based assessments and diary-based assessments for drug and symptom scores. Following a four-week baseline assessment, all subjects were randomized to receive SOD or placebo. Respiratory symptoms (drug and symptoms score and FEV1 were evaluated at the end of the 1st, 2nd, 3rd, and 4th weeks after randomization. Drug score, symptoms score, and FEV1 reversibility test results were analyzed using a Paired t test and repeated measure of ANOVA. Results: There was a significant difference in drug scores, symptoms score, and FEV1 reversibility test outcomes between SOD and placebo. SOD group showed a significant decrease in all outcome measures compared to those in placebo group. Conclusions: The use of SOD as antioxidants is effective in accelerating symptom relief for children with asthma and house dust mite allergy receiving house dust mite immunotherapy.

  10. Dual action of iNOS-derived nitric oxide in allergen-induced airway hyperreactivity in conscious, unrestrained guinea pigs

    NARCIS (Netherlands)

    Schuiling, M; Meurs, Herman; Zuidhof, A.B; Venema, N; Zaagsma, Hans

    1998-01-01

    Using a guinea pig model of acute allergic asthma, we recently established that a deficiency of nitric oxide (NO) contributes to airway hyperreactivity (AHR) after the early asthmatic reaction (EAR) and that restoration of NO activity may contribute to the (partial) reversal of AHR after the late

  11. Absence of Foxp3+ regulatory T cells during allergen provocation does not exacerbate murine allergic airway inflammation.

    Directory of Open Access Journals (Sweden)

    Abdul Mannan Baru

    Full Text Available Regulatory T cells (Tregs play a non-redundant role in maintenance of immune homeostasis. This is achieved by suppressing both, priming of naïve cells and effector cell functions. Although Tregs have been implicated in modulating allergic immune responses, their influence on distinct phases of development of allergies remains unclear. In this study, by using bacterial artificial chromosome (BAC-transgenic Foxp3-DTR (DEREG mice we demonstrate that the absence of Foxp3(+ Tregs during the allergen challenge surprisingly does not exacerbate allergic airway inflammation in BALB/c mice. As genetic disposition due to strain specificity may contribute significantly to development of allergies, we performed similar experiment in C57BL/6 mice, which are less susceptible to allergy in the model of sensitization used in this study. We report that the genetic background does not influence the consequence of this depletion regimen. These results signify the temporal regulation exerted by Foxp3(+ Tregs in limiting allergic airway inflammation and may influence their application as potential therapeutics.

  12. Absence of Foxp3+ regulatory T cells during allergen provocation does not exacerbate murine allergic airway inflammation.

    Science.gov (United States)

    Baru, Abdul Mannan; Ganesh, Venkateswaran; Krishnaswamy, Jayendra Kumar; Hesse, Christina; Untucht, Christopher; Glage, Silke; Behrens, Georg; Mayer, Christian Thomas; Puttur, Franz; Sparwasser, Tim

    2012-01-01

    Regulatory T cells (Tregs) play a non-redundant role in maintenance of immune homeostasis. This is achieved by suppressing both, priming of naïve cells and effector cell functions. Although Tregs have been implicated in modulating allergic immune responses, their influence on distinct phases of development of allergies remains unclear. In this study, by using bacterial artificial chromosome (BAC)-transgenic Foxp3-DTR (DEREG) mice we demonstrate that the absence of Foxp3(+) Tregs during the allergen challenge surprisingly does not exacerbate allergic airway inflammation in BALB/c mice. As genetic disposition due to strain specificity may contribute significantly to development of allergies, we performed similar experiment in C57BL/6 mice, which are less susceptible to allergy in the model of sensitization used in this study. We report that the genetic background does not influence the consequence of this depletion regimen. These results signify the temporal regulation exerted by Foxp3(+) Tregs in limiting allergic airway inflammation and may influence their application as potential therapeutics.

  13. Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airways inflammation.

    Directory of Open Access Journals (Sweden)

    Nicholas J Kenyon

    Full Text Available Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex alone. We found that ovalbumin (Ova-exposed mice treated with Dex-NP had significantly fewer total cells (2.78 ± 0.44 × 10(5 (n = 18 vs. 5.98 ± 1.3 × 10(5 (n = 13, P<0.05 and eosinophils (1.09 ± 0.28 × 10(5 (n = 18 vs. 2.94 ± 0.6 × 10(5 (n = 12, p<0.05 in the lung lavage than Ova-exposed mice alone. Also, lower levels of the inflammatory cytokines IL-4 (3.43 ± 1.2 (n = 11 vs. 8.56 ± 2.1 (n = 8 pg/ml, p<0.05 and MCP-1 (13.1 ± 3.6 (n = 8 vs. 28.8 ± 8.7 (n = 10 pg/ml, p<0.05 were found in lungs of the Dex-NP compared to control, and they were not lower in the Dex alone group. In addition, respiratory system resistance was lower in the Dex-NP compared to the other Ova-exposed groups suggesting a better therapeutic effect on airways hyperresponsiveness. Taken together, these findings from early-stage drug development studies suggest that the encapsulation and protection of anti-inflammatory agents such as corticosteroids in nanoparticle formulations can improve efficacy. Further development of novel drugs in nanoparticles is warranted to explore potential treatments for chronic inflammatory diseases such as asthma.

  14. Does Inhalation of Virgin Coconut Oil Accelerate Reversal of Airway Remodelling in an Allergic Model of Asthma?

    Directory of Open Access Journals (Sweden)

    N. A. Kamalaldin

    2017-01-01

    Full Text Available Many studies have been done to evaluate the effect of various natural products in controlling asthma symptoms. Virgin coconut oil (VCO is known to contain active compounds that have beneficial effects on human health and diseases. The objective of this study was to evaluate the effect of VCO inhalation on airway remodelling in a rabbit model of allergic asthma. The effects of VCO inhalation on infiltration of airway inflammatory cells, airway structures, goblet cell hyperplasia, and cell proliferation following ovalbumin induction were evaluated. Allergic asthma was induced by a combination of ovalbumin and alum injection and/or followed by ovalbumin inhalation. The effect of VCO inhalation was then evaluated via the rescue or the preventive route. Percentage of inflammatory cells infiltration, thickness of epithelium and mucosa regions, and the numbers of goblet and proliferative cells were reduced in the rescue group but not in preventive group. Analysis using a gas chromatography-mass spectrometry found that lauric acid and capric acid were among the most abundant fatty acids present in the sample. Significant improvement was observed in rescue route in alleviating the asthma symptoms, which indicates the VCO was able to relieve asthma-related symptoms more than preventing the onset of asthma.

  15. Chitin elicits CCL2 from airway epithelial cells and induces CCR2-dependent innate allergic inflammation in the lung

    Science.gov (United States)

    Roy, René M.; Wüthrich, Marcel; Klein, Bruce S.

    2012-01-01

    Chitin exposure in the lung induces eosinophilia and alternative activation of macrophages, and is correlated with allergic airway disease. However, the mechanism underlying chitin-induced polarization of macrophages is poorly understood. Here, we show that chitin induces alternative activation of macrophages in vivo, but does not do so directly in vitro. We further show that airway epithelial cells bind chitin in vitro and produce CCL2 in response to chitin both in vitro and in vivo. Supernatants of chitin exposed epithelial cells promoted alternative activation of macrophages in vitro, whereas antibody neutralization of CCL2 in the supernate abolished the alternative activation of macrophages. CCL2 acted redundantly in vivo, but mice lacking the CCL2 receptor, CCR2, showed impaired alternative activation of macrophages in response to chitin, as measured by arginase I, CCL17 and CCL22 expression. Furthermore, CCR2KO mice exposed to chitin had diminished ROS products in the lung, blunted eosinophil and monocyte recruitment, and impaired eosinophil functions as measured by expression of CCL5, IL13 and CCL11. Thus, airway epithelial cells secrete CCL2 in response to chitin and CCR2 signaling mediates chitin-induced alternative activation of macrophages and allergic inflammation in vivo. PMID:22851704

  16. Effect of montelukast on excessive airway narrowing response to methacholine in adult asthmatic patients not on controller therapy

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Diamant, Zuzana

    2009-01-01

    Excessive airway narrowing is an important determinant of fatal asthma. This pathophysiological feature is characterized by the absence of a dose-response plateau to methacholine (Mtc). We investigated if the leukotriene receptor antagonist (LTRA) montelukast (Mont) can induce a dose-response pla...

  17. Chlorinated pool attendance, airway epithelium defects and the risks of allergic diseases in adolescents: Interrelationships revealed by circulating biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, Alfred, E-mail: Alfred.bernard@uclouvain.be; Nickmilder, Marc; Dumont, Xavier

    2015-07-15

    It has been suggested that allergic diseases might be epithelial disorders driven by various environmental stressors but the epidemiological evidence supporting this concept is limited. In a cross-sectional study of 835 school adolescents (365 boys; mean age, 15.5 yr), we measured the serum concentrations of Club cell protein (CC16), surfactant-associated protein D (SP-D) and of total and aeroallergen-specific IgE. We used the serum CC16/SP-D concentration ratio as an index integrating changes in the permeability (SP-D) and secretory function (CC16) of the airway epithelium. In both sexes, early swimming in chlorinated pools emerged as the most consistent and strongest predictor of low CC16 and CC16/SP-D ratio in serum. Among girls, a low CC16/SP-D ratio was associated with increased odds (lowest vs. highest tertile) for pet sensitization (OR 2.97, 95% CI 1.19–8.22) and for hay fever in subjects sensitized to pollen (OR 4.12, 95% CI 1.28–14.4). Among boys, a low CC16/SP-D ratio was associated with increased odds for house-dust mite (HDM) sensitization (OR 2.01, 95% CI 1.11–3.73), for allergic rhinitis in subjects sensitized to HDM (OR 3.52, 95% CI 1.22–11.1) and for asthma in subjects sensitized to any aeroallergen (OR 3.38, 95% CI 1.17–11.0), HDM (OR 5.20, 95% CI 1.40–24.2) or pollen (OR 5.82, 95% CI 1.51–27.4). Odds for allergic sensitization or rhinitis also increased with increasing SP-D or decreasing CC16 in serum. Our findings support the hypothesis linking the development of allergic diseases to epithelial barrier defects due to host factors or environmental stressors such as early swimming in chlorinated pools. - Highlights: • We conducted a cross-sectional study of 835 school adolescents. • The airway epithelium integrity was evaluated by measuring serum pneumoproteins. • The risk of allergic diseases was associated with a defective airway epithelium. • Childhood swimming in chlorinated pools can cause persistent epithelial

  18. Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism.

    Science.gov (United States)

    Levy, Bruce D; Lukacs, Nicholas W; Berlin, Aaron A; Schmidt, Birgitta; Guilford, William J; Serhan, Charles N; Parkinson, John F

    2007-12-01

    Cellular recruitment during inflammatory/immune responses is tightly regulated. The ability to dampen inflammation is imperative for prevention of chronic immune responses, as in asthma. Here we investigated the ability of lipoxin A4 (LXA4) stable analogs to regulate airway responses in two allergen-driven models of inflammation. A 15-epi-LXA4 analog (ATLa) and a 3-oxa-15-epi-LXA4 analog (ZK-994) prevented excessive eosinophil and T lymphocyte accumulation and activation after mice were sensitized and aerosol-challenged with ovalbumin. At 50% and to a greater extent than equivalent doses of the CysLT1 receptor antagonist montelukast. Distinct from montelukast, ATLa treatment led to marked reductions in cysteinyl leukotrienes, interleukin-4 (IL-4), and IL-10, and both ATLa and ZK-994 inhibited levels of IL-13. In cockroach allergen-induced airway responses, both intraperitoneal and oral administration of ZK-994 significantly reduced parameters of airway inflammation and hyper-responsiveness in a dose-dependent manner. ZK-994 also significantly changed the balance of Th1/Th2-specific cytokine levels. Thus, the ATLa/LXA4 analog actions are distinct from CysLT1 antagonism and potently block both allergic airway inflammation and hyper-reactivity. Moreover, these results demonstrate these analogs' therapeutic potential as new agonists for the resolution of inflammation.

  19. Peripherally Generated Foxp3+ Regulatory T Cells Mediate the Immunomodulatory Effects of IVIg in Allergic Airways Disease.

    Science.gov (United States)

    Massoud, Amir H; Kaufman, Gabriel N; Xue, Di; Béland, Marianne; Dembele, Marieme; Piccirillo, Ciriaco A; Mourad, Walid; Mazer, Bruce D

    2017-04-01

    IVIg is widely used as an immunomodulatory therapy. We have recently demonstrated that IVIg protects against airway hyperresponsiveness (AHR) and inflammation in mouse models of allergic airways disease (AAD), associated with induction of Foxp3 + regulatory T cells (Treg). Using mice carrying a DTR/EGFP transgene under the control of the Foxp3 promoter (DEREG mice), we demonstrate in this study that IVIg generates a de novo population of peripheral Treg (pTreg) in the absence of endogenous Treg. IVIg-generated pTreg were sufficient for inhibition of OVA-induced AHR in an Ag-driven murine model of AAD. In the absence of endogenous Treg, IVIg failed to confer protection against AHR and airway inflammation. Adoptive transfer of purified IVIg-generated pTreg prior to Ag challenge effectively prevented airway inflammation and AHR in an Ag-specific manner. Microarray gene expression profiling of IVIg-generated pTreg revealed upregulation of genes associated with cell cycle, chromatin, cytoskeleton/motility, immunity, and apoptosis. These data demonstrate the importance of Treg in regulating AAD and show that IVIg-generated pTreg are necessary and sufficient for inhibition of allergen-induced AAD. The ability of IVIg to generate pure populations of highly Ag-specific pTreg represents a new avenue to study pTreg, the cross-talk between humoral and cellular immunity, and regulation of the inflammatory response to Ags. Copyright © 2017 by The American Association of Immunologists, Inc.

  20. Role of nitric oxide in the development and partial reversal of allergen-induced airway hyperreactivity in conscious, unrestrained guinea-pigs

    NARCIS (Netherlands)

    Schuiling, M; Zuidhof, A.B; Bonouvrie, M.A A; Venema, N; Zaagsma, Hans; Meurs, Herman

    1 Using a conscious, unrestrained guinea-pig model of allergic asthma, we investigated the role of endogenous nitric oxide (NO) in the regulation of airway (hyper)reactivity to histamine before and after the allergen-induced early and late asthmatic reactions, by examining the effect of inhalation

  1. The effects of PM2.5 on asthmatic and allergic diseases or symptoms in preschool children of six Chinese cities, based on China, Children, Homes and Health (CCHH) project.

    Science.gov (United States)

    Chen, Fei'er; Lin, Zhijing; Chen, Renjie; Norback, Dan; Liu, Cong; Kan, Haidong; Deng, Qihong; Huang, Chen; Hu, Yu; Zou, Zhijun; Liu, Wei; Wang, Juan; Lu, Chan; Qian, Hua; Yang, Xu; Zhang, Xin; Qu, Fang; Sundell, Jan; Zhang, Yinping; Li, Baizhan; Sun, Yuexia; Zhao, Zhuohui

    2018-01-01

    The urbanization and industrialization in China is accompanied by bad air quality, and the prevalence of asthma in Chinese children has been increasing in recent years. To investigate the associations between ambient PM 2.5 levels and asthmatic and allergic diseases or symptoms in preschool children in China, we assigned PM 2.5 exposure data from the Global Burden of Disease (GBD) project to 205 kindergartens at a spatial resolution of 0.1° × 0.1° in six cities in China (Shanghai, Nanjing, Chongqing, Changsha, Urumqi, and Taiyuan). A hierarchical multiple logistical regression model was applied to analyze the associations between kindergarten-level PM 2.5 exposure and individual-level outcomes of asthmatic and allergic symptoms. The individual-level variables, including gender, age, family history of asthma and allergic diseases, breastfeeding, parental smoking, indoor dampness, interior decoration pollution, household annual income, and city-level variable-annual temperature were adjusted. A total of 30,759 children (average age 4.6 years, 51.7% boys) were enrolled in this study. Apart from family history, indoor dampness, and decoration as predominant risk factors, we found that an increase of 10 μg/m 3 of the annual PM 2.5 was positively associated with the prevalence of allergic rhinitis by an odds ratio (OR) of 1.20 (95% confidence interval [CI] 1.11, 1.29) and diagnosed asthma by OR of 1.10 (95% CI 1.03, 1.18). Those who lived in non-urban (vs. urban) areas were exposed to more severe indoor air pollution arising from biomass combustion and had significantly higher ORs between PM 2.5 and allergic rhinitis and current rhinitis. Our study suggested that long-term exposure to PM 2.5 might increase the risks of asthmatic and allergic diseases or symptoms in preschool children in China. Compared to those living in urban areas, children living in suburban or rural areas had a higher risk of PM 2.5 exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The Ethanol Extract of Osmanthus fragrans Flowers Reduces Oxidative Stress and Allergic Airway Inflammation in an Animal Model

    Directory of Open Access Journals (Sweden)

    Chien-Ya Hung

    2013-01-01

    Full Text Available The Osmanthus fragrans flower, a popular herb in Eastern countries, contains several antioxidant compounds. Ben Cao Gang Mu, traditional Chinese medical literature, describes the usefulness of these flowers for phlegm and stasis reduction, arrest of dysentery with blood in the bowel, and stomachache and diarrhea treatment. However, modern evidence regarding the therapeutic efficacy of these flowers is limited. This study was aimed at assessing the antioxidative effects of the ethanol extract of O. fragrans flowers (OFE in vivo and evaluating its antioxidant maintenance and therapeutic effect on an allergic airway inflammation in mice. After OFE’s oral administration to mice, the values obtained in the oxygen radical absorbance capacity assay as well as the glutathione concentration in the lungs and spleens of mice increased while thiobarbituric acid reactive substances decreased significantly, indicating OFE’s significant in vivo antioxidant activity. OFE was also therapeutically efficacious in a mouse model of ovalbumin-induced allergic airway inflammation. Orally administered OFE suppressed ovalbumin-specific IgE production and inflammatory cell infiltration in the lung. Moreover, the antioxidative state of the mice improved. Thus, our findings confirm the ability of the O. fragrans flowers to reduce phlegm and suggest that OFE may be useful as an antiallergic agent.

  3. House Dust Mite-Induced Allergic Airway Disease Is Independent of IgE and FcεRIα.

    Science.gov (United States)

    McKnight, Christopher G; Jude, Joseph A; Zhu, Zhenqi; Panettieri, Reynold A; Finkelman, Fred D

    2017-12-01

    IgE contributes to disease exacerbations but not to baseline airway hyperresponsiveness (AHR) in human asthma. In rodent allergic airway disease (AAD), mast cell and IgE dependence for the induction of AHR has only been observed when mice are immunized with a relatively weak allergen without adjuvant. To evaluate the role of IgE in murine AAD that is induced by a potent allergen, we inoculated BALB/c and FVB/N background wild-type and IgE- or FcεRIα-deficient mice intratracheally with large or limiting doses of house dust mite extract (HDM) and evaluated AHR, pulmonary eosinophilia, goblet cell metaplasia, serum IgE, and lung mastocytosis. We found that neither IgE nor FcεRIα contributed to AAD, even in mice inoculated with the lowest dose of HDM, which readily induced detectable disease, but did not increase serum IgE or pulmonary mast cell levels. In contrast, high doses of HDM strikingly increased serum IgE and pulmonary mast cells, although both AHR and airway mast cell degranulation were equally elevated in wild-type and IgE-deficient mice. Surprisingly, allergen challenge of mice with severe AAD and pulmonary mastocytosis failed to acutely increase airway resistance, lung Newtonian resistance, or hysteresis. Overall, this study shows that, although mice may not reliably model acute asthma exacerbations, mechanisms that are IgE and FcεRIα independent are responsible for AHR and airway inflammation when low doses of a potent allergen are inhaled repetitively.

  4. Insulin modulates cytokine release and selectin expression in the early phase of allergic airway inflammation in diabetic rats

    Directory of Open Access Journals (Sweden)

    Vianna Elcio O

    2010-07-01

    Full Text Available Abstract Background Clinical and experimental data suggest that the inflammatory response is impaired in diabetics and can be modulated by insulin. The present study was undertaken to investigate the role of insulin on the early phase of allergic airway inflammation. Methods Diabetic male Wistar rats (alloxan, 42 mg/Kg, i.v., 10 days and controls were sensitized by s.c. injection of ovalbumin (OA in aluminium hydroxide 14 days before OA (1 mg/0.4 mL or saline intratracheal challenge. The following analyses were performed 6 hours thereafter: a quantification of interleukin (IL-1β, tumor necrosis factor (TNF-α and cytokine-induced neutrophil chemoattractant (CINC-1 in the bronchoalveolar lavage fluid (BALF by Enzyme-Linked Immunosorbent Assay, b expression of E- and P- selectins on lung vessels by immunohistochemistry, and c inflammatory cell infiltration into the airways and lung parenchyma. NPH insulin (4 IU, s.c. was given i.v. 2 hours before antigen challenge. Results Diabetic rats exhibited significant reduction in the BALF concentrations of IL-1β (30% and TNF-α (45%, and in the lung expression of P-selectin (30% compared to non-diabetic animals. This was accompanied by reduced number of neutrophils into the airways and around bronchi and blood vessels. There were no differences in the CINC-1 levels in BALF, and E-selectin expression. Treatment of diabetic rats with NPH insulin, 2 hours before antigen challenge, restored the reduced levels of IL-1β, TNF-α and P-selectin, and neutrophil migration. Conclusion Data presented suggest that insulin modulates the production/release of TNF-α and IL-1β, the expression of P- and E-selectin, and the associated neutrophil migration into the lungs during the early phase of the allergic inflammatory reaction.

  5. Evaluation of therapeutic sublingual vaccines in a murine model of chronic house dust mite allergic airway inflammation.

    Science.gov (United States)

    Tourdot, S; Airouche, S; Berjont, N; Da Silveira, A; Mascarell, L; Jacquet, A; Caplier, L; Langelot, M; Baron-Bodo, V; Moingeon, P

    2011-12-01

    Second generation therapeutic vaccines based upon recombinant allergens or natural extracts, potentially formulated in vector systems or adjuvants, are being developed. To this aim, preclinical studies in relevant animal models are needed to select proper allergens, formulations and administration schemes. To develop a chronic house dust mite (HDM) allergy model to evaluate sublingual therapeutic vaccine candidates. The BABL/c mice that were used were sensitized with Dermatophagoides pteronyssinus (Dpte) and Dermatophagoides farinae (Dfar) mite extracts by intraperitoneal injections followed by aerosol exposures. Animals subsequently underwent sublingual immunotherapy (SLIT) with either Dpte, Dfar or Dpte/Dfar extracts, twice a week for 8 weeks. SLIT efficacy was assessed by whole body plethysmography, lung histology and broncho-alveolar lavages cell counts. Specific T cell and antibody responses to major and minor HDM allergens were monitored in tissues and serum/saliva, respectively. Mice sensitized to Dpte and Dfar allergens exhibited strong airway hyperresponsiveness (AHR) and lung inflammatory infiltrates including eosinophils. Sensitized animals mounted Th2-biased cellular and humoral responses specific for group 1 and 2 major allergens, as well as group 5, 7 and 10 minor allergens. This phenotype was sustained for at least 2 months, allowing the evaluation of immunotherapeutic protocols with HDM extracts-based vaccines. In this model, SLIT decreased AHR and Th2 responses and induced HDM-specific IgAs in saliva. The Dpte/Dfar mix proved the most efficacious when compared to Dpte or Dfar extracts alone. The efficacy of a sublingual vaccine based on a Dpte/Dfar allergen extract mix was demonstrated in a well standardized murine model of chronic allergic airway inflammation based on clinically relevant mite allergens. The latter will be used as a benchmark for evaluation of future vaccines, including recombinant allergens. This HDM allergic airway inflammation

  6. Oral Administration of N-Acetyl-D Glucosamine Polymer Particles Down-Regulates Airway Allergic Responses

    National Research Council Canada - National Science Library

    Shibata, Yoshimi

    2006-01-01

    ... (IL-12, IL-18 and TNFo) that down-regulate allergic immune responses. We also found that administration of chitin particles resulted in less likely induce the production of IL-10 and prostaglandin E2 (PGE2...

  7. (ENA-78/CXCL5) in asthmatic children

    African Journals Online (AJOL)

    EL-HAKIM

    CXCL5) in asthmatic children: relation to eosinophil activation. INTRODUCTION. Airway inflammation is a characteristic feature of bronchial asthma. It contributes significantly to many features of this disease, including airflow obstruction, bronchial ...

  8. Single systemic administration of Ag85B of mycobacteria DNA inhibits allergic airway inflammation in a mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Karamatsu K

    2012-12-01

    Full Text Available Katsuo Karamatsu,1,2 Kazuhiro Matsuo,3 Hiroyasu Inada,4 Yusuke Tsujimura,1 Yumiko Shiogama,1,2 Akihiro Matsubara,1,2 Mitsuo Kawano,5 Yasuhiro Yasutomi1,21Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, 2Division of Immunoregulation, Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, 3Department of Research and Development, Japan BCG Laboratory, Tokyo, 4Department of Pathology, Suzuka University of Medical Science, Suzuka, 5Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, JapanAbstract: The immune responses of T-helper (Th and T-regulatory cells are thought to play a crucial role in the pathogenesis of allergic airway inflammation observed in asthma. The correction of immune response by these cells should be considered in the prevention and treatment of asthma. Native antigen 85B (Ag85B of mycobacteria, which cross-reacts among mycobacteria species, may play an important biological role in host–pathogen interaction since it elicits various immune responses by activation of Th cells. The current study investigated the antiallergic inflammatory effects of DNA administration of Ag85B from Mycobacterium kansasii in a mouse model of asthma. Immunization of BALB/c mice with alum-adsorbed ovalbumin followed by aspiration with aerosolized ovalbumin resulted in the development of allergic airway inflammation. Administration of Ag85B DNA before the aerosolized ovalbumin challenge protected the mice from subsequent induction of allergic airway inflammation. Serum and bronchoalveolar lavage immunoglobulin E levels, extent of eosinophil infiltration, and levels of Th2-type cytokines in Ag85B DNA-administered mice were significantly lower than those in control plasmid-immunized mice, and levels of Th1- and T-regulatory-type cytokines were enhanced by Ag85B

  9. Rhinovirus induction of fractalkine (CX3CL1 in airway and peripheral blood mononuclear cells in asthma.

    Directory of Open Access Journals (Sweden)

    Nadine Upton

    Full Text Available Rhinovirus infection is associated with the majority of asthma exacerbations. The role of fractalkine in anti-viral (type 1 and pathogenic (type 2 responses to rhinovirus infection in allergic asthma is unknown. To determine whether (1 fractalkine is produced in airway cells and in peripheral blood leucocytes, (2 rhinovirus infection increases production of fractalkine and (3 levels of fractalkine differ in asthmatic compared to non-asthmatic subjects. Fractalkine protein and mRNA levels were measured in bronchoalveolar lavage (BAL cells and peripheral blood mononuclear cells (PBMCs from non-asthmatic controls (n = 15 and mild allergic asthmatic (n = 15 subjects. Protein levels of fractalkine were also measured in macrophages polarised ex vivo to give M1 (type 1 and M2 (type 2 macrophages and in BAL fluid obtained from mild (n = 11 and moderate (n = 14 allergic asthmatic and non-asthmatic control (n = 10 subjects pre and post in vivo rhinovirus infection. BAL cells produced significantly greater levels of fractalkine than PBMCs. Rhinovirus infection increased production of fractalkine by BAL cells from non-asthmatic controls (P<0.01 and in M1-polarised macrophages (P<0.05, but not in BAL cells from mild asthmatics or in M2 polarised macrophages. Rhinovirus induced fractalkine in PBMCs from asthmatic (P<0.001 and healthy control subjects (P<0.05. Trends towards induction of fractalkine in moderate asthmatic subjects during in vivo rhinovirus infection failed to reach statistical significance. Fractalkine may be involved in both immunopathological and anti-viral immune responses to rhinovirus infection. Further investigation into how fractalkine is regulated across different cell types and into the effect of stimulation including rhinovirus infection is warranted to better understand the precise role of this unique dual adhesion factor and chemokine in immune cell recruitment.

  10. Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle relaxation in allergic asthma

    NARCIS (Netherlands)

    Maarsingh, H; Leusink, J; Bos, IST; Zaagsma, J; Meurs, H

    2006-01-01

    Background: Using guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC) nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO) production - due to competition with neuronal

  11. Is a high-fiber diet able to influence ovalbumin-induced allergic airway inflammation in a mouse model?

    Science.gov (United States)

    Zhang, Zhiyu; Shi, Lei; Pang, Wenhui; Wang, Xiaoting; Li, Jianfeng; Wang, Haibo; Shi, Guanggang

    2016-01-01

    More recently, a large amount of experimental and clinical discovered that dietary- fiber intake would decrease the susceptibility to allergic airway disease (AAD) and respiratory inflammation. To investigate whether a fiber-intake supplement is able to influence the induction of AAD and to elucidate the interactive relationship. AAD model mice and control mice were raised on a fundamental diet with standard 4% fiber content, whereas other mice were fed a 10% fiber-content diet in the high fiber-content group, along with a 25% fiber-content diet instead in very-high fiber-content group. All experimental mice were sensitized and challenged with ovalbumin to induce allergic inflammation in both the upper and lower airways. Hallmarks of AAD were examined in terms of eosinophil infiltration and goblet cell metaplasia in subepithelial mucosa, T-helper type 1 (Th1) to Th2 skewing of the immune response. Furthermore, to elucidate the interrelations, we generated 16S ribosomal DNA from fecal samples and further validated the variation of colony composition in each group. The excessive high-fiber supplement induced a promoting effect rather than a suppressive effect, including a rise in nasal rubbing and sneezing, an increase in eosinophil inflammation and goblet cell metaplasia in subepithelial mucosa, and promoted Th2 skewing of the immune response as well as the production of serum levels of ovalbumin-specific immunoglobulin E. Moreover, overconsumption of dietary fiber greatly altered the construction of bacterial flora in the intestinal tract, including an increased proportion of Firmicutes, Actinobacteria, and Proteobacteria, and a decreased proportion of Bacteroidetes. Our work indicated that, instead of a protecting impact, excessive fiber intake preformed a negative influence on the induction of AAD. Therefore, we suspected that an excessive supplement of dietary fiber might not be an advisable method for the prevention and treatment of AADs.

  12. Preventive and therapeutic anti-inflammatory properties of the sesquiterpene alpha-humulene in experimental airways allergic inflammation.

    Science.gov (United States)

    Rogerio, Alexandre P; Andrade, Edinéia L; Leite, Daniela F P; Figueiredo, Cláudia P; Calixto, João B

    2009-10-01

    alpha-Humulene and trans-caryophyllene are plant sesquiterpenes with pronounced anti-inflammatory properties. Here, we evaluated the effects of these compounds in an experimental model of airways allergic inflammation. Female BALB/c mice, sensitized to and challenged with ovalbumin received daily alpha-humulene or trans-caryophyllene (50 mg.kg(-1), orally) or alpha-humulene (1 mg.mL(-1), by aerosol) as either a preventive (for 22 days) or therapeutic (from the 18th to the 22nd day) treatment. Dexamethasone or budesonide was used as a positive control drug. Inflammation was determined on day 22 post-immunization by leukocyte recruitment, interleukin-5 (IL-5), CCL11, interferon-gamma (IFN-gamma) and leukotriene (LT)B(4) levels in bronchoalveolar lavage fluid (BALF). In addition, transcription factors [nuclear factor kappaB (NF-kappaB), activator protein 1 (AP-1)] and P-selectin in lung tissue were measured by immunohistochemistry and mucus secretion by histochemistry. Preventive or therapeutic treatments with alpha-humulene, but not with trans-caryophyllene, significantly reduced the eosinophil recruitment to the BALF. In addition, alpha-humulene recovery INF-gamma and reduced the IL-5, CCL11 and LTB(4) levels in BALF, as well as the IL-5 production in mediastinal lymph nodes (in vitro assay). Furthermore, alpha-humulene decreased the NF-kB and the AP-1 activation, the expression of P-selectin and the increased mucus secretion in the lung. alpha-Humulene, given either orally or by aerosol, exhibited marked anti-inflammatory properties in a murine model of airways allergic inflammation, an effect that seemed to be mediated via reduction of inflammatory mediators, adhesion molecule expression and transcription factors activation.

  13. Inhibitory Effect of Pycnogenol® on Airway Inflammation in Ovalbumin-Induced Allergic Rhinitis

    Directory of Open Access Journals (Sweden)

    Ceren Günel

    2016-12-01

    Full Text Available Background: The supplement Pycnogenol® (PYC has been used for the treatment of several chronic diseases including allergic rhinitis (AR. However, the in vivo effects on allergic inflammation have not been identified to date. Aims: To investigate the treatment results of PYC on allergic inflammation in a rat model of allergic rhinitis. Study Design: Animal experimentation. Methods: Allergic rhinitis was stimulated in 42 rats by intraperitoneal sensitization and intranasal challenge with Ovalbumin. The animals were divided into six subgroups: healthy controls, AR group, AR group treated with corticosteroid (dexamethasone 1 mg/kg; CS+AR, healthy rats group that were given only PYC of 10 mg/kg (PYC10, AR group treated with PYC of 3mg/kg (PYC3+AR, and AR group treated with PYC of 10 mg/kg (PYC10+AR. Interferon-γ (IFN-γ, interleukin-4 (IL-4, interleukin-10 (IL-10, and OVA-specific immunoglobulin E (Ig-E levels of serum were measured. Histopathological changes in nasal mucosa and expression of tumor necrosis factor-α (TNF-α and IL-1β were evaluated. Results: The levels of the IL-4 were significantly decreased in the PYC3+AR, PYC10+AR and CS+AR groups compared with the AR group (p=0.002, p<0.001, p=0.006. The production of the IFN-γ was significantly decreased in the PYC3+AR and PYC10+AR groups compared with the AR group (p=0.013, p=0.001. The administration of PYC to allergic rats suppressed the elevated IL-10 production, especially in the PYC3+AR group (p=0.006. Mucosal edema was significantly decreased respectively after treatment at dose 3 mg/kg and 10 mg/kg PYC (both, p<0.001. The mucosal expression of TNF-α has significantly decreased in the PYC3+AR and PYC10+AR groups (p=0.005, p<0.001, while the IL-1β expression significantly decreased in the CS+AR, PYC3+AR, and PYC10+AR groups (p<0.001, p=0.003, p=0.001. Conclusion: PYC has multiple suppressive effects on allergic response. Thus, PYC may be used as a supplementary agent in allergic

  14. Investigation of anti-asthmatic potential of Kanakasava in ovalbumin-induced bronchial asthma and airway inflammation in rats.

    Science.gov (United States)

    Arora, Poonam; Ansari, S H; Anjum, Varisha; Mathur, Rajani; Ahmad, Sayeed

    2017-02-02

    Kanakasava is an Indian traditional Ayurvedic formulation containing Datura (Datura metel), Vasaca (Adhatoda vasica), Dhataki (Woodfordia fruticosa) and Grape (Vitis vinifera) extracts as major constituents and used to treat pulmonary diseases including coughing, breathing difficulty and asthma. The present study was designed to assess the safety and therapeutic efficacy of Kanakasava against ovalbumin-induced bronchial asthma and related airway inflammation in rats due to lack of evidence based therapeutic efficacy data. Male wistar rats were sensitized with allergen (ovalbumin, 40mg/rat+aluminum hydroxide, 2.0mg/rat) and treated orally with standard dexamethasone (2.5mg/kg, b.w.) or Kanakasava (1.23 and 2.46ml/kg, b.w.) from day 1 to day 28. Inflammatory markers, including cell counts and cytokines such as interleukins (IL-4, IL-5, IL-1β), tumor necrosis factor (TNF-α), leukotriene (LTD-4), immunoglobulin (IgE), nitric oxide and nitrite levels in both blood and broncheo alveolar lavaged fluid (BALF) were analyzed. Abdominal mesentery was studied histologically for mast cell degranulation, whereas lung functions were investigated by spirometer. Method was also developed to quantify gallic acid and ethyl gallate content in Kanakasava by HPTLC for its quality control. None of the rats exhibited mortality and Kanakasava was found to be safe at the tested doses. Treatment with Kanakasava significantly (P<0.01) reversed elevated levels of IgE, cytokines, nitrites and influx of eosinophils and neutrophils in blood and BALF. These findings were further supported by the significant improvement in lung functions (P<0.01) and suppression (P<0.01) of degranulation of mast cells. The content of gallic acid and ethyl gallate in Kanakasava was found to be 1.94% and 0.98%, respectively. These findings demonstrated the preventive effect of Kanakasava in allergen induced model of asthma providing scientific basis for its traditional use in Ayurveda, since long time. Copyright

  15. Rutin has anti-asthmatic effects in an ovalbumin-induced asthmatic ...

    African Journals Online (AJOL)

    Allergic asthma is a chronic airway disorder characterised by airway inflammation, airway hyperresponsiveness (AHR) ... °C, 40–60 % humidity) and were supplied with water and food ad libitum. The mice were acclimatised to ..... Ovalbumin induced allergic rhinitis and development of prediabetes to rats: possible role of.

  16. GS143, an IκB ubiquitination inhibitor, inhibits allergic airway inflammation in mice

    International Nuclear Information System (INIS)

    Hirose, Koichi; Wakashin, Hidefumi; Oki, Mie; Kagami, Shin-ichiro; Suto, Akira; Ikeda, Kei; Watanabe, Norihiko; Iwamoto, Itsuo; Furuichi, Yasuhiro; Nakajima, Hiroshi

    2008-01-01

    Asthma is characterized by airway inflammation with intense eosinophil infiltration and mucus hyper-production, in which antigen-specific Th2 cells play critical roles. Nuclear factor-κB (NF-κB) pathway has been demonstrated to be essential for the production of Th2 cytokines and chemokines in the airways in murine asthma models. In the present study, we examined the effect of GS143, a novel small-molecule inhibitor of IκB ubiquitination, on antigen-induced airway inflammation and Th2 cytokine production in mice. Intranasal administration of GS143 prior to antigen challenge suppressed antigen-induced NF-κB activation in the lung of sensitized mice. Intranasal administration of GS143 also inhibited antigen-induced eosinophil and lymphocyte recruitment into the airways as well as the expression of Th2 cytokines and eotaxin in the airways. Moreover, GS143 inhibited antigen-induced differentiation of Th2 cells but not of Th1 cells in vitro. Taken together, these results suggest that IκB ubiquitination inhibitor may have therapeutic potential against asthma

  17. Serine protease inhibitor attenuates ovalbumin induced inflammation in mouse model of allergic airway disease.

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    Sanjay Saw

    Full Text Available BACKGROUND: Serine proteases promote inflammation and tissue remodeling by activating proteinase-activated receptors, urokinase, metalloproteinases and angiotensin. In the present study, 4-(2-Aminoethyl benzenesulfonyl fluoride (AEBSF a serine protease inhibitor was evaluated for prophylactic and therapeutic treatment in mouse model of airway allergy. METHODS: BALB/c mice were sensitized by i.p route and challenged with ovalbumin. They were treated i.n. with 2, 10 and 50 µg of AEBSF, one hour before or after challenge and euthanized to collect BALF (bronchoalveolar lavage fluid, blood and lungs. Proteolytic activity, total cell/eosinophil/neutrophil count eosinophil peroxidase activity (EPO, IL-4, IL-5, IL-10, IL-13, cysteinyl leukotrienes and 8-isoprostane were determined in BALF and immunoglobulins were measured in serum. H&E and PAS stained lung sections were examined for cellular infiltration and airway inflammation. RESULTS: Mice exposed to ovalbumin and treated with PBS showed increased cellular infiltration in lungs and higher serum IgE, IgG1 and IgG2a levels as compared to sham mice. Treatment with AEBSF reduced total cells/eosinophil/neutrophil infiltration. Both prophylactic and therapeutic AEBSF treatment of 10 or 50 µg reduced serum IgE and IgG1 significantly (p<0.05 than control. AEBSF treatment reduced the proteolytic activity in BALF. IL-4 IL-5 and IL-13 levels decreased significantly (p<0.05 after AEBSF treatment while IL-10 levels increased significantly (p<0.05 in BALF. Airway inflammation and goblet cell hyperplasia reduced as demonstrated by lung histopathology, EPO activity and cysteinyl leukotrienes in BALF after treatment. AEBSF treatment also suppressed oxidative stress in terms of 8-isoprostane in BALF. Among the treatment doses, 10 or 50 µg of AEBSF were most effective in reducing the inflammatory parameters. CONCLUSIONS: Prophylactic and therapeutic treatment with serine protease inhibitor attenuates the airway

  18. TH1 signatures are present in the lower airways of children with severe asthma, regardless of allergic status.

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    Wisniewski, Julia A; Muehling, Lyndsey M; Eccles, Jacob D; Capaldo, Brian J; Agrawal, Rachana; Shirley, Debbie-Ann; Patrie, James T; Workman, Lisa J; Schuyler, Alexander J; Lawrence, Monica G; Teague, W Gerald; Woodfolk, Judith A

    2017-09-20

    The pathogenesis of severe asthma in childhood remains poorly understood. We sought to construct the immunologic landscape in the airways of children with severe asthma. Comprehensive analysis of multiple cell types and mediators was performed by using flow cytometry and a multiplex assay with bronchoalveolar lavage (BAL) specimens (n = 68) from 52 highly characterized allergic and nonallergic children (0.5-17 years) with severe treatment-refractory asthma. Multiple relationships were tested by using linear mixed-effects modeling. Memory CCR5 + T H 1 cells were enriched in BAL fluid versus blood, and pathogenic respiratory viruses and bacteria were readily detected. IFN-γ + IL-17 + and IFN-γ - IL-17 + subsets constituted secondary T H types, and BAL fluid CD8 + T cells were almost exclusively IFN-γ + . The T H 17-associated mediators IL-23 and macrophage inflammatory protein 3α/CCL20 were highly expressed. Despite low T H 2 numbers, T H 2 cytokines were detected, and T H 2 skewing correlated with total IgE levels. Type 2 innate lymphoid cells and basophils were scarce in BAL fluid. Levels of IL-5, IL-33, and IL-28A/IFN-λ2 were increased in multisensitized children and correlated with IgE levels to dust mite, ryegrass, and fungi but not cat, ragweed, or food sources. Additionally, levels of IL-5, but no other cytokine, increased with age and correlated with eosinophil numbers in BAL fluid and blood. Both plasmacytoid and IgE + FcεRI + myeloid dendritic cells were present in BAL fluid. The lower airways of children with severe asthma display a dominant T H 1 signature and atypical cytokine profiles that link to allergic status. Our findings deviate from established paradigms and warrant further assessment of the pathogenicity of T H 1 cells in patients with severe asthma. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  19. Preventive and therapeutic anti-inflammatory properties of the sesquiterpene α-humulene in experimental airways allergic inflammation

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    Rogerio, Alexandre P; Andrade, Edinéia L; Leite, Daniela FP; Figueiredo, Cláudia P; Calixto, João B

    2009-01-01

    Background and purpose: α-Humulene and trans-caryophyllene are plant sesquiterpenes with pronounced anti-inflammatory properties. Here, we evaluated the effects of these compounds in an experimental model of airways allergic inflammation. Experimental approach: Female BALB/c mice, sensitized to and challenged with ovalbumin received daily α-humulene or trans-caryophyllene (50 mg·kg−1, orally) or α-humulene (1 mg·mL−1, by aerosol) as either a preventive (for 22 days) or therapeutic (from the 18th to the 22nd day) treatment. Dexamethasone or budesonide was used as a positive control drug. Inflammation was determined on day 22 post-immunization by leukocyte recruitment, interleukin-5 (IL-5), CCL11, interferon-γ (IFN-γ) and leukotriene (LT)B4 levels in bronchoalveolar lavage fluid (BALF). In addition, transcription factors [nuclear factor κB (NF-κB), activator protein 1 (AP-1)] and P-selectin in lung tissue were measured by immunohistochemistry and mucus secretion by histochemistry. Key results: Preventive or therapeutic treatments with α-humulene, but not with trans-caryophyllene, significantly reduced the eosinophil recruitment to the BALF. In addition, α-humulene recovery INF-γ and reduced the IL-5, CCL11 and LTB4 levels in BALF, as well as the IL-5 production in mediastinal lymph nodes (in vitro assay). Furthermore, α-humulene decreased the NF-kB and the AP-1 activation, the expression of P-selectin and the increased mucus secretion in the lung. Conclusions and implications: α-Humulene, given either orally or by aerosol, exhibited marked anti-inflammatory properties in a murine model of airways allergic inflammation, an effect that seemed to be mediated via reduction of inflammatory mediators, adhesion molecule expression and transcription factors activation. This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear

  20. The Integrin-blocking Peptide RGDS Inhibits Airway Smooth Muscle Remodeling in a Guinea Pig Model of Allergic Asthma

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Bos, I. Sophie T.; Gosens, Reinoud; Halayko, Andrew J.; Zaagsma, Johan; Meurs, Herman

    2010-01-01

    Rationale: Airway remodeling, including increased airway smooth muscle (ASM) mass and contractility, contributes to airway hyper-responsiveness in asthma. The mechanisms driving these changes are, however, incompletely understood. Recently, an important role for extracellular matrix proteins in

  1. Simvastatin Inhibits Goblet Cell Hyperplasia and Lung Arginase in a Mouse Model of Allergic Asthma: A Novel Treatment for Airway Remodeling?

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    Zeki, Amir A.; Bratt, Jennifer M.; Rabowsky, Michelle; Last, Jerold A.; Kenyon, Nicholas J.

    2010-01-01

    Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function, and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. The statins are cholesterol-lowering drugs that inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase, the rate-limiting step of cholesterol biosynthesis in the mevalonate pathway. These drugs have been associated with improved respiratory health and ongoing clinical trials are testing their therapeutic potential in asthma. We hypothesized that simvastatin treatment of ovalbumin-exposed mice would attenuate early features of airway remodeling, by a mevalonate-dependent mechanism. BALB/c mice were initially sensitized to ovalbumin, and then exposed to 1% ovalbumin aerosol for 2 weeks after sensitization for a total of six exposures. Simvastatin (40 mg/kg) or simvastatin plus mevalonate (20 mg/kg) were injected intraperitoneally before each ovalbumin exposure. Treatment with simvastatin attenuated goblet cell hyperplasia, arginase-1 protein expression, and total arginase enzyme activity, but did not alter airway hydroxyproline content or transforming growth factor-β1. Inhibition of goblet cell hyperplasia by simvastatin was mevalonate-dependent. No appreciable changes to airway smooth muscle cells were observed in any of the control or treatment groups. In conclusion, in an acute mouse model of allergic asthma, simvastatin inhibited early hallmarks of airway remodeling, indicators that can lead to airway thickening and fibrosis. Statins are potentially novel treatments for airway remodeling in asthma. Further studies utilizing sub-chronic or chronic allergen exposure models are needed to extend these initial findings. PMID:21078495

  2. Antigen-Specific IgG ameliorates allergic airway inflammation via Fcγ receptor IIB on dendritic cells

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    Karasuyama Hajime

    2011-04-01

    allergic airway inflammation via FcγRIIB on DCs.

  3. Neuropsychiatry phenotype in asthma: Psychological stress-induced alterations of the neuroendocrine-immune system in allergic airway inflammation

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    Isao Ohno

    2017-09-01

    Full Text Available Since the recognition of asthma as a syndrome with complex pathophysiological signs and symptoms, recent research has sought to classify asthma phenotypes based on its clinical and molecular pathological features. Psychological stress was first recognized as a potential immune system modulator of asthma at the end of the 19th century. The activation of the central nervous system (CNS upon exposure to psychological stress is integral for the initiation of signal transduction processes. The stress hormones, including glucocorticoids, epinephrine, and norepinephrine, which are secreted following CNS activation, are involved in the immunological alterations involved in psychological stress-induced asthma exacerbation. The mechanisms underlying this process may involve a pathological series of events from the brain to the lungs, which is attracting attention as a conceptually advanced phenotype in asthma pathogenesis. This review presents insights into the critical role of psychological stress in the development and exacerbation of allergic asthma, with a special focus on our own data that emphasizes on the continuity from the central sensing of psychological stress to enhanced eosinophilic airway inflammation.

  4. Neuropsychiatry phenotype in asthma: Psychological stress-induced alterations of the neuroendocrine-immune system in allergic airway inflammation.

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    Ohno, Isao

    2017-09-01

    Since the recognition of asthma as a syndrome with complex pathophysiological signs and symptoms, recent research has sought to classify asthma phenotypes based on its clinical and molecular pathological features. Psychological stress was first recognized as a potential immune system modulator of asthma at the end of the 19th century. The activation of the central nervous system (CNS) upon exposure to psychological stress is integral for the initiation of signal transduction processes. The stress hormones, including glucocorticoids, epinephrine, and norepinephrine, which are secreted following CNS activation, are involved in the immunological alterations involved in psychological stress-induced asthma exacerbation. The mechanisms underlying this process may involve a pathological series of events from the brain to the lungs, which is attracting attention as a conceptually advanced phenotype in asthma pathogenesis. This review presents insights into the critical role of psychological stress in the development and exacerbation of allergic asthma, with a special focus on our own data that emphasizes on the continuity from the central sensing of psychological stress to enhanced eosinophilic airway inflammation. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  5. [Specific immunotherapy in allergic asthma].

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    Bergmann, K-Ch

    2003-02-01

    Asthma is a chronic inflammatory disease of the airways considered as the result of a deregulated immune response, with a pivotal role played the TH2 cytokine phenotype. The treatment of allergic asthma is based on allergen avoidance, pharmacotherapy, allergen-specific immunotherapy, and patient education. Specific immunotherapy is able to normalize the upraised TH2 cytokine phenotype and indicated for patients who have demonstrable evidence of IgE-mediated clinically relevant sensitisation to pollens, house-dust mites and cat or dog allergens. The exposure to the allergens must be related to the appearance of symptoms. Randomised controlled trials in asthma have found that immunotherapy was effective (evidence 1a, strength of recommendation A) in reducing specific and non-specific bronchial hyperreactivity, asthmatic symptoms, and medication requirements. Patient selection is important and efficacy must be balanced against the risk of side effects. Immunotherapy should be used by pneumologists with a training in allergology in patients with mild asthma.

  6. Is there a march from early food sensitization to later childhood allergic airway disease? Results from two prospective birth cohort studies.

    Science.gov (United States)

    Alduraywish, Shatha A; Standl, Marie; Lodge, Caroline J; Abramson, Michael J; Allen, Katrina J; Erbas, Bircan; von Berg, Andrea; Heinrich, Joachim; Lowe, Adrian J; Dharmage, Shyamali C

    2017-02-01

    The march from early aeroallergen sensitization to subsequent respiratory allergy is well established, but it is unclear whether early life food sensitization precedes and further increases risk of allergic airway disease. To assess the association between food sensitization in the first 2 years of life and subsequent asthma and allergic rhinitis by age 10-12 years. We used data from two independent cohorts: the high-risk Melbourne Atopic Cohort Study (MACS) (n = 620) and the population-based LISAplus (n = 3094). Food sensitization was assessed at 6, 12, and 24 months in MACS and 24 months in LISAplus. Multiple logistic regressions were used to estimate associations between sensitization to food only, aeroallergen only, or both and allergic airway disease. When compared to non-sensitized children, sensitization to food only at 12 months in MACS and 24 months in LISAplus was associated with increased risk of current asthma (aOR = 2.2; 95% CI 1.1, 4.6 in MACS and aOR = 4.9; 2.4, 10.1 in LISAplus). Similar results were seen for allergic rhinitis. Additionally, cosensitization to food and aeroallergen in both cohorts at any tested point was a stronger predictor of asthma (at 24 months, aOR = 8.3; 3.7, 18.8 in MACS and aOR = 14.4; 5.0, 41.6 in LISAplus) and allergic rhinitis (at 24 months, aOR = 3.9; 1.9, 8.1 in MACS and aOR = 7.6; 3.0, 19.6 in LISAplus). In both cohorts, food sensitization (with or without aeroallergen sensitization) in the first two years of life increased the risk of subsequent asthma and allergic rhinitis. These findings support the role of early life food sensitization in the atopic march and suggest trials to prevent early onset have the potential to reduce the development of allergic airways disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Airway smooth muscle cells : regulators of airway inflammation

    NARCIS (Netherlands)

    Zuyderduyn, Suzanne

    2007-01-01

    Airways from asthmatic subjects are more responsive to bronchoconstrictive stimuli than airways from healthy subjects. Airway smooth muscle (ASM) cells mediate contraction of the airways by responding to the bronchoconstrictive stimuli, which was thought to be the primary role of ASM cells. In this

  8. Proteolytic activity in cowshed dust extracts induces C5a release in murine bronchoalveolar lavage fluids which may account for its protective properties in allergic airway inflammation.

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    Stiehm, Matthias; Bufe, Albrecht; Peters, Marcus

    2013-01-01

    Intranasal application of cowshed dust extract (CDE) during sensitisation in a murine model of experimental asthma leads to a significant alleviation of the clinical parameters of the allergic immune response. However, neither the immunological mechanisms underlying this protective effect nor all of the protective substances included in CDE have yet been described. Recently, complement factor 5a (C5a) receptor signalling has been identified to play a regulatory role in allergic airway disease. Thus we investigated whether CDE can activate the complement system to release biologically active C5a in the lung. Proteins included in CDE were identified by mass spectrometry. Complement cleaving activity of a serine protease identified in CDE was validated with the purified enzyme, and the biological activity of the released C5a was determined. C5a was applied in a murine model of allergy to prove its protective impact on allergic airway disease. CDE induced the release of C5a in murine bronchoalveolar lavages (BAL). We identified a serine protease from the midgut of tenebrio molitor larvae in CDEs which was able to induce the release of biologically active C5a in murine BAL. We applied C5a in different doses to female Balb/c mice during the sensitisation phase and during the first antigen challenge and showed that C5a has the ability to dampen important parameters of allergic airway inflammation, such as infiltration of proinflammatory cells into lung tissue or Th2 cytokine secretion by lung cells. We conclude that the C5a generating enzyme included in CDE might account for some of the allergy protective effects of CDE by generation of C5a in murine lungs.

  9. Interaction between allergic asthma and atherosclerosis

    Science.gov (United States)

    Liu, Conglin; Zhang, Jingying; Shi, Guo-Ping

    2015-01-01

    Prior studies have established an essential role of mast cells in allergic asthma and atherosclerosis. Mast cell deficiency or inactivation protects mice from allergen-induced airway hyper-responsiveness and diet-induced atherosclerosis, suggesting that mast cells share pathologic activities in both diseases. Allergic asthma and atherosclerosis are inflammatory diseases that contain similar sets of elevated numbers of inflammatory cells in addition to mast cells in the airway and arterial wall, such as macrophages, monocytes, T cells, eosinophils, and smooth muscle cells. Emerging evidence from experimental models and human studies points to a potential interaction between the two seemingly unrelated diseases. Patients or mice with allergic asthma have a high risk of developing atherosclerosis or vice versa, despite the fact that asthma is a Th2-oriented disease, whereas Th1 immunity promotes atherosclerosis. In addition to the preferred Th1/Th2 responses that may differentiate the two diseases, mast cells and many other inflammatory cells also contribute to their pathogenesis by much more than just T cell immunity. Here we summarize the different roles of airway and arterial wall inflammatory cells and vascular cells in asthma and atherosclerosis, and propose an interaction between the two diseases, although limited investigations are available to delineate the molecular and cellular mechanisms by which one disease increases the risk of the other. Results from mouse allergic asthma and atherosclerosis models and from human population studies lead to the hypothesis that patients with atherosclerosis may benefit from anti-asthmatic medications, or that the therapeutic regimens targeting atherosclerosis may also alleviate allergic asthma. PMID:26608212

  10. Reversible control by vitamin D of granulocytes and bacteria in the lungs of mice: an ovalbumin-induced model of allergic airway disease.

    Science.gov (United States)

    Gorman, Shelley; Weeden, Clare E; Tan, Daryl H W; Scott, Naomi M; Hart, Julie; Foong, Rachel E; Mok, Danny; Stephens, Nahiid; Zosky, Graeme; Hart, Prue H

    2013-01-01

    Vitamin D may be essential for restricting the development and severity of allergic diseases and asthma, but a direct causal link between vitamin D deficiency and asthma has yet to be established. We have developed a 'low dose' model of allergic airway disease induced by intraperitoneal injection with ovalbumin (1 µg) and aluminium hydroxide (0.2 mg) in which characteristics of atopic asthma are recapitulated, including airway hyperresponsiveness, antigen-specific immunoglobulin type-E and lung inflammation. We assessed the effects of vitamin D deficiency throughout life (from conception until adulthood) on the severity of ovalbumin-induced allergic airway disease in vitamin D-replete and -deficient BALB/c mice using this model. Vitamin D had protective effects such that deficiency significantly enhanced eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male but not female mice. Vitamin D also suppressed the proliferation and T helper cell type-2 cytokine-secreting capacity of airway-draining lymph node cells from both male and female mice. Supplementation of initially vitamin D-deficient mice with vitamin D for four weeks returned serum 25-hydroxyvitamin D to levels observed in initially vitamin D-replete mice, and also suppressed eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male mice. Using generic 16 S rRNA primers, increased bacterial levels were detected in the lungs of initially vitamin D-deficient male mice, which were also reduced by vitamin D supplementation. These results indicate that vitamin D controls granulocyte levels in the bronchoalveolar lavage fluid in an allergen-sensitive manner, and may contribute towards the severity of asthma in a gender-specific fashion through regulation of respiratory bacteria.

  11. Effect of budesonide and cetirizine hydrochloride on neurotrophic factor, airway function and chemokines CCL17 and CCL22 in patients with allergic rhinitis

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    Xiang Xu

    2017-11-01

    Full Text Available Objective: To investigate the effect of budesonide combined with cetirizine hydrochloride on neurotrophic factor, airway function and chemokines CCL17 and CCL12 in patients with allergic rhinitis. Methods: A total of 123 patients with Allergic Rhinitis were randomly divided into three groups, A group treated with budesonide nasal spray, B group treated with cetirizine hydrochloride, C group treated with budesonide combined with cetirizine hydrochloride, then the Neurotrophic factors, airway function indexes and chemokines CCL17 and CCL12 levels in three groups were compared. Results: Before the treatments, the three groups of patients in neurotrophic factor, airway function index and chemokines CCL17, CCL22 have no differences, Compared with before the treatments, after receiving different treatments, the three groups of patients in all indicators were Showed significant differences. In the indexes of neurotrophic factor (NGF, BDNF, NT-3mRNA expression, there was no significant difference between group A and group B, and group C was lower than group A and B. In airway function indexes (FVC, FEV1 and PEF, A group was significantly higher than B group, C group was significantly higher than A group; In the chemokines CCL17 and CCL22 indicators, C group was lower than A group, A group was lower than B group, the difference was significant. Conclusions: Budesonide combined with cetirizine hydrochloride in the treatment of Allergic Rhinitis, can effectively control the patients' neurotrophic factor, pulmonary ventilation and chemokine CC17, CCL22 indicators, the effect is better than Budesonide alone or Cetirizine hydrochloride.

  12. S-nitrosoglutathione reductase inhibition regulates allergen-induced lung inflammation and airway hyperreactivity.

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    Maria E Ferrini

    Full Text Available Allergic asthma is characterized by Th2 type inflammation, leading to airway hyperresponsivenes, mucus hypersecretion and tissue remodeling. S-Nitrosoglutathione reductase (GSNOR is an alcohol dehydrogenase involved in the regulation of intracellular levels of S-nitrosothiols. GSNOR activity has been shown to be elevated in human asthmatic lungs, resulting in diminished S-nitrosothiols and thus contributing to increased airway hyperreactivity. Using a mouse model of allergic airway inflammation, we report that intranasal administration of a new selective inhibitor of GSNOR, SPL-334, caused a marked reduction in airway hyperreactivity, allergen-specific T cells and eosinophil accumulation, and mucus production in the lungs in response to allergen inhalation. Moreover, SPL-334 treatment resulted in a significant decrease in the production of the Th2 cytokines IL-5 and IL-13 and the level of the chemokine CCL11 (eotaxin-1 in the airways. Collectively, these observations reveal that GSNOR inhibitors are effective not only in reducing airway hyperresponsiveness but also in limiting lung inflammatory responses mediated by CD4(+ Th2 cells. These findings suggest that the inhibition of GSNOR may provide a novel therapeutic approach for the treatment of allergic airway inflammation.

  13. Upper airway involvement in bronchiectasis is marked by early onset and allergic features

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    Michal Shteinberg

    2018-01-01

    Full Text Available The association of bronchiectasis with chronic rhinosinusitis (CRS has been reported. However, apart from primary ciliary dyskinesia (PCD and cystic fibrosis (CF, predisposing conditions have not been established. We aimed to define clinical and laboratory features that differentiate patients with bronchiectasis with upper airway symptoms (UASs and without PCD from patients without UASs. We reviewed charts of adults with bronchiectasis, excluding CF and PCD. UASs were defined as nasal discharge most days of the year, sinusitis or nasal polyps. Laboratory data included IgG, total IgE, blood eosinophils, sputum bacteriology and lung function. A radiologist blinded to UAS presence scored bronchiectasis (Reiff score and sino-nasal pathology (Lund–Mackay score. Of 197 patients, for the 70 (35% with UASs, symptoms started earlier (34±25 versus 46±24 years; p=0.001, disease duration was longer (median 24 versus 12 years; p=0.027, exacerbations were more frequent (median 3 versus 2 per year; p=0.14, and peripheral blood eosinophil (median 230 versus 200 μL−1; p=0.015 and total IgE (median 100 versus 42 IU·mL−1; p=0.085 levels were higher. The sinus computed tomography score was independently associated with exacerbations, with 1 point on the Lund–Mackay score associated with a 1.03-fold increase in the number of exacerbations per year (95% CI 1.0–1.05; p=0.004. These findings may implicate a higher disease burden in patients with UASs. We hypothesise that UASs precede and may in some cases lead to the development of bronchiectasis.

  14. Studying allergic inflammation and spirometry over menstrual cycles in well-controlled asthmatic women: Changes in progesterone and estradiol affect neither FENO levels nor lung function.

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    Nittner-Marszalska, Marita; Dor-Wojnarowska, Anna; Wolańczyk-Mędrala, Anna; Rosner-Tenerowicz, Anna; Zimmer, Mariusz; Dobek, Julia; Gomułka, Krzysztof; Parużyńska, Anna; Panaszek, Bernard

    2018-05-01

    It has been reported that female sex hormones influence on allergic inflammation and ventilation parameters in asthma but conclusions drawn by different researchers are divergent. The aim of our study was to assess the impact of progesterone (Pg) and estradiol (E) on the dynamics of allergic inflammation and spirometry test results in regularly menstruating women with stable allergic asthma. 13 women (28 days menstrual cycle), aged 18-45, taking no hormonal contraceptives, with mild and moderate asthma, without reported exacerbations at the near-ovulation and/or menstruation time, were monitored during two consecutive menstrual cycles. They had 4 visits per cycle (the first day of menstruation was assumed to be day 1 of the cycle; visits were carried out on days: 3-4, 10-11, 13-14 and 23-24). At each visit asthma symptoms, asthma control test (ACT) results, asthma treatment, fractioned nitric oxide (FENO) levels, spirometry test results, Pg and E, levels were analyzed. As a result of the study, no essential variability in FENO values and ventilation parameters' values in the course of menstruation cycle were observed. Negative correlation between FENO values and Pg concentrations was demonstrated (r = 0.27), but no correlation between FENO values and E levels was shown. No relationship between the ACT values and ventilation parameters and the levels of the sex hormones under investigation was detected. We conclude that changing levels of estradiol and progesterone (regardless of the negative correlation of progesterone and FENO values) affect neither the dynamics of allergic inflammation nor pulmonary function in women with stable allergic mild/moderate asthma. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts.

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    Sarna, Michal; Wojcik, Katarzyna A; Hermanowicz, Pawel; Wnuk, Dawid; Burda, Kvetoslava; Sanak, Marek; Czyż, Jarosław; Michalik, Marta

    2015-01-01

    During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT) can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs) derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned 'ventral' stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development.

  16. Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children

    NARCIS (Netherlands)

    Kersten, Elin T. G.; van Leeuwen, Janneke C.; Brand, Paul L. P.; Duiverman, Eric J.; de Jongh, Frans H. C.; Thio, Bernard J.; Driessen, Jean M. M.

    Rationale Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children. Methods: This was a double-blind,

  17. Mice deficient in the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation.

    Science.gov (United States)

    Kiwamoto, Takumi; Brummet, Mary E; Wu, Fan; Motari, Mary G; Smith, David F; Schnaar, Ronald L; Zhu, Zhou; Bochner, Bruce S

    2014-01-01

    Sialic acid-binding immunoglobulin-like lectin (Siglec)-F is a proapoptotic receptor on mouse eosinophils, but little is known about its natural tissue ligand. We previously reported that the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) is required for constitutive Siglec-F lung ligand synthesis. We therefore hypothesized that attenuation of ST3Gal-III will decrease Siglec-F ligand levels and enhance allergic eosinophilic airway inflammation. C57BL/6 wild-type mice and St3gal3 heterozygous or homozygous deficient (St3gal3(+/-) and St3gal3(-/-)) mice were used. Eosinophilic airway inflammation was induced through sensitization to ovalbumin (OVA) and repeated airway OVA challenge. Siglec-F human IgG1 fusion protein (Siglec-F-Fc) was used to detect Siglec-F ligands. Lung tissue and bronchoalveolar lavage fluid (BALF) were analyzed for inflammation, as well as various cytokines and chemokines. Serum was analyzed for allergen-specific immunoglobulin levels. Western blotting with Siglec-F-Fc detected approximately 500-kDa and approximately 200-kDa candidate Siglec-F ligands that were less abundant in St3gal3(+/-) lung extracts and nearly absent in St3gal3(-/-) lung extracts. After OVA sensitization and challenge, Siglec-F ligands were increased in wild-type mouse lungs but less so in St3gal3 mutants, whereas peribronchial and BALF eosinophil numbers were greater in the mutants, with the following rank order: St3gal3(-/-) ≥ St3gal3(+/-) > wild-type mice. Levels of various cytokines and chemokines in BALF were not significantly different among these 3 types of mice, although OVA-specific serum IgG1 levels were increased in St3gal3(-/-) mice. After OVA sensitization and challenge, St3gal3(+/-) and St3gal3(-/-) mice have more intense allergic eosinophilic airway inflammation and less sialylated Siglec-F ligands in their airways. One possible explanation for these findings is that levels of sialylated airway ligands for Siglec-F might be diminished in mice with

  18. Zinc supplementation alters airway inflammation and airway hyperresponsiveness to a common allergen

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    Morgan Carrie I

    2011-12-01

    Full Text Available Abstract Background Zinc supplementation can modulate immunity through inhibition of NF-κB, a transcription factor that controls many immune response genes. Thus, we sought to examine the mechanism by which zinc supplementation tempers the response to a common allergen and determine its effect on allergic airway inflammation. Methods Mice were injected with zinc gluconate prior to German cockroach (GC feces (frass exposure and airway inflammation was assessed. Primary bone marrow-derived neutrophils and DMSO-differentiated HL-60 cells were used to assess the role of zinc gluconate on tumor necrosis factor (TNFα expression. NF-κB:DNA binding and IKK activity were assessed by EMSA and in vitro kinase assay. Protein levels of A20, RIP1 and TRAF6 were assessed by Western blot analysis. Establishment of allergic airway inflammation with GC frass was followed by administration of zinc gluconate. Airway hyperresponsiveness, serum IgE levels, eosinophilia and Th2 cytokine production were assessed. Results Administration of zinc gluconate prior to allergen exposure resulted in significantly decreased neutrophil infiltration and TNFα cytokine release into the airways. This correlated with decreased NF-κB activity in the whole lung. Treatment with zinc gluconate significantly decreased GC frass-mediated TNFα production from bone-marrow derived neutrophils and HL-60 cells. We confirmed zinc-mediated decreases in NF-κB:DNA binding and IKK activity in HL-60 cells. A20, a natural inhibitor of NF-κB and a zinc-fingered protein, is a potential target of zinc. Zinc treatment did not alter A20 levels in the short term, but resulted in the degradation of RIP1, an important upstream activator of IKK. TRAF6 protein levels were unaffected. To determine the application for zinc as a therapeutic for asthma, we administered zinc following the establishment of allergic airway inflammation in a murine model. Zinc supplementation decreased airway hyperresponsiveness

  19. Targeting phosphoinositide 3-kinase δ for allergic asthma.

    Science.gov (United States)

    Rowan, Wendy C; Smith, Janet L; Affleck, Karen; Amour, Augustin

    2012-02-01

    Chronic inflammation in the lung has long been linked to the pathogenesis of asthma. Central to this airway inflammation is a T-cell response to allergens, with Th2 cytokines driving the differentiation, survival and function of the major inflammatory cells involved in the allergic cascade. PI3Kδ (phosphoinositide 3-kinase δ) is a lipid kinase, expressed predominantly in leucocytes, where it plays a critical role in immune receptor signalling. A selective PI3Kδ inhibitor is predicted to block T-cell activation in the lung, reducing the production of pro-inflammatory Th2 cytokines. PI3Kδ is also involved in B-cell and mast cell activation. Therefore the inhibition of PI3Kδ should dampen down the inflammatory cascade involved in the asthmatic response through a wide breadth of pharmacology. Current anti-inflammatory therapies, which are based on corticosteroids, are effective in controlling inflammation in mild asthmatics, but moderate/severe asthmatic patients remain poorly controlled, experiencing recurrent exacerbations. Corticosteroids have no effect on mast cell degranulation and do not act directly on B-cells, so, overall, a PI3Kδ inhibitor has the potential to deliver improvements in onset of action, efficacy and reduced exacerbations in moderate/severe asthmatics. Additionally, PI3Kδ inhibition is expected to block effects of Th17 cells, which are increasingly implicated in steroid-insensitive asthma.

  20. The effect of academic exam stress on mucosal and cellular airway immune markers among healthy and allergic individuals.

    Science.gov (United States)

    Trueba, Ana F; Rosenfield, David; Oberdörster, Eva; Vogel, Pia D; Ritz, Thomas

    2013-01-01

    Research suggests that psychological stress can exacerbate allergies, but relatively little is known about the effect of stress on mucosal immune processes central to allergic pathophysiology. In this study, we quantified vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ), and interleukin-4 concentrations in saliva (S) and exhaled breath condensate (EBC) during final exams and at midsemester among 23 healthy and 21 allergic rhinitis individuals. IFN-γs decreased during exams for both groups while VEGF(EBC) increased (and increases in VEGFs were a trend). Elevated negative affect ratings predicted higher VEGF(EBC) in allergic individuals. IFN-γ(EBC) increased in healthy individuals early during exams and then decreased, while allergic individuals showed a decrease in IFN-γ(EBC) throughout final exams. These findings suggest that psychological stress can suppress cellular immune function among allergic individuals while increasing VEGF. Copyright © 2012 Society for Psychophysiological Research.

  1. Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation

    OpenAIRE

    Murgia, Chiara; Grosser, Dion; Truong-Tran, Ai Q.; Roscioli, Eugene; Michalczyk, Agnes; Ackland, Margaret Leigh; Stoltenberg, Meredin; Danscher, Gorm; Lang, Carol; Knight, Darryl; Perozzi, Giuditta; Ruffin, Richard E.; Zalewski, Peter

    2011-01-01

    The apical cytoplasm of airway epithelium (AE) contains abundant labile zinc (Zn) ions that are involved in the protection of AE from oxidants and inhaled noxious substances. A major question is how dietary Zn traffics to this compartment. In rat airways, in vivo selenite autometallographic (Se-AMG)-electron microscopy revealed labile Zn-selenium nanocrystals in structures resembling secretory vesicles in the apical cytoplasm. This observation was consistent with the starry-sky Zinquin fluore...

  2. Systemic Administration of Human Bone Marrow-Derived Mesenchymal Stromal Cell Extracellular Vesicles Ameliorates Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation in Immunocompetent Mice.

    Science.gov (United States)

    Cruz, Fernanda F; Borg, Zachary D; Goodwin, Meagan; Sokocevic, Dino; Wagner, Darcy E; Coffey, Amy; Antunes, Mariana; Robinson, Kristen L; Mitsialis, S Alex; Kourembanas, Stella; Thane, Kristen; Hoffman, Andrew M; McKenna, David H; Rocco, Patricia R M; Weiss, Daniel J

    2015-11-01

    An increasing number of studies demonstrate that administration of either conditioned media (CM) or extracellular vesicles (EVs) released by mesenchymal stromal cells (MSCs) derived from bone marrow and other sources are as effective as the MSCs themselves in mitigating inflammation and injury. The goal of the current study was to determine whether xenogeneic administration of CM or EVs from human bone marrow-derived MSCs would be effective in a model of mixed Th2/Th17, neutrophilic-mediated allergic airway inflammation, reflective of severe refractory asthma, induced by repeated mucosal exposure to Aspergillus hyphal extract (AHE) in immunocompetent C57Bl/6 mice. Systemic administration of both CM and EVs isolated from human and murine MSCs, but not human lung fibroblasts, at the onset of antigen challenge in previously sensitized mice significantly ameliorated the AHE-provoked increases in airway hyperreactivity (AHR), lung inflammation, and the antigen-specific CD4 T-cell Th2 and Th17 phenotype. Notably, both CM and EVs from human MSCs (hMSCs) were generally more potent than those from mouse MSCs (mMSCs) in most of the outcome measures. The weak cross-linking agent 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride was found to inhibit release of both soluble mediators and EVs, fully negating effects of systemically administered hMSCs but only partly inhibited the ameliorating effects of mMSCs. These results demonstrate potent xenogeneic effects of CM and EVs from hMSCs in an immunocompetent mouse model of allergic airway inflammation and they also show differences in mechanisms of action of hMSCs versus mMSCs to mitigate AHR and lung inflammation in this model. There is a growing experience demonstrating benefit of mesenchymal stromal cell (MSC)-based cell therapies in preclinical models of asthma. In the current study, conditioned media (CM) and, in particular, the extracellular vesicle fraction obtained from the CM were as potent as the MSCs

  3. Review of fungus-induced asthmatic reactions

    NARCIS (Netherlands)

    Kauffman, H. F.; TOMEE, J. F.; van der Werf, T. S.; de Monchy, J. G.; Koëter, G. K.

    Fungus-induced obstructive airway disease in atopic individuals can be differentiated into two categories: first, uncomplicated asthmatic reactions due to high but transient exposure to fungal spores (fungal asthma), resulting in a T-H2-type response with immunoglobulin E-mediated reactions and

  4. Non-invasive optical imaging of eosinophilia during the course of an experimental allergic airways disease model and in response to therapy.

    Directory of Open Access Journals (Sweden)

    M Andrea Markus

    Full Text Available BACKGROUND: Molecular imaging of lung diseases, including asthma, is limited and either invasive or non-specific. Central to the inflammatory process in asthma is the recruitment of eosinophils to the airways, which release proteases and proinflammatory factors and contribute to airway remodeling. The aim of this study was to establish a new approach to non-invasively assess lung eosinophilia during the course of experimental asthma by combining non-invasive near-infrared fluorescence (NIRF imaging with the specific detection of Siglec-F, a lectin found predominantly on eosinophils. METHODOLOGY/PRINCIPAL FINDINGS: An ovalbumin (OVA-based model was used to induce asthma-like experimental allergic airway disease (EAAD in BALB/c mice. By means of a NIRF imager, we demonstrate that 48 h-72 h after intravenous (i.v. application of a NIRF-labeled anti-Siglec-F antibody, mice with EAAD exhibited up to 2 times higher fluorescence intensities compared to lungs of control mice. Furthermore, average lung intensities of dexamethasone-treated as well as beta-escin-treated mice were 1.8 and 2 times lower than those of untreated, EAAD mice, respectively and correlated with the reduction of cell infiltration in the lung. Average fluorescence intensities measured in explanted lungs confirmed the in vivo findings of significantly higher values in inflamed lungs as compared to controls. Fluorescence microscopy of lung cryosections localized the i.v. applied NIRF-labeled anti-Siglec-F antibody predominantly to eosinophils in the peribronchial areas of EAAD lungs as opposed to control lungs. CONCLUSION/SIGNIFICANCE: We show that monitoring the occurrence of eosinophils, a prominent feature of allergic asthma, by means of a NIRF-labeled antibody directed against Siglec-F is a novel and powerful non-invasive optical imaging approach to assess EAAD and therapeutic response in mice over time.

  5. Non-invasive optical imaging of eosinophilia during the course of an experimental allergic airways disease model and in response to therapy.

    Science.gov (United States)

    Markus, M Andrea; Dullin, Christian; Mitkovski, Miso; Prieschl-Grassauer, Eva; Epstein, Michelle M; Alves, Frauke

    2014-01-01

    Molecular imaging of lung diseases, including asthma, is limited and either invasive or non-specific. Central to the inflammatory process in asthma is the recruitment of eosinophils to the airways, which release proteases and proinflammatory factors and contribute to airway remodeling. The aim of this study was to establish a new approach to non-invasively assess lung eosinophilia during the course of experimental asthma by combining non-invasive near-infrared fluorescence (NIRF) imaging with the specific detection of Siglec-F, a lectin found predominantly on eosinophils. An ovalbumin (OVA)-based model was used to induce asthma-like experimental allergic airway disease (EAAD) in BALB/c mice. By means of a NIRF imager, we demonstrate that 48 h-72 h after intravenous (i.v.) application of a NIRF-labeled anti-Siglec-F antibody, mice with EAAD exhibited up to 2 times higher fluorescence intensities compared to lungs of control mice. Furthermore, average lung intensities of dexamethasone-treated as well as beta-escin-treated mice were 1.8 and 2 times lower than those of untreated, EAAD mice, respectively and correlated with the reduction of cell infiltration in the lung. Average fluorescence intensities measured in explanted lungs confirmed the in vivo findings of significantly higher values in inflamed lungs as compared to controls. Fluorescence microscopy of lung cryosections localized the i.v. applied NIRF-labeled anti-Siglec-F antibody predominantly to eosinophils in the peribronchial areas of EAAD lungs as opposed to control lungs. We show that monitoring the occurrence of eosinophils, a prominent feature of allergic asthma, by means of a NIRF-labeled antibody directed against Siglec-F is a novel and powerful non-invasive optical imaging approach to assess EAAD and therapeutic response in mice over time.

  6. Anti-inflammatory Potentials of Excretory/Secretory (ES and Somatic Products of Marshallagia marshalli on Allergic Airway Inflammation in BALB/c Mice

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    Sima PARANDE SHIRVAN

    2016-12-01

    Full Text Available Background: Inverse relationship between helminths infection and immune-mediated diseases has inspired researchers to investigate therapeutic potential of helminths in allergic asthma. Helminth unique ability to induce immunoregulatory responses has already been documented in several experimental studies. This study was designed to investigate whether excretory/secretory (ES and somatic products of Marshallagia marshalli modulate the development of ovalbumin-induced airway inflammation in a mouse model.Methods: This study was carried out at the laboratories of Immunology and Parasitology of Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran during spring and summer 2015. Allergic airway inflammation was induced in mice by intraperitoneal (IP injection with ovalbumin (OVA. The effects of ES and somatic products of M. marshalli were analyzed by inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF, pathological changes and IgE response.Results: Treatment with ES and somatic products of M. marshalli decreased cellular infiltration into BALF when they were administered during sensitization with allergen. Pathological changes were decreased in helminth-treated group, as demonstrated by reduced inflammatory cell infiltration, goblet cell hyperplasia, epithelial lesion and smooth muscle hypertrophy. However, no significant differences were observed in IgE serum levels, cytokines and eosinophil counts between different groups.Conclusion: This study provides new insights into anti-inflammatory effects of ES and somatic products of M. marshalli, during the development of non-eosinophilic model of asthma. Further study is necessary to characterize immunomodulatory molecules derived from M. marshalli as a candidate for the treatment of airway inflammation.

  7. Dental Erosion and Dentin Hypersensitivity among Adult Asthmatics and Non-asthmatics Hospital-based: A Preliminary Study.

    Science.gov (United States)

    Farag, Zahra Hassan Abdelaziz; Awooda, Elhadi Mohieldin

    2016-01-01

    Asthma is a chronic inflammatory condition affecting the airways leading to spasm and swelling of the airways. The medications taken for the treatment of asthma can result in dental erosion and dentin hypersensitivity. The aims of this study were to investigate the severity of dental erosion amongst adult asthmatics according to: gender, type and duration of medication taken and to compare dental erosion and dentin hypersensitivity between asthmatics and non-asthmatics. Comparative, cross-sectional hospital based study among 40 asthmatics (M=15 & F=25) and 40 non-asthmatics (M=18 & F=22) in the age range of 18-60 year selected purposefully from Al-Shaab Teaching Hospital in Khartoum city. The Basic Erosive Wear Index was used for dental erosion assessment. Dentine hypersensitivity was determined by giving ice cold water and rated using the Visual Analogue Scale. Chi-square and Student's t-test were used for statistical analysis with P value ≤.05. There was an association between severity of dental erosion and presence of asthma (P=0.03), where asthmatics had a higher degree of erosion (moderate and severe) and non-asthmatics a lower degree. No significant association was found between dental erosion and gender, type and duration of medication among asthmatics group. A statistically significant difference was revealed in the degree of dentin hypersensitivity (P=0.00) among asthmatics (35.13%) and non-asthmatics (14.13%). Asthmatic patients had a higher degree of dental erosion and dentin hypersensitivity compared to non-asthmatics. Among asthmatic patients there was no association between severity of dental erosion and gender, type and duration medication was taken for.

  8. Effects of Ex Vivo y-Tocopherol on Airway Macrophage ...

    Science.gov (United States)

    Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate y-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-mediated phagocytosis and expression of cell surface molecules associated with innate and adaptive immunity on sputum-derived macrophages. Cells from nonsmoking healthy (n = 6)and mild house dust mite-sensitive allergic asthmatics (n =6) were treated ex vivo with GT (300 uM) or saline (control). Phagocytosis of opsonized zymosan A bioparticles (Saccharomyces cerevisiae) and expression of surface molecules associated with innate and adaptive immunity were assessed using flow cytometry. GT caused significantly decreased (p innate and adaptive immune response elements, and atopic status appears to be an important factor. Recent studies on the effects of the fat-soluble steriod hormone vitamins D and E suggest that dietary suplementation with these vitamins may be helpful for the prevention or in the treatment of inflammatory and immune-mediated diseases, including atopic asthma.

  9. Kinetics of TH2 biomarkers in sputum of asthmatics following inhaled allergen.

    Science.gov (United States)

    Zuiker, Rob G J A; Ruddy, Marcella K; Morelli, Nicoletta; Mogg, Robin; Rivas, Veronica M; van Dyck, Kristien; De Lepeleire, Inge; Tanen, Michael R L; Boot, J Diderik; Kamerling, Ingrid M C; Diamant, Zuzana

    2015-01-01

    Allergen-induced late airway response offers important pharmacodynamic targets, including T helper 2 (TH2) biomarkers. However, detection of inflammatory markers has been limited in dithiothreitol-processed sputum. To test whether allergen-induced TH2 inflammatory markers can be reproducibly quantified by sensitive detection techniques in ultracentrifuged sputum and the effect of fluticasone (FP) on these endpoints. Thirteen allergic asthmatics with dual allergen-induced airway responses, documented during a single-blind placebo run-in period, participated in a double-blind, two-period crossover study. Each period consisted of three consecutive days, separated by ≥3 weeks. Following randomization, subjects inhaled FP (500 µg bid, five doses total) or placebo. On Day 2 in each study period, allergen challenge was performed and airway response measured by forced expiratory volume in 1 sec (FEV1) until 7 h post-challenge. Sputum was induced 24 h pre-allergen and 7 and 24 h post-allergen. Sputum samples were split into two portions: TH2 biomarkers were quantified by Meso Scale multiplex platform following ultracentrifugation, and cell differentials were counted on Giemsa-May-Grünwald-stained cytospins. Allergen-induced changes in inflammatory endpoints were compared between FP and placebo using a mixed model ANCOVA. Inhaled allergen induced dual airway responses in all subjects during both placebo periods with reproducible late asthmatic response (LAR) and increased sputum inflammatory biomarkers (IL-2, IL-4, IL-13, and eotaxin-1) and eosinophil counts. FP effectively blunted both the LAR and the inflammatory biomarkers. Combining novel, sensitive quantification methods with ultracentrifugation allows reproducible quantification of sputum biomarkers following allergen challenge, reversed by FP. This approach allows non-invasive identification of pharmacodynamic targets for anti-asthma therapies.

  10. The early asthmatic response is associated with glycolysis, calcium binding and mitochondria activity as revealed by proteomic analysis in rats

    Directory of Open Access Journals (Sweden)

    Xu Yu-Dong

    2010-08-01

    Full Text Available Abstract Background The inhalation of allergens by allergic asthmatics results in the early asthmatic response (EAR, which is characterized by acute airway obstruction beginning within a few minutes. The EAR is the earliest indicator of the pathological progression of allergic asthma. Because the molecular mechanism underlying the EAR is not fully defined, this study will contribute to a better understanding of asthma. Methods In order to gain insight into the molecular basis of the EAR, we examined changes in protein expression patterns in the lung tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques. Bioinformatic analysis of the proteomic data was then performed using PPI Spider and KEGG Spider to investigate the underlying molecular mechanism. Results In total, 44 differentially expressed protein spots were detected in the 2-DE gels. Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully identified using mass spectrometry. During subsequent bioinformatic analysis, the gene ontology classification, the protein-protein interaction networking and the biological pathway exploration demonstrated that the identified proteins were mainly involved in glycolysis, calcium binding and mitochondrial activity. Using western blot and semi-quantitative RT-PCR, we confirmed the changes in expression of five selected proteins, which further supports our proteomic and bioinformatic analyses. Conclusions Our results reveal that the allergen-induced EAR in asthmatic rats is associated with glycolysis, calcium binding and mitochondrial activity, which could establish a functional network in which calcium binding may play a central role in promoting the progression of asthma.

  11. Neutrophil Inhibitory Factor Selectively Inhibits the Endothelium-Driven Transmigration of Eosinophils In Vitro and Airway Eosinophilia in OVA-Induced Allergic Lung Inflammation

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    Silvia Schnyder-Candrian

    2012-01-01

    Full Text Available Leukocyte adhesion molecules are involved in cell recruitment in an allergic airway response and therefore provide a target for pharmaceutical intervention. Neutrophil inhibitory factor (NIF, derived from canine hookworm (Ancylostoma caninum, binds selectively and competes with the A-domain of CD11b for binding to ICAM-1. The effect of recombinant NIF was investigated. Intranasal administration of rNIF reduced pulmonary eosinophilic infiltration, goblet cell hyperplasia, and Th2 cytokine production in OVA-sensitized mice. In vitro, transendothelial migration of human blood eosinophils across IL-4-activated umbilical vein endothelial cell (HUVEC monolayers was inhibited by rNIF (IC50: 4.6±2.6 nM; mean ± SEM, but not across TNF or IL-1-activated HUVEC monolayers. Treatment of eosinophils with rNIF together with mAb 60.1 directed against CD11b or mAb 107 directed against the metal ion-dependent adhesion site (MIDAS of the CD11b A-domain resulted in no further inhibition of transendothelial migration suggesting shared functional epitopes. In contrast, rNIF increased the inhibitory effect of blocking mAbs against CD18, CD11a, and VLA-4. Together, we show that rNIF, a selective antagonist of the A-domain of CD11b, has a prominent inhibitory effect on eosinophil transendothelial migration in vitro, which is congruent to the in vivo inhibition of OVA-induced allergic lung inflammation.

  12. Sulfatide-activated type II NKT cells prevent allergic airway inflammation by inhibiting type I NKT cell function in a mouse model of asthma.

    Science.gov (United States)

    Zhang, Guqin; Nie, Hanxiang; Yang, Jiong; Ding, Xuhong; Huang, Yi; Yu, Hongying; Li, Ruyou; Yuan, Zhuqing; Hu, Suping

    2011-12-01

    Asthma is a common chronic inflammatory disease involving many different cell types. Recently, type I natural killer T (NKT) cells have been demonstrated to play a crucial role in the development of asthma. However, the roles of type II NKT cells in asthma have not been investigated before. Interestingly, type I and type II NKT cells have been shown to have opposing roles in antitumor immunity, antiparasite immunity, and autoimmunity. We hypothesized that sulfatide-activated type II NKT cells could prevent allergic airway inflammation by inhibiting type I NKT cell function in asthma. Strikingly, in our mouse model, activation of type II NKT cells by sulfatide administration and adoptive transfer of sulfatide-activated type II NKT cells result in reduced-inflammation cell infiltration in the lung and bronchoalveolar lavage fluid, decreased levels of IL-4 and IL-5 in the BALF; and decreased serum levels of ovalbumin-specific IgE and IgG1. Furthermore, it is found that the activation of sulfatide-reactive type II NKT cells leads to the functional inactivation of type I NKT cells, including the proliferation and cytokine secretion. Our data reveal that type II NKT cells activated by glycolipids, such as sulfatide, may serve as a novel approach to treat allergic diseases and other disorders characterized by inappropriate type I NKT cell activation.

  13. Role and interpretation of total serum IgE measurements in the diagnosis of allergic airway disease in adults

    NARCIS (Netherlands)

    Kerkhof, M; Dubois, AEJ; Postma, DS; Schouten, JP; de Monchy, JGR

    Background: While total IgE measurements are often used in clinical practice, it is unclear how they should be interpreted for the diagnosis of allergic disorders. We studied whether total IgE may be used to rule out or predict sensitization and whether there are age or gender differences. Methods:

  14. Efficiency and limitations of the upper airway mucosa as an air conditioner evaluated from the mechanisms of bronchoconstriction in asthmatic subjects.

    Science.gov (United States)

    Konno, A; Terada, N; Okamoto, Y; Togawa, K

    1985-01-01

    To elucidate a limit to the efficiency of the upper airway mucosa as an air conditioner, the temperatures of the inspiratory air and mucosa were measured in the cervical trachea. Both of them were affected only minimally by change of atmospheric air temperature during resting nose breathing, but were affected greatly by change of mode of breathing. During hyperventilation through the mouth, when the atmospheric air temperature was 1 degree C, a temperature difference of 9 degrees C was noted between inspiratory air in the cervical trachea and body temperature, together with a mucosal temperature fall by 1.86 +/- 0.61 degree C. Wearing of a mask caused a rise of 3 degrees C in the inspiratory air temperature in the cervical trachea.

  15. Call-Center Based Disease Management of Pediatric Asthmatics

    Science.gov (United States)

    2006-04-01

    Cagnani CE. Allergic rhinitis and asthma in children: disease management and outcomes. Current Allergy & Asthma Reports. 1(6):515-22, 2001. 58. Chan...of Pediatric Asthmatics PRINCIPAL INVESTIGATOR: James M. Quinn, M.D. CONTRACTING ORGANIZATION: The Geneva Foundation...CONTRACT NUMBER Call-Center Based Disease Management of Pediatric Asthmatics 5b. GRANT NUMBER DAMD17-02-1-0182 5c. PROGRAM ELEMENT NUMBER 6

  16. GM-CSF production from human airway smooth muscle cells is potentiated by human serum

    Directory of Open Access Journals (Sweden)

    Maria B. Sukkar

    2000-01-01

    Full Text Available Recent evidence suggests that airway smooth muscle cells (ASMC actively participate in the airway inflammatory process in asthma. Interleukin–1β (IL–1β and tumour necrosis factor–α (TNF–α induce ASMC to release inflammatory mediators in vitro. ASMC mediator release in vivo, however, may be influenced by features of the allergic asthmatic phenotype. We determined whether; (1 allergic asthmatic serum (AAS modulates ASMC mediator release in response to IL–1β and TNF–α, and (2 IL–1β/TNF–α prime ASMC to release mediators in response to AAS. IL–5 and GMCSF were quantified by ELISA in culture supernatants of; (1 ASMC pre-incubated with either AAS, non-allergic non-asthmatic serum (NAS or MonomedTM (a serum substitute and subsequently stimulated with IL–1β and TNF–α and (2 ASMC stimulated with IL–1β/TNF–α and subsequently exposed to either AAS, NAS or MonomedTM. IL-1g and TNF–α induced GM-CSF release in ASMC pre-incubated with AAS was not greater than that in ASMC pre-incubated with NAS or MonomedTM. IL–1β and TNF–α, however, primed ASMC to release GM-CSF in response to human serum. GM-CSF production following IL–1β/TNF–α and serum exposure (AAS or NAS was significantly greater than that following IL–1β /TNF–α and MonomedTM exposure or IL–1β/TNF–α exposure only. Whilst the potentiating effects of human serum were not specific to allergic asthma, these findings suggest that the secretory capacity of ASMC may be up-regulated during exacerbations of asthma, where there is evidence of vascular leakage.

  17. Acute airway effects of airborne formaldehyde in sensitized and non-sensitized mice housed in a dry or humid environment

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Søren Thor, E-mail: stl@nrcwe.dk; Wolkoff, Peder, E-mail: pwo@nrcwe.dk; Hammer, Maria, E-mail: mha@nrcwe.dk; Kofoed-Sørensen, Vivi, E-mail: vks@nrcwe.dk; Clausen, Per Axel, E-mail: pac@nrcwe.dk; Nielsen, Gunnar Damgård, E-mail: gdn@nrcwe.dk

    2013-05-01

    We investigated the role of air humidity and allergic sensitization on the acute airway response to inhaled formaldehyde (FA) vapor. Mice were sensitized to the immunogen ovalbumin (OVA) by three intraperitoneal injections followed by two aerosol challenges, giving rise to allergic airway inflammation. Control mice were sham sensitized by saline injections and challenged by saline aerosols. Once sensitized, the mice were housed at high (85–89%) or low (< 10%) relative humidity, respectively for 48 h prior to a 60-min exposure to either 0.4, 1.8 or about 5 ppm FA. Before, during and after exposure, breathing parameters were monitored. These included the specific markers of nose and lung irritations as well as the expiratory flow rate, the latter being a marker of airflow limitation. The sensory irritation response in the upper airways was not affected by allergic inflammation or changes in humidity. At high relative humidity, the OVA-sensitized mice had a decreased expiratory airflow rate compared to the saline control mice after exposure to approximately 5 ppm FA. This is in accordance with the observations that asthmatics are more sensitive than non-asthmatics to higher concentrations of airway irritants including FA. In the dry environment, the opposite trend was seen; here, the saline control mice had a significantly decreased expiratory airflow rate compared to OVA-sensitized mice when exposed to 1.8 and 4 ppm FA. We speculate that increased mucus production in the OVA-sensitized mice has increased the “scrubber effect” in the nose, consequently protecting the conducting and lower airways. - Highlights: ► Role of air humidity and allergy on sensitivity to an airway irritant was studied. ► In the humid environment, allergy amplified the effects of formaldehyde. ► In the dry environment, allergy reduced the effect of formaldehyde. ► Neither allergy nor humidity changed the formaldehyde-induced nasal irritation.

  18. The NK-2 receptor antagonist SR 48968C does not improve adenosine hyperresponsiveness and airway obstruction in allergic asthma

    NARCIS (Netherlands)

    Kraan, J; Vink-Klooster, H; Postma, DS

    Background When stimulated, excitatory nonadrenergic noncholinergic (e-NANC) nerves locally release tachykinins like Neurokinin (NK) A and Substance P, causing neurogenic inflammation and airway obstruction via activation of specific NK-1 and NK-2 receptors. The recently developed nonpeptide NK-2

  19. Airway wall thickness of allergic asthma caused by weed pollen or house dust mite assessed by computed tomography.

    Science.gov (United States)

    Liu, Liping; Li, Guangrun; Sun, Yuemei; Li, Jian; Tang, Ningbo; Dong, Liang

    2015-03-01

    Little was known about Airway wall thickness of asthma patients with different allergen allergy. So we explored the possible difference of Airway wall thickness of asthma patients mono-sensitized to weed pollen or HDM using high-resolution computed tomography. 85 severe asthma patients were divided into weed pollen group and HDM group according to relevant allergen. 20 healthy donors served as controls. Airway wall area, percentage wall area and luminal area at the trunk of the apical bronchus of the right upper lobe were quantified using HRCT and compared. The values of pulmonary function were assessed as well. There were differences between HDM group and weed pollen group in WA/BSA,WA% and FEF25-75% pred, and no significant difference in FEV1%pred, FEV1/FVC and LA/BSA. In weed pollen group, WA/BSA was observed to correlate with the duration of rhinitis, whereas in HDM group, WA/BSA and LA/BSA was observed to correlate with the duration of asthma. In weed pollen group, FEV1/FVC showed a weak but significant negative correlation with WA%, but in HDM group FEV1/FVC showed a significant positive correlation with WA% and a statistical negative correlation with LA/BSA. FEV1/FVC and FEF25-75% pred were higher and WA/BSA and LA/BSA were lower in healthy control group than asthma group. FEV1%pred and WA% was no significant difference between asthma patients and healthy subjects. There are differences between HDM mono-sensitized subjects and weed pollen mono-sensitized subjects, not only in airway wall thickness, but also small airway obstruction. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Serum Zinc Level in Asthmatic and Non-Asthmatic School Children

    Directory of Open Access Journals (Sweden)

    Atqah AbdulWahab

    2018-03-01

    Full Text Available Asthma is one of the most common chronic disorders among children. Zinc (Zn is an essential dietary antioxidant and may have a special role in assisting the airways of asthmatic subjects. The primary objective of this study was to measure serum Zn levels among asthmatic school children and to compare this to the serum Zn level in non-asthmatic children. The secondary objective was to investigate the relationship between Zn levels and the degree of asthma control. A cross-sectional study following forty asthmatic children and forty matched non-asthmatic children of both genders was conducted. Weight, height, body mass index (BMI, BMI Z-scores, serum Zn, hemoglobin, total protein, and albumin concentrations were measured in both groups. Serum immunoglobulin E (IgE levels, the forced expiratory volume in 1 second (FEV1, and dosage of inhaled steroids were measured in asthmatic school children. The results show the mean Zn level among asthmatic children was 12.78 ± 1.8 μmol/L. Hypozincemia was detected in four asthmatic children. Asthma and control groups were matched in age, gender, and BMI Z score (p > 0.05. No significant difference was observed in Zn levels, hemoglobin, albumin, and total protein between both groups (p > 0.05. Among asthmatics, Zn levels were not significantly associated with the degree of asthma control (well controlled, mean Zn = 12.9 ± 1.5, partially controlled, mean Zn = 11.9 ± 1.6, and uncontrolled, mean Zn = 3.62 ± 2.2 (p = 0.053. The Zn level was not correlated with the FEV1 Z score. There was no significant association between Zn level and the dosage of inhaled steroids or IgE concentrations (p > 0.05. The findings show that Zn may not play a major role in the degree of asthma control. Larger studies are needed to confirm these results.

  1. Apoptosis in the normal and inflamed airway epithelium: role of zinc in epithelial protection and procaspase-3 regulation.

    Science.gov (United States)

    Truong-Tran, Ai Q; Grosser, Dion; Ruffin, Richard E; Murgia, Chiara; Zalewski, Peter D

    2003-10-15

    The epithelium lining the airways is a physical barrier as well as a regulator of physiological and pathological events in the respiratory system. Damage to the epithelium by oxidants released from inflammatory cells is a critical factor in the pathogenesis of airway inflammatory diseases such as bronchial asthma. In these diseases, excessive apoptosis may be a likely mechanism responsible for damage to, and sloughing, of airway epithelial cells. Factors that increase the airway epithelium's resilience to apoptosis are likely to lessen the severity of this disease. One such factor is the dietary metal zinc. A special role for labile intracellular pools of zinc as anti-apoptotic agents in the regulation of the caspases, has emerged over the past two decades. This review focuses on caspase-inhibitory functions of zinc in airway epithelial cells, apparent abnormalities of zinc homeostasis in asthmatics and studies from the authors' laboratory which showed that zinc was strategically localized in the apical cytoplasm of airway epithelium to control caspase-3 activated apoptosis. These findings are discussed in the context of recent data from a murine model of allergic asthma, showing that loss of airway epithelial zinc was accompanied by changes in levels of both procaspase-3 and active caspase-3 and that nutritional zinc deprivation further increased airway epithelial apoptosis. We hypothesize that zinc has a protective role for the airway epithelium against oxyradicals and other noxious agents, with important implications for asthma and other inflammatory diseases where the epithelial barrier is vulnerable and compromised.

  2. Differential expression and function of breast regression protein 39 (BRP-39 in murine models of subacute cigarette smoke exposure and allergic airway inflammation

    Directory of Open Access Journals (Sweden)

    Coyle Anthony J

    2011-04-01

    Full Text Available Abstract Background While the presence of the chitinase-like molecule YKL40 has been reported in COPD and asthma, its relevance to inflammatory processes elicited by cigarette smoke and common environmental allergens, such as house dust mite (HDM, is not well understood. The objective of the current study was to assess expression and function of BRP-39, the murine equivalent of YKL40 in a murine model of cigarette smoke-induced inflammation and contrast expression and function to a model of HDM-induced allergic airway inflammation. Methods CD1, C57BL/6, and BALB/c mice were room air- or cigarette smoke-exposed for 4 days in a whole-body exposure system. In separate experiments, BALB/c mice were challenged with HDM extract once a day for 10 days. BRP-39 was assessed by ELISA and immunohistochemistry. IL-13, IL-1R1, IL-18, and BRP-39 knock out (KO mice were utilized to assess the mechanism and relevance of BRP-39 in cigarette smoke- and HDM-induced airway inflammation. Results Cigarette smoke exposure elicited a robust induction of BRP-39 but not the catalytically active chitinase, AMCase, in lung epithelial cells and alveolar macrophages of all mouse strains tested. Both BRP-39 and AMCase were increased in lung tissue after HDM exposure. Examining smoke-exposed IL-1R1, IL-18, and IL-13 deficient mice, BRP-39 induction was found to be IL-1 and not IL-18 or IL-13 dependent, while induction of BRP-39 by HDM was independent of IL-1 and IL-13. Despite the importance of BRP-39 in cellular inflammation in HDM-induced airway inflammation, BRP-39 was found to be redundant for cigarette smoke-induced airway inflammation and the adjuvant properties of cigarette smoke. Conclusions These data highlight the contrast between the importance of BRP-39 in HDM- and cigarette smoke-induced inflammation. While functionally important in HDM-induced inflammation, BRP-39 is a biomarker of cigarette smoke induced inflammation which is the byproduct of an IL-1

  3. Type 2 innate lymphoid cells-new members of the "type 2 franchise" that mediate allergic airway inflammation.

    Science.gov (United States)

    Mjösberg, Jenny; Spits, Hergen

    2012-05-01

    Type 2 innate lymphoid cells (ILC2s) are members of an ILC family, which contains NK cells and Rorγt(+) ILCs, the latter including lymphoid tissue inducer (LTi) cells and ILCs producing IL-17 and IL-22. ILC2s are dedicated to the production of IL-5 and IL-13 and, as such, ILC2s provide an early and important source of type 2 cytokines critical for helminth expulsion in the gut. Several studies have also demonstrated a role for ILC2s in airway inflammation. In this issue of the European Journal of Immunology, Klein Wolterink et al. [Eur. J. Immunol. 2012. 42: 1106-1116] show that ILC2s are instrumental in several models of experimental asthma where they significantly contribute to production of IL-5 and IL-13, key cytokines in airway inflammation. This study sheds light over the relative contribution of ILC2s versus T helper type 2 cells (Th2) in type 2 mediated allergen-specific inflammation in the airways as discussed in this commentary. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Steroid Phobia among Parents of Asthmatic Children: Myths and Truth.

    Science.gov (United States)

    Zedan, Magdy M; Ezz El Regal, Mohammed; A Osman, Engy; E Fouda, Ashraf

    2010-09-01

    Asthma is one of the most common chronic diseases of childhood. Inhaled corticosteroids (ICS) are the recommended controller drug for asthma treatment. The aim of our study was to determine concerns and fears of parents of children with asthma towards the use of ICS. One hundred parents of asthmatic children were interviewed using structural questionnaire. Airway inflammation was reported by only 6% of interviewed parents, whereas airway narrowing was addressed by 34%. Interesting data, 71% of parents were concerned with the role of steroids in asthma treatment, but more than half (53%) of them addressed fears from side effects. Apparent gaps were found in knowledge of parents of asthmatic children about ICS as controller asthma medication. So, physician and health providers should explain to asthmatic parents that airway inflammation is the core for asthma management. This may remove fears about ICS and thus improve adherence to treatment.

  5. CD14-DEPENDENT AIRWAY NEUTROPHIL RESPONSE TO INHALED LPS: ROLE OF ATOPY

    Science.gov (United States)

    Background: Inhaled endotoxin (LPS) is associated with airway neutrophilic (PMN) inflammation in both asthmatic and control subjects, with asthmatic subjects demonstrating possibly higher sensitivity. CD14 is the principal receptor mediating LPS responses in vivo. It is unkown ...

  6. Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs.

    Directory of Open Access Journals (Sweden)

    Julie G Ledford

    Full Text Available Surfactant protein-A (SP-A has well-established functions in reducing bacterial and viral infections but its role in chronic lung diseases such as asthma is unclear. Mycoplasma pneumoniae (Mp frequently colonizes the airways of chronic asthmatics and is thought to contribute to exacerbations of asthma. Our lab has previously reported that during Mp infection of non-allergic airways, SP-A aides in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated response and, in allergic mice, SP-A regulates eosinophilic infiltration and inflammation of the airway. In the current study, we used an in vivo model with wild type (WT and SP-A(-/- allergic mice challenged with the model antigen ovalbumin (Ova that were concurrently infected with Mp (Ova+Mp to test the hypothesis that SP-A ameliorates Mp-induced stimulation of eosinophils. Thus, SP-A could protect allergic airways from injury due to release of eosinophil inflammatory products. SP-A deficient mice exhibit significant increases in inflammatory cells, mucus production and lung damage during concurrent allergic airway disease and infection (Ova+Mp as compared to the WT mice of the same treatment group. In contrast, SP-A deficient mice have significantly decreased Mp burden compared to WT mice. The eosinophil specific factor, eosinophil peroxidase (EPO, which has been implicated in pathogen killing and also in epithelial dysfunction due to oxidative damage of resident lung proteins, is enhanced in samples from allergic/infected SP-A(-/- mice as compared to WT mice. In vitro experiments using purified eosinophils and human SP-A suggest that SP-A limits the release of EPO from Mp-stimulated eosinophils thereby reducing their killing capacity. These findings are the first to demonstrate that although SP-A interferes with eosinophil-mediated biologic clearance of Mp by mediating the interaction of Mp with eosinophils, SP-A simultaneously benefits the airway by limiting inflammation

  7. Fungal Microbiota in Chronic Airway Inflammatory Disease and Emerging Relationships with the Host Immune Response

    Directory of Open Access Journals (Sweden)

    Irene Zhang

    2017-12-01

    Full Text Available The respiratory tract is a complex system that is inhabited by niche-specific communities of microbes including bacteria, fungi, and viruses. These complex microbial assemblages are in constant contact with the mucosal immune system and play a critical role in airway health and immune homeostasis. Changes in the composition and diversity of airway microbiota are frequently observed in patients with chronic inflammatory diseases including chronic rhinosinusitis (CRS, cystic fibrosis, allergy, and asthma. While the bacterial microbiome of the upper and lower airways has been the focus of many recent studies, the contribution of fungal microbiota to inflammation is an emerging research interest. Within the context of allergic airway disease, fungal products are important allergens and fungi are potent inducers of inflammation. In addition, murine models have provided experimental evidence that fungal microbiota in peripheral organs, notably the gastrointestinal (GI tract, influence pulmonary health. In this review, we explore the role of the respiratory and GI microbial communities in chronic airway inflammatory disease development with a specific focus on fungal microbiome interactions with the airway immune system and fungal-bacterial interactions that likely contribute to inflammatory disease. These findings are discussed in the context of clinical and immunological features of fungal-mediated disease in CRS, allergy, and asthmatic patients. While this field is still nascent, emerging evidence suggests that dysbiotic fungal and bacterial microbiota interact to drive or exacerbate chronic airway inflammatory disease.

  8. Florfenicol inhibits allergic airway inflammation in mice by p38 MAPK-mediated phosphorylation of GATA 3.

    Science.gov (United States)

    Xinxin, Ci; Chi, Chen; Xiao, Chu; Xue, Xu; Yongjun, Yang; Junqing, Cui; Xuming, Deng

    2011-02-01

    Florfenicol has been shown to possess anti-inflammatory activity. However, its possible use for asthma has not yet been studied. First we investigated the anti-inflammatory properties of florfenicol using mice asthma model. BALB/c mice were immunized and challenged by ovalbumin. Treatment with florfenicol caused a marked reduction in inflammatory cells and three Th2 type cytokines in the bronchoalveolar lavage fluids of mice. The levels of ovalbumin-specific IgE and airway hyperresponsiveness were significantly altered after treatment with florfenicol. Histological studies using H&E and AB-PAS staining demonstrate that florfenicol substantially inhibited ovalbumin-induced inflammatory cells infiltration in lung tissue and goblet cell hyperplasia in the airway. These results were similar to those obtained with dexamethasone treatment. We then investigated which signal transduction mechanisms could be implicated in florfenicol activity. Our results suggested that the protective effect of florfenicol was mediated by the inhibition of the p38 MAPK-mediated phosphorylation of GATA 3. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. The involvement of central nervous system histamine receptors in psychological stress-induced exacerbation of allergic airway inflammation in mice.

    Science.gov (United States)

    Miyasaka, Tomomitsu; Okuyama-Dobashi, Kaori; Masuda, Chiaki; Iwami, Shunya; Sato, Miki; Mizoguchi, Hirokazu; Kawano, Tasuku; Ohkawara, Yuichi; Sakurada, Shinobu; Takayanagi, Motoaki; Ohno, Isao

    2016-09-01

    Psychological stress is one of the major risk factors for asthma exacerbation. Although histamine in the brain acts as an excitatory and inhibitory neurotransmitter associated with psychological stress, the contribution of brain histamine to psychological stress-induced exacerbation of asthma remains unclear. The objective of this study was to investigate the role of histamine receptors in the CNS on stress induced asthma aggravation. We monitored the numbers of inflammatory cells and interleukin (IL)-13 levels in bronchoalveolar lavage fluid, airway responsiveness to inhaled methacholine, mucus secretion in airway epithelial cells, and antigen-specific IgE contents in sera in a murine model of stress-induced asthma treated with epinastine (an H1R antagonist), thioperamide (an H3/4R antagonist), or solvent. All indicators of stress-induced asthma exacerbation were significantly reduced in stressed mice treated with epinastine compared with those treated with solvent, whereas treatment with thioperamide did not reduce the numbers of inflammatory cells in the stressed mice. These results suggest that H1R, but not H3/4R, may be involved in stress-induced asthma exacerbations in the central nervous system. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  10. Bronchial asthma, allergic rhinitis and cholecystectomy: An ...

    African Journals Online (AJOL)

    Background: Gallbladder has not been associated with any allergic condition what so ever. However, certain patients with bronchial asthma and cholelithiasis have reported to the author improvement in their asthmatic attack after cholecystectomy. Methods: This was an observational study on 22 bronchial asthma or allergic ...

  11. Synthetic Nanoparticles That Promote Tumor Necrosis Factor Receptor 2 Expressing Regulatory T Cells in the Lung and Resistance to Allergic Airways Inflammation

    Directory of Open Access Journals (Sweden)

    Rohimah Mohamud

    2017-12-01

    Full Text Available Synthetic glycine coated 50 nm polystyrene nanoparticles (NP (PS50G, unlike ambient NP, do not promote pulmonary inflammation, but instead, render lungs resistant to the development of allergic airway inflammation. In this study, we show that PS50G modulate the frequency and phenotype of regulatory T cells (Treg in the lung, specifically increasing the proportion of tumor necrosis factor 2 (TNFR2 expressing Treg. Mice pre-exposed to PS50G, which were sensitized and then challenged with an allergen a month later, preferentially expanded TNFR2+Foxp3+ Treg, which further expressed enhanced levels of latency associated peptide and cytotoxic T-lymphocyte associated molecule-4. Moreover, PS50G-induced CD103+ dendritic cell activation in the lung was associated with the proliferative expansion of TNFR2+Foxp3+ Treg. These findings provide the first evidence that engineered NP can promote the selective expansion of maximally suppressing TNFR2+Foxp3+ Treg and further suggest a novel mechanism by which NP may promote healthy lung homeostasis.

  12. Mangifera indica L. extract (Vimang) and mangiferin reduce the airway inflammation and Th2 cytokines in murine model of allergic asthma.

    Science.gov (United States)

    Rivera, Dagmar García; Hernández, Ivones; Merino, Nelson; Luque, Yilian; Álvarez, Alina; Martín, Yanet; Amador, Aylin; Nuevas, Lauro; Delgado, René

    2011-10-01

    The aim was to study the effects of Mangifera indica extract and its major component mangiferin on lung inflammation response and Th2 cytokine production using a murine experimental model of allergic asthma. BALB/c mice were intraperitoneally sensitized with 10 µg of ovoalbumin (OVA) adsorbed on aluminium hydroxide on days 0, 7 and 14. Seven days after the last injection, the mice were challenged with 2% aerosolized OVA inhalation for 30 min beginning on day 21 and continuing until day 24. To evaluate the protective effect, mice were orally treated with M. indica extract (50, 100 or 250 mg/kg) or mangiferin (50 mg/kg) from days 0 to 24. Anti-OVA immunoglobulin E, interleukin (IL)-4 and IL-5 were determined by ELISA and lungs were analysed by histology. M. indica extract and mangiferin produced a marked reduction of airway inflammation around vessels and bronchi, inhibition of IL-4 and IL-5 cytokines in bronchoalveolar lavage fluid and lymphocyte culture supernatant, IgE levels and lymphocyte proliferation. This is the first pre-clinical report of the anti-inflammatory properties of M. indica extract and mangiferin in experimental asthma and it could be an important part of pre-clinical requirement necessary for its use to complement the treatment of this complex disease. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  13. Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice

    DEFF Research Database (Denmark)

    Matheu, Victor; Treschow, Alexandra; Teige, Ingrid

    2005-01-01

    by therapy with CpG-ODN is only slightly and partially dependent on IFN-beta, while IFN-beta is not an absolute requirement for suppression of airway eosinophilia and IgE. Furthermore, our finding of mild synovitis is a warning for possible negative effects of CpG-ODN vaccination....... of CpG-ODN is not known. OBJECTIVE: Here, we aimed to elucidate the role of IFN-beta in the anti-allergic effect of CpG motifs. METHODS: We assessed the immune response in OVA-primed/OVA-challenged IFN-beta knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment......BACKGROUND: CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects...

  14. Role of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma

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    Chun Jerold

    2009-11-01

    Full Text Available Abstract Background Lysophosphatidic acid (LPA plays a critical role in airway inflammation through G protein-coupled LPA receptors (LPA1-3. We have demonstrated that LPA induced cytokine and lipid mediator release in human bronchial epithelial cells. Here we provide evidence for the role of LPA and LPA receptors in Th2-dominant airway inflammation. Methods Wild type, LPA1 heterozygous knockout mice (LPA1+/-, and LPA2 heterozygous knockout mice (LPA2+/- were sensitized with inactivated Schistosoma mansoni eggs and local antigenic challenge with Schistosoma mansoni soluble egg Ag (SEA in the lungs. Bronchoalveolar larvage (BAL fluids and lung tissues were collected for analysis of inflammatory responses. Further, tracheal epithelial cells were isolated and challenged with LPA. Results BAL fluids from Schistosoma mansoni egg-sensitized and challenged wild type mice (4 days of challenge showed increase of LPA level (~2.8 fold, compared to control mice. LPA2+/- mice, but not LPA1+/- mice, exposed to Schistosoma mansoni egg revealed significantly reduced cell numbers and eosinophils in BAL fluids, compared to challenged wild type mice. Both LPA2+/- and LPA1+/- mice showed decreases in bronchial goblet cells. LPA2+/- mice, but not LPA1+/- mice showed the decreases in prostaglandin E2 (PGE2 and LPA levels in BAL fluids after SEA challenge. The PGE2 production by LPA was reduced in isolated tracheal epithelial cells from LPA2+/- mice. These results suggest that LPA and LPA receptors are involved in Schistosoma mansoni egg-mediated inflammation and further studies are proposed to understand the role of LPA and LPA receptors in the inflammatory process.

  15. Effects of Isoprene- and Toluene-Generated Smog on Allergic ...

    Science.gov (United States)

    Reactions of organic compounds with nitric oxide (NO) and sunlight produce complex mixtures of pollutants including secondary organic aerosol (SOA), ozone (O3), nitrogen dioxide (NO2), and reactive aldehydes. The health effects of these photochemical smog mixtures in susceptible populations including asthmatics are unclear. We assessed effects of smog generated from mixtures of NO with isoprene (IS) or toluene (TL) on allergic inflammatory responses in Balb/cJ mice. House dust mite (HDM)-sensitized or control mice were all challenged with HDM intranasally 1 d prior to whole-body inhalation exposure to IS (chamber average 509 ppb NO2, 246 ppb O3, and 160 g/m3 SOA), TL (217 ppb NO2, 129 ppb O3, and 376 g/m3 SOA), or HEPA-filtered air (4 h/d for 2 days). Mice were necropsied within 3 h after the second exposure (2 d post-HDM challenge). Assessment of breathing parameters during exposure with double-chamber plethysmography showed a trend for increased specific airway resistance and decreased minute volume during the second day of TL exposure in both non-allergic and HDM-allergic mice. HDM-allergic air-exposed mice had significant increases in numbers of bronchoalveolar lavage (BAL) alveolar macrophages (AM) and eosinophils (EO), and trends for increases in BAL indices of lung injury in comparison with non-allergic air-exposed mice. Exposure to either IS or TL attenuated the increases in AM, EO, and lung injury markers in HDM-allergic mice. The results of this

  16. Diagnosing Allergic Rhinitis.

    Science.gov (United States)

    Scadding, Glenis K; Scadding, Guy W

    2016-05-01

    Allergic rhinitis (AR) is the most common immunologic disease in industrialized societies and has a significant impact on quality of life. Most asthmatics also have rhinitis. AR may present with comorbidities, including chronic otitis media with effusion, cough, and pollen-food cross-reactivity. AR may occur in isolation or be part of a mixed rhinitis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. The long-term programming effect of maternal 25-hydroxyvitamin D in pregnancy on allergic airway disease and lung function in offspring after 20 to 25 years of follow-up.

    Science.gov (United States)

    Hansen, Susanne; Maslova, Ekaterina; Strøm, Marin; Linneberg, Allan; Halldorsson, Thorhallur I; Granström, Charlotta; Dahl, Ronald; Hoffmann, Hans Jürgen; Olsen, Sjurdur F

    2015-07-01

    High prenatal vitamin D status has been linked to decreased risk of atopic diseases in early childhood, but whether such relations persist until adulthood has not been explored. We sought to examine the association between maternal 25-hydryxovitamin D (25[OH]D) concentrations and outcomes of allergic airway disease and lung function in offspring with 20 to 25 years of follow-up. In a prospective birth cohort with 965 pregnant women enrolled in 1988-1989, maternal 25(OH)D concentrations were quantified in serum from gestational week 30 (n = 850 [88%]). Offspring were followed in nationwide registries with complete follow-up to the age of 25 years (n = 850 [100%]). Additionally, at age 20 years, outcomes of allergic airway disease and lung function were assessed in a subset of offspring by using blood samples and spirometry (n = 410 [45%]) and a questionnaire (n = 641 [70%]). Exposure to a high maternal 25(OH)D concentration (≥125 nmol/L) was associated with an increased risk of asthma hospitalizations in offspring (hazard ratio [HR], 1.81; 95% CI, 0.78-4.16) during 25 years of follow-up compared with the reference group (75-hospitalizations (HR, 0.29; 95% CI, 0.08-1.02) and asthma medication use (HR, 0.58; 95% CI, 0.35-0.95) in those exposed to a low maternal 25(OH)D concentration (effect of a high maternal 25(OH)D concentration on outcomes of allergic airway disease and lung function at 20 to 25 years of age. In contrast, a high maternal 25(OH)D concentration might be associated with an increased risk of allergic diseases in offspring. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis: MR Imaging of Airway Mucus Contrasts as a Tool for Diagnosis.

    Science.gov (United States)

    Dournes, Gaël; Berger, Patrick; Refait, John; Macey, Julie; Bui, Stephanie; Delhaes, Laurence; Montaudon, Michel; Corneloup, Olivier; Chateil, Jean-François; Marthan, Roger; Fayon, Michaël; Laurent, François

    2017-10-01

    Purpose To assess the diagnostic accuracy of mucus contrast characterization by using magnetic resonance (MR) imaging to discriminate allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF). Materials and Methods The study was approved by the local Ethics Committee, and all patients or their parents gave written informed consent. One hundred ten consecutive patients with CF were screened between January 2014 and July 2015. All patients underwent a non-contrast material-enhanced MR protocol that included routine T1-weighted and T2-weighted sequences. The presence of mucus with both high T1 and low T2 signal intensities and the so-called inverted mucoid impaction signal (IMIS) sign was qualitatively and quantitatively assessed by two physicians who were blinded to all other data. The reference standard for a diagnosis of ABPA was the criteria of the Cystic Fibrosis Foundation Consensus Conference. ABPA status was followed up for 1 year. Reproducibility was assessed by using the κ test, correlation was assessed by using the Spearman coefficient, and diagnostic accuracy was assessed by calculating the sensitivity and specificity of IMIS. Results One hundred eight patients with CF were included (mean age, 20 years ± 11 [standard deviation]; range, 6-53 years): 18 patients with ABPA and 90 patients without ABPA. At the lobar level, inter- and intrareader reproducibility were very good (κ > 0.90). IMIS had 94% sensitivity (95% confidence interval [CI]: 73%, 99%) and 100% specificity (95% CI: 96%, 100%) for the diagnosis of ABPA. A complete resolution of IMIS was observed in patients with ABPA after 3 months of specific treatment that was significantly correlated with decrease in total immunoglobulin E level (ρ = 0.47; P = .04). Conclusion The IMIS sign was both specific and sensitive for the diagnosis of ABPA in CF. Allergic fungal inflammation appears to induce characteristic modifications of mucus contrasts that are assessable by using a noninvasive

  19. Effect ofAngelica glaucaessential oil on allergic airway changes induced by histamine and ovalbumin in experimental animals.

    Science.gov (United States)

    Sharma, Shilpa; Rasal, Vijaykumar P; Patil, Paragouda A; Joshi, Rajesh K

    2017-01-01

    Angelica glauca Edgew (Apiaceae) is used in traditional medicine for treatment of several diseases including bronchial asthma. The present investigation was aimed to evaluate broncho-relaxant activity of A. glauca essential oil in histamine and ovalbumin (OVA)-induced broncho constriction in experimental animals. Airway was induced using histamine aerosol in guinea pigs ( n = 24) and OVA aerosol in albino mice ( n = 24). The number of inflammatory cells, namely, absolute eosinophils count in blood, total immunoglobulin E (IgE) in serum, eosinophils, and neutrophils in bronchoalveolar lavage fluid (BALF) and histopathological examination of lung tissues were investigated in A. glauca oil and dexamethasone-treated groups. A. glauca oil 200 μL/kg was given orally, and dexamethasone 2 mg/kg was given intraperitoneal. Both the treatments were repeated daily for 7 days. Results were analyzed by one-way ANOVA, and P ≤ 0.05 was considered statistically significant. Treatment with A. glauca essential oil significantly ( P histamine-induced guinea pigs. Oral treatment of A. glauca oil significantly ( P histamine and OVA-induced bronchoconstriction in animals. The traditional use of A. glauca against asthma could be attributed to its bronchodilator property as observed in the present study.

  20. Can asthmatic subjects dive?

    Directory of Open Access Journals (Sweden)

    Yochai Adir

    2016-06-01

    Full Text Available Recreational diving with self-contained underwater breathing apparatus (scuba has grown in popularity. Asthma is a common disease with a similar prevalence in divers as in the general population. Due to theoretical concern about an increased risk for pulmonary barotrauma and decompression sickness in asthmatic divers, in the past the approach to asthmatic diver candidates was very conservative, with scuba disallowed. However, experience in the field and data in the current literature do not support this dogmatic approach. In this review the theoretical risk factors of diving with asthma, the epidemiological data and the recommended approach to the asthmatic diver candidate will be described.

  1. Genetics Home Reference: allergic asthma

    Science.gov (United States)

    ... breathing difficulty. These episodes, sometimes referred to as asthma attacks, are triggered by irritation of the inflamed airways. ... tobacco smoke, in people with allergic asthma . An asthma attack is characterized by tightening of the muscles around ...

  2. Exhaled carbon monoxide in asthmatics: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Huang Mao

    2010-04-01

    Full Text Available Abstract Background The non-invasive assessment of airway inflammation is potentially advantageous in asthma management. Exhaled carbon monoxide (eCO measurement is cheap and has been proposed to reflect airway inflammation and oxidative stress but current data are conflicting. The purpose of this meta-analysis is to determine whether eCO is elevated in asthmatics, is regulated by steroid treatment and reflects disease severity and control. Methods A systematic search for English language articles published between 1997 and 2009 was performed using Medline, Embase and Cochrane databases. Observational studies comparing eCO in non-smoking asthmatics and healthy subjects or asthmatics before and after steroid treatment were included. Data were independently extracted by two investigators and analyzed to generate weighted mean differences using either a fixed or random effects meta-analysis depending upon the degree of heterogeneity. Results 18 studies were included in the meta-analysis. The eCO level was significantly higher in asthmatics as compared to healthy subjects and in intermittent asthma as compared to persistent asthma. However, eCO could not distinguish between steroid-treated asthmatics and steroid-free patients nor separate controlled and partly-controlled asthma from uncontrolled asthma in cross-sectional studies. In contrast, eCO was significantly reduced following a course of corticosteroid treatment. Conclusions eCO is elevated in asthmatics but levels only partially reflect disease severity and control. eCO might be a potentially useful non-invasive biomarker of airway inflammation and oxidative stress in nonsmoking asthmatics.

  3. ASCORBID ACID IS DECREASED IN INDUCED SPUTUM OF MILD ASTHMATICS

    Science.gov (United States)

    ABSTRACTEvidence suggests that the antioxidant ascorbic acid (AA), plays an essential role in defending against oxidant attack in the airways. Decreased levels of AA have been reported in asthmatics but not at the site directly proximal to asthma pathology, i.e. the bronchial...

  4. Exploratory study comparing dysautonomia between asthmatic and non-asthmatic elite swimmers

    Directory of Open Access Journals (Sweden)

    M. Couto

    2015-01-01

    Full Text Available Background: Dysautonomia has been independently associated with training and exercise-induced bronchoconstriction. In addition, neurogenic airway inflammation was recently associated with swimmers-asthma. We aimed to assess the relation between autonomic nervous system and airway responsiveness of asthmatic elite swimmers. Methods: Twenty-seven elite swimmers, 11 of whom had asthma, were enrolled in this exploratory cross-sectional study. All performed spirometry with bronchodilation, skin prick tests and methacholine challenge according to the guidelines. Pupillometry was performed using PLR-200™ Pupillometer. One pupil light response curve for each eye was recorded and the mean values of pupil's maximal and minimal diameters, percentage of constriction, average and maximum constriction velocities (parasympathetic parameters, dilation velocity, and total time to recover 75% of the initial size (sympathetic parameters were used for analysis. Asthma was defined using IOC-MC criteria; subjects were divided into airway hyperesponsiveness (AHR severity according to methacholine PD20 in: no AHR, borderline, mild, moderate and severe AHR. Differences for pupillary parameters between groups and after categorization by AHR severity were assessed using SPSS 20.0 (p ≤ 0.05. In individuals with clinically relevant AHR, correlation between PD20 and pupillary parameters was investigated with Spearman's correlation test. Results: No statistically significant differences were observed between asthmatic and non-asthmatic swimmers regarding parasympathetic parameters. When stratified by AHR, maximal and minimal diameters and percentage of constriction were significantly lower among those with severe AHR. Among swimmers with clinically relevant AHR (n = 18, PD20 correlated with parasympathetic activity: maximal (r = 0.67, p = 0.002 and minimal diameters (r = 0.75, p < 0.001, percentage of constriction (r

  5. Inhibition of NF-κB Expression and Allergen-induced Airway Inflammation in a Mouse Allergic Asthma Model by Andrographolide

    OpenAIRE

    Li, Jing; Luo, Li; Wang, Xiaoyun; Liao, Bin; Li, Guoping

    2009-01-01

    Andrographolide from traditional Chinese herbal medicines previously showed it possesses a strong anti-inflammatory activity. In present study, we investigated whether Andrographolide could inhibit allergen-induced airway inflammation and airways hyper-responsiveness and explored the mechanism of Andrographolide on allergen-induced airway inflammation and airways hyper-responsiveness. After sensitized and challenged by ovalbumin, the BALB/c mice were administered intraperitoneally with Androg...

  6. An intranasal selective antisense oligonucleotide impairs lung cyclooxygenase-2 production and improves inflammation, but worsens airway function, in house dust mite sensitive mice

    Directory of Open Access Journals (Sweden)

    Pujols Laura

    2008-11-01

    Full Text Available Abstract Background Despite its reported pro-inflammatory activity, cyclooxygenase (COX-2 has been proposed to play a protective role in asthma. Accordingly, COX-2 might be down-regulated in the airway cells of asthmatics. This, together with results of experiments to assess the impact of COX-2 blockade in ovalbumin (OVA-sensitized mice in vivo, led us to propose a novel experimental approach using house dust mite (HDM-sensitized mice in which we mimicked altered regulation of COX-2. Methods Allergic inflammation was induced in BALBc mice by intranasal exposure to HDM for 10 consecutive days. This model reproduces spontaneous exposure to aeroallergens by asthmatic patients. In order to impair, but not fully block, COX-2 production in the airways, some of the animals received an intranasal antisense oligonucleotide. Lung COX-2 expression and activity were measured along with bronchovascular inflammation, airway reactivity, and prostaglandin production. Results We observed impaired COX-2 mRNA and protein expression in the lung tissue of selective oligonucleotide-treated sensitized mice. This was accompanied by diminished production of mPGE synthase and PGE2 in the airways. In sensitized mice, the oligonucleotide induced increased airway hyperreactivity (AHR to methacholine, but a substantially reduced bronchovascular inflammation. Finally, mRNA levels of hPGD synthase remained unchanged. Conclusion Intranasal antisense therapy against COX-2 in vivo mimicked the reported impairment of COX-2 regulation in the airway cells of asthmatic patients. This strategy revealed an unexpected novel dual effect: inflammation was improved but AHR worsened. This approach will provide insights into the differential regulation of inflammation and lung function in asthma, and will help identify pharmacological targets within the COX-2/PG system.

  7. Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13–Suppressed Elastin in Airway Fibroblasts in Asthma

    Science.gov (United States)

    Slade, David; Church, Tony D.; Francisco, Dave; Heck, Karissa; Sigmon, R. Wesley; Ghio, Michael; Murillo, Anays; Firszt, Rafael; Lugogo, Njira L.; Que, Loretta; Sunday, Mary E.; Kraft, Monica

    2016-01-01

    Elastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV1, 89 ± 3% predicted) and 30 normal control subjects (FEV1, 102 ± 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert’s resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV1/FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13–induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13–induced suppression of ELN expression in airway fibroblasts. PMID:26074138

  8. Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13-Suppressed Elastin in Airway Fibroblasts in Asthma.

    Science.gov (United States)

    Ingram, Jennifer L; Slade, David; Church, Tony D; Francisco, Dave; Heck, Karissa; Sigmon, R Wesley; Ghio, Michael; Murillo, Anays; Firszt, Rafael; Lugogo, Njira L; Que, Loretta; Sunday, Mary E; Kraft, Monica

    2016-01-01

    Elastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV1, 89 ± 3% predicted) and 30 normal control subjects (FEV1, 102 ± 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert's resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV1/FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13-induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13-induced suppression of ELN expression in airway fibroblasts.

  9. A Zinc Chelator TPEN Attenuates Airway Hyperresponsiveness Airway Inflammation in Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Satoru Fukuyama

    2011-01-01

    Conclusions: In pulmonary allergic inflammation induced in mice immunized with antigen without alum, zinc chelator inhibits airway inflammation and hyperresponsiveness. These findings suggest that zinc may be a therapeutic target of allergic asthma.

  10. Epidemiology of pollution-induced airway disease in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, T. [Japan Clinical Allergy Inst., Tokyo (Japan)

    1997-12-31

    Air pollution has been implicated as one of the factors responsible for the increased incidence of allergic diseases seen over recent years. Epidemiological studies in Japan demonstrate that atopic subjects living in urban areas are more likely to suffer from the effects of air pollution, with increased coughing, sputum production, wheezing and throat irritation. Furthermore, animal studies show that high concentrations of pollutant gases can promote airway sensitization. The incidence of allergic Rhinitis and asthma have been shown to be greater in areas where there is heavy traffic and hence high levels of automobile exhaust emissions. Intranasal administration of diesel exhaust particles in mice produces a stimulatory effect on immunoglobulin E production, and a similar finding has also been shown with suspended particulate matter in air. Air pollutants, such as ozone and nitrogen dioxide (NO{sub 2}), have been shown to stimulate the production of granulocyte-macrophage colony stimulating factor, which may play a vital role in airway hyperreactivity and asthma. In comparative studies of asthma in urban and rural areas, history of airway infection and a younger age of onset were found to be significantly greater in urban areas. When the asthmatic patients were divided into two groups according to environmental NO{sub 2} levels (group I: NO{sub 2}>30 ppb, group II: NO{sub 2}<30 ppb), no significant difference regarding the various parameters was noted between the two groups, except for a greater severity of asthma in adults in group I, and a greater severity in chrildren in group II. These studies imply that air pollution may be one reason for the increase in allergic diseases in Japan, but a definitive conclusion cannot be drawn, and further, investigation is warranted. (au)

  11. Exploratory study comparing dysautonomia between asthmatic and non-asthmatic elite swimmers.

    Science.gov (United States)

    Couto, M; Silva, D; Santos, P; Queirós, S; Delgado, L; Moreira, A

    2015-01-01

    Dysautonomia has been independently associated with training and exercise-induced bronchoconstriction. In addition, neurogenic airway inflammation was recently associated with swimmers-asthma. We aimed to assess the relation between autonomic nervous system and airway responsiveness of asthmatic elite swimmers. Twenty-seven elite swimmers, 11 of whom had asthma, were enrolled in this exploratory cross-sectional study. All performed spirometry with bronchodilation, skin prick tests and methacholine challenge according to the guidelines. Pupillometry was performed using PLR-200™ Pupillometer. One pupil light response curve for each eye was recorded and the mean values of pupil's maximal and minimal diameters, percentage of constriction, average and maximum constriction velocities (parasympathetic parameters), dilation velocity, and total time to recover 75% of the initial size (sympathetic parameters) were used for analysis. Asthma was defined using IOC-MC criteria; subjects were divided into airway hyperesponsiveness (AHR) severity according to methacholine PD20 in: no AHR, borderline, mild, moderate and severe AHR. Differences for pupillary parameters between groups and after categorization by AHR severity were assessed using SPSS 20.0 (p ≤ 0.05). In individuals with clinically relevant AHR, correlation between PD20 and pupillary parameters was investigated with Spearman's correlation test. No statistically significant differences were observed between asthmatic and non-asthmatic swimmers regarding parasympathetic parameters. When stratified by AHR, maximal and minimal diameters and percentage of constriction were significantly lower among those with severe AHR. Among swimmers with clinically relevant AHR (n = 18), PD20 correlated with parasympathetic activity: maximal (r = 0.67, p = 0.002) and minimal diameters (r = 0.75, pdysautonomia and AHR in asthmatic swimmers. Copyright © 2014 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S

  12. Airway Remodelling in Asthma: From Benchside to Clinical Practice

    Directory of Open Access Journals (Sweden)

    Céline Bergeron

    2010-01-01

    Full Text Available Airway remodelling refers to the structural changes that occur in both large and small airways relevant to miscellaneous diseases including asthma. In asthma, airway structural changes include subepithelial fibrosis, increased smooth muscle mass, gland enlargement, neovascularization and epithelial alterations. Although controversial, airway remodelling is commonly attributed to an underlying chronic inflammatory process. These remodelling changes contribute to thickening of airway walls and, consequently, lead to airway narrowing, bronchial hyper-responsiveness, airway edema and mucous hypersecretion. Airway remodelling is associated with poor clinical outcomes among asthmatic patients. Early diagnosis and prevention of airway remodelling has the potential to decrease disease severity, improve control and prevent disease expression. The relationship between structural changes and clinical and functional abnormalities clearly deserves further investigation. The present review briefly describes the characteristic features of airway remodelling observed in asthma, its clinical consequences and relevance for physicians, and its modulation by therapeutic approaches used in the treatment of asthmatic patients.

  13. The effect of IL-13 and IL-13R130Q, a naturally occurring IL-13 polymorphism, on the gene expression of human airway smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Amegadzie Bernard

    2005-01-01

    Full Text Available Abstract Background Growing evidence shows that interleukin 13 (IL-13 may play an essential role in the development of airway inflammation and bronchial hyper-responsiveness (BHR, two defining features of asthma. Although the underlying mechanisms remain unknown, a number of reports have shown that IL-13 may exert its deleterious effects in asthma by directly acting on airway resident cells, including epithelial cells and airway smooth muscle cells. In this report, we hypothesize that IL-13 may participate in the pathogenesis of asthma by activating a set of "pro-asthmatic" genes in airway smooth muscle (ASM cells. Methods Microarray technology was used to study the modulation of gene expression of airway smooth muscle by IL-13 and IL-13R130Q. TaqMan™ Real Time PCR and flow cytometry was used to validate the gene array data. Results IL-13 and the IL-13 polymorphism IL-13R130Q (Arg130Gln, recently associated with allergic asthma, seem to modulate the same set of genes, which encode many potentially interesting proteins including vascular cellular adhesion molecule (VCAM-1, IL-13Rα2, Tenascin C and Histamine Receptor H1, that may be relevant for the pathogenesis of asthma. Conclusions The data supports the hypothesis that gene modulation by IL-13 in ASM may be essential for the events leading to the development of allergic asthma.

  14. Downregulation of integrin β4 decreases the ability of airway epithelial cells to present antigens.

    Directory of Open Access Journals (Sweden)

    Chi Liu

    Full Text Available Airway epithelial cells have been demonstrated to be accessory antigen presentation cells (APC capable of activating T cells and may play an important role in the development of allergic airway inflammation of asthma. In asthmatic airways, loss of expression of the adhesion molecule integrin β4 (ITGB4 and an increase in Th2 inflammation bias has been observed in our previous study. Given that ITGB4 is engaged in multiple signaling pathways, we studied whether disruption of ITGB4-mediated cell adhesion may contribute to the adaptive immune response of epithelial cells, including their ability to present antigens, induce the activate and differentiate of T cells. We silenced ITGB4 expression in bronchial epithelial cells with an effective siRNA vector and studied the effects of ITGB4 silencing on the antigen presentation ability of airway epithelial cells. T cell proliferation and cytokine production was investigated after co-culturing with ITGB4-silenced epithelial cells. Surface expression of B7 homologs and the major histocompatibility complex (MHC class II was also detected after ITGB4 was silenced. Our results demonstrated that silencing of ITGB4 resulted in impaired antigen presentation processes and suppressed T cell proliferation. Meanwhile, decrease in Th1 cytokine production and increase in Th17 cytokine production was induced after co-culturing with ITGB4-silenced epithelial cells. Moreover, HLA-DR was decreased and the B7 homologs expression was different after ITGB4 silencing. Overall, this study suggested that downregulation of ITGB4 expression in airway epithelial cells could impair the antigen presentation ability of these cells, which further regulate airway inflammation reaction in allergic asthma.

  15. Effects of ASM-024, a modulator of acetylcholine receptor function, on airway responsiveness and allergen-induced responses in patients with mild asthma.

    Science.gov (United States)

    Boulet, Louis-Philippe; Gauvreau, Gail M; Cockcroft, Donald W; Davis, Beth; Vachon, Luc; Cormier, Yvon; O'Byrne, Paul M

    2015-01-01

    To evaluate the safety, tolerability and clinical activity of ASM-024, a new cholinergic compound with dual nicotinic and muscarinic activity, in mild allergic asthma. The present study involved 24 stable, mild allergic asthmatic subjects. In a cross-over design, ASM-024 (50 mg or 200 mg) or placebo were administered once daily by nebulization over three periods of nine consecutive days separated by a three-week washout. The effect of each treatment on the forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% decline in FEV1 (PC20), early and late asthmatic responses, and allergen-induced inflammation were measured. Seventeen subjects completed the study. During treatment with ASM-024 at 50 mg or 200 mg, the PC20 value increased respectively from a mean (± SD) 2.56±3.86 mg/mL to 4.11 mg/mL (P=0.007), and from 3.12±4.37 mg/mL to 5.23 mg/mL (P=0.005) (no change with placebo). On day 7 (day preceding allergen challenge), postdosing FEV1 increased by 2.0% with 50 mg (P=0.005) and 1.9% with 200 mg (P=0.008) (placebo -1.1%). ASM-24 had no inhibitory effect on early and late asthmatic responses, nor on sputum eosinophil or neutrophil levels. ASM-024 induced no serious adverse events, but caused cough in 22% and 48% of the subjects with 50 mg and 200 mg, respectively, compared with 10% who were on placebo. ASM-024 did not inhibit allergen-induced asthmatic response and related airway inflammation, but reduced methacholine airway responsiveness and slightly improved lung function. The mechanism by which ASM-024 improves these outcomes requires further study.

  16. Effect of oral L-arginine on airway hyperresponsiveness to histamine in asthma

    NARCIS (Netherlands)

    de Gouw, H. W.; Verbruggen, M. B.; Twiss, I. M.; Sterk, P. J.

    1999-01-01

    Nitric oxide (NO) may exert protective properties within the airways of asthmatic patients. It was postulated that airways obstruction in asthma may be associated with endogenous NO deficiency caused by limited availability of NO synthase substrate. In a double blind, crossover study 14 asthmatic

  17. Effects of omalizumab therapy on allergic rhinitis: a pilot study.

    Science.gov (United States)

    Masieri, S; Cavaliere, C; Begvarfaj, E; Rosati, D; Minni, A

    2016-12-01

    The use of omalizumab, a humanized monoclonal antibody able to binding Ig-E, is currently authorized only for treatment of severe bronchial asthma. The use of omalizumab in other Ig-E related diseases is off-label, although some studies have provided promising results about it. The aim of this study was to evaluate if therapy with omalizumab in patients affected by asthma and allergic rhinitis has an impact also on allergic rhinitis-related symptoms. A longitudinal study was conducted on 11 patients affected by severe asthma and a periodic allergic rhinitis. Patients were treated with omalizumab for 24 weeks with a monthly subcutaneous administration at the dosage recommended by the current guidelines. We observed at the start and at the end of treatment: rhinitis symptoms using the Visual Analogue Scale (VAS); the state of nasal mucosa with fiberoptic nasal endoscopy; airways inflammation by measuring the Fractional Exhaled Nitric Oxide (FeNO); asthmatic symptomatology by means of the Asthma Control Test; the amount of total Ig-E in a blood sample; and the use of symptomatic drugs before and after treatment. VAS scores to measure general symptomatology and symptoms including nasal obstruction, rhinorrhea, itching and sneezing were significantly reduced. Turbinate hypertrophy was resolved in six of nine patients. Furthermore, eight patients (73%) reduced or eliminated the use of symptomatic drugs. Our data confirm the efficacy of omalizumab in the treatment of allergic rhinitis. Controlled studies will now have to be carried out to confirm these preliminary data and will specify indications for a very efficacious but still significantly expensive therapy.

  18. Increasing ventilation as an intervention in homes of asthmatic children

    DEFF Research Database (Denmark)

    Hogaard, Nina Viskum; Rubak, Sune Leisgaard Mørck; Halken, Susanne

    2016-01-01

    In children asthma is the most frequent chronic disease and house dust mite (HDM) allergy the most frequent cause of allergic asthma. Indoors most of the time, children are exposed to many indoor air pollutants that may act as asthma triggers. Reducing this exposure may improve asthma control...... in children. We conducted a double-blind, placebo-controlled intervention study with 46 asthmatic, house dust mite allergic children. The aim was to investigate the association between indoor air quality in homes and severity of asthma, in particular the effect of increased ventilation rate and expected lower...

  19. The Contribution of Allergen-Specific IgG to the Development of Th2-Mediated Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Jesse W. Williams

    2012-01-01

    Full Text Available In both human asthmatics and animal models of allergy, allergen-specific IgG can contribute to Th2-mediated allergic inflammation. Mouse models have elucidated an important role for IgG and Fc-gamma receptor (FcγR signaling on antigen presenting cells (APC for the induction of airway inflammation. These studies suggest a positive feedback loop between IgG produced by the adaptive B cell response and FcγR signaling on innate immune cells. Studies of IgG and FcγRs in humans with asthma or allergic lung disease have been more controversial. Some reports have identified associations between allergen-specific IgG and severity of allergic responses, while other studies have found associations of IgG subclass IgG4 with allergic tolerance. In this paper, we review the literature to help define the nature of IgG and FcγR signaling on innate immune cells and how it contributes to the development of allergic immune responses.

  20. Similar levels of nitric oxide in exhaled air in non-asthmatic rhinitis and asthma after bronchial allergen challenge

    NARCIS (Netherlands)

    Lopuhaä, C. E.; Koopmans, J. G.; Jansen, H. M.; van der Zee, J. S.

    2003-01-01

    Background: Nitric oxide in exhaled air (eNO) is elevated in allergic asthma compared with healthy subjects and has been proposed as a marker of bronchial inflammation. However, eNO is elevated to a lesser extent in allergic non-asthmatic rhinitis as well. Considering the distinctive clinical

  1. Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition.

    Science.gov (United States)

    Allen, Jodi C; Seidel, Petra; Schlosser, Tobias; Ramsay, Emma E; Ge, Qi; Ammit, Alaina J

    2012-01-01

    Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

  2. [The place of attack of beta-2 receptor stimulating bronchodilators. Fenoterol (Berotec) in allergic airway obstruction in dogs, hypersensitive to Ascaris suum].

    Science.gov (United States)

    Zimmermann, I; Bugalho de Almeida, A A; Walkenhorst, W; Ulmer, W T

    1980-04-15

    On dogs sensitive against Ascaris suum extract an increase of the airway resistance can be caused by challenge alone on the upper part or the lower part of the airways by Ascaris suum extract. Fenoterol as beta 2-receptor stimulator is capable to decrease this reaction by deposition of this drug on the upper part as on the lower part of the airways. The effect of Fenoterol on the upper part of the airways is much stronger and lasts much longer than on the lower part of the airways or by intravenous route. A direct effect of the beta 2-receptor stimulator Fenoterol on the sensoric part of the reflex way of the reflex bronchoconstriction must be considered. It will be also discussed that the local application of Fenoterol on the upper part of the airways may influence also the reaction of the bronchial muscles in the lower part of the airways without a direct resorptive-systemic effect. The relationship of these findings for the clinical situation on man has to be investigated.

  3. Allergic Bronchopulmonary Aspergillosis: A Perplexing Clinical Entity

    OpenAIRE

    Shah, Ashok; Panjabi, Chandramani

    2016-01-01

    In susceptible individuals, inhalation of Aspergillus spores can affect the respiratory tract in many ways. These spores get trapped in the viscid sputum of asthmatic subjects which triggers a cascade of inflammatory reactions that can result in Aspergillus-induced asthma, allergic bronchopulmonary aspergillosis (ABPA), and allergic Aspergillus sinusitis (AAS). An immunologically mediated disease, ABPA, occurs predominantly in patients with asthma and cystic fibrosis (CF). A set of criteria, ...

  4. Rhinosinusitis and the lower airways

    NARCIS (Netherlands)

    Hellings, Peter W.; Hens, Greet

    2009-01-01

    The interaction between upper and lower airway disease has been recognized for centuries, with recent studies showing a direct link between upper and airway inflammation in allergic patients. The mechanisms underlying the interaction between nasal and bronchial inflammation have primarily been

  5. Intra-luminal exposure of murine airways to peroxynitrite causes inflammation but not hyperresponsiveness

    NARCIS (Netherlands)

    Muijsers, RBR; van der Veeken, A; Habernickel, J; Folkerts, G; Postma, DS; Nijkamp, FP

    Objective and design: There is increasing evidence for the involvement of reactive nitrogen species like peroxynitrite (ONOO-) in airway pathology, for example during allergic airway inflammation. Therefore, the effect of peroxynitrite exposure on airway responsiveness and inflammation was studied.

  6. Noninvasive positive pressure ventilation in acute asthmatic attack

    Directory of Open Access Journals (Sweden)

    A. Soroksky

    2010-03-01

    Full Text Available Asthma is characterised by reversible airway obstruction. In most patients, control of disease activity is easily achieved. However, in a small minority, asthma may be fatal. Between the two extremes lie patients with severe asthmatic attacks, refractory to standard treatment. These patients are at an increased risk of recurrent severe attacks, with respiratory failure, and mechanical ventilation. Invasive mechanical ventilation of the asthmatic patient is associated with a higher risk of complications and, therefore, is a measure of last resort. Noninvasive positive pressure ventilation (NPPV is another treatment modality that may be beneficial in patients with severe asthmatic attack who are at an increased risk of developing respiratory failure. These patients have the potential to benefit from early respiratory support in the form of NPPV. However, reports of NPPV in asthmatic patients are scarce, and its usage in asthmatic attacks is, therefore, still controversial. Only a few reports of NPPV in asthma have been published over the last decade. These studies mostly involve small numbers of patients and those who have problematic methodology. In this article we review the available evidence for NPPV in asthma and try to formulate our recommendations for NPPV application in asthma based on the available evidence and reports.

  7. Allergen uptake, activation, and IL-23 production by pulmonary myeloid DCs drives airway hyperresponsiveness in asthma-susceptible mice.

    Directory of Open Access Journals (Sweden)

    Ian P Lewkowich

    Full Text Available Maladaptive, Th2-polarized inflammatory responses are integral to the pathogenesis of allergic asthma. As regulators of T cell activation, dendritic cells (DCs are important mediators of allergic asthma, yet the precise signals which render endogenous DCs "pro-asthmatic", and the extent to which these signals are regulated by the pulmonary environment and host genetics, remains unclear. Comparative phenotypic and functional analysis of pulmonary DC populations in mice susceptible (A/J, or resistant (C3H to experimental asthma, revealed that susceptibility to airway hyperresponsiveness is associated with preferential myeloid DC (mDC allergen uptake, and production of Th17-skewing cytokines (IL-6, IL-23, whereas resistance is associated with increased allergen uptake by plasmacytoid DCs. Surprisingly, adoptive transfer of syngeneic HDM-pulsed bone marrow derived mDCs (BMDCs to the lungs of C3H mice markedly enhanced lung IL-17A production, and rendered them susceptible to allergen-driven airway hyperresponsiveness. Characterization of these BMDCs revealed levels of antigen uptake, and Th17 promoting cytokine production similar to that observed in pulmonary mDCs from susceptible A/J mice. Collectively these data demonstrate that the lung environment present in asthma-resistant mice promotes robust pDC allergen uptake, activation, and limits Th17-skewing cytokine production responsible for driving pathologic T cell responses central to the development of allergen-induced airway hyperresponsiveness.

  8. Airway resistance at maximum inhalation as a marker of asthma and airway hyperresponsiveness

    Directory of Open Access Journals (Sweden)

    O'Connor George T

    2011-07-01

    Full Text Available Abstract Background Asthmatics exhibit reduced airway dilation at maximal inspiration, likely due to structural differences in airway walls and/or functional differences in airway smooth muscle, factors that may also increase airway responsiveness to bronchoconstricting stimuli. The goal of this study was to test the hypothesis that the minimal airway resistance achievable during a maximal inspiration (Rmin is abnormally elevated in subjects with airway hyperresponsiveness. Methods The Rmin was measured in 34 nonasthmatic and 35 asthmatic subjects using forced oscillations at 8 Hz. Rmin and spirometric indices were measured before and after bronchodilation (albuterol and bronchoconstriction (methacholine. A preliminary study of 84 healthy subjects first established height dependence of baseline Rmin values. Results Asthmatics had a higher baseline Rmin % predicted than nonasthmatic subjects (134 ± 33 vs. 109 ± 19 % predicted, p = 0.0004. Sensitivity-specificity analysis using receiver operating characteristic curves indicated that baseline Rmin was able to identify subjects with airway hyperresponsiveness (PC20 min % predicted, FEV1 % predicted, and FEF25-75 % predicted, respectively. Also, 80% of the subjects with baseline Rmin min > 145% predicted had hyperresponsive airways, regardless of clinical classification as asthmatic or nonasthmatic. Conclusions These findings suggest that baseline Rmin, a measurement that is easier to perform than spirometry, performs as well as or better than standard spirometric indices in distinguishing subjects with airway hyperresponsiveness from those without hyperresponsive airways. The relationship of baseline Rmin to asthma and airway hyperresponsiveness likely reflects a causal relation between conditions that stiffen airway walls and hyperresponsiveness. In conjunction with symptom history, Rmin could provide a clinically useful tool for assessing asthma and monitoring response to treatment.

  9. Effect of the anti-IL-17 antibody on allergic inflammation in an obesity-related asthma model.

    Science.gov (United States)

    Liang, Lin; Hur, Jung; Kang, Ji Young; Rhee, Chin Kook; Kim, Young Kyoon; Lee, Sook Young

    2018-04-19

    The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

  10. Anthropogenic Climate Change and Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Hueiwang Anna Jeng

    2012-02-01

    Full Text Available Climate change is expected to have an impact on various aspects of health, including mucosal areas involved in allergic inflammatory disorders that include asthma, allergic rhinitis, allergic conjunctivitis and anaphylaxis. The evidence that links climate change to the exacerbation and the development of allergic disease is increasing and appears to be linked to changes in pollen seasons (duration, onset and intensity and changes in allergen content of plants and their pollen as it relates to increased sensitization, allergenicity and exacerbations of allergic airway disease. This has significant implications for air quality and for the global food supply.

  11. Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways.

    Science.gov (United States)

    Brown, Robert H; Reynolds, Curt; Brooker, Allison; Talalay, Paul; Fahey, Jed W

    2015-09-15

    It is widely recognized that deep inspiration (DI), either before methacholine (MCh) challenge (Bronchoprotection, BP) or after MCh challenge (Bronchodilation, BD) protects against this challenge in healthy individuals, but not in asthmatics. Sulforaphane, a dietary antioxidant and antiinflammatory phytochemical derived from broccoli, may affect the pulmonary bronchoconstrictor responses to MCh and the responses to DI in asthmatic patients. Forty-five moderate asthmatics were administered sulforaphane (100 μmol daily for 14 days), BP, BD, lung volumes by body-plethsmography, and airway morphology by computed tomography (CT) were measured pre- and post sulforaphane consumption. Sulforaphane ameliorated the bronchoconstrictor effects of MCh on FEV1 significantly (on average by 21 %; p = 0.01) in 60 % of these asthmatics. Interestingly, in 20 % of the asthmatics, sulforaphane aggravated the bronchoconstrictor effects of MCh and in a similar number was without effect, documenting the great heterogeneity of the responsiveness of these individuals to sulforaphane. Moreover, in individuals in whom the FEV1 response to MCh challenge decreased after sulforaphane administration, i.e., sulforaphane was protective, the activities of Nrf2-regulated antioxidant and anti-inflammatory genes decreased. In contrast, individuals in whom sulforaphane treatment enhanced the FEV1 response to MCh, had increased expression of the activities of these genes. High resolution CT scans disclosed that in asthmatics sulforaphane treatment resulted in a significant reduction in specific airway resistance and also increased small airway luminal area and airway trapping modestly but significantly. These findings suggest the potential value of blocking the bronchoconstrictor hyperresponsiveness in some types of asthmatics by phytochemicals such as sulforaphane.

  12. Current management of allergic rhinitis in children

    NARCIS (Netherlands)

    Georgalas, Christos; Terreehorst, Ingrid; Fokkens, Wytske

    2010-01-01

    Over the last 20 years, there has been significant progress in our understanding of the pathophysiology of allergic rhinitis, including the discovery of new inflammatory mediators, the link between asthma and allergic rhinitis ('one airway-one disease' concept) and the introduction of novel

  13. 2007 San Diego wildfires and asthmatics.

    Science.gov (United States)

    Vora, Chirag; Renvall, Marian J; Chao, Peter; Ferguson, Paul; Ramsdell, Joe W

    2011-02-01

    This case series reports the changes in the respiratory health of eight asthmatic subjects and the relationship with air quality associated with the October 2007 firestorm in San Diego County of California. Participants were eight subjects with asthma enrolled in Asthma Clinical Research Network (ACRN) (NIH# U10-HL074218) studies at the University of California San Diego (UCSD), School of Medicine, who had study data collected immediately prior, during and 1 month after the 5-day firestorm in San Diego County. Air quality deteriorated to an extreme average of 71.5 mg/m(3) small particulate matter less than 2.5 μm (PM(2.5)) during the firestorm. Respiratory health data included morning and evening peak expiratory flow rates (PEFR), morning and evening Forced Expiratory Volume in one second (FEV(1)), rescue medication usage, and sputum eosinophils. Morning and evening PEFR and FEV(1) rates remained stable. The two subjects tested during the fires had elevated eosinophil counts and rescue medication usage was increased in five of the eight subjects. Pulmonary function test values were stable during the wildfires for all eight subjects but there was a statistically significant increase in rescue medication usage during the wildfires that correlated with PM(2.5) values. The two subjects tested during the fires showed increases in sputum eosinophil counts consistent with increased airways inflammation. These findings suggest that poor air quality associated with wildfires resulted in an increase in airways inflammation in these asthmatic subjects, but pulmonary function tests remained stable, possibly due to increased rescue medication usage. This is especially pertinent as there is an increase in incidence of wildfires this decade.

  14. Allergic rhinitis and asthma: the link further unraveled

    NARCIS (Netherlands)

    Braunstahl, Gert-Jan; Hellings, Peter W.

    2003-01-01

    Allergic asthma and rhinitis are manifestations of the atopic syndrome. Although the diseases commonly occur together, it is still unclear why some allergic patients develop only asthma and others only rhinitis. The reason for the variety in clinical expression of allergic airway disease is not

  15. Analysis of anti-asthmatic drug patents published in China between 2004 and 2013.

    Science.gov (United States)

    Xie, Hua; Zhang, Huiyun; Cao, Ke; He, Ping; Dai, Hongliang; He, Shaoheng

    2016-01-01

    We previously reported that 789 anti-allergic patents were granted in China between 1988 and 2008, but the number of patents seems to have grown much faster in China in recent years. Therefore, it is necessary to analyse the patents for anti-asthmatic products between 2004 and 2013 to give pharmaceutical companies and individuals a better understanding of potential candidates for anti-asthmatic drug development from patents published in China. The current report analyses the scientific progress that supports anti-asthmatic drug patent applications and reviews the published patent literature in China from 2004 to 2013. The rapid increase in the number of anti-asthmatic patents in China indicates that more specific discoveries have been made and that more people are aware of the importance of intellectual property protection in China. Holding patents may guarantee protection for an innovative new product.

  16. The effect of omalizumab on eosinophilic inflammation of the respiratory tract in patients with allergic asthma.

    Science.gov (United States)

    Kupryś-Lipińska, Izabela; Molińska, Katarzyna; Kuna, Piotr

    2016-01-01

    Bronchial asthma is characterised by high levels of immunoglobulin E (IgE) and overproduction of pro-inflammatory cytokines, including interleukins IL-4, IL-13 and IL-5 needed for, amongst other things, the production of IgE and the differentiation, maturation, migration and survival of eosinophils. Eosinophils are one of the most important cells in allergic inflammation. Their presence in tissue is linked to the persistence of inflammatory infiltrate, tissue damage and remodelling. Although these cells are very sensitive to corticosteroids, some asthmatic patients do not respond to high doses of these drugs, even when administered systemically. Transbronchial biopsies and bronchoalveolar lavage performed in patients with steroid-resistant asthma have demonstrated higher levels of eosinophils and Th2-type cytokines (IL-4 and IL-5) compared to steroid-sensitive patients. Clinical studies have confirmed that the very effective treatment in these cases is therapy with omalizumab - an anti-IgE monoclonal antibody. The paper discusses the efficacy of omalizumab in reducing eosinophil number in peripheral blood and in the airways of asthmatic patients based on basic, clinical, observational studies and case reports. The significance of omalizumab therapy in asthma control and mechanisms that regulate the effects of omalizumab on eosinophils are evaluated.

  17. Inhibition of Release of Vasoactive and Inflammatory Mediators in Airway and Vascular Tissues and Macrophages by a Chinese Herbal Medicine Formula for Allergic Rhinitis

    Directory of Open Access Journals (Sweden)

    George Binh Lenon

    2007-01-01

    Full Text Available Herbal therapies are being used increasingly for the treatment of allergic rhinitis. The aim of this study was to investigate the possible pharmacological actions and cellular targets of a Chinese herbal formula (RCM-101, which was previously shown to be effective in reducing seasonal allergic rhinitis symptoms in a randomized, placebo-controlled clinical trial. Rat and guinea pig isolated tissues (trachea and aorta were used to study the effects of RCM-101 on responses to various mediators. Production of leukotriene B4 in porcine neutrophils and of prostaglandin E2 and nitric oxide (NO in Raw 264.7 cells were also measured. In rat and guinea pig tracheal preparations, RCM-101 inhibited contractile responses to compound 48/80 but not those to histamine (guinea pig preparations or serotonin (rat preparations. Contractile responses of guinea pig tracheal preparations to carbachol and leukotriene C4, and relaxant responses to substance P and prostaglandin E2 were not affected by RCM-101. In rat aortic preparations, precontracted with phenylephrine, endothelium-dependent relaxant responses to acetylcholine and endothelium-independent relaxant responses to sodium nitroprusside were not affected by RCM-101. However, RCM-101 inhibited relaxations to l-arginine in endothelium-denuded rat aortic preparations, which had been pre-incubated with lipopolysaccharide. RCM-101 did not affect leukotriene B4 formation in isolated porcine neutrophils, induced by the calcium ionophore A23187; however, it inhibited prostaglandin E2 and NO production in lipopolysaccharide-stimulated murine macrophages (Raw 264.7 cells.The findings indicate that RCM-101 may have multiple inhibitory actions on the release and/or synthesis of inflammatory mediators involved in allergic rhinitis.

  18. Evaluation of Right Ventricular Function by Tissue Doppler Echocardiography in Asthmatic Children

    Directory of Open Access Journals (Sweden)

    Mehdi Ghaderian

    2016-11-01

    Full Text Available BackgroundAsthma is the most chronic inflammatory disorder of the airways in children and asthmatic patients can experience cardiac dysfunction, pulmonary hypertension and finally cor pulmonale later in life. We aimed to investigate Right Ventricular (RV functions in asthmatic children by conventional and tissue Doppler echocardiography (TDE.Materials and Methods Pulmonary function tests, conventional and TDE examinations were performed on 42 asthmatic and 42 age- and gender matched healthy controls subjects (n=42.Results Compared with healthy children the RV wall was statistically thicker among asthmatic patients (P= 0.01. Conventional echocardiography had not significant difference between cases and controls, but TDE had significant difference between these two groups. Peak E’ velocity, A’ velocity, E’/A’ ratio and S’ in lateral and medial sites of tricuspid annulus valve, were significantly differ from control group in our patients (P

  19. Positioning the principles of precision medicine in care pathways for allergic rhinitis and chronic rhinosinusitis - A EUFOREA-ARIA-EPOS-AIRWAYS ICP statement

    DEFF Research Database (Denmark)

    Hellings, P W; Fokkens, W J; Bachert, C

    2017-01-01

    approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim...... of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient...

  20. Upper and lower airway patency are associated in young children

    DEFF Research Database (Denmark)

    Chawes, Bo Lund Krogsgaard; Kreiner-Møller, Eskil; Bisgaard, Hans

    2010-01-01

    Although allergic rhinitis and asthma frequently coexist, the nature of this association is poorly understood. Therefore, we examined whether upper and lower airway patency are associated.......Although allergic rhinitis and asthma frequently coexist, the nature of this association is poorly understood. Therefore, we examined whether upper and lower airway patency are associated....

  1. NO in exhaled air of asthmatic children is reduced by the leukotriene receptor antagonist montelukast

    DEFF Research Database (Denmark)

    Bisgaard, H; Loland, L; Oj, J A

    1999-01-01

    Nitric oxide in exhaled air (FENO) is increased in asthmatic children, probably reflecting aspects of airway inflammation. We have studied the effect of the leukotriene receptor antagonist (LTRA) montelukast on FENO with a view to elucidate potential anti-inflammatory properties of LTRAs. Twenty-...

  2. Goishi tea consumption inhibits airway hyperresponsiveness in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Nakamura Hiroyuki

    2011-08-01

    Full Text Available Abstract Background Airway hyperresponsiveness (AHR is one of the important traits that characterize bronchial asthma. Goishi tea is a post-heating fermented tea that has been reported to have higher free radical scavenging activity. In this study, we evaluated the prophylactic effects of Goishi tea on AHR in BALB/c mice. Results The number of inflammatory cells in BAL fluid was considerably reduced in Goishi tea/Der f and Gallic acid/Der f groups as compared with Tap water/Der f group. Regarding inflammatory cells in BAL, a significant reduction of eosinophils and neutrophils was observed in Goishi tea-treated mice (p Der f group (p Der f group. In asthmatic mice (Tap water/Der f group, the intensity of airway resistance increased simultaneously with the increase in acetylcholine concentration in a dose-dependant way. AHR was significantly inhibited in Goishi tea/Der f and Gallic acid/Der f (p Der f group. Regarding serum specific-IgG1, significantly lower levels of this antibody were observed in Goishi tea/Der f and Gallic acid/Der f groups as compared with the Tap water/Der f group (p Conclusions The results suggest that Goishi tea consumption exerted an inhibitory effect on eosinophilic and neutrophilic infiltration in the lung, attenuated the increase in airway resistance and increased the production of adiponectin; thus reducing Der f induced allergic inflammatory process in mice.

  3. Occurrence of allergic bronchopulmonary mycosis in patients with asthma: An Eastern India experience

    Directory of Open Access Journals (Sweden)

    Sarkar Anirban

    2010-01-01

    Full Text Available Background: Allergic bronchopulmonary mycosis (ABPM is a clinical syndrome associated with immune sensitivity to various fungi notably Aspergillus spp. that colonize the airways of asthmatics. Early diagnosis and treatment with systemic corticosteroids is the key in preventing the progression of the disease to irreversible lung fibrosis. Aims: To study the occurrence of ABPM among asthma patients with fungal sensitization attending a chest clinic of a tertiary hospital of eastern India. The clinico-radiological and aetiological profiles are also described. Materials and Methods: All consecutive patients with asthma presenting to the chest clinic over a period of one year were screened for cutaneous hypersensitivity to 12 common fungal antigens. The skin test positive cases were further evaluated for ABPM using standard criteria. Results: One hundred and twenty-six asthma patients were screened using twelve common fungal antigens; forty patients (31.74% were found to be skin test positive, and ABPM was diagnosed in ten patients (7.93%. Of the 10 cases of ABPM, nine cases were those of allergic bronchopulmonary aspergillosis (ABPA and one case was identified as caused by sensitization to Penicillium spp. A majority of the cases of ABPM had advanced disease and had significantly lower FEV1 compared to non-ABPM skin test positive asthmatics. Central bronchiectasis on high resolution CT scan was the most sensitive and specific among the diagnostic parameters. Conclusion: There is a significant prevalence of ABPM in asthma patients attending our hospital and this reinforces the need to screen asthma patients for fungal sensitisation. This will help in early diagnosis and prevention of irreversible lung damage.

  4. Environmental Effects on Fractional Exhaled Nitric Oxide in Allergic Children

    Directory of Open Access Journals (Sweden)

    Stefania La Grutta

    2012-01-01

    Full Text Available Fractional exhaled nitric oxide (FeNO is a non-invasive marker of airway inflammation in asthma and respiratory allergy. Environmental factors, especially indoor and outdoor air quality, may play an important role in triggering acute exacerbations of respiratory symptoms. The authors have reviewed the literature reporting effects of outdoor and indoor pollutants on FeNO in children. Although the findings are not consistent, urban and industrial pollution—mainly particles (PM2.5 and PM10, nitrogen dioxide (NO2, and sulfur dioxide (SO2—as well as formaldehyde and electric baseboard heating have been shown to increase FeNO, whilst ozone (O3 tends to decrease it. Among children exposed to Environmental Tobacco Smoke (ETS with a genetic polymorphisms in nitric oxide synthase genes (NOS, a higher nicotine exposure was associated with lower FeNO levels. Finally, although more studies are needed in order to better investigate the effect of gene and environment interactions which may affect the interpretation of FeNO values in the management of children with asthma, clinicians are recommended to consider environmental exposures when taking medical histories for asthma and respiratory allergy. Further research is also needed to assess the effects of remedial interventions aimed at reducing/abating environmental exposures in asthmatic/allergic patients.

  5. Immunoregulatory Effects of Paeoniflorin Exerts Anti-asthmatic Effects via Modulation of the Th1/Th2 Equilibrium.

    Science.gov (United States)

    Zhang, Tianzhu; Yang, Zhaocong; Yang, Shihai; Du, Juan; Wang, Shumin

    2015-12-01

    Paeoniflorin has been demonstrated to exert anti-inflammatory and immunomodulatory effects in the animal study. In this study, we investigated immunoregulatory effects of paeoniflorin on anti-asthmatic effects and underlying mechanisms. Asthma model was established by ovalbumin-induced. A total of 50 mice were randomly assigned to five experimental groups: control, model, dexamethasone (2 mg/kg), and paeoniflorin (10 and 20 mg/kg). Airway resistance (Raw) were measured by the forced oscillation technique; histological studies were evaluated by the hematoxylin and eosin (HE) staining; Th1/Th2 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA); Th1/Th2 cells were evaluated by flow cytometry (FCM); and GATA3 and T-bet were evaluated by Western blot. Our study demonstrated that, compared with model group, paeoniflorin inhibited ovalbumin (OVA)-induced increases in Raw and eosinophil count; interleukin (IL)-4, IgE levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-γ level in bronchoalveolar lavage fluid; histological studies demonstrated that paeoniflorin substantially inhibited OVA-induced eosinophilia in lung tissue and lung tissue compared with model group. Flow cytometry studies demonstrated that paeoniflorin can regulate Th1/Th2 balance. These findings suggest that paeoniflorin may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

  6. The link between allergic rhinitis and allergic asthma: a prospective population-based study. The Copenhagen Allergy Study.

    Science.gov (United States)

    Linneberg, A; Henrik Nielsen, N; Frølund, L; Madsen, F; Dirksen, A; Jørgensen, T

    2002-11-01

    It has been hypothesized that allergic rhinitis and allergic asthma are manifestations of the same disease entity. We aimed to investigate the relationship between allergic rhinitis and allergic asthma. Participants in a population-based study of 15-69-year-olds in 1990 were invited to a follow-up in 1998. A total of 734 subjects were examined on two occasions eight years apart. Allergic rhinitis to pollen was defined as a history of nasal symptoms on exposure to pollens and IgE specific to pollen. Allergic asthma to pollen was defined as a history of lower airway symptoms on exposure to pollens and IgE specific to pollen. Similarly, diagnoses of allergic rhinitis and allergic asthma to animals or mite were defined. At follow-up, all subjects with allergic asthma to pollen (n = 52) had in addition allergic rhinitis to pollen. In the longitudinal analysis, there were a total of 28 new (incident) cases of allergic asthma to pollen. They all had allergic rhinitis to pollen at baseline, or had developed allergic rhinitis to pollen at follow-up. Accordingly, allergic rhinitis to animals and mite were ubiquitous in subjects with allergic asthma to animals and mite, respectively. The results support the hypothesis that allergic rhinitis and allergic asthma are manifestations of the same disease entity.

  7. Dengue 2 virus enhancement in asthmatic and non asthmatic individual

    Directory of Open Access Journals (Sweden)

    Maria G. Guzman

    1992-12-01

    Full Text Available During the 1981 dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS Cuban epidemic, bronchial asthma (BA was frequently found as a personal or family antecedent in dengue hemorragic fever patients. Considering that antibody dependent enhancement (ADE plays an important role in the etiopathogenic mechanism of DHF/DSS, we decide to study the Dengue 2 virus (D2V capability of replication in peripheral blood leukocytes (PBL from asthmatic patients and healthy persons. In 90% of asthmatic patients and 53.8% of control group it was obtained PBL with a significant D2V enhancing activity (X² p < 0.01. Power enhancement was higher in asthmatic group. This is the first in vitro study relating BA and the dengue 2 virus immuno enhancement. The results obtained support the role of BA as a risk factor for DHF/DSS as already described on epidemiological data.

  8. Microbial content of household dust associated with exhaled NO in asthmatic children

    Science.gov (United States)

    Johansson, Elisabet; Reponen, Tiina; Vesper, Stephen; Levin, Linda; Lockey, James; Ryan, Patrick; Bernstein, David I.; Villareal, Manuel; Hershey, Gurjit K. Khurana; Schaffer, Chris; LeMasters, Grace

    2013-01-01

    Exhaled nitric oxide (eNO) is increasingly used as a non-invasive measure of airway inflammation. Despite this, little information exists regarding the potential effects of indoor microbial components on eNO. We determined the influence of microbial contaminants in house dust and other indoor environmental characteristics on eNO levels in seven-year-olds with and without a physician- diagnosis of asthma. The study included 158 children recruited from a birth cohort study, and 32 were physician-diagnosed as asthmatic. The relationship between eNO levels and exposures to home dust streptomycetes, endotoxin, and molds was investigated. Streptomycetes and endotoxin were analyzed both as loads and concentrations in separate models. Dog, cat, and dust mite allergens also were evaluated. In the multivariate exposure models high streptomycetes loads and concentrations were significantly associated with a decrease in eNO levels in asthmatic (p Dust endotoxin was not significant. The relationship between eNO and indoor exposure to common outdoor molds was u-shaped. In non-asthmatic children, none of the exposure variables were significantly associated with eNO levels. To our knowledge, this is the first study demonstrating a significant association between microbial components in the indoor environment and eNO levels in asthmatic children. This study demonstrates the importance of simultaneously assessing multiple home exposures of asthmatic children to better understand opposing effects. Common components of the indoor Streptomyces community may beneficially influence airway inflammation. PMID:23807177

  9. Treatment of allergic asthma: Modulation of Th2 cells and their responses

    Directory of Open Access Journals (Sweden)

    Erb Klaus J

    2011-08-01

    Full Text Available Abstract Atopic asthma is a chronic inflammatory pulmonary disease characterised by recurrent episodes of wheezy, laboured breathing with an underlying Th2 cell-mediated inflammatory response in the airways. It is currently treated and, more or less, controlled depending on severity, with bronchodilators e.g. long-acting beta agonists and long-acting muscarinic antagonists or anti-inflammatory drugs such as corticosteroids (inhaled or oral, leukotriene modifiers, theophyline and anti-IgE therapy. Unfortunately, none of these treatments are curative and some asthmatic patients do not respond to intense anti-inflammatory therapies. Additionally, the use of long-term oral steroids has many undesired side effects. For this reason, novel and more effective drugs are needed. In this review, we focus on the CD4+ Th2 cells and their products as targets for the development of new drugs to add to the current armamentarium as adjuncts or as potential stand-alone treatments for allergic asthma. We argue that in early disease, the reduction or elimination of allergen-specific Th2 cells will reduce the consequences of repeated allergic inflammatory responses such as lung remodelling without causing generalised immunosuppression.

  10. Allergic reactions during anesthesia.

    Science.gov (United States)

    Levy, J H

    1988-01-01

    Any drug or blood product administered in the perioperative period has the potential to produce a life-threatening allergic (immune reaction) called anaphylaxis. Anaphylactic reactions represent adverse reactions mediated by immunospecific antibodies (IgE and IgG) that interact with mast cells, basophils, or the complement system to liberate vasoactive mediators and recruit other inflammatory cells. Activation of humoral and cellular pathways produces characteristic responses in the respiratory (bronchospasm and upper airway edema), cardiovascular (vasodilation and increased capillary permeability), and cutaneous systems (wheal and flare). Other predictable adverse drug reactions may mimic anaphylaxis to produce similar physiologic consequences independent of allergy (immune responses). Rapid and timely cardiopulmonary intervention with airway maintenance, epinephrine, and volume expansion is essential to avoid an adverse outcome. Severe reactions may be protracted, especially during anesthesia, requiring even larger doses of catecholamines and intensive care observation.

  11. Overexpression of Notch ligand Delta-like-1 by dendritic cells enhances their immunoregulatory capacity and exerts antiallergic effects on Th2-mediated allergic asthma in mice.

    Science.gov (United States)

    Lee, Chen-Chen; Lin, Chu-Lun; Leu, Sy-Jye; Lee, Yueh-Lun

    2018-02-01

    Dendritic cells (DCs) are professional antigen-presenting cells, and Notch ligand Delta-like-1 (DLL1) on DCs was implicated in type 1T helper (Th1) differentiation. In this study, we produced genetically engineered bone marrow-derived DCs that expressed DLL1 (DLL1-DCs) by adenoviral transduction. DLL1-DCs exerted a fully mature phenotype, and had positive effects on expression levels of interleukin (IL)-12 and costimulatory molecules. Coculture of allogeneic T cells with ovalbumin (OVA)-pulsed DLL1-DCs enhanced T cell proliferative responses and promoted Th1 cell differentiation. Furthermore, adoptive transfer of OVA-stimulated DLL1-DCs into asthmatic mice alleviated the cardinal features of allergic asthma, including immunoglobulin E (IgE) production, airway hyperresponsiveness (AHR), airway inflammation, and production of Th2-type cytokines. Notably, enhanced levels of the Th1-biased IgG 2a response and interferon (IFN)-γ production were observed in these mice. Taken together, these data indicate that DLL1-DCs promoted Th1 cell development to alter the Th1/Th2 ratio and ameliorate Th2-mediated allergic asthma in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Anti-allergic activity of 2,4,6-trihydroxy-3-geranylacetophenone (tHGA) via attenuation of IgE-mediated mast cell activation and inhibition of passive systemic anaphylaxis.

    Science.gov (United States)

    Tan, Ji Wei; Israf, Daud Ahmad; Harith, Hanis Hazeera; Md Hashim, Nur Fariesha; Ng, Chean Hui; Shaari, Khozirah; Tham, Chau Ling

    2017-03-15

    tHGA, a geranyl acetophenone compound originally isolated from a local shrub called Melicope ptelefolia, has been previously reported to prevent ovalbumin-induced allergic airway inflammation in a murine model of allergic asthma by targeting cysteinyl leukotriene synthesis. Mast cells are immune effector cells involved in the pathogenesis of allergic diseases including asthma by releasing cysteinyl leukotrienes. The anti-asthmatic properties of tHGA could be attributed to its inhibitory effect on mast cell degranulation. As mast cell degranulation is an important event in allergic responses, this study aimed to investigate the anti-allergic effects of tHGA in cellular and animal models of IgE-mediated mast cell degranulation. For in vitro model of IgE-mediated mast cell degranulation, DNP-IgE-sensitized RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA to induce degranulation. For IgE-mediated passive systemic anaphylaxis, Sprague Dawley rats were sensitized by intraperitoneal injection of DNP-IgE before challenged with DNP-BSA. Both in vitro and in vivo models showed that tHGA significantly inhibited the release of preformed mediators (β-hexosaminidase and histamine) as well as de novo mediators (interleukin-4, tumour necrosis factor-α, prostaglandin D 2 and leukotriene C 4 ). Pre-treatment of tHGA also prevented IgE-challenged RBL-2H3 cells and peritoneal mast cells from undergoing morphological changes associated with mast cell degranulation. These findings indicate that tHGA possesses potent anti-allergic activity via attenuation of IgE-mediated mast cell degranulation and inhibition of IgE-mediated passive systemic anaphylaxis. Thus, tHGA may have the potential to be developed as a mast cell stabilizer for the treatment of allergic diseases in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. December 2004 45 Bronchial Asthma, Allergic Rhinitis and chole

    African Journals Online (AJOL)

    user

    2004-12-02

    Dec 2, 2004 ... Background: Gallbladder has not been associated with any allergic condition what so ever. However, certain patients with bronchial asthma and cholelithiasis have reported to the author improvement in their asthmatic attack after cholecystectomy. Methods: This was an observational study on 22 bronchial ...

  14. Different Profile of Interleukin-10 Production in Circulating T Cells from Atopic Asthmatics Compared with Healthy Subjects

    Directory of Open Access Journals (Sweden)

    K Matsumoto

    2004-01-01

    Full Text Available BACKGROUND: Interleukin (IL-10 is a pleiotropic cytokine released from various cells, including T cells. Although IL-10 is suggested to inhibit allergic responses, its role in asthma remains uncertain. The purpose of the present study was to compare the profile of IL-10 in circulating T cells from stable atopic asthmatics, atopic nonasthmatics and healthy controls.

  15. T-Cell repertoire in the blood and lungs of atopic asthmatics before and after ragweed challenge

    NARCIS (Netherlands)

    Yurovsky, V. V.; Weersink, E. J.; Meltzer, S. S.; Moore, W. C.; Postma, D. S.; Bleecker, E. R.; White, B.

    1998-01-01

    T cells play a pivotal role in initiating and orchestrating allergic responses in asthma. The goal of this work was to learn whether ragweed challenge in the lungs alters the T-cell repertoire expressed in the blood and lungs of atopic asthmatics. Analyses of cell numbers, differentials, and T-cell

  16. T-cell repertoire in the blood and lungs of atopic asthmatics before and after ragweed challenge

    NARCIS (Netherlands)

    Yurovsky, VV; Weersink, EJM; Meltzer, SS; Moore, WC; Postma, DS; Bleecker, ER; White, B

    T cells play a pivotal role in initiating and orchestrating allergic responses in asthma. The goal of this work was to learn whether ragweed challenge in the lungs alters the T-cell repertoire expressed in the blood and lungs of atopic asthmatics. Analyses of cell numbers, differentials, and T-cell

  17. Allergic rhinitis

    NARCIS (Netherlands)

    Greiner, Alexander N.; Hellings, Peter W.; Rotiroti, Guiseppina; Scadding, Glenis K.

    2011-01-01

    Allergic rhinitis is a very common disorder that affects people of all ages, peaking in the teenage years. It is frequently ignored, underdiagnosed, misdiagnosed, and mistreated, which not only is detrimental to health but also has societal costs. Although allergic rhinitis is not a serious illness,

  18. Allergic sensitization

    DEFF Research Database (Denmark)

    van Ree, Ronald; Hummelshøj, Lone; Plantinga, Maud

    2014-01-01

    Allergic sensitization is the outcome of a complex interplay between the allergen and the host in a given environmental context. The first barrier encountered by an allergen on its way to sensitization is the mucosal epithelial layer. Allergic inflammatory diseases are accompanied by increased pe...

  19. Development of a regional-scale pollen emission and transport modeling framework for investigating the impact of climate change on allergic airway disease

    Science.gov (United States)

    Zhang, R.; Duhl, T.; Salam, M. T.; House, J. M.; Flagan, R. C.; Avol, E. L.; Gilliland, F. D.; Guenther, A.; Chung, S. H.; Lamb, B. K.; VanReken, T. M.

    2014-03-01

    Exposure to bioaerosol allergens such as pollen can cause exacerbations of allergenic airway disease (AAD) in sensitive populations, and thus cause serious public health problems. Assessing these health impacts by linking the airborne pollen levels, concentrations of respirable allergenic material, and human allergenic response under current and future climate conditions is a key step toward developing preventive and adaptive actions. To that end, a regional-scale pollen emission and transport modeling framework was developed that treats allergenic pollens as non-reactive tracers within the coupled Weather Research and Forecasting Community Multiscale Air Quality (WRF/CMAQ) modeling system. The Simulator of the Timing and Magnitude of Pollen Season (STaMPS) model was used to generate a daily pollen pool that can then be emitted into the atmosphere by wind. The STaMPS is driven by species-specific meteorological (temperature and/or precipitation) threshold conditions and is designed to be flexible with respect to its representation of vegetation species and plant functional types (PFTs). The hourly pollen emission flux was parameterized by considering the pollen pool, friction velocity, and wind threshold values. The dry deposition velocity of each species of pollen was estimated based on pollen grain size and density. An evaluation of the pollen modeling framework was conducted for southern California (USA) for the period from March to June 2010. This period coincided with observations by the University of Southern California's Children's Health Study (CHS), which included O3, PM2.5, and pollen count, as well as measurements of exhaled nitric oxide in study participants. Two nesting domains with horizontal resolutions of 12 and 4 km were constructed, and six representative allergenic pollen genera were included: birch tree, walnut tree, mulberry tree, olive tree, oak tree, and brome grasses. Under the current parameterization scheme, the modeling framework tends to

  20. Detrimental effects of albuterol on airway responsiveness requires airway inflammation and is independent of β-receptor affinity in murine models of asthma

    Directory of Open Access Journals (Sweden)

    Aimi Steven

    2011-03-01

    Full Text Available Abstract Background Inhaled short acting β2-agonists (SABA, e.g. albuterol, are used for quick reversal of bronchoconstriction in asthmatics. While SABA are not recommended for maintenance therapy, it is not uncommon to find patients who frequently use SABA over a long period of time and there is a suspicion that long term exposure to SABA could be detrimental to lung function. To test this hypothesis we studied the effect of long-term inhaled albuterol stereoisomers on immediate allergic response (IAR and airway hyperresponsiveness (AHR in mouse models of asthma. Methods Balb/C mice were sensitized and challenged with ovalbumin (OVA and then we studied the IAR to inhaled allergen and the AHR to inhaled methacholine. The mice were pretreated with nebulizations of either racemic (RS-albuterol or the single isomers (S- and (R-albuterol twice daily over 7 days prior to harvest. Results We found that all forms of albuterol produced a significant increase of IAR measured as respiratory elastance. Similarly, we found that AHR was elevated by albuterol. At the same time a mouse strain that is intrinsically hyperresponsive (A/J mouse was not affected by the albuterol isomers nor was AHR induced by epithelial disruption with Poly-L-lysine affected by albuterol. Conclusions We conclude that long term inhalation treatment with either isomer of albuterol is capable of precipitating IAR and AHR in allergically inflamed airways but not in intrinsically hyperresponsive mice or immunologically naïve mice. Because (S-albuterol, which lacks affinity for the β2-receptor, did not differ from (R-albuterol, we speculate that isomer-independent properties of the albuterol molecule, other than β2-agonism, are responsible for the effect on AHR.

  1. Allergic rhinitis.

    Science.gov (United States)

    Greiner, Alexander N; Hellings, Peter W; Rotiroti, Guiseppina; Scadding, Glenis K

    2011-12-17

    Allergic rhinitis is a very common disorder that affects people of all ages, peaking in the teenage years. It is frequently ignored, underdiagnosed, misdiagnosed, and mistreated, which not only is detrimental to health but also has societal costs. Although allergic rhinitis is not a serious illness, it is clinically relevant because it underlies many complications, is a major risk factor for poor asthma control, and affects quality of life and productivity at work or school. Management of allergic rhinitis is best when directed by guidelines. A diagnostic trial of a pharmacotherapeutic agent could be started in people with clinically identified allergic rhinitis; however, to confirm the diagnosis, specific IgE reactivity needs to be recorded. Documented IgE reactivity has the added benefit of guiding implementation of environmental controls, which could substantially ameliorate symptoms of allergic rhinitis and might prevent development of asthma, especially in an occupational setting. Many classes of drug are available, effective, and safe. In meta-analyses, intranasal corticosteroids are superior to other treatments, have a good safety profile, and treat all symptoms of allergic rhinitis effectively. First-generation antihistamines are associated with sedation, psychomotor retardation, and reduced academic performance. Only immunotherapy with individually targeted allergens has the potential to alter the natural history of allergic rhinitis. Patients' education is a vital component of treatment. Even with the best pharmacotherapy, one in five affected individuals remains highly symptomatic, and further research is needed in this area. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Piper nigrum extract ameliorated allergic inflammation through inhibiting Th2/Th17 responses and mast cells activation.

    Science.gov (United States)

    Bui, Thi Tho; Piao, Chun Hua; Song, Chang Ho; Shin, Hee Soon; Shon, Dong-Hwa; Chai, Ok Hee

    2017-12-01

    Piper nigrum (Piperaceae) is commonly used as a spice and traditional medicine in many countries. P. nigrum has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the effect of P. nigrum on allergic asthma has not been known. This study investigated the effect of P. nigrum ethanol extracts (PNE) on airway inflammation in asthmatic mice model. In the ovalbumin (OVA)-induced allergic asthma model, we analysed the number of inflammatory cells and cytokines production in bronchoalveolar lavage fluid (BALF) and lung tissue; histological structure; as well as the total immunoglobulin (Ig)E, anti-OVA IgE, anti-OVA IgG 1 and histamine levels in serum. The oral administration (200 mg/kg) of PNE reduced the accumulation of inflammatory cells (eosinophils, neutrophils in BALF and mast cells in lung tissue); regulated the balance of the cytokines production of Th1, Th2, Th17 and Treg cells, specifically, inhibited the expressions of GATA3, IL-4, IL-6, IL-1β, RORγt, IL-17A, TNF-α and increased the secretions of IL-10, INF-γ in BALF and lung homogenate. Moreover, PNE suppressed the levels of total IgE, anti-OVA IgE, anti-OVA IgG 1 and histamine release in serum. The histological analysis showed that the fibrosis and infiltration of inflammatory cells were also ameliorated in PNE treated mice. On the other hand, PNE inhibited the allergic responses via inactivation of rat peritoneal mast cells degranulation. These results suggest that PNE has therapeutic potential for treating allergic asthma through inhibiting Th2/Th17 responses and mast cells activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Objective assessments of allergic and nonallergic rhinitis in young children

    DEFF Research Database (Denmark)

    Chawes, B L K; Kreiner-Møller, E; Bisgaard, H

    2009-01-01

    BACKGROUND: Allergic and nonallergic rhinitis are common childhood disorders. OBJECTIVE: To study nasal eosinophilia and nasal airway patency in young children with allergic and nonallergic rhinitis to assess the pathology behind such diagnoses. METHODS: We investigated 255 children at six years...

  4. Azithromycin ameliorates airway remodeling via inhibiting airway epithelium apoptosis.

    Science.gov (United States)

    Liu, Yuanqi; Pu, Yue; Li, Diandian; Zhou, Liming; Wan, Lihong

    2017-02-01

    Azithromycin can benefit treating allergic airway inflammation and remodeling. In the present study, we hypothesized that azithromycin alleviated airway epithelium injury through inhibiting airway epithelium apoptosis via down regulation of caspase-3 and Bax/Bcl2 ratio in vivo and in vitro. Ovalbumin induced rat asthma model and TGF-β1-induced BEAS-2B cell apoptosis model were established, respectively. In vivo experiments, airway epithelium was stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to histologically evaluate the airway inflammation and remodeling. Airway epithelium apoptotic index (AI) was further analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), while expression of apoptosis related gene (Bax, Bcl2, Caspase-3) in lungs were measured by qRT-PCR and western blotting, respectively. In vitro experiments, apoptosis were evaluated by Flow cytometry (FCM) and TUNEL. Above apoptosis related gene were also measured by qRT-PCR and western blotting. Compared with the OVA group, azithromycin significantly reduced the inflammation score, peribronchial smooth muscle layer thickness, epithelial thickening and goblet cell metaplasia (Pazithromycin-treated rats (Pazithromycin significantly suppressed TGF-β1-induced BEAS-2B cells apoptosis (PAzithromycin is an attractive treatment option for reducing airway epithelial cell apoptosis by improving the imbalance of Bax/Bcl-2 ratio and inhibiting Caspase-3 level in airway epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Allergic Rhinitis

    Science.gov (United States)

    ... dust mites, are in dust. Dust mites are tiny living creatures found in bedding, mattresses, carpeting, and upholstered furniture. They live on dead skin cells and other things found in house dust. How is allergic rhinitis diagnosed? If your ...

  6. Endothelin-1 As A Biochemical Marker in Asthmatic Children Using Induced Sputum Method

    International Nuclear Information System (INIS)

    Noureldin, A.M.; Ahmed, A.M.; Ayad, S.K.

    2004-01-01

    Endothelin-1 is a physiological normal potent bronchoconstrictor peptide produced in the respiratory airways and increase excessively their inflammation. Endothelin-1 (Et-1) level was measured by radioimmunoassay (RIA) in saliva, sputum and plasma of thirty children suffering from mild to moderate asthma with age ranged from 6-12 years. Ten healthy children of matching age and sex were used as control group. The patients were further classified according to previous regular treatment into 21 steroid dependent and 9 non-steroid dependent. The results revealed that the saliva, sputum and plasma levels of ET-1 in asthmatic patients were significantly higher than that of control children. In both control and asthmatic children, ET-1 levels were more pronounced in the order of saliva>sputum>plasma. On the other hand, the saliva, sputum and plasma levels of ET-1 were significantly lower in steroid dependent asthmatic children than that of the non-steroid dependent ones. High levels of ET-1 in mild to moderate asthmatic children clarify the implication of this biochemical mediator marker in the pathology of the disease. The regular inhaled steroid therapy reduced the level of this mediator but did not return to the basal levels of controls, so, ET-1 antagonist may be useful in management of bronchial asthma in children. Moreover, ET-1 in sputum was more valuable biochemical indicator to monitor airway inflammation than in plasma

  7. House dust mite induced allergic rhinitis in children in primary care : Epidemiology and Management

    NARCIS (Netherlands)

    C.M.A. de Bot (Cindy)

    2012-01-01

    textabstractAllergic rhinitis (AR) is an allergen-induced, upper-airway inflammatory disease. The characteristic symptoms of allergic rhinitis are a runny nose, sneezing, congestion, redness of the eyes, watering eyes, and itching of the eyes, nose and throat. Previously, allergic rhinitis was

  8. Indoleamine 2,3-dioxygenase expression in patients with allergic rhinitis: a case-control study

    Directory of Open Access Journals (Sweden)

    Luukkainen Annika

    2011-12-01

    Full Text Available Abstract Background Indoleamine 2,3-dioxygenase (IDO is a tryptophan catalyzing enzyme. It has been suggested that it has a role in lower airway allergic inflammations, but its role in allergic rhinitis has not been investigated. Objective Our aim was to evaluate the expression of IDO in the nasal mucosa of allergic rhinitis patients allergic to birch pollen during peak exposure to birch pollen allergen and compare it to non-atopic patients. Methods IDO expression was immunohistochemically evaluated from nasal specimens obtained in- and off-season from otherwise healthy non-smoking volunteers both allergic to birch pollen (having mild or moderate allergic rhinoconjunctivitis and non-allergic controls. Results: The IDO expression levels were low in healthy controls and remained low also in patients allergic to birch pollen. There were no differences in the expression of IDO in- and off-season in either healthy or allergic subjects. Conclusions There is a controversy in the role of IDO in upper and lower airways during allergic airway disease. It seems that IDO is associated to allergic inflammations of the lower airways, but does not have a local role in the nasal cavity at least in mild or moderate forms of allergic rhinitis.

  9. Quantitative analysis of dynamic airway changes after methacholine and salbutamol inhalation on xenon-enhanced chest CT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sang Joon; Goo, Jin Mo; Kim, Jong Hyo; Park, Eun-Ah [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Lee, Chang Hyun [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Jung, Jae-Woo; Park, Heung-Woo [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of); Cho, Sang-Heon [Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of)

    2012-11-15

    To investigate the dynamic changes in airways in response to methacholine and salbutamol inhalation and to correlate the xenon ventilation index on xenon-enhanced chest CTs in asthmatics. Thirty-one non-smokers (6 normal, 25 asthmatics) underwent xenon-enhanced chest CT and pulmonary function tests. Images were obtained at three stages (basal state, after methacholine inhalation and after salbutamol inhalation), and the total xenon ventilation index (TXVI) as well as airway values were measured and calculated. The repeated measures ANOVA and Spearman's correlation coefficient were used for statistical analysis. TXVI in the normal group did not significantly change (P > 0.05) with methacholine and salbutamol. For asthmatics, however, the TXVI significantly decreased after methacholine inhalation and increased after salbutamol inhalation (P < 0.05). Of the airway parameters, the airway inner area (IA) significantly increased after salbutamol inhalation in all airways (P < 0.01) in asthmatics. Airway IA, wall thickness and wall area percentage did not significantly decrease after methacholine inhalation (P > 0.05). IA of the large airways was well correlated with basal TXVI, FEV{sub 1} and FVC (P < 0.05). Airway IA is the most reliable parameter for reflecting the dynamic changes after methacholine and salbutamol inhalation, and correlates well with TXVI in asthmatics on xenon-enhanced CT. (orig.)

  10. Leukotrienes and leukotriene modifiers in pediatric allergic diseases ...

    African Journals Online (AJOL)

    Leukotrienes are potent pro-inflammatory lipid mediators derived from arachidonic acid through several enzymatic pathways. They have an essential role in allergic inflammation, where they induce bronchoconstriction, airway edema, and chemotaxis of the inflammatory cells in the airways, nasal and conjunctival tissues.

  11. Barrier disrupting effects of alternaria alternata extract on bronchial epithelium from asthmatic donors.

    Science.gov (United States)

    Leino, Marina S; Loxham, Matthew; Blume, Cornelia; Swindle, Emily J; Jayasekera, Nivenka P; Dennison, Patrick W; Shamji, Betty W H; Edwards, Matthew J; Holgate, Stephen T; Howarth, Peter H; Davies, Donna E

    2013-01-01

    Sensitization and exposure to the allergenic fungus Alternaria alternata has been associated with increased risk of asthma and asthma exacerbations. The first cells to encounter inhaled allergens are epithelial cells at the airway mucosal surface. Epithelial barrier function has previously been reported to be defective in asthma. This study investigated the contribution of proteases from Alternaria alternata on epithelial barrier function and inflammatory responses and compared responses of in vitro cultures of differentiated bronchial epithelial cells derived from severely asthmatic donors with those from non-asthmatic controls. Polarised 16HBE cells or air-liquid interface (ALI) bronchial epithelial cultures from non-asthmatic or severe asthmatic donors were challenged apically with extracts of Alternaria and changes in inflammatory cytokine release and transepithelial electrical resistance (TER) were measured. Protease activity in Alternaria extracts was characterised and the effect of selectively inhibiting protease activity on epithelial responses was examined using protease inhibitors and heat-treatment. In 16HBE cells, Alternaria extracts stimulated release of IL-8 and TNFα, with concomitant reduction in TER; these effects were prevented by heat-treatment of the extracts. Examination of the effects of protease inhibitors suggested that serine proteases were the predominant class of proteases mediating these effects. ALI cultures from asthmatic donors exhibited a reduced IL-8 response to Alternaria relative to those from healthy controls, while neither responded with increased thymic stromal lymphopoietin (TSLP) release. Only cultures from asthmatic donors were susceptible to the barrier-weakening effects of Alternaria. Therefore, the bronchial epithelium of severely asthmatic individuals may be more susceptible to the deleterious effects of Alternaria.

  12. Effect of Selective Cysteinyl Leukotriene Receptor Antagonists on Airway Inflammation and Matrix Metalloproteinase Expression in a Mouse Asthma Model

    Directory of Open Access Journals (Sweden)

    Chia-Hsiu Hsu

    2012-08-01

    Conclusion: Cysteinyl leukotriene receptor plays a more important role than CysLT in the pathogenesis of allergic airway inflammation. MMP-2 and -9 may be more sensitive indicators of airway remodeling.

  13. TIM-3 is not essential for development of airway inflammation induced by house dust mite antigens

    Directory of Open Access Journals (Sweden)

    Yoshihisa Hiraishi

    2016-10-01

    Conclusions: Our findings indicate that, in mice, TIM-3 is not essential for development of HDM-induced acute or chronic allergic airway inflammation, although it appears to be involved in reduced lymphocyte recruitment during HDM-induced chronic allergic airway inflammation.

  14. Trichuris suis ova therapy for allergic rhinitis

    DEFF Research Database (Denmark)

    Bager, Peter; Arnved, John; Rønborg, Steen

    2010-01-01

    Parasitic helminth infections can protect against allergic airway inflammation in experimental models and have been associated with a reduced risk of atopy and a reduced course of asthma in some observational studies. Although no clinical evidence exists to support the use of helminth therapy for...

  15. Subcutaneous and Sublingual Immunotherapy in a Mouse Model of Allergic Asthma

    NARCIS (Netherlands)

    Hesse, Laura; Nawijn, Martijn C

    2017-01-01

    Allergic asthma, caused by inhaled allergens such as house dust mite or grass pollen, is characterized by reversible airway obstruction, associated with an eosinophilic inflammation of the airways, as well as airway hyper responsiveness and remodeling. The inhaled allergens trigger a type-2

  16. Asthmatic Children And Immunological Effects Of BCG Vaccine Key words: Asthmatic children, BCG vaccine

    International Nuclear Information System (INIS)

    Saaed, A.I.

    2011-01-01

    A TH2 screwed immune response is known to play a crucial role in the pathogenesis of allergy, so, preventing the differentiation of TH cells. The TH2 cells are appeared as a logical therapeutic approach to atopic asthma. The purpose of TH1 study was to determine the possible role of BCG vaccine on asthma and whether a TH1 type immune response elicited by BCG immunization could suppress the allergic sensitization in childhood asthma. Seventy asthmatic patients (50 atopic and 20 non-atopic) and fifty healthy individuals were subjected to TH1 study. Tuberculin test was performed for all groups then subjects with positive tuberculin test were excluded. The BCG vaccine was given for all groups with assessment of TH1 and TH2 cytokine response by measuring total IgE, IL-4 (for TH2 response) and INF-γ (for TH1 response). Significant reduction in IgE and IL-4, and elevation in INF-γ were determined in group I (atopic asthma) following BCG vaccination. There was non-significant change observed in IgE and IL-4 levels of group II while significant reduction in IL-4 and significant increase in INF-γ was observed after BCG vaccine

  17. Impact on allergic immune response after treatment with vitamin A

    DEFF Research Database (Denmark)

    Matheu, Victor; Berggård, Karin; Barrios, Yvelise

    2009-01-01

    ABSTRACT: BACKGROUND: Vitamin A may have some influence on the immune system, but the role in allergy modulation is still unclear. OBJECTIVE: To clarify whether high levels of retinoic acid (RA) affects allergic response in vivo, we used a murine experimental model of airway allergic disease....... METHODS: Ovalbumin (OVA)-immunization/OVA-challenge (OVA/OVA) and house dust mite (HDM)-immunization/HDM-challenge (HDM/HDM) experimental murine models of allergic airway disease, using C57Bl.10/Q groups of mice (n = 10) treated subcutaneously with different concentrations of all-trans RA (0, 50, 500...... and 2,500 ug) every 2-days were used to assess the allergic immune response. RESULTS: Levels of total and specific-IgE in sera were increased in all groups of RA treated OVA/OVA and HDM/HDM mice. Percentage and total amount of recruited eosinophil in airways by bronchoalveolar lavage fluid (BALF) were...

  18. Old dilemma : asthma with irreversible airway obstruction or COPD

    NARCIS (Netherlands)

    Fattahi, Fatemeh; Vonk, Judith M.; Bulkmans, Nicole; Fleischeuer, Ruth; Gouw, Annette; Grunberg, Katrien; Mauad, Thais; Popper, Helmut; Felipe-Silva, Aloisio; Vrugt, Bart; Wright, Joanne L.; Yang, Hui-Min; Kocks, Janwillem W. H.; Hylkema, Machteld N.; Postma, Dirkje S.; Timens, Wim; ten Hacken, Nick H. T.

    2015-01-01

    Older asthmatic patients may develop fixed airway obstruction and clinical signs of chronic obstructive pulmonary disease (COPD). We investigated the added value of pathological evaluation of bronchial biopsies to help differentiate asthma from COPD, taking into account smoking, age, and inhaled

  19. DETERMINATION OF THE HABITS OF ASTHMATIC PATIENTS ABOUT USING SUBSTANCE CONTAINING PERFUME

    Directory of Open Access Journals (Sweden)

    Ercan GOCGELDI

    2005-06-01

    Full Text Available Introduction: Air pollution, perfume, aerosol substances, odors of paint and detergent are the most important non-specific irritants stimulating the asthmatic attack. The odors of these substances exist for long time and form the serious risk for the asthmatic patients. This study was planned to determine the frequency of using perfume and substance containing perfume and the sensitivities to the substances among the asthmatic patients using inhaling steroid and b2-mimetic ant asthmatic drugs. Methods: This is a descriptive study and conducted among patients who applied to the Allergic Diseases outpatient service of Gulhane Military Medical Academia in October-December 2004. 83 asthmatic patients who accepted to participate to the study filled out a questionnaire that including patients habits relating perfume, cleaners with perfume, perfume for living room, toilets and bathrooms, and having dyspnea or not when exposed any kind of perfumes and using any b2-mimetik or not. Results: 73.5% (n=61 of participants were male, and 26.5 % (n=22 were women. Their ages were from 18 to 57 years. 79.5% (n=66 of participants expressed that they were sensitive to the odors mentioned and experienced the respiratory problems when they were at the surroundings by odour and 26.5% (n=22 of participants sometimes used the B2-mimetic antiasthmatic drugs for this reason. On the other hand; It was found that 68.7% (n=57 of participants regularly used the perfume for themselves everyday, 85.5% (n=71 of participants washed their clothings by using cleaners and/or softeners with perfume, 44.6% (n=37 of participants used the perfume for their rooms frequently, 62.7% (n=52 of participants used substance with perfume in their toilets and bathrooms. Conclusion: We conclude that the asthmatic patients have not sufficient knowledge about non-spesific irritants stimulating the asthmatic attack, and don’t behave sensitive. It’s important to plan properly the medical

  20. Effects of Hyeonggaeyeongyo-Tang in Ovalbumin-Induced Allergic Rhinitis Model

    OpenAIRE

    Se Hyang Hong; Soon Re Kim; Han-Seok Choi; Jin Mo Ku; Hye Sook Seo; Yong Cheol Shin; Seong-Gyu Ko

    2014-01-01

    Allergic rhinitis (AR) is an allergic inflammation of the nasal airways. The prevalence of AR is increasing worldwide. We investigated whether Hyeonggaeyeongyo-tang (HYT) is effective to suppress the progression of AR induced by ovalbumin (OVA). Male BALB/c mice were used for this study. Allergic rhinitis was induced by OVA. Treatment with HYT was assessed to study the effect of HYT on allergic rhinitis in mice. Histological analysis, immunohistochemistry, multiplex cytokine assay, blood anal...

  1. Clinical characteristics of childhood asthmatics in Johannesburg

    African Journals Online (AJOL)

    Objectives. To describe the clinical features of Caucasian childhood asthmatics in Johannesburg in order to compare these with a similar population of black asthmatic children resident in Soweto_. Design. In a prospective study, a history was obtained by means of an investigator-administered questionnaire. Main outcome ...

  2. S100A12 and the Airway Smooth Muscle: Beyond Inflammation and Constriction

    OpenAIRE

    Camoretti-Mercado, Blanca; Karrar, Eltayeb; Nu?ez, Luis; Bowman, Marion A Hofmann

    2012-01-01

    Airway inflammation, lung remodeling, and Airway Hyperresponsiveness (AHR) are major features of asthma and Chronic Obstructive Pulmonary Disease (COPD). The inflammatory response to allergens, air pollutants, and other insults is likely to play a key role in promoting structural changes in the lung including the overabundance of Airway Smooth Muscle (ASM) seen in asthmatics. These alterations or remodeling could, in turn, impact the immunmodulatory actions of the ASM, the ASM's contractile p...

  3. Serum periostin level is not associated with allergic rhinitis or allergic sensitization in Korean children.

    Science.gov (United States)

    Kim, Dong Young; Kim, Jeong Hong; Lee, Keun-Hwa; Hong, Seong-Chul; Lee, Hye-Sook; Kang, Ju Wan

    2017-02-01

    Periostin is a matricellular protein, synthesized in the airway epithelium and induced by interleukin (IL)-4 and IL-13. The significance of periostin as a biomarker of T helper type 2 cell (Th2)-induced airway inflammation, and as a measure of the response to Th2-targeted therapy, has recently been highlighted. We explored the relationship between serum periostin and allergic rhinitis in Korean children. Data for fifth and sixth grade children from six randomly selected elementary schools located in Jeju and Seogwipo City, Korea, were investigated. Serum periostin levels were determined by enzyme-linked immunosorbent assay. Sex, school grade, body mass index, and presence of allergic nasal symptoms were obtained via a self-reported survey and skin prick testing was performed. There were no significant differences between groups, when stratification was applied according to sex, grade, presence of atopy, and presence of allergic nasal symptoms. Sex and body mass index were significantly associated with serum periostin levels in multivariate linear regression analysis. However, allergic rhinitis was not associated with serum periostin levels. Allergic rhinitis or allergic sensitization in Korean children did not influence serum periostin levels. Further studies are required to investigate the significance of serum periostin levels in pediatric allergic rhinitis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Allergic reactions

    Science.gov (United States)

    ... that don't bother most people (such as venom from bee stings and certain foods, medicines, and pollens) can ... person. If the allergic reaction is from a bee sting, scrape the ... more venom. If the person has emergency allergy medicine on ...

  5. [The asthmatic patient and his/her family dynamics].

    Science.gov (United States)

    Vázquez Nava, Francisco; Santos Díaz, Aidee del Pilar; Martínez Burnes, Julio; Caballero Rico, Frida; Morales González, Francisco; Prado Lobato, Simón Carlos

    2003-01-01

    Asthma is a chronic disorder of the airways that modify behavior response of persons and affect family function. To determine if there is a disorder of the familial dynamics in asthmatic patients of Tamaulipas. An observational, comparative, open and cross-sectional study was performed to determine: family categorization, family function and evaluation of conjugal subsystem. We included 300 persons who were 30 to 50 years old, male and female: 100 subjects with asthma diagnosis, 100 with diabetes type 2 and 100 healthy people. The asthmatic subjects' age average was of 45.67 years, complete nuclear family was documented in 15% of sick persons, women were the family head in 50% of the cases, we appreciated great family dysfunction in relation to: adaptability function (50%), participation (63%), family grow-up (61%) and feeling manifestations (64%). In 53% of the conjugal couple cases of the patients, do not carry out her family functions like: communication 59%, share out functions 59%, sexual satisfaction 60%, and making decision 59%. It is only feasible to treat these patients when there is an active participation of the family members.

  6. Exhaled nitric oxide collected with two different mouthpieces: a study in asthmatic patients

    Directory of Open Access Journals (Sweden)

    A.S. Leme

    2002-10-01

    Full Text Available Techniques for collecting exhaled nitric oxide (ENO recommend the use of antibacterial filters of 0.3 µm. The aim of the present study was to compare the measurements of ENO obtained with two different filtering devices. Air samples from 17 asthmatic and 17 non-asthmatic subjects were collected by a recommended off-line technique using two different mouthpieces: 1 the Sievers disposable tool (A under a breathing pressure of 18 cmH2O, and 2 a mouthpiece containing a HEPA filter (B under a breathing pressure of 12 cmH2O. The nitric oxide samples were collected into an impermeable reservoir bag. Values for ENO were compared using two-way repeated measures ANOVA followed by the Tukey test. Agreement was assessed by Bland-Altman analysis. ENO values obtained with mouthpieces A and B were comparable for asthmatic (mean ± SEM, 42.9 ± 6.9 vs 43.3 ± 6.6 ppb and non-asthmatic (13.3 ± 1.3 vs 13.7 ± 1.1 ppb subjects. There was a significant difference in ENO between asthmatics and non-asthmatics using either mouthpiece A (P<0.001 or B (P<0.001. There was a positive correlation between mouthpiece A and mouthpiece B for both groups. The Bland-Altman limits of agreement were considered to be acceptable. Mouthpiece B was less expensive than A, and these data show that it can be used without compromising the result. Our data confirm reports of higher ENO values in the presence of airway inflammation.

  7. Airway remodeling and its reversibility in equine asthma

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Lavoie

    2017-06-01

    Full Text Available Despite effective therapies for controlling its clinical manifestations, human asthma remains an incurable disease. It is now recognized that inflammation induced structural changes (remodeling of the airways are responsible for the progressive loss of lung function in asthmatic patients. However, the peripheral airways, where most of the remodeling occurs in severe asthmatic patients, cannot be safely sampled in humans, and therefore, little is known of the effects of current therapies at reversing the established asthmatic remodeling, especially those occurring in the peripheral airways. Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, experiments in which the disease is artificially induced have been shown to have limited translational potential for humans. To the contrary, horses naturally suffer from an asthma-like condition which shares marked similarities with human asthma making this model unique to investigate the kinetics, reversibility, as well as the physiological consequences of tissue remodeling (Bullone and Lavoie 2015. We reported an increased deposition of smooth muscle, collagen and elastic fibers in the peripheral airways of affected horses, which was correlated with the lung function (Herszberg et al., 2006; Setlakwe et al., 2014. The airway subepithelial collagen depositions were almost completely reversed with 6 to 12 months of treatment with either antigen avoidance or inhaled corticosteroids (ICS administration, and there was a modest (30% on average decrease in airway smooth muscle (Leclere et al., 2011. A recent study also found that ICS combined with long-acting ß2-agonists drugs (LABA and ICS monotherapy similarly induced a 30% decrease of the airway smooth muscle mass at 3 months (Buollone, 2017. However, only ICS/LABA and antigen avoidance decreased airway luminal neutrophilia. The findings indicate the enhance therapeutic effect of ICS

  8. ِIncreased expression of T- cell- surface CXCR4 in asthmatic children.

    African Journals Online (AJOL)

    Ehab

    express CXCR 3 and CCR 5, whereas Th-2 subset expresses CCR3, CCR4, CCR8 and CXCR4 receptors10. Of these, Th-2 cell-expressed chemokine receptors, CXCR4, and its ligand SDF-. 1, have been shown to be the most relevant for Th-. 2-type allergic airway responses 11. The results presented demonstrate that.

  9. Characteristics and predictors of allergic rhinitis undertreatment in primary care.

    Science.gov (United States)

    Spinozzi, F; Murgia, N; Baldacci, S; Maio, S; Pala, A P; Casciari, C; dell'Omo, M; Viegi, G

    2016-03-01

    Although allergic rhinitis is considered a raising medical problem in many countries it is often undertreated. The reasons for this phenomenon are not completely clear.The aim of this study is to evaluate factors associated with allergic rhinitis under-/no treatment.A sample of 518 allergic rhinitis patients recruited by their primary care physicians, as a part of the ARGA study, were invited to fill in a specific questionnaire regarding rhinitis symptoms, treatment, and rhinitis-related work/social disability. Chi-square test and logistic regression were performed to assess risk factors for allergic rhinitis under-/no treatment.Over one out of four patients had no treatment despite the symptoms and 13.5% were inadequately treated. Participants with asthma (OR 0.47, 95% CI 0.30-0.75) and conjunctivitis (0.44, 95% CI 0.27-0.71) were at lower risk of allergic rhinitis under-/no treatment: in asthmatics this reduction was related mainly to the concomitant asthma treatment (OR 0.19, 95% CI 0.10-0.37).Asthmatics with under-/not treated rhinitis had the highest prevalence of rhinitis-related quality of life impairment.Under-/no treatment for allergic rhinitis is still rather frequent despite the relevance of this disease. The simultaneous presence of asthma and an anti-asthmatic therapy are able to influence positively the treatment. Targeted interventions toward a better characterization and a tight follow-up of rhinitis patient without asthma are needed. © The Author(s) 2015.

  10. Relationship of Circulating Hyaluronic Acid Levels to Disease Control in Asthma and Asthmatic Pregnancy

    Science.gov (United States)

    Eszes, Noémi; Toldi, Gergely; Bohács, Anikó; Ivancsó, István; Müller, Veronika; Rigó Jr., János; Losonczy, György; Vásárhelyi, Barna; Tamási, Lilla

    2014-01-01

    Uncontrolled asthma is a risk factor for pregnancy-related complications. Hyaluronic acid (HA), a potential peripheral blood marker of tissue fibrosis in various diseases, promotes eosinophil survival and plays a role in asthmatic airway inflammation as well as in physiological processes necessary to maintain normal pregnancy; however the level of circulating HA in asthma and asthmatic pregnancy is unknown. We investigated HA levels in asthmatic patients (N = 52; asthmatic pregnant (AP) N = 16; asthmatic non-pregnant (ANP) N = 36) and tested their relationship to asthma control. Serum HA level was lower in AP than in ANP patients (27 [24.7–31.55] vs. 37.4 [30.1–66.55] ng/mL, p = 0.006); the difference attenuated to a trend after its adjustment for patients’ age (p = 0.056). HA levels and airway resistance were positively (r = 0.467, p = 0.004), HA levels and Asthma Control Test (ACT) total score inversely (r = −0.437, p = 0.01) associated in ANP patients; these relationships remained significant even after their adjustments for age. The potential value of HA in the determination of asthma control was analyzed using ROC analysis which revealed that HA values discriminate patients with ACT total score ≥20 (controlled patients) and <20 (uncontrolled patients) with a 0.826 efficacy (AUC, 95% CI: 0.69–0.97, p = 0.001) when 37.4 ng/mL is used as cut-off value in ANP group, and with 0.78 efficacy (AUC, 95% CI: 0.65–0.92, p = 0.0009) in the whole asthmatic cohort. In conclusion circulating HA might be a marker of asthma control, as it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease of HA level in pregnancy may be the consequence of pregnancy induced immune tolerance. PMID:24736408

  11. Air trapping on HRCT in asthmatics: correlation with pulmonary function test

    International Nuclear Information System (INIS)

    Hwang, Jung Hwa; Cha, Chull Hee; Park, Jai Soung; Kim, Young Beom; Lee, Hae Kyung; Choi, Deuk Lin; Kim, Kyung Ho; Park, Choon Sik

    1997-01-01

    To evaluate on the basis of the pulmonary function test the correlation between the extent of air trapping on HRCT with the severity of airway obstruction and also to identify the prognostic effect of the extent of air trapping after treatment of asthma. Thirty five patients with clinically diagnosed bronchial asthma and air trapping, as seen on HRCT, were included in this study. We quantitatively analysed on HRCT the extent of air trapping and then statistically compared this with the clinical parameters of the pulmonary function test. We classified the patients into two groups on the basis of the pulmonary function test and clinical status : Group 1 (N=35), the total number of asthmatic patients; Group 2 (N=18), relatively stable asthmatics without acute asthmatic attack who showed FEV1 of more than 80% of the predicted value. Using the functional paramenters of PEFR, one of the obijective indicators of improvement in airway obstruction, we also classified the patients into three groups on the basis of interval between treatment and clinical improvement. The result of this was as follows : group 1, asymptomatic group (initial PEFR within normal limit, N=7); group 2, early responder (improvement of PEFR within three hospital days, N=18); group 3, late responder (improvement of PEFR within fourteen hospital days should there be a number here). Using HRCT, we then statistically analysed the differences between the three groups in the extent of air trapping. Among the total of 35 asthmatics, the extent of air trapping on HRCT showed significant correlation with FEV1 (r= -0.6161, p < 0.001) and MEFR (r= -0.6012, p < 0.001). Among the relatively stable asthmatics who showed FEV1 more than 80% of the predicted value, MEFR (r= -0.7553, p < 0.001) and FEF75 (r= -0.7529, p=0.012) showed statistically significant correlation with the extent of air trapping on HRCT, but there was no significant correlation between air trapping on HRCT and FEV1. In the three groups of

  12. Airflow pattern complexity and airway obstruction in asthma.

    Science.gov (United States)

    Veiga, Juliana; Lopes, Agnaldo J; Jansen, José M; Melo, Pedro L

    2011-08-01

    The scientific and clinical value of a measure of complexity is potentially enormous because complexity appears to be lost in the presence of illness. The authors examined the effect of elevated airway obstruction on the complexity of the airflow (Q) pattern of asthmatic patients analyzing the airflow approximate entropy (ApEnQ). This study involved 11 healthy controls, 11 asthmatics with normal spirometric exams, and 40 asthmatics with mild (14), moderate (14), and severe (12) airway obstructions. A significant (P fundamentals and suggest that the airflow pattern becomes less complex in asthmatic patients, which may reduce the adaptability of the respiratory system to perform the exercise that is associated with daily life activities. This analysis was able to identify respiratory changes in patients with mild obstruction with an adequate accuracy (83%). Higher accuracies were obtained in patients with moderate and severe obstructions. The analysis of airflow pattern complexity by the ApEnQ was able to provide new information concerning the changes associated with asthma. In addition, this analysis was also able to contribute to the detection of the adverse effects of asthma. Because these measurements are easy to perform, such a technique may represent an alternative and/or a complement to other conventional exams to help the clinical evaluations of asthmatic patients.

  13. Airway responses and inflammation in subjects with asthma after four days of repeated high-single-dose allergen challenge

    Directory of Open Access Journals (Sweden)

    Schulze Johannes

    2012-09-01

    Full Text Available Abstract Background Both standard and low-dose allergen provocations are an established tool in asthma research to improve our understanding of the pathophysiological mechanism of allergic asthma. However, clinical symptoms are less likely to be induced. Therefore, we designed a protocol for repetitive high-dose bronchial allergen challenges to generate clinical symptoms and airway inflammation. Methods A total of 27 patients aged 18 to 40 years with positive skin-prick tests and mild asthma underwent repetitive high-dose allergen challenges with household dust mites for four consecutive days. Pulmonary function and exhaled NO were measured at every visit. Induced sputum was analysed before and after the allergen challenges for cell counts, ECP, IL-5, INF-γ, IL-8, and the transcription factor Foxp3. Results We found a significant decrease in pulmonary function, an increased use of salbutamol and the development of a late asthmatic response and bronchial hyperresponsiveness, as well as a significant induction of eNO, eosinophils, and Th-2 cytokines. Repeated provocation was feasible in the majority of patients. Two subjects had severe adverse events requiring prednisolone to cope with nocturnal asthma symptoms. Conclusions Repeated high-dose bronchial allergen challenges resulted in severe asthma symptoms and marked Th-2-mediated allergic airway inflammation. The high-dose challenge model is suitable only in an attenuated form in diseased volunteers for proof-of-concept studies and in clinical settings to reduce the risk of severe asthma exacerbations. Trial registration ClinicalTrials.govNCT00677209

  14. [Severe asthmatic crisis during general anesthesia in a patient with IgG4 related disease].

    Science.gov (United States)

    Moriya, Machika; Oda, Shinya; Nakane, Masaki; Kawamae, Kaneyuki

    2014-04-01

    We experienced severe asthmatic crisis during general anesthesia in a 45-year-old man with IgG4-related disease, COPD and athma undergoing removal of submandibular gland. The ventilatiory failure was caused by the stimulation of the operation, sputum, and neostigmine. His serum IgG4 level was extremely high. IgG4 related disease is a recently emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. It is associated with an elevated serum level of IgG4 and an allergic disease. We must be careful in perioperative management of the patients with IgG4-related disease because general anesthesia can induce asthmatic crisis.

  15. Pharmacokinetics of nebulized and oral procaterol in asthmatic and non-asthmatic subjects in relation to doping analysis

    DEFF Research Database (Denmark)

    Krogh, Nanna; Backer, Vibeke; Rzeppa, Sebastian

    2016-01-01

    The purpose of the present study was to investigate pharmacokinetics of procaterol in asthmatics and non-asthmatics after nebulized and oral administration in relation to doping. Ten asthmatic and ten non-asthmatic subjects underwent two pharmacokinetic trials. At first trial, 4 μg procaterol was...

  16. Illicium verum Extract and Trans-Anethole Attenuate Ovalbumin-Induced Airway Inflammation via Enhancement of Foxp3+ Regulatory T Cells and Inhibition of Th2 Cytokines in Mice.

    Science.gov (United States)

    Sung, Yoon-Young; Kim, Seung-Hyung; Kim, Dong-Seon; Lee, Ji-Eun; Kim, Ho Kyoung

    2017-01-01

    Illicium verum is used in traditional medicine to treat inflammation. The study investigates the effects of IVE and its component, trans -anethole (AET), on airway inflammation in ovalbumin- (OVA-) induced asthmatic mice. Asthma was induced in BALB/c mice by systemic sensitization to OVA, followed by intratracheal, intraperitoneal, and aerosol allergen challenges. IVE and AET were orally administered for four weeks. We investigated the effects of treatment on airway hyperresponsiveness, IgE production, pulmonary eosinophilic infiltration, immune cell phenotypes, Th2 cytokine production in bronchoalveolar lavage, Th1/Th2 cytokine production in splenocytes, forkhead box protein 3 (Foxp3) expression, and lung histology. IVE and AET ameliorated OVA-driven airway hyperresponsiveness ( p < 0.01), pulmonary eosinophilic infiltration ( p < 0.05), mucus hypersecretion ( p < 0.01), and IL-4, IL-5, IL-13, and CCR3 production ( p < 0.05), as well as IgE levels ( p < 0.01). IVE and AET increased Foxp3 expression in lungs ( p < 0.05). IVE and AET reduced IL-4 and increased IFN- γ production in the supernatant of splenocyte cultures ( p < 0.05). Histological studies showed that IVE and AET inhibited eosinophilia and lymphocyte infiltration in lungs ( p < 0.01). These results indicate that IVE and AET exert antiasthmatic effects through upregulation of Foxp3 + regulatory T cells and inhibition of Th2 cytokines, suggesting that IVE may be a potential therapeutic agent for allergic lung inflammation.

  17. Illicium verum Extract and Trans-Anethole Attenuate Ovalbumin-Induced Airway Inflammation via Enhancement of Foxp3+ Regulatory T Cells and Inhibition of Th2 Cytokines in Mice

    Directory of Open Access Journals (Sweden)

    Yoon-Young Sung

    2017-01-01

    Full Text Available Illicium verum is used in traditional medicine to treat inflammation. The study investigates the effects of IVE and its component, trans-anethole (AET, on airway inflammation in ovalbumin- (OVA- induced asthmatic mice. Asthma was induced in BALB/c mice by systemic sensitization to OVA, followed by intratracheal, intraperitoneal, and aerosol allergen challenges. IVE and AET were orally administered for four weeks. We investigated the effects of treatment on airway hyperresponsiveness, IgE production, pulmonary eosinophilic infiltration, immune cell phenotypes, Th2 cytokine production in bronchoalveolar lavage, Th1/Th2 cytokine production in splenocytes, forkhead box protein 3 (Foxp3 expression, and lung histology. IVE and AET ameliorated OVA-driven airway hyperresponsiveness (p<0.01, pulmonary eosinophilic infiltration (p<0.05, mucus hypersecretion (p<0.01, and IL-4, IL-5, IL-13, and CCR3 production (p<0.05, as well as IgE levels (p<0.01. IVE and AET increased Foxp3 expression in lungs (p<0.05. IVE and AET reduced IL-4 and increased IFN-γ production in the supernatant of splenocyte cultures (p<0.05. Histological studies showed that IVE and AET inhibited eosinophilia and lymphocyte infiltration in lungs (p<0.01. These results indicate that IVE and AET exert antiasthmatic effects through upregulation of Foxp3+ regulatory T cells and inhibition of Th2 cytokines, suggesting that IVE may be a potential therapeutic agent for allergic lung inflammation.

  18. In vitro histamine release from basophils of asthmatic and atopic individuals in D2O

    International Nuclear Information System (INIS)

    Tung, R.; Lichtenstein, L.M.

    1982-01-01

    It was found that spontaneous histamine release from human basophils in H 2 O-based buffers is negligible; in D 2 O-based buffers, however, release is observed with the cells of some donors. Analysis of this phenomenon revealed release from the basophils of 1 of 22 control individuals (5%), 15 of 47 patients with allergic rhinitis (32%), and 14 of 20 asthmatic patients (70%). The difference between both patient groups and controls and between atopics and asthmatics was highly significant. That D 2 O release was not cytotoxic is suggested by the finding that 37 0 was optimal, with inhibition at 4 0 C or 46 0 C as well as by EDTA, 2-deoxyglucose, and dibromoacetophenone, an inhibitor of phospholipase A 2 . The release mechanism was unusual in that dibutyryl cAMP and agonists that cause an increase in cAMP lead to no inhibition. No correlation was noted between the total serum IgE level (and thus the number of IgE receptors on the basophil surface) and the magnitude of D 2 O release. No increase in D 2 O release was observed in 17 ragweed-sensitive patients through a ragweed season. A unique property of D 2 O release was the loss of reactivity by preincubating cells at 37 0 C for 30 min before adding D 2 O. Non-D 2 O-reactive cells could be ''converted'' to D 2 O-reactive cells by incubation with antigen in the whole blood phase during leukocyte isolation; these cells showed the same loss of releaseability at 37 0 C and an inhibitor profile similar to D 2 O-responsive cells from ragweed allergic or asthmatic patients. We suggest that D 2 O-based buffers reveal, in atopic and asthmatic patients, in vivo basophil activation; whether this is due to IgE cross-links, to C split products, or to other stimuli is not yet clear

  19. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy ... to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear ...

  20. Time spent in vigorous physical activity is associated with increased exhaled nitric oxide in non-asthmatic adolescents.

    Science.gov (United States)

    Sachs-Olsen, Christine; Berntsen, Sveinung; Lødrup Carlsen, Karin Cecilie; Anderssen, Sigmund Alfred; Mowinckel, Petter; Carlsen, Kai-Håkon

    2013-01-01

    Physical activity (PA) is important in preventing disease, but endurance elite athletes have increased prevalence of asthma and airway inflammation. We aimed to determine if PA was associated with increased fractional exhaled nitric oxide (FENO ) in asthmatic and non-asthmatic adolescents. FENO was recorded (Niox Mino®, Aerocrine AB, Stockholm, Sweden) in 169 adolescents (13-14 years) in a nested case-control analysis from the Environment and Childhood Asthma study, Oslo, 92 adolescents with and 77 without asthma. They underwent clinical examination, lung function measurements and treadmill run measuring peak oxygen uptake, and objectively recorded PA for four consecutive days. PA was classified as moderate, vigorous and very vigorous, and total number of hours of each category was recorded for each subject. Associations between FENO and PA were tested using linear robust multiple regression analyses. In non-asthmatic adolescents, FENO was associated with daily hours of vigorous to very vigorous (r=0.27, P=0.02) and very vigorous PAs (r=0.25, P=0.036) in bivariate analyses. In multivariate analyses, FENO was associated with vigorous to very vigorous PA [regression coefficients (95% confidence interval) 1.9 (0.6, 3.1); P=0.004] and more strongly with very vigorous PA [3.9 (1.5, 6.4); P=0.002] in non-asthmatic but not in asthmatic adolescents. Total daily PA was not associated with FENO in either group. Thus, 1 h of very vigorous PA per day increased FENO by 3.9ppb. Vigorous to very vigorous PA, contrasting total daily PA, was significantly associated with increased FENO in non-asthmatic adolescents, suggesting that intensive PA may induce airway inflammation independent of asthma. © 2012 Blackwell Publishing Ltd.

  1. Allergen-induced bronchial inflammation in house dust mite-allergic patients with or without asthma

    NARCIS (Netherlands)

    Lopuhaä, C. E.; Out, T. A.; Jansen, H. M.; Aalberse, R. C.; van der Zee, J. S.

    2002-01-01

    Background It is presently unknown which factors determine the occurrence and persistence of asthma in house dust mite-allergic individuals. The level of allergen-specific IgE antibodies does not seem to be decisive for asthmatic symptoms. Moreover, levels of exposure to mite allergens do not seem

  2. Differing response of asthmatics to sulfur dioxide exposure with continuous and intermittent exercise

    Energy Technology Data Exchange (ETDEWEB)

    Kehrl, H.R.; Roger, L.J.; Hazucha, M.J.; Horstman, D.H.

    1986-08-29

    Ten mild asthmatics were initially exposed in an environmental chamber (26 C, 70% RH) to clean air and 1.0 ppm sulfur dioxide while performing three sets of 10 minutes treadmill exercise (ventilation = 41 1/min) and 15 minutes rest. To evaluate the effects of the pattern and duration of exercise on the response to sulfur dioxide exposure, the subjects were then exposed to the same environmental conditions, while exercising continuously for 30 minutes. Specific airways resistance (SRaw) was measured by body plethysmography prior to exposures and after each exercise. All SRaw responses with sulfur dioxide exposure were significantly different than the clean air responses. It appears that asthmatics show an attenuated response to repetitive exercise in a 1.00 ppm sulfur dioxide atmosphere and that the response to sulfur dioxide exposure develops rapidly and is maintained during 30 minutes continuous exercise.

  3. Non-invasive sampling methods of inflammatory biomarkers in asthma and allergic rhinitis

    NARCIS (Netherlands)

    Boot, Johan Diderik

    2009-01-01

    In this thesis, a series of clinical studies have been described, in which we applied, evaluated or modified novel and existing non- or semi-invasive sampling methods and detection techniques for the assessment of biomarkers in allergic airway inflammation.

  4. Tai-Chi-Chuan Exercise Improves Pulmonary Function and Decreases Exhaled Nitric Oxide Level in Both Asthmatic and Nonasthmatic Children and Improves Quality of Life in Children with Asthma

    Directory of Open Access Journals (Sweden)

    Hsin-Chia Lin

    2017-01-01

    Full Text Available Tai-Chi-Chuan (TCC is an exercise of low-to-moderate intensity which is suitable for asthmatic patients. The aim of our study is to investigate improvements of the lung function, airway inflammation, and quality of life of asthmatic children after TCC. Participants included sixty-one elementary school students and they were divided into asthmatic (n=29 and nonasthmatic (n=32 groups by the International Study of Asthma and Allergies in Childhood (ISAAC questionnaire. Among them, 20 asthmatic and 18 nonasthmatic children volunteered to participate in a 60-minute TCC exercise weekly for 12 weeks. Baseline and postintervention assessments included forced expiratory volume in one second (FEV1, forced vital capacity (FVC, peak expiratory flow rate (PEFR, fractional exhaled nitric oxide (FeNO level, and Standardised Pediatric Asthma Quality of Life Questionnaire (PAQLQ(S. After intervention, the level of FeNO decreased significantly; PEFR and the FEV1/FVC also improved significantly in both asthmatic group and nonasthmatic group after TCC. The asthmatic children also had improved quality of life after TCC. The results indicated that TCC could improve the pulmonary function and decrease airway inflammation in both children with mild asthma and those without asthma. It also improves quality of life in mild asthmatic children. Nevertheless, further studies are required to determine the effect of TCC on children with moderate-to-severe asthma.

  5. Asthma control in severe asthmatics under treatment with omalizumab: a cross-sectional observational study in Italy.

    Science.gov (United States)

    Novelli, Federica; Latorre, Manuela; Vergura, Letizia; Caiaffa, Maria Filomena; Camiciottoli, Gianna; Guarnieri, Gabriella; Matucci, Andrea; Macchia, Luigi; Vianello, Andrea; Vultaggio, Alessandra; Celi, Alessandro; Cazzola, Mario; Paggiaro, Pierluigi

    2015-04-01

    Few data are available on the proportion of asthmatics achieving a good asthma control (according GINA guidelines) and on the level of airway inflammation during omalizumab treatment. The aim of this cross-sectional national observational study was to assess the level of control (according to GINA guidelines) achieved in a group of asthmatics on omalizumab treatment, and to characterize the factors that influence the lack of control. We studied 306 asthmatics under omalizumab treatment for a median of 32 months (range 4-120). The level of control according to GINA was good in 25.2%, partial in 47.1% and poor in 24.5% of patients (data were missing for the remaining 3.2%). Comparison between poorly controlled and partially or well controlled asthmatics showed a statistically significant higher prevalence of some comorbidities in the first group, namely obesity, gastro-oesophageal reflux disease (GORD), aspirin intolerance and mental disorders (all p omalizumab treatment, a high percentage of asthmatics obtain a good or partial control of asthma. Comorbidities are associated with the lack of asthma control and persistence of exacerbations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Defective Resensitization in Human Airway Smooth Muscle Cells Evokes β-Adrenergic Receptor Dysfunction in Severe Asthma.

    Directory of Open Access Journals (Sweden)

    Manveen K Gupta

    Full Text Available β2-adrenergic receptor (β2AR agonists (β2-agonist are the most commonly used therapy for acute relief in asthma, but chronic use of these bronchodilators paradoxically exacerbates airway hyper-responsiveness. Activation of βARs by β-agonist leads to desensitization (inactivation by phosphorylation through G-protein coupled receptor kinases (GRKs which mediate β-arrestin binding and βAR internalization. Resensitization occurs by dephosphorylation of the endosomal βARs which recycle back to the plasma membrane as agonist-ready receptors. To determine whether the loss in β-agonist response in asthma is due to altered βAR desensitization and/or resensitization, we used primary human airway smooth muscle cells (HASMCs isolated from the lungs of non-asthmatic and fatal-asthmatic subjects. Asthmatic HASMCs have diminished adenylyl cyclase activity and cAMP response to β-agonist as compared to non-asthmatic HASMCs. Confocal microscopy showed significant accumulation of phosphorylated β2ARs in asthmatic HASMCs. Systematic analysis of desensitization components including GRKs and β-arrestin showed no appreciable differences between asthmatic and non-asthmatic HASMCs. However, asthmatic HASMC showed significant increase in PI3Kγ activity and was associated with reduction in PP2A activity. Since reduction in PP2A activity could alter receptor resensitization, endosomal fractions were isolated to assess the agonist ready β2ARs as a measure of resensitization. Despite significant accumulation of β2ARs in the endosomes of asthmatic HASMCs, endosomal β2ARs cannot robustly activate adenylyl cyclase. Furthermore, endosomes from asthmatic HASMCs are associated with significant increase in PI3Kγ and reduced PP2A activity that inhibits β2AR resensitization. Our study shows that resensitization, a process considered to be a homeostasis maintaining passive process is inhibited in asthmatic HASMCs contributing to β2AR dysfunction which may underlie

  7. Anxiety and stress in mothers of food-allergic children.

    Science.gov (United States)

    Lau, Gar-Yen; Patel, Nisha; Umasunthar, Thisanayagam; Gore, Claudia; Warner, John O; Hanna, Heather; Phillips, Katherine; Zaki, Amirah Mohd; Hodes, Matthew; Boyle, Robert J

    2014-05-01

    Previous reports suggest that parents especially mothers of food-allergic children may have increased anxiety. Studies with an appropriate control group have not been undertaken, and the determinants of such anxiety are not known. We compared measures of anxiety and stress in mothers of food-allergic children and atopic non-food-allergic children, with anxiety and stress in mothers of children with no chronic illness. Cross-sectional study of mothers attending a hospital appointment for their 8- to 16-year-old child. Mothers of children with food allergy, asthma but no food allergy or no chronic illness completed questionnaires including State-Trait Anxiety Inventory, Perceived Stress Scale and measures of anxiety and psychologic adjustment in their child. Forty mothers of food-allergic children, 18 mothers of asthmatic children without food allergy and 38 mothers of children with no chronic illness (controls) were recruited. Mothers of food-allergic children showed increased state anxiety – median anxiety score 38.0 (IQR 30.0, 44.0) food allergy, 27.0 (22.0, 40.0) control p = 0.012; and increased stress – median stress score 18.5 (12.0, 22.0) food allergy, 14.0 (7.5, 19.5)control p = 0.035. No significant differences were seen between mothers in the asthmatic group and controls. In multivariate analysis, previous food anaphylaxis(p = 0.008) and poorly controlled asthma (p = 0.004) were associated with increased maternal anxiety. Child anxiety and adjustment did not differ between food-allergic and control groups. Mothers of food-allergic children have increased anxiety and stress compared with mothers of children with no chronic illness. Anaphylaxis and poorly controlled asthma are associated with maternal anxiety.

  8. Airway responsiveness to mannitol in asthma is associated with chymase-positive mast cells and eosinophilic airway inflammation

    DEFF Research Database (Denmark)

    Sverrild, Asger; Bergqvist, A; Baines, K J

    2016-01-01

    BACKGROUND: Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway...... tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell-associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol. METHODS: Airway hyperresponsiveness to inhaled mannitol was measured in 23 non......-smoking, corticosteroid-free asthmatic individuals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were divided into phenotypes based on the presence of chymase. mRNA expression of mast cell-associated genes was measured by real-time PCR. RESULTS...

  9. Outdoor air pollution, climatic changes and allergic bronchial asthma.

    Science.gov (United States)

    D'Amato, G; Liccardi, G; D'Amato, M; Cazzola, M

    2002-09-01

    Both the prevalence and severity of respiratory allergic diseases such as bronchial asthma have increased in recent years. Among the factors implicated in this "epidemic" are indoor and outdoor airborne pollutants. Urbanisation with its high levels of vehicle emissions and Westernised lifestyle parallels the increase in respiratory allergy in most industrialised countries, and people who live in urban areas tend to be more affected by the disease than those of rural areas. In atopic subjects, exposure to air pollution increases airway responsiveness to aeroallergens. Pollen is a good model with which to study the interrelationship between air pollution and respiratory allergic diseases. Biological aerosols carrying antigenic proteins, such as pollen grains or plant-derived paucimicronic components, can produce allergic symptoms. By adhering to the surface of these airborne allergenic agents, air pollutants could modify their antigenic properties. Several factors influence this interaction, i.e., type of air pollutant, plant species, nutrient balance, climatic factors, degree of airway sensitisation and hyperresponsiveness of exposed subjects. However, the airway mucosal damage and the impaired mucociliary clearance induced by air pollution may facilitate the penetration and the access of inhaled allergens to the cells of the immune system, and so promote airway sensitisation. As a consequence, an enhanced immunoglobulin E-mediated response to aeroallergens and enhanced airway inflammation favoured by air pollution could account for the increasing prevalence of allergic respiratory diseases in urban areas.

  10. HRCT findings of asthmatic children under maintenance therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Hyun Sook; Park, Jai Soung; Goo, Dong Erk; Lee, Hae Kyung; Kwon, Kui Hyang; Choi, Deuk Lin; Pyun, Bok Yang [Soonchunhyang University Hospital, Seoul (Korea, Republic of)

    2000-05-01

    The purpose of this study was to evaluate the HRCT findings of bronchial asthma during maintenance bronchodilator therapy and to determine whether there were irreversible bronchial changes occurred in pediatric patients with this condition. HRCT findings of the lung in 21 asthmatic children (14 boys and 7 girls aged between 3.5 and 13.8 (mean: 7.7) years) who were receiving maintenance bronchodilator therapy were retrospectively studied. At the time of CT examination, 16 were receiving nonsteroid bronchodilator therapy only, and five were receiving both bronchodilator and steroid therapy. Thirteen patients were defined as allergic and eight were nonallergic. The clinical severity of chronic asthma was graded as severe in seven cases, and moderate in 14. The duration of the disease ranged from 4 months to 6 years (mean 3.2 years). HRCT was performed in 19 cases for evaluation of the atelectasis, hyperinflation, and prominent bronchovascular bundles seen on plain radiographs, and in two cases for evaluation following acute exacerbation. A CT W-2000 scanner (Hitachi Medical Co. Tokyo, Japan) was used during the end inspiratory phase, and in addition, ten patients were scanned during the expiratory phase. Scans were reviewed for evidence of bronchial thickening, bronchiectasis, emphysema, abnormal density, mucus plugs, and other morphological abnormalities. The presence of bronchial wall thickening or air trapping was evaluated according to the duration, severity and type of asthma. Among the 21 patients, 7 (33.3%) had normal HRCT findings, while in 14 (66.7%), bronchial wall thickening was demonstrated. Eleven of the 14 patients with bronchial wall thickening(78.6%) also had air trapping. No patient was suffering from bronchiectasis or emphysema. There were no statistically significant correlations between the presence of bronchial wall thickening or air trapping and the duration of the disease, its severity, or type of asthma. There was, however, a statistically

  11. Reversibility of pulmonary function after inhaling salbutamol in different doses and body postures in asthmatic children.

    Science.gov (United States)

    Visser, R; Kelderman, S; de Jongh, F H C; van der Palen, J; Thio, B J

    2015-10-01

    Pulmonary medication is often delivered in the form of medical aerosols designed for inhalation. Recently, breath actuated inhalers (BAI's) gained popularity as they can be used without spacers. A major drawback of BAI's is the impaction in the upper airway. Stretching the upper airway by a forward leaning body posture with the neck extended ("sniffing position") during inhalation may reduce upper airway impaction and improve pulmonary deposition. Aim of this study was to investigate the reversibility of lung function with different doses salbutamol inhaled with a BAI in the forward leaning posture compared to the standard posture in asthmatic children. 22 clinically stable asthmatic children, 5-14 years old, performed four reversibility measurements. Children inhaled 200 μg or 400 μg salbutamol with a BAI in the standard or in the forward leaning posture with the neck extended in a randomized single-blinded cross-over design. Reversibility of lung function after inhaling salbutamol in the forward leaning posture was not significantly different compared to inhalation in the standard posture. Mean FEV1 reversibility was significantly greater after inhaling 400 μg salbutamol compared to 200 μg salbutamol in the standard posture (9.4% ± 9.5% versus 4.5% ± 7.5%, difference 4.9% (95CI 0.9; 9.0%); p = 0.021). In clinically stable asthmatic children, inhalation of salbutamol with a BAI in a forward leaning posture does not increase reversibility of lung function. Inhalation of 400 μg compared to 200 μg salbutamol with a BAI does improve reversibility. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Early-lifetime exposure to air pollution and allergic sensitization in children with asthma.

    Science.gov (United States)

    Mortimer, Kathleen; Neugebauer, Romain; Lurmann, Frederick; Alcorn, Siana; Balmes, John; Tager, Ira

    2008-12-01

    Observations on the association between exposure to common outdoor air pollutants and allergic sensitization have not been consistent. Little research has been done on the effects of prenatal exposure or the effect among asthmatics. The association between prenatal and early-life exposures and outdoor air pollutants with allergic sensitization was examined within a cohort of 170 children ages 6-11 years with asthma, living in the Central Valley of California. Allergic sensitization was ascertained by skin-prick tests to 14 allergens. Prenatal and early-life exposure to ozone (O(3)), nitrogen dioxide (NO(2)), carbon monoxide (CO) and particulate matter with a median aerodynamic diameter pollutants were seen for sensitization to allergens in general or to at least one indoor allergen. Exposure to traffic-related pollutants during pregnancy may increase the risk of sensitization to outdoor allergens among asthmatic children.

  13. Limonene and its ozone-initiated reaction products attenuate allergic lung inflammation in mice

    DEFF Research Database (Denmark)

    Hansen, Jitka S; Nørgaard, Asger W; Koponen, Ismo K

    2016-01-01

    and pulmonary irritation was investigated in addition to ovalbumin-specific antibodies, inflammatory cells, total protein and surfactant protein D in bronchoalveolar lavage fluid and hemeoxygenase-1 and cytokines in lung tissue. Overall, airway allergy was not exacerbated by any of the exposures. In contrast...... or the reaction mixture can exacerbate allergic lung inflammation and whether airway irritation is enhanced in allergic BALB/cJ mice. Naïve and allergic (ovalbumin sensitized) mice were exposed via inhalation for three consecutive days to clean air, ozone, limonene or an ozone-limonene reaction mixture. Sensory......, it was found that limonene and the ozone-limonene reaction mixture reduced allergic inflammation possibly due to antioxidant properties. Ozone induced sensory irritation in both naïve and allergic mice. However, allergic but not naïve mice were protected from pulmonary irritation induced by ozone. This study...

  14. A Population-based Clinical Study of Allergic and Non-allergic Asthma

    DEFF Research Database (Denmark)

    Knudsen, T.B.; Thomsen, S.F.; Nolte, H.

    2009-01-01

    to have AHR, OR = 0.40, (0.24-0.66), p 0.001, food allergy, OR = 0.28, (0.11-0.73), p = 0.009, and symptoms of rhinitis, OR = 0.08 (0.05-0.14) compared with subjects with allergic asthma. Subjects with non-allergic asthma had had persistent symptoms within the last 4 weeks more often than subjects......Background. The aim of this study was to describe differences between allergic and non-allergic asthma in a large community-based sample of Danish adolescents and adults. Methods. A total of 1,186 subjects, 14 to 44 years of age, who in a screening questionnaire had reported a history of airway...... individuals had clinical asthma of whom 61% had allergic asthma, whereas 39% had non-allergic asthma. Subjects with non-allergic asthma were more likely to be females, OR = 2.24 (1.32-3.72), p = 0.003, and to have cough as the predominant symptom, OR = 1.96, (1.19-3.23), p = 0.008, but were less likely...

  15. Fragranced consumer products: effects on asthmatics.

    Science.gov (United States)

    Steinemann, Anne

    2018-01-01

    Fragranced consumer products, such as cleaning supplies, air fresheners, and personal care products, can emit a range of air pollutants and trigger adverse health effects. This study investigates the prevalence and types of effects of fragranced products on asthmatics in the American population. Using a nationally representative sample ( n  = 1137), data were collected with an on-line survey of adults in the USA, of which 26.8% responded as being medically diagnosed with asthma or an asthma-like condition. Results indicate that 64.3% of asthmatics report one or more types of adverse health effects from fragranced products, including respiratory problems (43.3%), migraine headaches (28.2%), and asthma attacks (27.9%). Overall, asthmatics were more likely to experience adverse health effects from fragranced products than non-asthmatics (prevalence odds ratio [POR] 5.76; 95% confidence interval [CI] 4.34-7.64). In particular, 41.0% of asthmatics report health problems from air fresheners or deodorizers, 28.9% from scented laundry products coming from a dryer vent, 42.3% from being in a room cleaned with scented products, and 46.2% from being near someone wearing a fragranced product. Of these effects, 62.8% would be considered disabling under the definition of the Americans with Disabilities Act. Yet 99.3% of asthmatics are exposed to fragranced products at least once a week. Also, 36.7% cannot use a public restroom if it has an air freshener or deodorizer, and 39.7% would enter a business but then leave as quickly as possible due to air fresheners or some fragranced product. Further, 35.4% of asthmatics have lost workdays or a job, in the past year, due to fragranced product exposure in the workplace. More than twice as many asthmatics would prefer that workplaces, health care facilities and health care professionals, hotels, and airplanes were fragrance-free rather than fragranced. Results from this study point to relatively simple and cost-effective ways to

  16. Temporal relationship of allergic rhinitis with asthma and other co-morbidities in a Mediterranean country: a retrospective study in a tertiary reference allergy clinic.

    Science.gov (United States)

    Makris, M; Koulouris, S; Koti, I; Aggelides, X; Sideri, K; Chliva, C; Vassilatou, E; Kalogeromitros, D

    2010-01-01

    Allergic rhinitis is a global health problem which causes major illness and represents a risk factor for asthma. The primary aim of the study was to record the clinical pattern of allergic rhinitis and its temporal relation with asthma in a Greek population. Three-hundred and sixteen subjects with documented diagnosis of allergic rhinitis in a two-year period were included in this study. All participants completed a standardised questionnaire with full retrospective epidemiological data for rhinitis; in addition, serum IgE measurement and skin prick tests with 22 common inhalant allergens were carried out, while spirometry was performed in subjects with self-reported or doctor-diagnosed asthma. All subjects with at least one positive skin test were included in study analysis. One-hundred and sixty five out of 316 patients (49.1%) stated self reported-asthma while in 63/316 (19.9%) asthma was documented with spirometry. One hundred out of 165 (60.6%) had rhinitis as first clinical manifestation while in 24/165 (14.5%) asthma symptoms appeared first; the remaining 31/165 (24.9%) reported simultaneous onset of upper and lower airways' symptoms. About 68.5% were sensitised to seasonal allergens exclusively, while 50% were sensitised to ≥ 1 of Parietaria, grasses sp., Olea eur. The duration of rhinitis in the subpopulation of patients with self-reported asthma (n=165) was significantly higher compared with non-asthmatics (mean=3.22 years, p<0.001). Survival analysis for the estimation of asthma onset showed that the mean time interval with rhinitis only is 16.6 years (median 12 years, incidence 0.0596). The unique environmental conditions and the aerobiology of each area clearly affect the clinical features of respiratory allergy. Copyright © 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

  17. Comparison between exercise performance in asthmatic children and healthy controls--Physical Activity Questionnaire application.

    Science.gov (United States)

    Santos-Silva, Rita; Melo, Cláudia; Gonçalves, Daniel; Coelho, Janine; Carvalho, Fernanda

    2014-01-01

    The PAQ questionnaire (Physical Activity Questionnaire - Kowalski, Crocker, Donen) is a self-administered 7-day recall validated questionnaire that measures physical activity levels in young people. A final activity score is obtained (1 indicates low and 5 indicates high physical activity level). Our aim was to determine whether there was any difference between the level of physical activity of children with controlled allergic disease and healthy children. We used the PAQ questionnaire with a group of asthmatic children attending hospital outpatient clinic and a group of healthy children matched for age. 155 children with allergic disease (median age of 11 years; 63% males) and 158 healthy controls (median age of 10 years; 46% males) answered the questionnaire. There were no differences in the overall level of physical activity, estimated by PAQ score, between allergic and healthy children (2,40±0,7 vs 2,48±0,62; p=0,32). Performance in physical education classes and after school sports activity was found to be different between the study groups; healthy children were more active (p=0,011) and did more sports between 6 and 10 pm (p=0,036). No other statistically significant differences were found between the study groups. Despite the fact that a majority of the parents of allergic children stated that their child's disease was a barrier to physical activity, in our study there seems to be no difference between the level of physical activity of controlled asthmatic children and their healthy peers. Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  18. Laryngeal effects of nasal allergen provocation in singers with allergic rhinitis

    NARCIS (Netherlands)

    Verguts, Monique M. L.; Eggermont, Anita; Decoster, Wivine; de Jong, Felix I. C. R. S.; Hellings, Peter W.

    2011-01-01

    In spite of our recent insight into nasobronchial interaction mechanisms in allergic airway disease, the association between allergic rhinitis and voice complaints remains obscure. To evaluate the effects of nasal allergen provocation and seasonal grass pollen exposure on subjective and objective

  19. Exacerbation of asthma and airway infection: is the virus the villain?

    Directory of Open Access Journals (Sweden)

    Lusmaia D.C. Costa

    2014-11-01

    Conclusions: Respiratory viruses are present in the majority of asthmatic children during episodes of exacerbation. The involved physiopathological mechanisms are yet to be fully established, and the synergism between allergic inflammation and viral infection appears to determine uncontrolled disease. The role of other triggering and protective agents is yet to be clearly determined.

  20. A Population-based Clinical Study of Allergic and Non-allergic Asthma

    DEFF Research Database (Denmark)

    Knudsen, T.B.; Thomsen, S.F.; Nolte, H.

    2009-01-01

    Background. The aim of this study was to describe differences between allergic and non-allergic asthma in a large community-based sample of Danish adolescents and adults. Methods. A total of 1,186 subjects, 14 to 44 years of age, who in a screening questionnaire had reported a history of airway...... symptoms suggestive of asthma and/or allergy, or who were taking any medication for these conditions were clinically examined. All participants were interviewed about respiratory symptoms, and furthermore skin test reactivity, lung function, and airway responsiveness were measured. Results. A total of 489...... individuals had clinical asthma of whom 61% had allergic asthma, whereas 39% had non-allergic asthma. Subjects with non-allergic asthma were more likely to be females, OR = 2.24 (1.32-3.72), p = 0.003, and to have cough as the predominant symptom, OR = 1.96, (1.19-3.23), p = 0.008, but were less likely...

  1. The impact of allergic rhinitis and asthma on human nasal and bronchial epithelial gene expression.

    Directory of Open Access Journals (Sweden)

    Ariane H Wagener

    Full Text Available BACKGROUND: The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium. OBJECTIVE: Defining gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. METHODS: This cross-sectional study included 18 subjects (6 allergic asthma and allergic rhinitis; 6 allergic rhinitis; 6 healthy controls. The estimated false discovery rate comparing 6 subjects per group was approximately 5%. RNA was extracted from isolated and cultured epithelial cells from bronchial brushings and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array. Data were analysed using R and Bioconductor Limma package. For gene ontology GeneSpring GX12 was used. RESULTS: The study was successfully completed by 17 subjects (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls. Using correction for multiple testing, 1988 genes were differentially expressed between healthy lower and upper airway epithelium, whereas in allergic rhinitis with or without asthma this was only 40 and 301 genes, respectively. Genes influenced by allergic rhinitis with or without asthma were linked to lung development, remodeling, regulation of peptidases and normal epithelial barrier functions. CONCLUSIONS: Differences in epithelial gene expression between the upper and lower airway epithelium, as observed in healthy subjects, largely disappear in patients with allergic rhinitis with or without asthma, whilst new differences emerge. The present data identify several pathways and genes that might be

  2. The Impact of Allergic Rhinitis and Asthma on Human Nasal and Bronchial Epithelial Gene Expression

    Science.gov (United States)

    Wagener, Ariane H.; Zwinderman, Aeilko H.; Luiten, Silvia; Fokkens, Wytske J.; Bel, Elisabeth H.; Sterk, Peter J.; van Drunen, Cornelis M.

    2013-01-01

    Background The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium. Objective Defining gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. Methods This cross-sectional study included 18 subjects (6 allergic asthma and allergic rhinitis; 6 allergic rhinitis; 6 healthy controls). The estimated false discovery rate comparing 6 subjects per group was approximately 5%. RNA was extracted from isolated and cultured epithelial cells from bronchial brushings and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array). Data were analysed using R and Bioconductor Limma package. For gene ontology GeneSpring GX12 was used. Results The study was successfully completed by 17 subjects (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). Using correction for multiple testing, 1988 genes were differentially expressed between healthy lower and upper airway epithelium, whereas in allergic rhinitis with or without asthma this was only 40 and 301 genes, respectively. Genes influenced by allergic rhinitis with or without asthma were linked to lung development, remodeling, regulation of peptidases and normal epithelial barrier functions. Conclusions Differences in epithelial gene expression between the upper and lower airway epithelium, as observed in healthy subjects, largely disappear in patients with allergic rhinitis with or without asthma, whilst new differences emerge. The present data identify several pathways and genes that might be potential targets for

  3. Acid-Sensing Ion Channel 1a Contributes to Airway Hyperreactivity in Mice

    Science.gov (United States)

    Reznikov, Leah R.; Meyerholz, David K.; Adam, Ryan J.; Abou Alaiwa, Mahmoud; Jaffer, Omar; Michalski, Andrew S.; Powers, Linda S.; Price, Margaret P.; Stoltz, David A.; Welsh, Michael J.

    2016-01-01

    Neurons innervating the airways contribute to airway hyperreactivity (AHR), a hallmark feature of asthma. Several observations suggested that acid-sensing ion channels (ASICs), neuronal cation channels activated by protons, might contribute to AHR. For example, ASICs are found in vagal sensory neurons that innervate airways, and asthmatic airways can become acidic. Moreover, airway acidification activates ASIC currents and depolarizes neurons innervating airways. We found ASIC1a protein in vagal ganglia neurons, but not airway epithelium or smooth muscle. We induced AHR by sensitizing mice to ovalbumin and found that ASIC1a-/- mice failed to exhibit AHR despite a robust inflammatory response. Loss of ASIC1a also decreased bronchoalveolar lavage fluid levels of substance P, a sensory neuropeptide secreted from vagal sensory neurons that contributes to AHR. These findings suggest that ASIC1a is an important mediator of AHR and raise the possibility that inhibiting ASIC channels might be beneficial in asthma. PMID:27820848

  4. General, but not myeloid or type II lung epithelial cell, myeloid differentiation factor 88 deficiency abrogates house dust mite induced allergic lung inflammation

    NARCIS (Netherlands)

    Anas, A. A.; Yang, J.; Daan de Boer, J.; Roelofs, J. J. T. H.; Hou, B.; de Vos, A. F.; van der Poll, T.

    2017-01-01

    Asthma is a highly prevalent chronic allergic inflammatory disease of the airways affecting people worldwide. House dust mite (HDM) is the most common allergen implicated in human allergic asthma. HDM-induced allergic responses are thought to depend upon activation of pathways involving Toll-like

  5. Involvement of tachykinin NK1 receptor in the development of allergen-induced airway hyperreactivity and airway inflammation in conscious, unrestrained guinea pigs

    NARCIS (Netherlands)

    Schuiling, M; Zuidhof, A.B; Zaagsma, Hans; Meurs, Herman

    It has been suggested that tachykinin NK1 receptor-mediated neurogenic inflammation, characterized by microvascular leakage, mucus secretion, and infiltration and activation of inflammatory cells in the airways, may be involved in allergic asthma. Therefore, in a guinea pig model of allergic asthma,

  6. Suppression of Sirtuin-1 Increases IL-6 Expression by Activation of the Akt Pathway During Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Lingling Tang

    2017-10-01

    Full Text Available Background/Aims: A growing number of studies have demonstrated that the activity and expression level of sirtuin-1 (SIRT1 are decreased in asthma patients; however, the mechanisms underlying decreased SIRT1 expression and function are still not completely understood. Interleukin (IL-6 plays important roles in inflammation during allergic asthma. In this study, we examined whether loss of SIRT1 activity regulated the expression of IL-6 and further verified the underlying mechanisms. Methods: The human airway epithelial cell line 16HBE was used to test the effects of the SIRT1 inhibitor (salermide on expression of IL-6. IL-6 mRNA and protein expression were assessed with real-time polymerase chain reaction (PCR, immunochemistry, and ELISA. OVA-challenged mice were used as an asthma model to investigate the effect of SIRT1 activation on IL-6 and relative Akt phosphorylation level. Results: We found that inhibition of SIRT1 increased IL-6 mRNA and protein levels in a time-dependent manner, which was accompanied by increased Akt pathway activation in 16HBE cells. Furthermore activation of Akt showed upregulated expression of the IL-6 protein whereas Akt inhibitor, LY294002 or Akt siRNA significantly inhibited SIRT1-regulated IL-6 expression. Conversely, activation of SIRT1 inhibited Akt activation and IL-6 expression in an asthmatic mice model and 16HBE cells. Conclusion: Our results indicate the potential role of SIRT1 in regulating inflammation by modulation of IL-6 expression in an Akt-dependent manner during allergic asthma.

  7. Allergen-specific subcutaneous immunotherapy in allergic asthma : immunologic mechanisms and improvement

    NARCIS (Netherlands)

    Taher, Yousef A.; Henricks, Paul A. J.; van Oosterhout, Antoon J. M.

    2010-01-01

    Allergic asthma is a disease characterized by persistent allergen-driven airway inflammation, remodeling, and airway hyperresponsiveness. CD4(+) T-cells, especially T-helper type 2 cells, play a critical role in orchestrating the disease process through the release of the cytokines IL-4, IL-5, and

  8. Differences in allergen-induced T cell activation between allergic asthma and rhinitis: Role of CD28, ICOS and CTLA-4

    Directory of Open Access Journals (Sweden)

    Lacoeuille Yannick

    2011-02-01

    Full Text Available Abstract Background Th2 cell activation and T regulatory cell (Treg deficiency are key features of allergy. This applies for asthma and rhinitis. However with a same atopic background, some patients will develop rhinitis and asthma, whereas others will display rhinitis only. Co-receptors are pivotal in determining the type of T cell activation, but their role in allergic asthma and rhinitis has not been explored. Our objective was to assess whether allergen-induced T cell activation differs from allergic rhinitis to allergic rhinitis with asthma, and explore the role of ICOS, CD28 and CTLA-4. Methods T cell co-receptor and cytokine expressions were assessed by flow cytometry in PBMC from 18 house dust mite (HDM allergic rhinitics (R, 18 HDM allergic rhinitics and asthmatics (AR, 13 non allergic asthmatics (A and 20 controls, with or without anti-co-receptors antibodies. Results In asthmatics (A+AR, a constitutive decrease of CTLA-4+ and of CD4+CD25+Foxp3+ cells was found, with an increase of IFN-γ+ cells. In allergic subjects (R + AR, allergen stimulation induced CD28 together with IL-4 and IL-13, and decreased the proportion of CTLA-4+, IL-10+ and CD4+CD25+Foxp3+ cells. Anti-ICOS and anti-CD28 antibodies blocked allergen-induced IL-4 and IL-13. IL-13 production also involved CTLA-4. Conclusions T cell activation differs between allergic rhinitis and asthma. In asthma, a constitutive, co-receptor independent, Th1 activation and Treg deficiency is found. In allergic rhinitis, an allergen-induced Treg cell deficiency is seen, as well as an ICOS-, CD28- and CTLA-4-dependent Th2 activation. Allergic asthmatics display both characteristics.

  9. Tartrazine exclusion for allergic asthma.

    Science.gov (United States)

    Ardern, K D; Ram, F S

    2001-01-01

    Tartrazine is the best known and one of the most commonly used food additives. Food colorants are also used in many medications as well as foods. There has been conflicting evidence as to whether tartrazine causes exacerbations of asthma with some studies finding a positive association especially in individuals with cross-sensitivity to aspirin. To assess the overall effect of tartrazine (exclusion or challenge) in the management of asthma. A search was carried out using the Cochrane Airways Group specialised register. Bibliographies of each RCT was searched for additional papers. Authors of identified RCTs were contacted for further information for their trials and details of other studies. RCTs of oral administration of tartrazine (as a challenge) versus placebo or dietary avoidance of tartrazine versus normal diet were considered. Studies which focused upon allergic asthma, were also included. Studies of tartrazine exclusion for other allergic conditions such as hay fever, allergic rhinitis and eczema were only considered if the results for subjects with asthma were separately identified. Trials could be in either adults or children with asthma or allergic asthma (e.g. sensitivity to aspirin or food items known to contain tartrazine). Study quality was assessed and data abstracted by two reviewers independently. Outcomes were analysed using RevMan 4.1.1. Ninety abstracts were found, of which 18 were potentially relevant. Six met the inclusion criteria, but only three presented results in a format that permitted analysis and none could be combined in a meta-analysis. In none of the studies did tartrazine challenge or avoidance in diet significantly alter asthma outcomes. Due to the paucity of available evidence, it is not possible to provide firm conclusions as to the effects of tartrazine on asthma control. However, the six RCTs that could be included in this review all arrived at the same conclusion. Routine tartrazine exclusion may not benefit most patients

  10. Tomatidine Attenuates Airway Hyperresponsiveness and Inflammation by Suppressing Th2 Cytokines in a Mouse Model of Asthma

    Directory of Open Access Journals (Sweden)

    Chieh-Ying Kuo

    2017-01-01

    Full Text Available Tomatidine is isolated from the fruits of tomato plants and found to have anti-inflammatory effects in macrophages. In the present study, we investigated whether tomatidine suppresses airway hyperresponsiveness (AHR and eosinophil infiltration in asthmatic mice. BALB/c mice were sensitized with ovalbumin and treated with tomatidine by intraperitoneal injection. Airway resistance was measured by intubation analysis as an indication of airway responsiveness, and histological studies were performed to evaluate eosinophil infiltration in lung tissue. Tomatidine reduced AHR and decreased eosinophil infiltration in the lungs of asthmatic mice. Tomatidine suppressed Th2 cytokine production in bronchoalveolar lavage fluid. Tomatidine also blocked the expression of inflammatory and Th2 cytokine genes in lung tissue. In vitro, tomatidine inhibited proinflammatory cytokines and CCL11 production in inflammatory BEAS-2B bronchial epithelial cells. These results indicate that tomatidine contributes to the amelioration of AHR and eosinophil infiltration by blocking the inflammatory response and Th2 cell activity in asthmatic mice.

  11. Immunomodulation of the allergic inflammatory response: new developments.

    Science.gov (United States)

    Araujo, Maria I; Campos, Regis A; Cardoso, Luciana S; Oliveira, Sergio C; Carvalho, Edgar M

    2010-06-01

    Studies of the molecular mechanisms associated with allergic diseases have lead to a better understanding of the complex processes that underlie their pathogenesis. These mechanisms involve Th2- and Th1-type cells and also some recently described cytokines, such as IL-25 and IL-33. Regulatory mechanisms of allergic inflammation have also been identified. For instance, IL-10, a cytokine produced by many cell types, promotes a decrease in IgE production, and inhibits the release of histamine and other inflammatory mediators by mast cells. Recently, a variety of regulatory cells have been discovered, which, either by direct contact or through the production of IL-10 and/or TGF-beta, can inhibit the allergic inflammatory response. IL-10 is produced in high levels by cells of helminth-infected individuals. There is some evidence that such infections protect against the development of allergic diseases. In asthmatic individuals living in endemic areas of schistosomiasis, it has been shown in in vitro studies that there is a modulation of the Th2 response, both by mechanisms involving IL-10, which is produced mainly by monocytes and CD4+CD25+ T regulatory cells, and also by the expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in CD4+ T cells. Studies using parasite antigens to induce the modulation of allergic inflammatory response are being conducted by several groups of researchers and represent new perspectives for the treatment of allergic diseases.

  12. Ozone exposure, vitamin C intake, and genetic susceptibility of asthmatic children in Mexico City: a cohort study

    Science.gov (United States)

    2013-01-01

    Background We previously reported that asthmatic children with GSTM1 null genotype may be more susceptible to the acute effect of ozone on the small airways and might benefit from antioxidant supplementation. This study aims to assess the acute effect of ozone on lung function (FEF25-75) in asthmatic children according to dietary intake of vitamin C and the number of putative risk alleles in three antioxidant genes: GSTM1, GSTP1 (rs1695), and NQO1 (rs1800566). Methods 257 asthmatic children from two cohort studies conducted in Mexico City were included. Stratified linear mixed models with random intercepts and random slopes on ozone were used. Potential confounding by ethnicity was assessed. Analyses were conducted under single gene and genotype score approaches. Results The change in FEF25-75 per interquartile range (60 ppb) of ozone in persistent asthmatic children with low vitamin C intake and GSTM1 null was −91.2 ml/s (p = 0.06). Persistent asthmatic children with 4 to 6 risk alleles and low vitamin C intake showed an average decrement in FEF25-75 of 97.2 ml/s per 60 ppb of ozone (p = 0.03). In contrast in children with 1 to 3 risk alleles, acute effects of ozone on FEF25-75 did not differ by vitamin C intake. Conclusions Our results provide further evidence that asthmatic children predicted to have compromised antioxidant defense by virtue of genetic susceptibility combined with deficient antioxidant intake may be at increased risk of adverse effects of ozone on pulmonary function. PMID:23379631

  13. Augmentation of arginase 1 expression by exposure to air pollution exacerbates the airways hyperresponsiveness in murine models of asthma

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    Amatullah Hajera

    2011-02-01

    Full Text Available Abstract Background Arginase overexpression contributes to airways hyperresponsiveness (AHR in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR. Methods To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA and challenged with nebulized PBS (OVA/PBS or OVA (OVA/OVA for three consecutive days (sub-acute model or 12 weeks (chronic model, which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O3, or HEPA-filtered air (FA, for 4 hours. After the CAP+O3 exposures, mice underwent tracheal cannulation and were treated with an aerosolized arginase inhibitor (S-boronoethyl-L-cysteine; BEC or vehicle, immediately before determination of respiratory function and methacholine-responsiveness using the flexiVent®. Lungs were then collected for comparison of arginase activity, protein expression, and immunohistochemical localization. Results Compared to FA, arginase activity was significantly augmented in the lungs of CAP+O3-exposed OVA/OVA mice in both the sub-acute and chronic models. Western blotting and immunohistochemical staining revealed that the increased activity was due to arginase 1 expression in the area surrounding the airways in both models. Arginase inhibition significantly reduced the CAP+O3-induced increase in AHR in both models. Conclusions This study demonstrates that arginase is upregulated following environmental exposures in murine models of

  14. Contribution of Phadebas IgE test to typification of allergic patients

    International Nuclear Information System (INIS)

    Cap, J.; Spanar, E.; Holan, J.; Zahradny, V.

    1976-01-01

    Experience is reported with the examination of serum immunoglobulin E in a control group (n=22), in a group of asthmatics with bacterial allergy (n=25) and in a group of asthmatics with antibody allergy (n=33). In the examination by radioimmunosorbent method (Phadebas IgE Test) the levels of IgE over 500 mU/ml were considered as proof of allergy of the antibody type where other etiological factors could be excluded. A marked immunosuppressive effect of corticoids on the level of IgE is pointed out. The method mentioned is considered as suitable for the objective typification of allergic patients. (author)

  15. Psychosomatic treatment for allergic diseases.

    Science.gov (United States)

    Yoshihara, Kazufumi

    2015-01-01

    Many reports have been published concerning how psychosocial stress influences the occurrence and progression of allergic diseases such as bronchial asthma and atopic dermatitis. As for asthma, a typical allergic disease often accompanied by psychosomatic related problems, the Global Initiative for Asthma (GINA), international medical guidelines for asthma, describes psychosocial problems as causative factors of poor asthma control and as risk factors for asthma exacerbation, even if symptoms are well controlled. However, because there is little high quality evidence for effective treatments for asthma patients with psychosocial problems, concrete assessments and treatments for such problems is scarcely described in GINA. Therefore, psychosomatic intervention for asthma patients is not effectively conducted on a worldwide scale. In contrast, the "Japanese Guidelines for the Diagnosis and Treatment of Psychosomatic Diseases" describe the assessment and treatment of psychosomatic disorders in detail. In the guidelines, psychosocial factors are classified into five categories; 1) Relation between stress and asthma occurrence or progression, 2) Relation between emotion and asthma symptoms, 3) Problems related to a patient's character and behaviors, 4) Problems of daily life and Quality of Life (QOL), and 5) Problems related to family relationships and life history. The employment of a self-administered questionnaire, the "Psychosomatic Questionnaire related to Asthmatic Occurrence and Progression", is useful for clarifying psychosocial factors and for setting up treatment strategies according to the problems identified. The Japanese guidelines have been proven to be useful, but empirical evidence for their effectiveness is still relatively limited. It will be necessary in the future to accumulate high-quality evidence and to revise the psychosomatic approaches in the guidelines that are universally valid.

  16. Exercise induced bronchospasm in asthmatic and non-asthmatic obese children.

    Science.gov (United States)

    del Río-Navarro, B; Cisneros-Rivero, M; Berber-Eslava, A; Espínola-Reyna, G; Sienra-Monge, J

    2000-01-01

    to investigate the spirometric response to the exercise challenge in asthmatic and non-asthmatic obese children. it was a prospective, longitudinal, open label clinical trial with four groups of children from 8 to 16 years. The group 1 had 15 asthmatic non-obese children. The group 2 had 15 asthmatic obese children. The group 3 had 15 non-asthmatic obese children. The group 4 had 13 control healthy children. Spirometry measures were realized at baseline, and after exercise at 2, 5, 10, 15, 20, 25, 30 and 60 minutes. Exercise challenge was performed on a walking band at 6 km/h speed and a slope of 10 degrees with a duration of 6 to 8 minutes. Data were are analyzed by repeated measures ANOVA. the mean age was 11.8 +/- 2.1, and the mean height was 150.2 +/- 11.3 cm, the mean weight was 46.3 +/- 17.15 in the group 1, 59.4 +/- 11.9 in the group 2, 67.8 +/- 20.6 in the group 3, and 44.2 +/- 9.7 in the group 4. The mean values of forced expiratory volume in one second (FEV1) for each group are shown on table II. the non-asthmatic obese children had a significant decrease in FEV1, meanwhile the asthmatic obese children had a deeper decrease in FEV1 than the asthmatic non-obese children. Obesity ay be a conditioning factor for bronchial hyperreactivity to the exercise.

  17. Respiratory function in children of asthmatic mothers

    Directory of Open Access Journals (Sweden)

    Marco A. Valadares

    2013-03-01

    Conclusions: The frequency of spirometry alterations in children of asthmatic mothers was high; the restrictive pattern was more often observed that the obstructive. There was a higher incidence of obstructive test results in those who presented clinical symptoms of asthma, with a higher frequency of clinical diagnosis of asthma than that found in the literature.

  18. Bronchial hyperresponsiveness and anti-asthmatic therapy

    NARCIS (Netherlands)

    Kraan, Jan

    1990-01-01

    Many asthmatic patients experience shortness of breath or wheezing, when exposed to cold air, or irritants like baking fumes, exhaust gases or cigarette smoke. This clinical phenomenon has been called bronchial hypemsponsiveness (BHR), which is defined as an exaggerated broncho-obstructive response

  19. Maximal airway narrowing in humans in vivo. Histamine compared with methacholine

    NARCIS (Netherlands)

    Sterk, P. J.; Timmers, M. C.; Dijkman, J. H.

    1986-01-01

    Maximal airway narrowing to inhaled nonsensitizing stimuli is limited to a mild degree in nonasthmatic and mildly asthmatic subjects. We investigated whether this limitation is due to a nonspecific inhibitory mechanism (with regard to the agonist) by comparing the maximal response plateaus of

  20. The effectiveness of fish oil supplementation in asthmatic rats is limited by an inefficient action on ASM function.

    Science.gov (United States)

    Miranda, D T S Z; Zanatta, A L; Dias, B C L; Fogaça, R T H; Maurer, J B B; Donatti, L; Calder, P C; Nishiyama, A

    2013-09-01

    Episodes of acute exacerbation are the major clinical feature of asthma and therefore represent an important focus for developing novel therapies for this disease. There are many reports that the n-3 fatty acids found in fish oil exert anti-inflammatory effects, but there are few studies of the action of fish oil on airway smooth muscle (ASM) function. In the present investigation, we evaluated the effect of fish oil supplementation on smooth muscle force of contraction in ovalbumin-induced asthmatic Wistar rats, and its consequences on static lung compliance, mucus production, leukocyte chemotaxis and production of proinflammatory cytokines. Fish oil supplementation suppressed the infiltration of inflammatory cells into the lung in asthmatic animals (2.04 ± 0.19 × 10(6) cells vs. 3.33 ± 0.43 × 10(6) cells in the control asthmatic group; P < 0.05). Static lung compliance increased with fish oil supplementation in asthmatic rats (0.640 ± 0.053 mL/cm H2O vs. 0.399 ± 0.043 mL/cm H2O; P < 0.05). However, fish oil did not prevent asthma-associated lung eosinophilia and did not affect the concentrations of tumor necrosis factor-α and interleukin-1β in lung tissue or the proportion of the airways obliterated with mucus. Fish oil had no effect on the force of contraction in asthmatic rats in response to acetylcholine (3.026 ± 0.274 mN vs. 2.813 ± 0.364 mN in the control asthmatic group). In conclusion, although fish oil exerts some benefits in this model of asthma, its effectiveness appears to be limited by an inefficient action on airway smooth muscle function.

  1. IL-25 Promotes Th2 Immunity Responses in Asthmatic Mice via Nuocytes Activation.

    Directory of Open Access Journals (Sweden)

    Chao Wang

    Full Text Available Interleukin-25 (IL-25 is a potent activator of type-2 immune responses, and is responsible for airway inflammation in asthma. Previous reports have shown that IL-25 expressed hyper-reactivity in an experimental mouse-model of asthma. In addition, the production of IL-13/IL-5 promoted by nuocytes induced airway inflammation. Thus, it has been questioned whether blocking IL-25 against its receptor IL-17BR could inhibit the expression of IL-13 and IL-5 via nuocytes, and further protect against inflammation in ovalbumin (OVA induced mouse-model of asthma.In this study, in order to investigate the correlation among IL-25, IL-5, IL-13 and nuocyte activities, we used OVA-sensitization and -challenging to induce the mouse model of asthma. The murine asthmatic model was validated by histology. The expressions of IL-5, IL-13 and IL-25 were detected by ELISA, quantitative real-time PCR, and western blotting of the lung tissue. Nuocyte activation was identified by the levels of ICOS (clone C398.4A and T1/ST2 (cloneDJ8 (acting as nuocytes surface markers in the bronchoalveolar lavage fluid (BALF. This, in turn, was done by means of flow cytometry. The expressions of IL-25, IL-5 and IL-13 in our murine model were detected in the BALF.The mice sensitized and challenged with OVA showed a high expression of IL-25 in both the mRNA and protein levels in lungs. The expressions of ICOS and T1/ST2 in BALF were increased. A significant correlation between IL-25 mRNA, protein, and other Th2-cell producing cytokines (such as IL-5 and IL-13 moreover were identified. Furthermore, when the asthmatic mice were treated with anti-IL-25, both the inflammatory cells' infiltration and the inflammatory cytokines' secretion were significantly decreased. The present findings indicate that IL-25 might be involved in a series of asthmatic immune responses, playing an important role in the increase of nuocytes, and that its activation is necessary in maintaining Th2 central memory and

  2. Regional deposition of saline aerosols of different tonicities in normal and asthmatic subjects

    International Nuclear Information System (INIS)

    Phipps, P.R.; Gonda, I.; Anderson, S.D.; Bailey, D.; Bautovich, G.

    1994-01-01

    Nonisotonic aerosols are frequently used in the diagnosis and therapy of lung disease. The purpose of this work was to study the difference in the pattern of deposition of aerosols containing aqueous solutions of different tonicities. 99m Technetium-diethyltriaminepentaacetic acid ( 99m Tc-DTPA)-labelled saline aerosols, with mass median aerodynamic diameter 3.7-3.8 μm and geometric standard deviation 1.4, were inhaled under reproducible breathing conditions on two occasions. Hypotonic and hypertonic solutions were used in 11 normals subjects, isotonic and hypertonic solutions in 9 asthmatics. The regional deposition was quantified by a penetration index measured with the help of a tomographic technique. There was a small but significant increase (6.7%) in the penetration index of the hypotonic as compared to the hypertonic aerosols in the normal subjects. The region that was markedly affected was the trachea. The differences in the penetration of the isotonic and hypertonic aerosols in the asthmatics appeared to be strongly dependent on the state of the airways at the time of the study. These findings can be interpreted in terms of effects of growth or shrinkage of nonisotonic aerosols, as well as of airway narrowing, on regional deposition of aerosols. Tonicity of aerosols appears to affect their deposition both through physical and physiological mechanisms. This should be taken into account when interpreting the effects of inhaled aqueous solutions of various tonicities in patients in vivo. (au) (44 refs.)

  3. Regional deposition of saline aerosols of different tonicities in normal and asthmatic subjects

    Energy Technology Data Exchange (ETDEWEB)

    Phipps, P.R.; Gonda, I. (Department of Pharmacy, University of Sydney, Sydney (Australia)); Anderson, S.D. (Department of Thoracic and Nuclear Medicine, Royal Prince Alfred Hospital, Camperdown (Australia)); Bailey, D.; Bautovich, G. (Department of Nuclear Medicine, Royal Prince Alfred Hospital, Camperdown (Australia))

    1994-08-01

    Nonisotonic aerosols are frequently used in the diagnosis and therapy of lung disease. The purpose of this work was to study the difference in the pattern of deposition of aerosols containing aqueous solutions of different tonicities. [sup 99m]Technetium-diethyltriaminepentaacetic acid ([sup 99m]Tc-DTPA)-labelled saline aerosols, with mass median aerodynamic diameter 3.7-3.8 [mu]m and geometric standard deviation 1.4, were inhaled under reproducible breathing conditions on two occasions. Hypotonic and hypertonic solutions were used in 11 normals subjects, isotonic and hypertonic solutions in 9 asthmatics. The regional deposition was quantified by a penetration index measured with the help of a tomographic technique. There was a small but significant increase (6.7%) in the penetration index of the hypotonic as compared to the hypertonic aerosols in the normal subjects. The region that was markedly affected was the trachea. The differences in the penetration of the isotonic and hypertonic aerosols in the asthmatics appeared to be strongly dependent on the state of the airways at the time of the study. These findings can be interpreted in terms of effects of growth or shrinkage of nonisotonic aerosols, as well as of airway narrowing, on regional deposition of aerosols. Tonicity of aerosols appears to affect their deposition both through physical and physiological mechanisms. This should be taken into account when interpreting the effects of inhaled aqueous solutions of various tonicities in patients in vivo. (au) (44 refs.).

  4. Impaired glucose metabolism and bronchial hyperresponsiveness in obese prepubertal asthmatic children.

    Science.gov (United States)

    Karampatakis, Nikolaos; Karampatakis, Theodoros; Galli-Tsinopoulou, Assimina; Kotanidou, Eleni P; Tsergouli, Katerina; Eboriadou-Petikopoulou, Maria; Haidopoulou, Katerina

    2017-02-01

    The prevalence of asthma and obesity has risen in parallel over the last decades, but the exact mechanisms linking these two diseases still remain unclear. The aim of the present study was to investigate the associations between bronchial hyperresponsiveness (BHR), impaired glucose metabolism, obesity, and asthma in prepubertal children. A total of 71 prepubertal children were included in the study and divided in four groups according to the presence of asthma and their Body Mass Index (BMI): Group 1-Healthy Controls (HC), Group 2-Non Obese Asthmatics (NOA), Group 3-Obese Non Asthmatics (ONA), Group 4-Obese Asthmatics (OA) Αll children underwent spirometry and bronchial hyperresponsiveness testing by using the cumulative Provoking Dose of mannitol (PD 15, primary study variable); homeostasis model assessment-estimated insulin resistance (HOMA-IR) index was calculated in order to evaluate insulin resistance. Obese children also underwent an oral glucose tolerance testing (OGTT). A statistically significant difference in bronchial hyperreactivity (mean ± SD) was detected in the group of obese asthmatic children who had lower values ​​of PD 15 , (174.16 ± 126.42) as compared to normal weight asthmatic children (453.93 ± 110.27), (P HOMA-IR ≥2.5), had significantly lower PD 15 values (89.05 ± 42.75) as ​​compared to those with HOMA-IR <2.5 (259.27 ± 125.75), (P = 0.006). Finally, obese asthmatic children with impaired OGTT had likewise significantly lower PD 15 (81.02 ± 42.16) measurements as compared to children with normal OGTT (267.3 ± 112.62), (P = 0.001). Our findings suggest that obesity per se does not correlate to airway hyperreactivity unless it is accompanied by glucose intolerance and insulin resistance. Pediatr Pulmonol. 2017;52:160-166. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Management of Allergic Rhinitis

    OpenAIRE

    Sausen, Verra O.; Marks, Katherine E.; Sausen, Kenneth P.; Self, Timothy H.

    2005-01-01

    Allergic rhinitis is the most common chronic childhood disease. Reduced quality of life is frequently caused by this IgE-mediated disease, including sleep disturbance with subsequent decreased school performance. Asthma and exercise-induced bronchospasm are commonly seen concurrently with allergic rhinitis, and poorly controlled allergic rhinitis negatively affects asthma outcomes. Nonsedating antihistamines or intranasal azelastine are effective agents to manage allergic rhinitis, often in c...

  6. Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

    Science.gov (United States)

    Kim, Mi Ae; Shin, Seung Woo; Park, Jong Sook; Uh, Soo Taek; Chang, Hun Soo; Bae, Da Jeong; Cho, You Sook; Park, Hae Sim; Yoon, Ho Joo; Choi, Byoung Whui; Kim, Yong Hoon; Park, Choon Sik

    2017-11-01

    Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease

  7. Effect of Smoking Abstinence and Reduction in Asthmatic Smokers Switching to Electronic Cigarettes: Evidence for Harm Reversal

    Directory of Open Access Journals (Sweden)

    Riccardo Polosa

    2014-05-01

    Full Text Available Electronic cigarettes (e-cigs are marketed as safer alternatives to tobacco cigarettes and have shown to reduce their consumption. Here we report for the first time the effects of e-cigs on subjective and objective asthma parameters as well as tolerability in asthmatic smokers who quit or reduced their tobacco consumption by switching to these products. We retrospectively reviewed changes in spirometry data, airway hyper-responsiveness (AHR, asthma exacerbations and subjective asthma control in smoking asthmatics who switched to regular e-cig use. Measurements were taken prior to switching (baseline and at two consecutive visits (Follow-up/1 at 6 (±1 and Follow-up/2 at 12 (±2 months. Eighteen smoking asthmatics (10 single users, eight dual users were identified. Overall there were significant improvements in spirometry data, asthma control and AHR. These positive outcomes were noted in single and dual users. Reduction in exacerbation rates was reported, but was not significant. No severe adverse events were noted. This small retrospective study indicates that regular use of e-cigs to substitute smoking is associated with objective and subjective improvements in asthma outcomes. Considering that e-cig use is reportedly less harmful than conventional smoking and can lead to reduced cigarette consumption with subsequent improvements in asthma outcomes, this study shows that e-cigs can be a valid option for asthmatic patients who cannot quit smoking by other methods.

  8. Limonene and its ozone-initiated reaction products attenuate allergic lung inflammation in mice.

    Science.gov (United States)

    Hansen, Jitka S; Nørgaard, Asger W; Koponen, Ismo K; Sørli, Jorid B; Paidi, Maya D; Hansen, Søren W K; Clausen, Per Axel; Nielsen, Gunnar D; Wolkoff, Peder; Larsen, Søren Thor

    2016-11-01

    Inhalation of indoor air pollutants may cause airway irritation and inflammation and is suspected to worsen allergic reactions. Inflammation may be due to mucosal damage, upper (sensory) and lower (pulmonary) airway irritation due to activation of the trigeminal and vagal nerves, respectively, and to neurogenic inflammation. The terpene, d-limonene, is used as a fragrance in numerous consumer products. When limonene reacts with the pulmonary irritant ozone, a complex mixture of gas and particle phase products is formed, which causes sensory irritation. This study investigated whether limonene, ozone or the reaction mixture can exacerbate allergic lung inflammation and whether airway irritation is enhanced in allergic BALB/cJ mice. Naïve and allergic (ovalbumin sensitized) mice were exposed via inhalation for three consecutive days to clean air, ozone, limonene or an ozone-limonene reaction mixture. Sensory and pulmonary irritation was investigated in addition to ovalbumin-specific antibodies, inflammatory cells, total protein and surfactant protein D in bronchoalveolar lavage fluid and hemeoxygenase-1 and cytokines in lung tissue. Overall, airway allergy was not exacerbated by any of the exposures. In contrast, it was found that limonene and the ozone-limonene reaction mixture reduced allergic inflammation possibly due to antioxidant properties. Ozone induced sensory irritation in both naïve and allergic mice. However, allergic but not naïve mice were protected from pulmonary irritation induced by ozone. This study showed that irritation responses might be modulated by airway allergy. However, aggravation of allergic symptoms was observed by neither exposure to ozone nor exposure to ozone-initiated limonene reaction products. In contrast, anti-inflammatory properties of the tested limonene-containing pollutants might attenuate airway allergy.

  9. Development of asthmatic inflammation in mice following early-life exposure to ambient environmental particulates and chronic allergen challenge

    Directory of Open Access Journals (Sweden)

    Cristan Herbert

    2013-03-01

    Childhood exposure to environmental particulates increases the risk of development of asthma. The underlying mechanisms might include oxidant injury to airway epithelial cells (AEC. We investigated the ability of ambient environmental particulates to contribute to sensitization via the airways, and thus to the pathogenesis of childhood asthma. To do so, we devised a novel model in which weanling BALB/c mice were exposed to both ambient particulate pollutants and ovalbumin for sensitization via the respiratory tract, followed by chronic inhalational challenge with a low mass concentration of the antigen. We also examined whether these particulates caused oxidant injury and activation of AEC in vitro. Furthermore, we assessed the potential benefit of minimizing oxidative stress to AEC through the period of sensitization and challenge by dietary intervention. We found that characteristic features of asthmatic inflammation developed only in animals that received particulates at the same time as respiratory sensitization, and were then chronically challenged with allergen. However, these animals did not develop airway hyper-responsiveness. Ambient particulates induced epithelial injury in vitro, with evidence of oxidative stress and production of both pro-inflammatory cytokines and Th2-promoting cytokines such as IL-33. Treatment of AEC with an antioxidant in vitro inhibited the pro-inflammatory cytokine response to these particulates. Ambient particulates also induced pro-inflammatory cytokine expression following administration to weanling mice. However, early-life dietary supplementation with antioxidants did not prevent the development of an asthmatic inflammatory response in animals that were exposed to particulates, sensitized and challenged. We conclude that injury to airway epithelium by ambient environmental particulates in early life is capable of promoting the development of an asthmatic inflammatory response in sensitized and antigen-challenged mice. These

  10. The allergic scholar

    African Journals Online (AJOL)

    children. Allergic rhinitis. Allergic rhinitis is a condition which occurs due to inflammation of the epithelial lining of the nasal mucosa. This inflammatory process is ... is TNF-α. TNF-α levels increase dramatically approximately. Figure 2: Common atopic diseases in childhood. Anaphylaxis. Allergic rhinitis. Asthma. Atopic.

  11. Allergic rhinosinusitis in children

    African Journals Online (AJOL)

    Chantel

    sent in persistent allergic rhinitis will eventually occur in the mucous mem- branes of the ostiomeatal units in the middle meati leading ultimately to allergic inflammation of the sinuses. The other important factor is that sinusi- tis may also occur as a result of viral infections in these allergic children as it does in normal children.

  12. Does treatment of gastro-esophageal reflux disease with omeprazole decrease allergic rhinitis symptoms?

    Directory of Open Access Journals (Sweden)

    Afshin Shirkani

    2014-08-01

    Full Text Available Background: Allergic rhinitis is the most common type of allergic disease among population. Its accurate treatment is very important for cutting of allergic march. On the other hand, gasteroesophageal reflux disease (GERD is one of the most common gastrointestinal problems among allergic patients mainly asthmatic cases. It might conflict treatment. Despite of asthma, a few studies have been conducted on the impact of GERD treatment on allergic rhinitis symptoms. In this study, we assessed GERD treatment and its effects on improving of allergic rhinitis patients with GERD. Materials and Methods: In a prospective cross-sectional study, March - September 2012, 103 consecutive patients with persistent moderate to severe seasonal allergic rhinitis enrolled. For allergic rhinitis patients with GERD 20 mg omeperazole once daily for 6 weeks prescribed, empirically. Conventional allergy treatment continued and finally the allergic rhinitis symptoms were assessed clinically and recorded before, 5th, 10th and 30th days of omeprazole treatment period. Results: Our study included 103 patients with seasonal allergic rhinitis who were divided into GERD (n=33, 38% and non-GERD (n=70, 68% groups with the mean age 28 and 25.7 years, respectively. The first group developed significant improvement for GERD symptoms on days 5, 10 and 30 after beginning of therapy (P=0.03. No association was found between GERD treatment and relief of allergic symptoms or TNSS improvement (P>0.05. Data analyzed by Epi info (ver 7 and SPSS software (ver 11.5, and by Chi squeare test and paired T test. P lower than 0.05 was considered as significant. Conclusion: This study showed no significant association between empirical treatment of GERD and improvement of allergic symptoms in patients with allergic rhinitis. However, further studies with a larger sample size might be needed.

  13. Peripheral blood T lymphocytes from asthmatic patients are primed for enhanced expression of interleukin (IL)-4 and IL-5 mRNA : associations with lung function and serum IgE

    NARCIS (Netherlands)

    Borger, P; Ten Hacken, NHT; Vellenga, E; Kauffman, HF; Postma, DS

    Background The TH2-like cytokines interleukin (IL)-4 and IL-5 play a pivotal role in airway wall inflammation in asthma and these cytokines are increased in peripheral blood and bronchoalveolar lavage fluid from asthmatic patients. It is unclear why specifically TH2-like cytokines are increased in

  14. Nonallergic rhinitis and lower airway disease.

    Science.gov (United States)

    Rondón, C; Bogas, G; Barrionuevo, E; Blanca, M; Torres, M J; Campo, P

    2017-01-01

    In the past years, several investigators have demonstrated the existence of local nasal responses in some patients with typical allergic rhinitis symptoms but without atopy and have defined a new phenotype called local allergic rhinitis (LAR) or 'entopy'. In a percentage of LAR subjects, the upper airway disease is also associated with lower airway symptoms. After the description of this phenotype, the differential diagnosis between LAR and nonallergic rhinitis (NAR) has become a challenge for the clinician. To correctly identify LAR patients is of high importance for treatment and management of these patients, and for an appropriate inclusion of patients in clinical trials and genetics studies. The treatment of LAR patients, in contrast with NAR, is oriented to allergen avoidance and specific treatment. Allergen immunotherapy, the aetiological treatment for allergic respiratory diseases, has demonstrated to be an effective and safe treatment in LAR, increasing immunological tolerance, and reducing the clinical symptoms and the use of medication. In this article, the important and novel aspects of LAR in terms of mechanisms, diagnosis and treatment will be discussed. Also, the involvement of the lower airway and the potential role of IgE in the bronchial disease will be also reviewed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Neutrophils are a major source of the epithelial barrier disrupting cytokine oncostatin M in patients with mucosal airways disease.

    Science.gov (United States)

    Pothoven, Kathryn L; Norton, James E; Suh, Lydia A; Carter, Roderick G; Harris, Kathleen E; Biyasheva, Assel; Welch, Kevin; Shintani-Smith, Stephanie; Conley, David B; Liu, Mark C; Kato, Atsushi; Avila, Pedro C; Hamid, Qutayba; Grammer, Leslie C; Peters, Anju T; Kern, Robert C; Tan, Bruce K; Schleimer, Robert P

    2017-06-01

    We have previously shown that oncostatin M (OSM) levels are increased in nasal polyps (NPs) of patients with chronic rhinosinusitis (CRS), as well as in bronchoalveolar lavage fluid, after segmental allergen challenge in allergic asthmatic patients. We also showed in vitro that physiologic levels of OSM impair barrier function in differentiated airway epithelium. We sought to determine which hematopoietic or resident cell type or types were the source of the OSM expressed in patients with mucosal airways disease. Paraffin-embedded NP sections were stained with fluorescence-labeled specific antibodies against OSM, GM-CSF, and hematopoietic cell-specific markers. Live cells were isolated from NPs and matched blood samples for flow cytometric analysis. Neutrophils were isolated from whole blood and cultured with the known OSM inducers GM-CSF and follistatin-like 1, and OSM levels were measured in the supernatants. Bronchial biopsy sections from control subjects, patients with moderate asthma, and patients with severe asthma were stained for OSM and neutrophil elastase. OSM staining was observed in NPs, showed colocalization with neutrophil elastase (n = 10), and did not colocalize with markers for eosinophils, macrophages, T cells, or B cells (n = 3-5). Flow cytometric analysis of NPs (n = 9) showed that 5.1% ± 2% of CD45 + cells were OSM + , and of the OSM + cells, 56% ± 7% were CD16 + Siglec-8 - , indicating neutrophil lineage. Only 0.6 ± 0.4% of CD45 + events from matched blood samples (n = 5) were OSM + , suggesting that increased OSM levels in patients with CRS was locally stimulated and produced. A majority of OSM + neutrophils expressed arginase 1 (72.5% ± 12%), suggesting an N2 phenotype. GM-CSF levels were increased in NPs compared with those in control tissue and were sufficient to induce OSM production (P < .001) in peripheral blood neutrophils in vitro. OSM + neutrophils were also observed at increased levels in biopsy specimens

  16. Patterns of psychosocial adaptation and allergic disorders in Korean schoolchildren.

    Science.gov (United States)

    Park, JinAh; Kim, Byoung-Ju; Kwon, Ji-Won; Song, Young Hwa; Yu, Jinho; Kim, Hyo-Bin; Lee, So-Yeon; Kim, Woo Kyung; Jee, Hye Mi; Kim, Kyung Won; Kim, Kyu-Earn; Hong, Soo-Jong; Shin, Yee-Jin

    2011-01-01

    To date, there is little evidence to support an association between symptoms of pediatric allergic disorders and psychosocial factors in the general population, particularly in Asian countries. The current study aims to investigate the relationship between psychosocial factors and symptoms of allergic disorders and to investigate the association between behavior problems and biomarkers of atopy. A cross-sectional survey of parental responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and the Korean version of the Child Behavior Checklist (CBCL) was conducted from one elementary school in Seoul, Korea. Skin prick tests for 18 major allergens were also performed. A total of 780 children with valid CBCL surveys were included in the study. Externalizing problems were significantly larger in children with asthmatic symptoms, while internalizing problems were significantly larger in children with symptoms of both asthma and allergic rhinitis. Social adaptations were significantly lower in children with symptoms of allergic rhinitis and atopic dermatitis. Boys with more positive allergens via the skin prick tests showed larger internalizing problems. While school children with allergic symptoms have been reported to have more difficulties with psychosocial adaptation, the patterns of psychosocial problems varied somewhat according to the types of atopic disorder. There was a positive relationship between atopy and behavior problems, especially in boys. Copyright © 2010 S. Karger AG, Basel.

  17. Role of airway epithelial barrier dysfunction in pathogenesis of asthma.

    Science.gov (United States)

    Gon, Yasuhiro; Hashimoto, Shu

    2018-01-01

    Bronchial asthma is characterized by persistent cough, increased sputum, and repeated wheezing. The pathophysiology underlying these symptoms is the hyper-responsiveness of the airway along with chronic airway inflammation. Repeated injury, repair, and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium; such changes are believed to have a significant association with the pathophysiology of asthma. Damage to the barrier functions of the airway epithelium enhances mucosal permeability of foreign substances in the airway epithelium of patients with asthma. Thus, epithelial barrier fragility is closely involved in releasing epithelial cytokines (e.g., TSLP, IL-25, and IL-33) because of the activation of airway epithelial cells, dendritic cells, and innate group 2 innate lymphoid cells (ILC2). Functional abnormalities of the airway epithelial cells along with the activation of dendritic cells, Th2 cells, and ILC2 form a single immunopathological unit that is considered to cause allergic airway inflammation. Here we use the latest published literature to discuss the potential pathological mechanisms regarding the onset and progressive severity of asthma with regard to the disruption of the airway epithelial function. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  18. Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial

    DEFF Research Database (Denmark)

    Bager, Peter; Arnved, John; Rønborg, Steen

    2010-01-01

    Parasitic helminth infections can protect against allergic airway inflammation in experimental models and have been associated with a reduced risk of atopy and a reduced course of asthma in some observational studies. Although no clinical evidence exists to support the use of helminth therapy...... for allergic disease, the helminth Trichuris suis has demonstrated efficacy in treatment of inflammatory bowel disease....

  19. Fragranced consumer products: effects on asthmatics

    OpenAIRE

    Steinemann, Anne

    2017-01-01

    Fragranced consumer products, such as cleaning supplies, air fresheners, and personal care products, can emit a range of air pollutants and trigger adverse health effects. This study investigates the prevalence and types of effects of fragranced products on asthmatics in the American population. Using a nationally representative sample (n = 1137), data were collected with an on-line survey of adults in the USA, of which 26.8% responded as being medically diagnosed with asthma or an asthma-lik...

  20. Allergic rhinitis: more than just a stuffy nose.

    Science.gov (United States)

    Borres, Magnus P

    2009-07-01

    Allergic rhinitis is more than just sneezing and an itchy nose. Complications of this disease are numerous and can have a significant impact, both mentally and physically. That is why it is important not only to detect, investigate and treat allergic rhinitis but also to actively identify potential complications. Mental functions such as learning, sleep and activity levels can deteriorate, and the eustachian tubes, sinuses and airway functions can be affected. Otitis, sinusitis and asthma are overrepresented among individuals who suffer from allergic rhinitis. This article highlights how allergic rhinitis can affect cognitive functions, and what consequences this can have on school performance, work and quality of life. Health professionals and school personnel need to increase their awareness of the ramifications of this disease and actively work to prevent deterioration in both academic achievement and workplace productivity.

  1. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy to ...

  2. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. ... or caregiver. Older kids and adults can choose ACTs that they can do on their own. Share ...

  3. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ... for fitting ACTs into daily life Airway Clearance Techniques | Webcast To learn more about how you can ...

  4. NKT Cells in the Induced Sputum of Severe Asthmatics

    Directory of Open Access Journals (Sweden)

    Agnes Hamzaoui

    2006-01-01

    of the sputum and monoclonal antibodies to CD3, CD4, CD8, CD56, CD25, and TCRγδ. The number of NKT (CD3+CD56+ cells was significantly higher in the sputum of severe asthmatics compared with mild asthmatic and healthy control groups (P<.05. CD8+CD56+ cells were the predominant subtype of the increased NKT cells in severe asthmatics. CD3+CD56+Vα24+, TCRγδ+ CD56+, and CD4+CD25+ T cells were significantly increased in severe asthmatic patients. These results suggest that the immunopathogenesis of severe asthmatics vary between severe and mild asthmatics, and that CD8+CD56+ NKT cells may play an important role in the immunopathogenesis of severe asthma.

  5. Responsiveness to oral prednisolone in severe asthma is related to the degree of eosinophilic airway inflammation.

    Science.gov (United States)

    Sousa, A R; Marshall, R P; Warnock, L C; Bolton, S; Hastie, A; Symon, F; Hargadon, B; Marshall, H; Richardson, M; Brightling, C E; Haldar, P; Milone, R; Chalk, P; Williamson, R; Panettieri, R; Knowles, R; Bleecker, E R; Wardlaw, A J

    2017-07-01

    Patients with severe asthma appear relatively corticosteroid resistant. Corticosteroid responsiveness is closely related to the degree of eosinophilic airway inflammation. The extent to which eosinophilic airway inflammation in severe asthma responds to treatment with systemic corticosteroids is not clear. To relate the physiological and inflammatory response to systemic corticosteroids in asthma to disease severity and the baseline extent of eosinophilic inflammation. Patients with mild/moderate and severe asthma were investigated before and after 2 weeks of oral prednisolone (Clintrials.gov NCT00331058 and NCT00327197). We pooled the results from two studies with common protocols. The US study contained two independent centres and the UK one independent centre. The effect of oral corticosteroids on FEV 1 , Pc20, airway inflammation and serum cytokines was investigated. Baseline measurements were compared with healthy subjects. Thirty-two mild/moderate asthmatics, 50 severe asthmatics and 35 healthy subjects took part. At baseline, both groups of asthmatics had a lower FEV 1 and Pc20 and increased eosinophilic inflammation compared to healthy subjects. The severe group had a lower FEV 1 and more eosinophilic inflammation compared to mild/moderate asthmatics. Oral prednisolone caused a similar degree of suppression of eosinophilic inflammation in all compartments in both groups of asthmatics. There were small improvements in FEV 1 and Pc20 for both mild/ moderate and severe asthmatics with a correlation between the baseline eosinophilic inflammation and the change in FEV 1 . There was a ~50% reduction in the serum concentration of CXCL10 (IP-10), CCL22 (MDC), CCL17 (TARC), CCL-2 (MCP-1) and CCL-13 (MCP-4) in both asthma groups after oral corticosteroids. Disease severity does not influence the response to systemic corticosteroids. The study does not therefore support the concept that severe asthma is associated with corticosteroid resistance. Only baseline

  6. Antioxidant status in acute asthmatic attack in children

    International Nuclear Information System (INIS)

    Al-Abdulla, N.O.; Al-Naama, L.M.; Hassan, M.K.

    2010-01-01

    Objectives: To determine the oxidant - antioxidant imbalance in asthmatic children, by measuring the levels of malondialdehyde (MDA) as an oxidant marker of lipid peroxidation as well as antioxidant compounds like vitamin C, vitamin E and uric acid and to investigate whether their concentrations are associated with more severe asthma. Methods: This case controlled prospective study was conducted on 219 children aged 1-12 years, attending Basra Maternity and Children Hospital. Included were 98 asthmatic children during acute attack and 121 non asthmatic, apparently healthy children. Serum malondialdehyde (MDA) as an oxidant marker of lipid peroxidation, and vitamin C, vitamin E and uric acid (as antioxidants) were estimated in asthmatic children during acute attack and compared with non-asthmatic children. Results: Asthmatic children during exacerbation of their asthma have significant lower serum levels of antioxidant compounds like vitamin C, vitamin E and uric acid (p<0.001) and significantly high malondialdehyde as compared with the controls. MDA was significantly elevated (P< 0.001), while that of vitamin C, vitamin E and uric acid were significantly decreased with increasing severity of asthmatic attack (P<0.001). A significant negative correlation between MDA with vitamin C (P<0.05, r = - 0.44) was observed in severe asthmatic attacks. Conclusion: Asthmatic patients during acute attack suffer a high degree of reactive oxygen species formation causing considerable oxidative stress that is indicated by the high level of oxidants (MDA) and low level of antioxidants. (author)

  7. Airway Responsiveness to Psychological Processes in Asthma and Health

    Directory of Open Access Journals (Sweden)

    Thomas eRitz

    2012-09-01

    Full Text Available Psychosocial factors have been found to impact airway pathophysiology in respiratory disease with considerable consistency. Influences on airway mechanics have been studied particularly well. The goal of this article is to review the literature on airway responses to psychological stimulation, discuss potential pathways of influence, and present a well-established emotion-induction paradigm to study airway obstruction elicited by unpleasant stimuli. Observational studies have found systematic associations between lung function and daily mood changes. The laboratory –based paradigm of bronchoconstrictive suggestion has been used successfully to elicit airway obstruction in a substantial proportion of asthmatic individuals. Other studies have demonstrated an enhancement of airway responses to standard airway challenges with exercise, allergens, or methacholine. Standardized emotion-induction techniques have consistently shown airway constriction during unpleasant stimulation, with surgery, blood and injury stimuli being particularly powerful. Findings with various forms of stress induction have been more mixed. A number of methodological factors may account for variability across studies, such as choice of measurement technique, temporal association between stimulation and measurement, and the specific quality and intensity of the stimulus material, in particular the extent of implied action-orientation. Research has also begun to elucidate physiological processes associated with psychologically induced airway responses, with vagal excitation and ventilatory influences being the most likely candidate pathways, whereas the role of specific central nervous system pathways and inflammatory processes has been less studied. The technique of emotion-induction using films has the potential to become a standardized challenge paradigm for the further exploration of airway hyperresponsiveness mediated by central nervous system processes.

  8. Buffering airway acid decreases exhaled nitric oxide in asthma.

    Science.gov (United States)

    Gaston, Benjamin; Kelly, Robin; Urban, Peter; Liu, Lei; Henderson, Edward M; Doctor, Allan; Teague, W Gerald; Fitzpatrick, Anne; Erzurum, Serpil; Hunt, John F

    2006-10-01

    The human airway is believed to be acidified in asthma. In an acidic environment nitrite is converted to nitric oxide (NO). We hypothesized that buffering airway lining fluid acid would decrease the fraction of exhaled NO (F(ENO)). We treated 28 adult nonsmoking subjects (9 healthy control subjects, 11 subjects with mild intermittent asthma, and 8 subjects with persistent asthma) with 3 mL of 10 mmol/L phosphate buffered saline (PBS) through a nebulizer and then serially measured F(ENO) levels. Six subjects also received PBS mouthwash alone. F(ENO) levels decreased after buffer inhalation. The maximal decrease occurred between 15 and 30 minutes after treatment; F(ENO) levels returned to pretreatment levels by 60 minutes. The decrease was greatest in subjects with persistent asthma (-7.1 +/- 1.0 ppb); this was more than in those with either mild asthma (-2.9 +/- 0.3 ppb) or healthy control subjects (-1.7 +/- 0.3 ppb, P mouthwash. Neutralizing airway acid decreases F(ENO) levels. The magnitude of this change is greatest in persistent asthma. These data suggest that airway pH is a determinant of F(ENO) levels downstream from NO synthase activation. Airway biochemistry modulates F(ENO) levels. For example, nitrite is converted to NO in the airway, particularly the inflamed airway, by means of acid-based chemistry. Thus airway pH should be considered in interpreting clinical F(ENO) values. In fact, PBS challenge testing integrates airway pH and F(ENO) analysis, potentially improving the utility of F(ENO) as a noninvasive test for the type and severity of asthmatic airway inflammation.

  9. Inhalation of concentrated PM2.5 from Mexico City acts as an adjuvant in a guinea pig model of allergic asthma.

    Science.gov (United States)

    Falcon-Rodriguez, Carlos Iván; De Vizcaya-Ruiz, Andrea; Rosas-Pérez, Irma Aurora; Osornio-Vargas, Álvaro Román; Segura-Medina, Patricia

    2017-09-01

    Exposure to Particulate Matter (PM) could function as an adjuvant depending on the city of origin in mice allergic asthma models. Therefore, our aim was to determine whether inhalation of fine particles (PM2.5) from Mexico City could act as an adjuvant inducing allergic sensitization and/or worsening the asthmatic response in guinea pig, as a suitable model of human asthma. Experimental groups were Non-Sensitized (NS group), sensitized with Ovalbumin (OVA) plus Aluminum hydroxide (Al(OH)3) as adjuvant (S + Adj group), and sensitized (OVA) without adjuvant (S group). All the animals were exposed to Filtered Air (FA) or concentrated PM2.5 (5 h/daily/3 days), employing an aerosol concentrator system, PM2.5 composition was characterized. Lung function was evaluated by barometric plethysmography (Penh index). Inflammatory cells present in bronchoalveolar lavage were counted as well as OVA-specific IgG1 and IgE were determined by ELISA assay. Our results showed in sensitized animals without Al(OH)3, that the PM2.5 exposure (609 ± 12.73 μg/m3) acted as an adjuvant, triggering OVA-specific IgG1 and IgE concentration. Penh index increased ∼9-fold after OVA challenge in adjuvant-sensitized animals as well as in S + PM2.5 group (∼6-fold), meanwhile NS + FA and S + FA lacked response. S + Adj + PM2.5 group showed an increase significantly of eosinophils and neutrophils in bronchoalveolar lavage. PM2.5 composition was made up of inorganic elements and Polycyclic Aromatic Hydrocarbons, as well as endotoxins and β-glucan, all these components could act as adjuvant. Our study demonstrated that acute inhalation of PM2.5 acted as an adjuvant, similar to the aluminum hydroxide effect, triggering allergic asthma in a guinea pig model. Furthermore, in sensitized animals with aluminum hydroxide an enhancing influence of PM2.5 exposure was observed as specific-hyperresponsiveness to OVA challenge (quickly response) and eosinophilic and neutrophilic airway

  10. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger

    2013-01-01

    Rationale – Chronic Obstructive Pulmonary Disease (COPD) is a combination of chronic bronchitis and emphysema, which both may lead to airway obstruction. Under normal circumstances, airway dimensions vary as a function of inspiration level. We aim to study the influence of COPD and emphysema on t...... in causing airway narrowing, the latter most likely due to loss of elastic recoil of surrounding tissue....

  11. Sensitisation to minor cat allergen components is associated with type-2 biomarkers in young asthmatics.

    Science.gov (United States)

    Tsolakis, N; Malinovschi, A; Nordvall, L; Mattsson, L; Lidholm, J; Pedroletti, C; Janson, C; Borres, M P; Alving, K

    2018-03-25

    Cat allergy is a major trigger of asthma worldwide. Molecular patterns of cat sensitisation vary between individuals, but their relationship to inflammation in asthmatics has not been extensively studied. To investigate the prevalence and levels of IgE antibodies against different cat allergen components and their relationship to type-2 inflammation and total IgE among young asthmatic subjects sensitised to furry animals. Patients with asthma (age 10-35 years; n=266) and IgE sensitisation to cat, dog or horse extract (ImmunoCAP), were analysed for IgE to the cat allergen components Fel d 1 (secretoglobin), Fel d 2 (serum albumin), Fel d 4 and Fel d 7 (lipocalins). Independent associations between IgE-antibody concentrations, and fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, and total IgE were analysed by multiple linear regression after adjustment for possible confounders. The level of IgE against Fel d 2 was independently related to FeNO (p=0.012) and total IgE (pcat extract did not independently relate to these inflammatory markers (p=0.23-0.51). Levels of IgE to lipocalin (Fel d 4) and serum albumin (Fel d 2), but not to secretoglobin (Fel d 1) or cat extract, were independently associated with type-2 biomarkers and total IgE in young asthmatics. We suggest that measurement of IgE to minor cat allergen components may be useful when investigating asthma morbidity in cat allergic subjects. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Influence of sublingual immunotherapy on the expression of Mac-1 integrin in neutrophils from asthmatic children.

    Science.gov (United States)

    Ciepiela, Olga; Zawadzka-Krajewska, Anna; Kotula, Iwona; Pyrzak, Beata; Demkow, Urszula

    2013-01-01

    Asthma can be effectively treated with sublingual immunotherapy. The influence of -sublingual immunotherapy on the function of granulocytes in asthmatic patients is largely unknown. Mac-1 integrin is a transmembrane protein containing α (CD11b) and β (CD18) chains. High expression of the complex is found on the surface of neutrophils, NK cells, and macrophages. CD11b/CD18 may bind to CD23, ICAM-1, ICAM-2, and ICAM-4. It plays a crucial role in diapedesis of neutrophils. The aim of the present study was to assess Mac-1 expression on neutrophils from asthmatic children before and after sublingual immunotherapy. Twenty five children aged of 8.1 ± 3.1 suffering from atopic asthma and allergic rhinitis, shortlisted for specific immunotherapy, served as the study group. Fifteen healthy individuals, aged 9.8 ± 3.4, served as a control group. The assessment of CD11b and CD18 expression on cells from peripheral blood was performed with a flow cytometer. The tests were performed before and after 12 months of sublingual immunotherapy. In the asthmatic children, 98.08 (90.79-99.12)% of Mac-1 positive neutrophils were detected. The group was divided into two subgroups: of more than 98% and less than 95% of neutrophils with CD11b/CD18 expression in the sample. After immunotherapy, the percentage of Mac-1 positive granulocytes increased to 99.60 (99.29-99.68)%, p = 0.01. In the control group, 90.56 (87.08-88.86)% granulocytes were Mac-1 positive, p = 0.002. We conclude that sublingual immunotherapy strongly influences the function of the immunological system, including Mac-1 expression on neutrophils.

  13. The inhaled Rho kinase inhibitor Y-27632 protects against allergen-induced acute bronchoconstriction, airway hyperresponsiveness, and inflammation

    NARCIS (Netherlands)

    Schaafsma, Dedmer; Bos, I. Sophie T.; Zuidhof, Annet B.; Zaagsma, Johan; Meurs, Herman

    Recently, we have shown that allergen-induced airway hyperresponsiveness (AHR) after the early (EAR) and late (LAR) asthmatic reaction in guinea pigs could be reversed acutely by inhalation of the Rho kinase inhibitor Y-27632. The present study addresses the effects of pretreatment with inhaled

  14. Skin prick test results of atopic asthmatic subjects in a chest disease clinic in Sanliurfa

    Directory of Open Access Journals (Sweden)

    İbrahim Koç

    2015-06-01

    Full Text Available Objective: Skin prick test (SPT is used widely to determine the allergens in atopic patients. In this study, we aimed to determine the spectrum of aeroallergen sensitivity of atopic asthmatic subjects in Şanlıurfa district. Methods: We evaluated clinical, demographic findings and SPT results of 95 male and 162 female in a total 257 patients who had asthma and allergic symptoms. Results: Most common allergens causing a sensitivity reaction detected in our clinic were as follows; cockroach (56.8%, wheat pollen (53.3%, corn pollen (47.4%, grass pollen (36.5%, poplar tree pollen (26%, house dust mite (19.4%, pepper (16.7% and cat dander (15.1%. Conclusion: High levels of sensitivity to wheat and corn pollens and relatively low sensitivity levels of cat dander results meet our expectations in the area of agricultural land and where pet ownership is not common.

  15. Asthma and allergic rhinitis in childhood: what's new.

    Science.gov (United States)

    Mastrorilli, Carla; Posa, Daniela; Cipriani, Francesca; Caffarelli, Carlo

    2016-12-01

    Novel approaches are currently offered for the diagnostic workup and therapeutic management of allergic rhinitis and asthma. New predictive biomarkers of allergy and asthma are available. Primary and secondary prevention, earlier intervention, and modification of the natural history of allergic rhinitis and asthma are being intensively investigated. This review highlights advances in the understanding of the etiology, diagnosis, and management of atopic airway diseases in childhood, as well as prenatal and early-life risk factors and strategies for prevention. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Rutin has anti-asthmatic effects in an ovalbumin-induced asthmatic ...

    African Journals Online (AJOL)

    asthmatic mouse model ... 1Department of Pediatrics, Shandong Jining No.1 People's Hospital, Shandong 272000, 2Department of Pediatrics, Affiliated ..... BALF levels of IL-4, IL-5, and IL-13 versus the control group (Figure 3). However, the level of IFN-γ was slightly lower than the control group level. Rutin administration ...

  17. Superoxide dismutase levels and peak expiratory flow in asthmatic children

    Directory of Open Access Journals (Sweden)

    Arie Kurniasih

    2016-11-01

    Full Text Available Background Asthma is a chronic inflammatory process which involve variety of cells such as inflammatory mediators, reactive oxygen species (ROS, and cytokines. The inflammatory process would be exacerbated in the presence of oxidative stress. Superoxide dismutase (SOD is the first important enzyme to protect the respiratory tract against oxidative stress. The decreased of SOD has a correlation with increased of airway obstruction and bronchospasm. Objective To assess for a correlation between superoxide dismutase (SOD levels and peak expiratory flow, as well as to determine the impact of SOD levels for predicting asthma attacks. Methods We conducted a prospective cohort study at Dr. Sardjito Hospital, Yogyakarta, between February and April 2011 involving asthmatic children aged 5-18 years. Subjects’ serum SOD levels and peak expiratory flow were measured at the same time point. We then performed a prospective study following up on the same subjects to find out if they had a recurrent asthma attack within one month of the tests. We also reassessed their peak expiratory flow one month after blood specimens were obtained. Results Thirty-nine patients were enrolled in this study. There was no significant correlation between SOD level and peak expiratory flow [r=0.289; 95%CI -0.025 to 0.47; P=0.074]. However, older age was significantly associated with higher peak expiratory flow (=0.5; 95%CI 3.10 to 11.57; P=0.01. Lower levels of SOD increased the risk of asthma attacks in a month following the initial measurements (RR=5.5; 95%CI 1.6 to 18.9; P=0.009. Conclusion Superoxide dismutase (SOD level is not significantly associated with peak expiratory flow. However, we find a relationship between older age and higher peak expiratory flow and a relationship between lower SOD levels and risk of asthma attacks within one month following the tests.

  18. Fringe Controls Naïve CD4+T Cells Differentiation through Modulating Notch Signaling in Asthmatic Rat Models

    Science.gov (United States)

    Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

    2012-01-01

    The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4+T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4+T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4+T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4+T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma. PMID:23071776

  19. Fringe controls naïve CD4(+)T cells differentiation through modulating notch signaling in asthmatic rat models.

    Science.gov (United States)

    Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

    2012-01-01

    The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4(+)T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4(+)T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4(+)T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4(+)T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma.

  20. Short-term growth in asthmatic children using fluticasone propionate

    NARCIS (Netherlands)

    Visser, M. J.; van Aalderen, W. M.; Elliott, B. M.; Odink, R. J.; Brand, P. L.

    1998-01-01

    Inhaled corticosteroids may reduce short-term growth velocity in asthmatic children and knemometry is the most sensitive tool to detect this short-term growth suppression. To compare lower leg growth velocity, as measured by knemometry, in asthmatic children during and after treatment with inhaled

  1. Short-term growth in asthmatic children using fluticasone propionate

    NARCIS (Netherlands)

    Visser, MJ; van Aalderen, WMC; Elliott, BM; Odink, RJ; Brand, PLP

    Background: Inhaled corticosteroids may reduce short-term growth velocity in asthmatic children and knemometry is the most sensitive tool to detect this short-term growth suppression. Study objective: To compare lower leg growth velocity, as measured by knemometry, in asthmatic children during and

  2. The frequency of vitamin D deficiency among asthmatic Egyptian ...

    African Journals Online (AJOL)

    Objective: To detect the frequency of vitamin D insufficiency and deficiency among Egyptian asthmatic children and to correlate vitamin D levels to the severity of asthma. Methods: This case control study was conducted on 60 asthmatic children and 40 healthy controls. All were subjected to clinical history taking including ...

  3. daily, sustained-release theophylline on sleep in nocturnal asthmatics

    African Journals Online (AJOL)

    asthmatics. Design. Double-blind, randomised, cross-over, placebo- controlled trial over 22 days. Seven-day period to establish therapeutic levels of theophylline (11.8 ± 3 mg/I); ... (range 3 - 11 minutes); WSW increased from 33 minutes. (range 17 - 66 ... adults (age range 20 - 51 years), diagnosed as asthmatics according ...

  4. Endogenous heparin levels in the controlled asthmatic patient ...

    African Journals Online (AJOL)

    Background. Since heparin possesses anti-inflammatory properties, it is hypothesised that asthmatic patients have decreased levels of circulating heparin compared with healthy individuals. Design. We compared endogenous heparin levels in controlled asthmatic patients (53 adults) from the Asthma Clinic at ...

  5. NKT Cells in the Induced Sputum of Severe Asthmatics

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available To determine whether there was a specific inflammatory process in severe asthmatics, the phenotypic characteristics of induced sputum immune cells were analysed among patients with severe asthma. Twenty-two induced sputa (10 severe asthmatics were studied. Flow cytometric analysis was performed using immune cells of the sputum and monoclonal antibodies to CD3, CD4, CD8, CD56, CD25, and TCRγδ . The number of NKT (CD3 + CD 56+ cells was significantly higher in the sputum of severe asthmatics compared with mild asthmatic and healthy control groups ( p<.05 . CD8+CD 56+ cells were the predominant subtype of the increased NKT cells in severe asthmatics. CD3 +CD56+Vα24 +, TCRγδ CD56+, and CD4+CD25+ T cells were significantly increased in severe asthmatic patients. These results suggest that the immunopathogenesis of severe asthmatics vary between severe and mild asthmatics, and that CD8+ CD 56+ NKT cells may play an important role in the immunopathogenesis of severe asthma.

  6. Gastroesophageal reflux episodes in asthmatic patients and their temporal relation with sleep architecture

    Directory of Open Access Journals (Sweden)

    L. Mello-Fujita

    2008-02-01

    Full Text Available Gastroesophageal reflux (GER is common in asthma patients and can contribute to sleep disruption. The aim of the present study was to determine the time-related distribution of GER events together with their impact on sleep in asthmatic subjects with GER disease symptoms. The inclusion criteria were: 18-65 years, controlled moderate to severe asthma and GER-compatible clinical evidence. The exclusion criteria were: chronic obstructive lung disease, smoking, infections of the upper airways, use of oral corticosteroids, other co-morbidities, pregnancy, sleep-related disorders, night-time shift work, and the use of substances with impact on sleep. Asthmatic patients with nocturnal symptoms were excluded. All-night polysomnography and esophageal pH monitoring were recorded simultaneously. Of the 147 subjects selected, 31 patients and 31 controls were included. Seventeen patients were classified as DeMeester positive and 14 as DeMeester negative. Both groups displayed similar outcomes when general variables were considered. Sleep stage modification one minute prior to GER was observed in the DeMeester-positive group. Awakening was the most frequent occurrence at GER onset and during the 1-min period preceding 38% of the nocturnal GER. Sleep stage 2 was also prevalent and preceded 36% of GER events. In the DeMeester-negative group, awakening was the most frequent response before and during GER. Modifications in sleep stages, arousals or awakenings were associated with 75% of the total GER events analyzed during the period of one minute before and after the fall of esophageal pH below 4 in the DeMeester-positive group. These data provide evidence that sleep modifications precede the GER events in asthmatic patients.

  7. Immunopathogenesis of allergic rhinitis

    African Journals Online (AJOL)

    EL-HAKIM

    markers such as the vascular cell adhesion molecule-1. Chemoattractants including eotaxin,. IL-5, and RANTES lead to the characteristic infiltration by eosinophils, basophils, Th2 lymphocytes, and mast cells in chronic allergic rhinitis.15. Figure 2. Cell and mediator pathways underlying the pathogenesis of allergic rhinitis.

  8. Allergic rhinosinusitis in children

    African Journals Online (AJOL)

    Chantel

    inflammatory oede- ma present in persis- tent allergic rhinitis will eventually occur in the mucous mem- branes of the ostiomeatal units in the middle meati leading ultimately to allergic ... most children over the age of 6 months. These are excellent tests .... flax oil or fatty fish is of a high omega 3 and essential amino acid.

  9. Allergic Bronchopulmonary Aspergillosis (ABPA)

    Science.gov (United States)

    ... ABPA most commonly affects people with asthma or cystic fibrosis. Many people with ABPA also suffer from allergic conditions such as atopic dermatitis (eczema), urticaria (hives) , allergic rhinitis (hay fever) and sinusitis . Symptoms & Diagnosis Symptoms If you have asthma, the first noticeable ...

  10. The allergic march

    African Journals Online (AJOL)

    Several studies have demonstrated the allergic march from atopic eczema to the development of asthma and allergic rhinitis. Rhodes et al.2 studied 100 infants from atopic families over a 22-year period in the UK. The prevalence of atopic eczema reached a peak in 20% of children at 1 year of age and then declined to just ...

  11. Determinants of peripheral airway function in adults with and without asthma.

    Science.gov (United States)

    Robinson, Paul D; King, Gregory G; Sears, Malcolm R; Hong, Chuen Y; Hancox, Robert J

    2017-08-01

    Peripheral airway involvement in asthma remains poorly understood. We investigated impulse oscillometry (IOS) measures of peripheral airway function in a population-based birth cohort. Pre- and post-bronchodilator spirometry and IOS measures of respiratory resistance and reactance were measured in 915 participants at age 38 years. Current asthma was associated with impairments in both spirometry and IOS parameters. These impairments were greater in men and in those with childhood persistent asthma. Spirometry and IOS values for those whose asthma was in remission were not different to non-asthmatic participants. There were significant changes in IOS in both asthmatic and non-asthmatic participants after bronchodilator, but between-group differences persisted. Higher BMIs were associated with impairments in IOS but not spirometry. Cumulative tobacco use was associated with spirometric airflow obstruction in both sexes, whereas cannabis use was associated with impairments in IOS in women. Despite higher lifetime exposure, there were few associations between cannabis and IOS in men. Asthma is associated with abnormalities in IOS measures of peripheral airway dysfunction. This association is stronger in men and in those with asthma persisting since childhood. Tobacco and cannabis use are associated with different patterns of spirometry and IOS abnormalities and may affect the bronchial tree at different airway generations with differences in susceptibility between sexes. © 2017 Asian Pacific Society of Respirology.

  12. Determinants of allergic rhinitis in young children with asthma.

    Science.gov (United States)

    Moussu, Lise; Saint-Pierre, Philippe; Panayotopoulos, Virginie; Couderc, Rémy; Amat, Flore; Just, Jocelyne

    2014-01-01

    In the preschool period, allergic rhinitis (AR) is infrequent and thus under-diagnosed. However, recent works have highlighted the occurrence of AR in toddlers although the causes of AR in this young population remain unknown. The objective of this study was to identify determinants of AR in young children with asthma. We carried out a case-control study of 227 children with active asthma and enrolled in the Trousseau Asthma Program. AR and other allergic diseases (asthma, food allergy and eczema) were diagnosed by medical doctors using standardized questionnaires. Parental history of AR and asthma, biological markers of atopy (total IgE, blood eosinophilia, allergic sensitization towards food and aeroallergens) and environmental parameters were also collected. Forty one of the children (18.1%) had AR. By univariate logistic regression analysis, AR was mainly associated with peanut sensitization (OR = 6.75; p = 0.002); food allergy (OR = 4.31; p = 0.026); mold exposure (OR = 3.81 pfood allergy and peanut sensitization three models of multivariate logistic regression were performed and confirmed that AR is associated with peanut sensitization but also food allergy and mold exposure. A random forest analysis was also performed to explain AR. The results reinforced the logistic analysis that peanut sensitization and mold exposure were the principal determinants of AR. These results stress the importance of investigating AR in young children with asthma to potentially diagnose a particularly severe allergic asthmatic phenotype. Moreover, these data evoke the hypothesis that peanut could be an aeroallergen.

  13. Epigenomics and allergic disease.

    Science.gov (United States)

    Lockett, Gabrielle A; Patil, Veeresh K; Soto-Ramírez, Nelís; Ziyab, Ali H; Holloway, John W; Karmaus, Wilfried

    2013-12-01

    Allergic disease development is affected by both genes and the environment, and epigenetic mechanisms are hypothesized to mediate these environmental effects. In this article, we discuss the link between the environment, DNA methylation and allergic disease, as well as questions of causality inherent to analyses of DNA methylation. From the practical side, we describe characteristics of allergic phenotypes and contrast different epidemiologic study designs used in epigenetic research. We examine methodological considerations, how best to conduct preprocessing and analysis of DNA methylation data sets, and the latest methods, technologies and discoveries in this rapidly advancing field. DNA methylation and other epigenetic marks are firmly entwined with allergic disease, a link that may hold the basis for future allergic disease diagnosis and treatment.

  14. [Changes in small airway function in rhinitis without asthma].

    Science.gov (United States)

    Ji, Junfeng; Wang, Qiuping; Zhang, Yong; Wang, Zhiyi; Shi, Xu; Guan, Weijie; Wu, Kunmin; Xu, Li; Chen, Wei; Xue, Fei; Jiang, Manjie; Cheng, You; Wang, Tianyou; Zhong, Nanshan

    2015-11-01

    Observe the changes of small airway function in patients with rhinitis but without asthma and/or lower airway symptoms. Between June 2008 and December 2012, we recruited 903 subjects, including 377 with allergic rhinitis (AR), 262 with non-allergic rhinitis (NAR) and 264 healthy subjects. All subjects underwent meticulous history taking, nasal examination, allergen skin prick test, blood routine test, serum total immunoglobin E assay, pulmonary ventilation function test and bronchial challenge test. The indices of FEV1/FVC%, MEF25pred% and MMEFpred% were lower in AR group than in the control group (P rhinitis group and the control group (P > 0.05). The positive rate of airway hyperresponsiveness(AHR) in AR group and in NAR group was 12.2%, 6.1% respectively. Indices of small airway function were all lower in the AHR group than NAHR group in rhinitis. Compared with healthy controls, small airway function in patients with rhinitis has apparent changes, part of rhinitis patients has AHR, and is associated with small airway function changes.

  15. Airway inflammation and tachykinins: prospects for the development of tachykinin receptor antagonists.

    Science.gov (United States)

    Joos, G F; De Swert, K O; Pauwels, R A

    2001-10-19

    The tachykinins substance P and neurokinin A are contained within sensory airway nerves. Immune cells form an additional source of tachykinins in inflamed airways. Elevated levels of tachykinins have been recovered from the airways of patients with asthma and chronic obstructive pulmonary disease. Airway inflammation leads to an upregulation of tachykinin NK(1) and NK(2) receptors. Preclinical studies have indicated a role for the tachykinin NK(1), NK(2) and NK(3) receptors in bronchoconstriction, airway hyperresponsiveness and airway inflammation caused by allergic and nonallergic stimuli. Compounds that are able to block two or three tachykinin receptors hold promise for the treatment of airways diseases such as asthma and/or chronic obstructive pulmonary disease.

  16. The TLR5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens

    OpenAIRE

    Wilson, Rhonda H.; Maruoka, Shuichiro; Whitehead, Gregory S.; Foley, Julie F.; Flake, Gordon P.; Sever, Michelle L.; Zeldin, Darryl C.; Kraft, Monica; Garantziotis, Stavros; Nakano, Hideki; Cook, Donald N.

    2012-01-01

    Allergic asthma is a complex disease characterized by eosinophilic pulmonary inflammation, mucus production and reversible airway obstruction 1 . Exposure to indoor allergens is a clear risk factor for asthma, but this disease is also associated with high household levels of total and Gram-negative bacteria 2 . The ability of bacterial products to act as adjuvants 3 suggests they might promote asthma by priming allergic sensitization to inhaled allergens. In support of this idea, house dust e...

  17. Response localization of the pharmacological agents histamine and salbutamol along the respiratory system by forced oscillations in asthmatic subjects.

    Science.gov (United States)

    Wouters, E F; Polko, A H; Visser, B F

    1989-01-01

    The bronchodilating effect of 1 mg and 0.4 mg salbutamol on the impedance of the respiratory system was studied in 25 asthmatic subjects after histamine-induced bronchoconstriction. Histamine caused an increase of respiratory resistance (Rrs) at lower frequencies and a frequency dependence of Rrs. Respiratory reactance (Xrs) decreased at all frequencies after histamine challenge. These changes can be explained by peripheral airway obstruction. Impedance measurements performed 5 min after inhalation of 1 mg and 0.4 mg salbutamol showed a decrease of Rrs values at lower frequencies, a disappearance of the frequency dependence of Rrs, and a significant increase of Xrs values. No significant differences in absolute changes of Rrs and Xrs are observed between the salbutamol regimens. These changes after inhalation of salbutamol can be explained by supposing a predominant action on the peripheral airways.

  18. The link between allergic rhinitis and allergic asthma

    DEFF Research Database (Denmark)

    Linneberg, A; Henrik Nielsen, N; Frølund, L

    2002-01-01

    BACKGROUND: It has been hypothesized that allergic rhinitis and allergic asthma are manifestations of the same disease entity. We aimed to investigate the relationship between allergic rhinitis and allergic asthma. METHODS: Participants in a population-based study of 15-69-year-olds in 1990 were ...

  19. Gingival immunologic defense index: a new indicator for evaluating dental plaque infection risk in allergic children

    Directory of Open Access Journals (Sweden)

    Seno Pradopo

    2008-03-01

    Full Text Available There is a possible relationship between dental plaque and children allergic diseases. According to literatures, gingivitis suffered mostly by allergic children than control. Case reports also revealed that dental plaque control therapy was able to reduce, even eliminate rhinosinusitis and asthmatic symptoms without additional medications. However, the exact method for confirming the gingivitis-related allergy is still uncertain. Allergic diseases have multifactorial etiologies and dental plaque had been proposed as a new trigger of allergic symptoms. Nevertheless, since not every child with gingivitis suffered from allergy or vice versa, this uncertain phenomenon may lead to patients or other clinician disbelief. The objective of the present study was to propose a new method, which involving the Gingival immunologic defense index (GIDI to evaluate the susceptibility to allergic diseases. GIDI is an index that had been developed earlier for evaluating gingival immunologic defense with respect to immunoglobulin A (IgA levels. This index based on the simple count of the inflamed gingival surfaces of a child plus the measurement of salivary IgA content. It provides clinicians with important information about the immunologic defense potential of each subject. Interestingly, most allergic children also had inherited IgA deficiency, thus this concept is likely. Based on literatures, GIDI could be a potential index for evaluating the risk of allergic diseases through gingival health assessment. However, prior investigation to the value of Indonesian GIDI index which related to allergy should be conducted.

  20. The differences of eosinophil- and neutrophil-related inflammation in elderly allergic and non-allergic chronic obstructive pulmonary disease.

    Science.gov (United States)

    Tsai, Jaw-Ji; Liao, En-Chih; Hsu, Jeng-Yuan; Lee, Wen-Jane; Lai, Yiu-Kay

    2010-11-01

    Chronic obstructive pulmonary disease (COPD) is a common disease in the elderly population and is characterized by airway inflammation. Whether it is a progressive condition resulting from allergic inflammation or a distinct condition involving a pathogen-induced reaction remains unclear. To determine the role of allergic inflammation in the pathogenesis of elderly COPD. A total of 63 elderly adults (21 mite-allergic COPD patients, 29 non-allergic COPD patients, and 13 normal controls) were recruited in this study. The serum-specific IgE for mites, level of interleukin-5 (IL-5), IL-8, leptin, adiponectin, regulated upon activation normal T cell expressed and secreted (RANTES), growth-related oncogene-α (GRO-α), vitamin E, and glutathione (GSH) were determined. The serum levels of GRO-α in patients with COPD were higher in comparison to normal controls (105.8 ± 32.7 vs. 7.5 ± 7.5 pg/mL, p= .021). Compared to patients with non-allergic COPD, patients with mite allergies had a higher serum level of IL-8 (63.2 ± 12.6 vs. 35.0 ± 8.2 pg/mL, p= .022). Although both IL-5 and RANTES levels were increased in COPD patients, there were no significant differences between allergic and non-allergic COPD. There were also no differences in serum levels of leptin, adiponectin, vitamin E, and GSH between COPD patients and normal controls. The increased serum levels of GRO-α indicate that it may have potential as a candidate biomarker for elderly COPD patients. There was no difference of eosinophils-related chemokines in allergic and non-allergic COPD. These results indicated that both adipokines and eosinophil-related chemokines only play trivial roles in the pathogenesis of COPD.

  1. Plasminogen activator inhibitor-1 (PAI-1 and urokinase plasminogen activator (uPA in sputum of allergic asthma patients.

    Directory of Open Access Journals (Sweden)

    Sebastian Zukowski

    2008-06-01

    Full Text Available Urokinase plasminogen activator (uPA and its inhibitor (PAI-1 have been associated with asthma. The aim of this study was to evaluate concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs. The study was performed on 19 HDM-AAs and 8 healthy nonatopic controls (HCs. Concentration of uPA and PAI-1 was evaluated in induced sputum supernatants using ELISA method. In HDM-AAs the median sputum concentration of uPA (128 pg/ml; 95% CI 99 to 183 pg/ml and PAI-1 (4063 pg/ml; 95%CI 3319 to 4784 pg/ml were significantly greater than in HCs (17 pg/ml; 95%CI 12 to 32 pg/ml; p<0.001 and 626 pg/ml; 95%CI 357 to 961 pg/ml; p<0.001 for uPA and PAI-1 respectively. The sputum concentration of uPA correlated with sputum total cell count (r=0.781; p=0.0001 and with logarithmically transformed exhaled nitric oxide concentration (eNO (r=0.486; p=0.035 but not with FEV1 or bronchial reactivity to histamine. On the contrary, the sputum PAI-1 concentration correlated with FEV1 (r=-0,718; p=0.0005 and bronchial reactivity to histamine expressed as log(PC20 (r=-0.824; p<0.0001 but did not correlate with sputum total cell count or eNO. The results of this study support previous observations linking PAI-1 with airway remodeling and uPA with cellular inflammation. Moreover, the observed effect of uPA seems to be independent of its fibrynolytic activity.

  2. [Allergic rhinitis in children].

    Science.gov (United States)

    Richter, Darko

    2011-01-01

    Allergic rhinitis is the most prevalent form of chronic rhinitis in children. It is driven by allergic inflammation and is commonly associated with other atopic diseases such as asthma and atopic eczema. The main allergens are primarily aeroallergens: house dust mite, and tree, grass and weed pollen. It is, however, not exceptional to experience symptoms of allergic rhinoconjunctivitis in conjunction with food allergy and oral food allergy syndrome, especially in infants and toddlers. Allergic rhinitis is often associated with allergic asthma, either preceding it, or developing later and making it more difficult to treat. The mainstay of treatment is exposure prophylaxis, antihistamines, leukotriene antagonists and intranasal corticosteroids. Allergic rhinitis is one of the prime indications for specific allergen immunotherapy, which may have a preventive effect on the development of asthma. Allergic rhinitis associated with intermittent or mild persistent asthma may be a good indication for concomitant combination treatment with antihistamines and leukotriene antagonists. Intranasal corticosteroids should not be withheld in more severe forms. Shortterm (up to 3 months) use of intranasal corticosteroids has not been associated with any significant local or systemic side effects.

  3. Cephalometric Evaluation of Children with Allergic Rhinitis and Mouth Breathing.

    Science.gov (United States)

    Agostinho, Helena Afonso; Furtado, Ivo Ãlvares; Silva, Francisco Salvado; Ustrell Torrent, Josep

    2015-01-01

    Orthodontists frequently treat children with mouth breathing. The purpose of the present study was to examine dental positions, skeletal effects and the pharyngeal airway space of children with chronic allergic rhinitis, when compared with a control group exhibiting a normal breathing pattern. Seventy Caucasian children from Santa Maria University Hospital - North Lisbon Hospital Center were evaluated, between September 2009 and February 2013. The study group comprised of 35 children with chronic allergic rhinitis, both genders, aged 5 - 14, with positive reaction to allergens, mouth breathing and malocclusion. The control group was composed of 35 children, both genders, displaying normal nasal breathing and malocclusion, who resorted to the orthodontic department. Measures of Ricketts, Steiner and McNamara's analysis were used and the t- Student test was applied to the data obtained. Statistically significant differences were observed between the oral and nasal breathers, respectively: lower facial height (49.1/45.9 mm), Frankfurt â mandibular plane angle (30.1/26.9º) and Sela-Nasion - oclusal plane angle (17.3/15º), maxillary length (78.4/82.4 mm), mandibular length (102.4/107 mm), overbite (0.8/3.1mm) and overjet (4/4.7 mm). Comparison between the allergic rhinitis and control group showed that there is an increased lower facial height, larger Frankfurt â mandibular plane angle and Sela-Nasion oclusal plane angle in children with chronic allergic rhinitis. This group also had a shorter maxillary and mandibular length, less overbite and decreased upper airway space. Children with allergic rhinitis and mouth breathing have longer faces, shorter maxillas and mandibles and a narrowed pharyngeal airway space. No statistical differences between the groups in sagital relationships or in dental inclinations were found.

  4. The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus.

    Directory of Open Access Journals (Sweden)

    Abigail Morris

    Full Text Available Heparanase is an endo-β-glucuronidase that specifically cleaves heparan sulfate proteoglycans in the extracellular matrix. Expression of this enzyme is increased in several pathological conditions including inflammation. We have investigated the role of heparanase in pulmonary inflammation in the context of allergic and non-allergic pulmonary cell recruitment using heparanase knockout (Hpa-/- mice as a model. Following local delivery of LPS or zymosan, no significant difference was found in the recruitment of neutrophils to the lung between Hpa-/- and wild type (WT control. Similarly neutrophil recruitment was not inhibited in WT mice treated with a heparanase inhibitor. However, in allergic inflammatory models, Hpa-/- mice displayed a significantly reduced eosinophil (but not neutrophil recruitment to the airways and this was also associated with a reduction in allergen-induced bronchial hyperresponsiveness, indicating that heparanase expression is associated with allergic reactions. This was further demonstrated by pharmacological treatment with a heparanase inhibitor in the WT allergic mice. Examination of lung specimens from patients with different severity of chronic obstructive pulmonary disease (COPD found increased heparanase expression. Thus, it is established that heparanase contributes to allergen-induced eosinophil recruitment to the lung and could provide a novel therapeutic target for the development of anti-inflammatory drugs for the treatment of asthma and other allergic diseases.

  5. Allergic Inflammation Leads to Neuropathic Pain via Glial Cell Activation.

    Science.gov (United States)

    Yamasaki, Ryo; Fujii, Takayuki; Wang, Bing; Masaki, Katsuhisa; Kido, Mizuho A; Yoshida, Mari; Matsushita, Takuya; Kira, Jun-Ichi

    2016-11-23

    Allergic and atopic disorders have increased over the past few decades and have been associated with neuropsychiatric conditions, such as autism spectrum disorder and asthmatic amyotrophy. Myelitis presenting with neuropathic pain can occur in patients with atopic disorder; however, the relationship between allergic inflammation and neuropathic pain, and the underlying mechanism, remains to be established. We studied whether allergic inflammation affects the spinal nociceptive system. We found that mice with asthma, atopic dermatitis, or atopic diathesis had widespread and significantly more activated microglia and astroglia in the spinal cord than those without atopy, and displayed tactile allodynia. Microarray analysis of isolated microglia revealed a dysregulated phenotype showing upregulation of M1 macrophage markers and downregulation of M2 markers in atopic mice. Among the cell surface protein genes, endothelin receptor type B (EDNRB) was most upregulated. Immunohistochemical analysis revealed that EDNRB expression was enhanced in microglia and astroglia, whereas endothelin-1, an EDNRB ligand, was increased in serum, lungs, and epidermis of atopic mice. No EDNRA expression was found in the spinal cord. Expression of FBJ murine osteosarcoma viral oncogene homolog B was significantly higher in the dorsal horn neurons of asthma mice than nonatopic mice. The EDNRB antagonist BQ788 abolished glial and neural activation and allodynia. We found increased serum endothelin-1 in atopic patients with myelitis and neuropathic pain, and activation of spinal microglia and astroglia with EDNRB upregulation in an autopsied case. These results suggest that allergic inflammation induces diffuse glial activation, influencing the nociceptive system via the EDNRB pathway. The prevalence of allergic disorders has markedly increased over the past few decades. Allergic disorders are associated with neuropsychiatric conditions; however, the relationship between allergic inflammation

  6. Histophatologic changes of lung in asthmatic male rats treated with hydro-alcoholic extract of Plantago major and theophylline

    Directory of Open Access Journals (Sweden)

    Farah Farokhi

    2013-03-01

    Full Text Available Objective: Plantago major (P. major is one of the medicinal crops in the world which has therapeutic properties for treatment of respiratory and gastrointestinal diseases. Theophylline is commonly used for the treatment of respiratory diseases. In this study, we investigated the protective effects of hydro-alcoholic extract of P. major on lung in asthmatic male rats. Materials and Methods: 32 male adult rats were randomly divided into 4 groups: The control group (C received normal saline; Asthma (A group received a normal diet; Asthma group treated with Theophylline (200 mg/kg b.w. (T; Asthma group which received p.major (100 mg/kg b.w. (P. Asthma was induced by citric acid, 0.1 mg in form of spraying. The injection of P.major extract and theophylline was administered intraperitoneally for four weeks. At the end of the treatment, all of the rats were sacrificed and lungs were taken out, fixed, and stained with H&E, toluidine blue, and PAS, then histological studies were followed with light microscope. Results: Results showed that, in asthmatic group, the mean number of mast cells was significantly increased (p<0.05. Thickness of alveolar epithelium and accumulation of glycoprotein in airways was increased. Moreover, in some of alveolar sac hemorrhaging was observed. Administration of p.major extract in asthmatic rats restored these changes towards normal group.Conclusion: The present study revealed that P. major compared with theophylline, has a protective effect on lung in asthmatic rats.

  7. Distribution of radioactive aerosol in the airways of children and adolescents with bronchial hyper-responsiveness

    International Nuclear Information System (INIS)

    Backer, V.; Mortensen, J.

    1992-01-01

    The purpose of this study was to examine the relationship between the pulmonary distribution of inhaled radioaerosol, bronchial responsiveness, and lung function in children and adolescents. The participating subjects were divided into three groups: (1) 14 asthmatics with bronchial hyper-responsiveness (BHR), (2) five non-asthmatic subjects with BHR, and (3) 20 controls without BHR. Pulmonary distribution of [ 99 Tc m ] albumin radioaerosol, maximal expiratory flow when 25% of forced vital capacity remain to be exhaled (MEF 25 ), and bronchial responsiveness to inhaled histamine were measured. Twenty subjects (52%) has irregular central distribution and 19 subjects (48%) had regular distribution of radioaerosol in their lungs. No difference in distribution of radioaerosol was found between the three groups of children. The median MEF 25 among non-asthmatic subjects (80% predicted) was lower than that found in controls (92% predicted) but higher than that found in asthmatic subjects (55% predicted). A relationship was found between reduced flow at the peripheral airways, as indicated by MEF 25 and the degree of central distribution of radioaerosol. Furthermore, subjects with irregular central distribution of radioaerosol had an increase degree of bronchial responsiveness. In conclusion, children and adolescents who have flow rates in the peripheral airways or increased degree of bronchial responsiveness tend to have abnormal distribution of radioaerosols. (author)

  8. Anti-Inflammatory Effects of Ginsenoside Rg3 via NF-κB Pathway in A549 Cells and Human Asthmatic Lung Tissue

    Directory of Open Access Journals (Sweden)

    In-Seung Lee

    2016-01-01

    Full Text Available Objective. There is limited information of the anti-inflammatory effects of Rg3 on inflamed lung cells and tissues. Therefore, we confirmed the anti-inflammatory mechanism of ginsenoside Rg3 in inflamed human airway epithelial cells (A549 and tissues whether Rg3 regulates nuclear factor kappa B (NF-κB activity. Methods. To induce the inflammation, IL-1β (10 ng/ml was treated to A549 cells for 4 h. The effects of Rg3 on NF-κB activity and COX-2 expression were evaluated by western blotting analysis in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. Using multiplex cytokines assay, the secretion levels of NF-κB-mediated cytokines/chemokines were measured. Result. Rg3 showed the significant inhibition of NF-κB activity thereby reduced COX-2 expression was determined in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. In addition, among NF-κB-mediated cytokines, the secretion levels of IL-4, TNF-α, and eotaxin were significantly decreased by Rg3 in asthma tissues. Even though there was no significant difference, IL-6, IL-9, and IL-13 secretion showed a lower tendency compared to saline-treated human asthmatic airway epithelial tissues. Conclusion. The results from this study demonstrate the potential of Rg3 as an anti-inflammatory agent through regulating NF-κB activity and reducing the secretion of NF-κB-mediated cytokines/chemokines.

  9. House dust mite allergen induces asthma via TLR4 triggering of airway structural cells

    Science.gov (United States)

    HAMMAD, Hamida; CHIEPPA, Marcello; PERROS, Frederic; WILLART, Monique A.; GERMAIN, Ronald N.; LAMBRECHT, Bart N.

    2009-01-01

    Barrier epithelial cells and airway dendritic cells (DC) make up the first line of defence against inhaled substances like house dust mite (HDM) allergen and endotoxin. We hypothesized that these cells need to communicate to cause allergic disease. Using irradiated chimeric mice, we demonstrate that TLR4 expression on radioresistant lung structural cells is required and sufficient for DC activation in the lung and for priming of effector T helper responses to HDM. TLR4 triggering on structural cells caused production of the innate proallergic cytokines thymic stromal lymphopoietin, granulocyte-macrophage colony stimulating factor, interleukin-25 and IL-33. The absence of TLR4 on structural cells, but not on hematopoietic cells, abolished HDM driven allergic airway inflammation. Finally, inhalation of a TLR4 antagonist to target exposed epithelial cells suppressed the salient features of asthma including bronchial hyperreactivity. Our data identify an innate immune function of airway epithelial cells that drives allergic inflammation via activation of mucosal DCs. PMID:19330007

  10. Allergic Rhinitis Quiz

    Science.gov (United States)

    ... the best strategy for managing