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Sample records for allergic airway diseases

  1. Long-Acting Beta Agonists Enhance Allergic Airway Disease

    PubMed Central

    Knight, John M.; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O.; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A.; Milner, Joshua D.; Zhang, Yuan; Mandal, Pijus K.; Luong, Amber; Kheradmand, Farrah

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  2. Long-Acting Beta Agonists Enhance Allergic Airway Disease.

    PubMed

    Knight, John M; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A; Milner, Joshua D; Zhang, Yuan; Mandal, Pijus K; Luong, Amber; Kheradmand, Farrah; McMurray, John S; Corry, David B

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6.

  3. Lysophosphatidylcholine plays critical role in allergic airway disease manifestation

    PubMed Central

    Bansal, Preeti; Gaur, Shailendera Nath; Arora, Naveen

    2016-01-01

    Phospholipase A2 (sPLA2), pivotal for allergic and inflammatory response, hydrolyses phosphatidylcholine (PC) to lysophosphatidylcholine (LPC). In present study, the role of LPC in allergic airway disease manifestation was studied using mouse model. Balb/c mice were immunized using cockroach extract (CE) and LPC release was blocked by sPLA2 inhibitor. Airway hyperresponse (AHR), lung-histology, total and differential leukocyte count (TLC&DLC), Th2 type cytokines, sPLA2 activity and LPC levels in bronchoalveolar lavage fluid (BALF) were measured. Exogenous LPC was given to the mice with or without CE sensitization, to demonstrate its role in allergic airway disease manifestation. Anti-CD1d antibody was given to study the involvement of natural killer T (NKT) cells in LPC induced response. AHR, lung-inflammation, TLC, DLC, Th2 type cytokines, sPLA2 activity and LPC levels were increased on CE challenge. sPLA2 activity and LPC release was blocked by sPLA2-inhibitor, which decreased AHR, and inflammatory parameters. Exogenous LPC with or without CE sensitization increased above parameters. CE challenge or LPC exposure increased LY49C+TCRβ+ NKT cells in BALF and spleen, which was reduced by anti-CD1d antibody, accompanied with reduction in AHR and allergic airway inflammation parameters. Conclusively, LPC induces allergic airway disease manifestation and it does so probably via CD1d-restricted LY49C+TCRβ+ NKT cells. PMID:27282246

  4. Hyperresponsiveness in the human nasal airway: new targets for the treatment of allergic airway disease.

    PubMed Central

    Turner, P J; Foreman, J C

    1999-01-01

    Allergic rhinitis is a condition which affects over 15% of the population in the United Kingdom. The pathological process involves two stages: nasal inflammation, and the development of nasal airway hyperresponsiveness (AHR) to allergen and a number of other stimuli. This results in the amplification of any subsequent allergic reaction, contributing to the chronic allergic state. A number of different hypotheses have been proposed to explain the underlying mechanism of AHR, including a role for eosinophil-derived proteins, free radicals and neuropeptides. While there may be a number of independent pathways which can result in AHR, evidence obtained from both animal models and in vivo experiments in humans indicate that some mediators may interact with one another, resulting in AHR. Further research into these interactions may open new avenues for the pharmacological treatment of chronic allergic rhinitis, and possibly other allergic airway diseases. PMID:10704051

  5. Restoring airway epithelial barrier dysfunction: a new therapeutic challenge in allergic airway disease.

    PubMed

    Steelant, B; Seys, S F; Boeckxstaens, G; Akdis, C A; Ceuppens, J L; Hellings, P W

    2016-09-01

    An intact functional mucosal barrier is considered to be crucial for the maintenance of airway homeostasis as it protects the host immune system from exposure to allergens and noxious environmental triggers. Recent data provided evidence for the contribution of barrier dysfunction to the development of inflammatory diseases in the airways, skin and gut. A defective barrier has been documented in chronic rhinosinusitis, allergic rhinitis, asthma, atopic dermatitis and inflammatory bowel diseases. However, it remains to be elucidated to what extent primary (genetic) versus secondary (inflammatory) mechanisms drive barrier dysfunction. The precise pathogenesis of barrier dysfunction in patients with chronic mucosal inflammation and its implications on tissue inflammation and systemic absorption of exogenous particles are only partly understood. Since epithelial barrier defects are linked with chronicity and severity of airway inflammation, restoring the barrier integrity may become a useful approach in the treatment of allergic diseases. We here provide a state-of-the-art review on epithelial barrier dysfunction in upper and lower airways as well as in the intestine and the skin and on how barrier dysfunction can be restored from a therapeutic perspective.

  6. [Research progress on role of chemokine receptor CCR3 signaling in allergic airway diseases].

    PubMed

    Xu, Yi; Liu, Yuehui

    2012-12-01

    Allergic airway diseases have been identified as chronic inflammatory diseases of respiratory membranes, characterized by infiltration of many inflammatory cells, especially eosinophils. The expression of CCR3 is abundant on the cell surface of eosinophils. Increased accumulation of CCR3-driven inflammatory cells is thought to favor the development of allergy. In this review, we survey the properties of CCR3 and its ligands and highlight the roles of CCR3 signaling in allergic airway diseases.

  7. Prevention of house dust mite induced allergic airways disease in mice through immune tolerance.

    PubMed

    Agua-Doce, Ana; Graca, Luis

    2011-01-01

    Allergic airways disease is a consequence of a Th2 response to an allergen leading to a series of manifestations such as production of allergen-specific IgE, inflammatory infiltrates in the airways, and airway hyper-reactivity (AHR). Several strategies have been reported for tolerance induction to allergens leading to protection from allergic airways disease. We now show that CD4 blockade at the time of house dust mite sensitization induces antigen-specific tolerance in mice. Tolerance induction is robust enough to be effective in pre-sensitized animals, even in those where AHR was pre-established. Tolerant mice are protected from airways eosinophilia, Th2 lung infiltration, and AHR. Furthermore, anti-CD4 treated mice remain immune competent to mount immune responses, including Th2, to unrelated antigens. Our findings, therefore, describe a strategy for tolerance induction potentially applicable to other immunogenic proteins besides allergens.

  8. Exhaled NO: Determinants and Clinical Application in Children With Allergic Airway Disease

    PubMed Central

    Kim, Hyo-Bin; Eckel, Sandrah P.

    2016-01-01

    Nitric oxide (NO) is endogenously released in the airways, and the fractional concentration of NO in exhaled breath (FeNO) is now recognized as a surrogate marker of eosinophilic airway inflammation that can be measured using a noninvasive technique suitable for young children. Although FeNO levels are affected by several factors, the most important clinical determinants of increased FeNO levels are atopy, asthma, and allergic rhinitis. In addition, air pollution is an environmental determinant of FeNO that may contribute to the high prevalence of allergic disease. In this review, we discuss the mechanism for airway NO production, methods for measuring FeNO, and determinants of FeNO in children, including host and environmental factors such as air pollution. We also discuss the clinical utility of FeNO in children with asthma and allergic rhinitis and further useful directions using FeNO measurement. PMID:26540497

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

    PubMed Central

    Eyring, Kenneth R.; Pedersen, Brent S.; Yang, Ivana V.; Schwartz, David A.

    2015-01-01

    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. PMID:26642056

  10. A pathogenic role for the integrin CD103 in experimental allergic airways disease.

    PubMed

    Fear, Vanessa S; Lai, Siew Ping; Zosky, Graeme R; Perks, Kara L; Gorman, Shelley; Blank, Fabian; von Garnier, Christophe; Stumbles, Philip A; Strickland, Deborah H

    2016-11-01

    The integrin CD103 is the αE chain of integrin αEβ7 that is important in the maintenance of intraepithelial lymphocytes and recruitment of T cells and dendritic cells (DC) to mucosal surfaces. The role of CD103 in intestinal immune homeostasis has been well described, however, its role in allergic airway inflammation is less well understood. In this study, we used an ovalbumin (OVA)-induced, CD103-knockout (KO) BALB/c mouse model of experimental allergic airways disease (EAAD) to investigate the role of CD103 in disease expression, CD4(+) T-cell activation and DC activation and function in airways and lymph nodes. We found reduced airways hyper-responsiveness and eosinophil recruitment to airways after aerosol challenge of CD103 KO compared to wild-type (WT) mice, although CD103 KO mice showed enhanced serum OVA-specific IgE levels. Following aerosol challenge, total numbers of effector and regulatory CD4(+) T-cell subsets were significantly increased in the airways of WT but not CD103 KO mice, as well as a lack of DC recruitment into the airways in the absence of CD103. While total airway DC numbers, and their in vivo allergen capture activity, were essentially normal in steady-state CD103 KO mice, migration of allergen-laden airway DC to draining lymph nodes was disrupted in the absence of CD103 at 24 h after aerosol challenge. These data support a role for CD103 in the pathogenesis of EAAD in BALB/c mice through local control of CD4(+) T cell and DC subset recruitment to, and migration from, the airway mucosa during induction of allergic inflammation.

  11. FACTORS THAT INFLUENCE THE RELATIVE POTENCY OF DIESEL EXHAUST PARTICLES AS ADJUVANTS IN ALLERGIC AIRWAY DISEASE

    EPA Science Inventory

    Description: Studies have shown that diesel exhaust particles (DEP) worsen respiratory diseases including allergic asthma. The adjuvant effects of DEP in the airways have been widely reported; however, the precise determinants and mechanisms of these effects are ill-defined. S...

  12. Reduced levels of maternal progesterone during pregnancy increase the risk for allergic airway diseases in females only.

    PubMed

    Hartwig, Isabel R V; Bruenahl, Christian A; Ramisch, Katherina; Keil, Thomas; Inman, Mark; Arck, Petra C; Pincus, Maike

    2014-10-01

    Observational as well as experimental studies support that prenatal challenges seemed to be associated with an increased risk for allergic airway diseases in the offspring. However, insights into biomarkers involved in mediating this risk are largely elusive. We here aimed to test the association between endogenous and exogenous factors documented in pregnant women, including psychosocial, endocrine, and life style parameters, and the risk for allergic airway diseases in the children later in life. We further pursued to functionally test identified factors in a mouse model of an allergic airway response. In a prospectively designed pregnancy cohort (n = 409 families), women were recruited between the 4th and 12th week of pregnancy. To investigate an association between exposures during pregnancy and the incidence of allergic airway disease in children between 3 and 5 years of age, multiple logistic regression analyses were applied. Further, in prenatally stressed adult offspring of BALB/c-mated BALB/c female mice, asthma was experimentally induced by ovalbumin (OVA) sensitization. In addition to the prenatal stress challenge, some pregnant females were treated with the progesterone derivative dihydrodydrogesterone (DHD). In humans, we observed that high levels of maternal progesterone in early human pregnancies were associated with a decreased risk for an allergic airway disease (asthma or allergic rhinitis) in daughters (adjusted OR 0.92; 95% confidence interval [CI] 0.84 to 1.00) but not sons (aOR 1.02, 95% CI 0.94-1.10). In mice, prenatal DHD supplementation of stress-challenged dams attenuated prenatal stress-induced airway hyperresponsiveness exclusively in female offspring. Reduced levels of maternal progesterone during pregnancy-which can result from high stress perception-increase the risk for allergic airway diseases in females but not in males. Key messages: Lower maternal progesterone during pregnancy increases the risk for allergic airway disease

  13. Bromodomain and Extra-Terminal Protein Inhibition Attenuates Neutrophil-dominant Allergic Airway Disease.

    PubMed

    Manni, Michelle L; Mandalapu, Sivanarayana; Salmeron, Andres; Lora, Jose M; Kolls, Jay K; Alcorn, John F

    2017-02-24

    Atopic asthma is a prevalent respiratory disease that is characterized by inflammation, mucus hypersecretion, and airway hyperresponsiveness. The complexity of this heterogeneous disorder has commanded the need to better define asthma phenotypes based on underlying molecular mechanisms of disease. Although classically viewed as a type 2-regulated disease, type 17 helper T (Th17) cells are known to be influential in asthma pathogenesis, predominantly in asthmatics with neutrophilia and severe refractory disease. Bromodomain and extra-terminal domain (BET) chromatin adaptors serve as immunomodulators by directly regulating Th17 responses and Th17-mediated pathology in murine models of autoimmunity and infection. Based on this, we hypothesized that BET proteins may also play an essential role in neutrophil-dominant allergic airway disease. Using a murine model of neutrophil-dominant allergic airway disease, we demonstrate that BET inhibition limits pulmonary inflammation and alters the Th17-related inflammatory milieu in the lungs. In addition, inhibition of BET proteins improved lung function (specifically quasi-static lung compliance and tissue elastance) and reduced mucus production in airways. Overall, these studies show that BET proteins may have a critical role in asthma pathogenesis by altering type 17 inflammation, and thus interfering with BET-dependent chromatin signaling may provide clinical benefits to patients suffering from asthma.

  14. Bromodomain and Extra-Terminal Protein Inhibition Attenuates Neutrophil-dominant Allergic Airway Disease

    PubMed Central

    Manni, Michelle L.; Mandalapu, Sivanarayana; Salmeron, Andres; Lora, Jose M.; Kolls, Jay K.; Alcorn, John F.

    2017-01-01

    Atopic asthma is a prevalent respiratory disease that is characterized by inflammation, mucus hypersecretion, and airway hyperresponsiveness. The complexity of this heterogeneous disorder has commanded the need to better define asthma phenotypes based on underlying molecular mechanisms of disease. Although classically viewed as a type 2-regulated disease, type 17 helper T (Th17) cells are known to be influential in asthma pathogenesis, predominantly in asthmatics with neutrophilia and severe refractory disease. Bromodomain and extra-terminal domain (BET) chromatin adaptors serve as immunomodulators by directly regulating Th17 responses and Th17-mediated pathology in murine models of autoimmunity and infection. Based on this, we hypothesized that BET proteins may also play an essential role in neutrophil-dominant allergic airway disease. Using a murine model of neutrophil-dominant allergic airway disease, we demonstrate that BET inhibition limits pulmonary inflammation and alters the Th17-related inflammatory milieu in the lungs. In addition, inhibition of BET proteins improved lung function (specifically quasi-static lung compliance and tissue elastance) and reduced mucus production in airways. Overall, these studies show that BET proteins may have a critical role in asthma pathogenesis by altering type 17 inflammation, and thus interfering with BET-dependent chromatin signaling may provide clinical benefits to patients suffering from asthma. PMID:28233801

  15. The nitrated fatty acid 10-nitro-oleate attenuates allergic airway disease.

    PubMed

    Reddy, Aravind T; Lakshmi, Sowmya P; Dornadula, Sireesh; Pinni, Sudheer; Rampa, Dileep R; Reddy, Raju C

    2013-09-01

    Asthma is a serious, growing problem worldwide. Inhaled steroids, the current standard therapy, are not always effective in this chronic inflammatory disease and can cause adverse effects. We tested the hypothesis that nitrated fatty acids (NFAs) may provide an effective alternative treatment. NFAs are endogenously produced by nonenzymatic reaction of NO with unsaturated fatty acids and exert anti-inflammatory actions both by activating the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)γ and via PPAR-independent mechanisms, but whether they might ameliorate allergic airway disease was previously untested. We found that pulmonary delivery of the NFA 10-nitro-oleic acid (OA-NO2) reduced the severity of murine allergic airway disease, as assessed by various pathological and molecular markers. Fluticasone, an inhaled steroid commonly used to treat asthma, produced similar effects on most end points, but only OA-NO2 induced robust apoptosis of neutrophils and their phagocytosis by alveolar macrophages. This suggests that OA-NO2 may be particularly effective in neutrophil-rich, steroid-resistant severe asthma. In primary human bronchial epithelial cells, OA-NO2 blocked phosphorylation and degradation of IκB and enhanced inhibitory binding of PPARγ to NF-κB. Our results indicate that the NFA OA-NO2 is efficacious in preclinical models of allergic airway disease and may have potential for treating asthma patients.

  16. EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS

    EPA Science Inventory

    EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS (P. Singhl, D.W. Winsett2, M.J. Daniels2,
    C.A.J. Dick', K.B. Adlerl and M.I. Gilmour2, INCSU, Raleigh, N.C., 2NHEERL/ORD/ USEPA, RTP, N.C. and 3UNC, Chapel Hill, N.C.)The interaction between ...

  17. Alterations of the Murine Gut Microbiome with Age and Allergic Airway Disease.

    PubMed

    Vital, Marius; Harkema, Jack R; Rizzo, Mike; Tiedje, James; Brandenberger, Christina

    2015-01-01

    The gut microbiota plays an important role in the development of asthma. With advanced age the microbiome and the immune system are changing and, currently, little is known about how these two factors contribute to the development of allergic asthma in the elderly. In this study we investigated the associations between the intestinal microbiome and allergic airway disease in young and old mice that were sensitized and challenged with house dust mite (HDM). After challenge, the animals were sacrificed, blood serum was collected for cytokine analysis, and the lungs were processed for histopathology. Fecal pellets were excised from the colon and subjected to 16S rRNA analysis. The microbial community structure changed with age and allergy development, where alterations in fecal communities from young to old mice resembled those after HDM challenge. Allergic mice had induced serum levels of IL-17A and old mice developed a greater allergic airway response compared to young mice. This study demonstrates that the intestinal bacterial community structure differs with age, possibly contributing to the exaggerated pulmonary inflammatory response in old mice. Furthermore, our results show that the composition of the gut microbiota changes with pulmonary allergy, indicating bidirectional gut-lung communications.

  18. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis.

    PubMed

    Trompette, Aurélien; Gollwitzer, Eva S; Yadava, Koshika; Sichelstiel, Anke K; Sprenger, Norbert; Ngom-Bru, Catherine; Blanchard, Carine; Junt, Tobias; Nicod, Laurent P; Harris, Nicola L; Marsland, Benjamin J

    2014-02-01

    Metabolites from intestinal microbiota are key determinants of host-microbe mutualism and, consequently, the health or disease of the intestinal tract. However, whether such host-microbe crosstalk influences inflammation in peripheral tissues, such as the lung, is poorly understood. We found that dietary fermentable fiber content changed the composition of the gut and lung microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes. The gut microbiota metabolized the fiber, consequently increasing the concentration of circulating short-chain fatty acids (SCFAs). Mice fed a high-fiber diet had increased circulating levels of SCFAs and were protected against allergic inflammation in the lung, whereas a low-fiber diet decreased levels of SCFAs and increased allergic airway disease. Treatment of mice with the SCFA propionate led to alterations in bone marrow hematopoiesis that were characterized by enhanced generation of macrophage and dendritic cell (DC) precursors and subsequent seeding of the lungs by DCs with high phagocytic capacity but an impaired ability to promote T helper type 2 (TH2) cell effector function. The effects of propionate on allergic inflammation were dependent on G protein-coupled receptor 41 (GPR41, also called free fatty acid receptor 3 or FFAR3), but not GPR43 (also called free fatty acid receptor 2 or FFAR2). Our results show that dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation.

  19. Allergic airway disease in mice alters T and B cell responses during an acute respiratory poxvirus infection.

    PubMed

    Walline, Crystal C; Sehra, Sarita; Fisher, Amanda J; Guindon, Lynette M; Kratzke, Ian M; Montgomery, Jessica B; Lipking, Kelsey P; Glosson, Nicole L; Benson, Heather L; Sandusky, George E; Wilkes, David S; Brutkiewicz, Randy R; Kaplan, Mark H; Blum, Janice S

    2013-01-01

    Pulmonary viral infections can exacerbate or trigger the development of allergic airway diseases via multiple mechanisms depending upon the infectious agent. Respiratory vaccinia virus transmission is well established, yet the effects of allergic airway disease on the host response to intra-pulmonary vaccinia virus infection remain poorly defined. As shown here BALB/c mice with preexisting airway disease infected with vaccinia virus developed more severe pulmonary inflammation, higher lung virus titers and greater weight loss compared with mice inoculated with virus alone. This enhanced viremia was observed despite increased pulmonary recruitment of CD8(+) T effectors, greater IFNγ production in the lung, and high serum levels of anti-viral antibodies. Notably, flow cytometric analyses of lung CD8(+) T cells revealed a shift in the hierarchy of immunodominant viral epitopes in virus inoculated mice with allergic airway disease compared to mice treated with virus only. Pulmonary IL-10 production by T cells and antigen presenting cells was detected following virus inoculation of animals and increased dramatically in allergic mice exposed to virus. IL-10 modulation of host responses to this respiratory virus infection was greatly influenced by the localized pulmonary microenvironment. Thus, blocking IL-10 signaling in virus-infected mice with allergic airway disease enhanced pulmonary CD4(+) T cell production of IFNγ and increased serum anti-viral IgG1 levels. In contrast, pulmonary IFNγ and virus-specific IgG1 levels were reduced in vaccinia virus-treated mice with IL-10 receptor blockade. These observations demonstrate that pre-existing allergic lung disease alters the quality and magnitude of immune responses to respiratory poxviruses through an IL-10-dependent mechanism.

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

    EPA Science Inventory

    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...

  1. A novel microbe-based treatment that attenuates the inflammatory profile in a mouse model of allergic airway disease

    PubMed Central

    Bazett, Mark; Biala, Agnieszka; Huff, Ryan D.; Bosiljcic, Momir; Gunn, Hal; Kalyan, Shirin; Hirota, Jeremy A.

    2016-01-01

    There is an unmet need for effective new and innovative treatments for asthma. It is becoming increasingly evident that bacterial stimulation can have beneficial effects at attenuating allergic airway disease through immune modulation. Our aim was to test the ability of a novel inactivated microbe-derived therapeutic based on Klebsiella (KB) in a model of allergic airway disease in mice. BALB/c mice were exposed intranasally to house dust mite (HDM) for two weeks. Mice were treated prophylactically via subcutaneous route with either KB or placebo for one week prior to HDM exposure and throughout the two week exposure period. 24 hours after the last exposure, lungs were analysed for inflammatory cell infiltrate, gene expression, cytokine levels, goblet cell metaplasia, and serum was analysed for allergen-specific serum IgE levels. HDM exposed mice developed goblet cell hyperplasia, elevated allergen-specific serum IgE, airway eosinophilia, and a concomitant increase in TH2 cytokines including IL-4, IL-13 and IL-5. Treatment with KB attenuated HDM-mediated airway eosinophilia, total bronchoalveolar lavage (BAL) cell numbers, BAL TH2 cytokine production, and goblet cell metaplasia. Our prophylactic intervention study illustrates the potential of subcutaneous treatment with bacterial derived biologics as a promising approach for allergic airway disease treatment. PMID:27734946

  2. Effects of concentrated ambient particles and diesel engine exhaust on allergic airway disease in Brown Norway rats.

    PubMed

    Harkema, Jack R; Wagner, James G; Kaminski, Norbert E; Morishita, Masako; Keeler, Gerald J; McDonald, Jacob D; Barrett, Edward G

    2009-11-01

    Increased concentrations of airborne fine particulate matter (PM2.5; particulate matter with an aerodynamic diameter < or = 2.5 microm) are associated with increases in emergency room visits and hospitalizations of asthmatic patients. Emissions from local stationary combustion sources (e.g., coal-burning power plants) or mobile motor vehicles (e.g., diesel-powered trucks) have been identified as potential contributors to the development or exacerbation of allergic airway disease. In the present study, a rodent model of allergic airway disease was used to study the effects of concentrated ambient particles (CAPs) or diesel engine exhaust (DEE) on the development of allergic airway disease in rats sensitized to the allergen ovalbumin (OVA). The overall objective of our project was to understand the effects of PM2.5 on the development of OVA-induced allergic airway disease. Our specific aims were to test the following hypotheses: (1) exposure to CAPs during OVA challenge enhances epithelial remodeling of the airway and inflammation in rats previously sensitized to the allergen; and (2) exposure to DEE during OVA sensitization, or during OVA challenge, exacerbates epithelial remodeling of the airway and inflammation in rats. In the DEE studies, Brown Norway (BN) rats were sensitized with three daily intranasal (IN) instillations of 0.5% OVA, and then two weeks later were challenged with IN OVA or saline for 3 consecutive days. Rats were exposed to DEE diluted to mass concentrations of 30 or 300 microg/m3 diesel exhaust particles (DEPs) or to filtered air during either the sensitization or challenge periods. For the CAPs studies, the same OVA sensitization and challenge rat model was used but exposures to Detroit, Michigan, CAPs were limited to the OVA challenge period. Two separate 3-day CAPs exposures were conducted (week 1, high mean mass concentration = 595 microg/m3; week 2, low mean mass concentration = 356 microg/m3) during OVA challenge. In both the DEE and CAPs

  3. Silibinin attenuates allergic airway inflammation in mice

    SciTech Connect

    Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu; Piao, Hong Mei; Li, Liang chang; Li, Guang Zhao; Lin, Zhen Hua; Yan, Guang Hai

    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.

  4. A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.

    PubMed

    Lee, Kyung Sun; Kim, So Ri; Park, Hee Sun; Park, Seoung Ju; Min, Kyung Hoon; Lee, Ka Young; Choe, Yeong Hun; Hong, Sang Hyun; Han, Hyo Jin; Lee, Young Rae; Kim, Jong Suk; Atlas, Daphne; Lee, Yong Chul

    2007-12-31

    Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.

  5. Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease.

    PubMed

    Foong, Rachel E; Bosco, Anthony; Troy, Niamh M; Gorman, Shelley; Hart, Prue H; Kicic, Anthony; Zosky, Graeme R

    2016-09-01

    Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness is increased in vitamin D-deficient mice. In this study, we hypothesize that vitamin D deficiency would exacerbate house dust mite (HDM)-induced inflammation and alterations in lung structure and function. A BALB/c mouse model of vitamin D deficiency was established by dietary manipulation. Responsiveness to methacholine, airway smooth muscle (ASM) mass, mucus cell metaplasia, lung and airway inflammation, and cytokines in bronchoalveolar lavage (BAL) fluid were assessed. Gene expression patterns in mouse lung samples were profiled by RNA-Seq. HDM exposure increased inflammation and inflammatory cytokines in BAL, baseline airway resistance, tissue elastance, and ASM mass. Vitamin D deficiency enhanced the HDM-induced influx of lymphocytes into BAL, ameliorated the HDM-induced increase in ASM mass, and protected against the HDM-induced increase in baseline airway resistance. RNA-Seq identified nine genes that were differentially regulated by vitamin D deficiency in the lungs of HDM-treated mice. Immunohistochemical staining confirmed that protein expression of midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid droplet-associated, which is associated with ASM remodeling, was downregulated. Protein expression studies in human bronchial epithelial cells also showed that addition of vitamin D decreased MID1 expression. Differential regulation of these genes by vitamin D deficiency could determine lung inflammation and pathophysiology and suggest that the effect of vitamin D deficiency on HDM-induced allergic airways disease is complex.

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

    SciTech Connect

    Bernard, Alfred 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

  7. Wogonin Induces Eosinophil Apoptosis and Attenuates Allergic Airway Inflammation

    PubMed Central

    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

  8. Airway Fibrinogenolysis and the Initiation of Allergic Inflammation

    PubMed Central

    Millien, Valentine Ongeri; Lu, Wen; Mak, Garbo; Yuan, Xiaoyi; Knight, J. Morgan; Porter, Paul; Kheradmand, Farrah

    2014-01-01

    The past 15 years of allergic disease research have produced extraordinary improvements in our understanding of the pathogenesis of airway allergic diseases such as asthma. Whereas it was previously viewed as largely an immunoglobulin E-mediated process, the gradual recognition that T cells, especially Type 2 T helper (Th2) cells and Th17 cells, play a major role in asthma and related afflictions has inspired clinical trials targeting cytokine-based inflammatory pathways that show great promise. What has yet to be clarified about the pathogenesis of allergic inflammatory disorders, however, are the fundamental initiating factors, both exogenous and endogenous, that drive and sustain B- and T-cell responses that underlie the expression of chronic disease. Here we review how proteinases derived from diverse sources drive allergic responses. A central discovery supporting the proteinase hypothesis of allergic disease pathophysiology is the role played by airway fibrinogen, which in part appears to serve as a sensor of unregulated proteinase activity and which, when cleaved, both participates in a novel allergic signaling pathway through Toll-like receptor 4 and forms fibrin clots that contribute to airway obstruction. Unresolved at present is the ultimate source of airway allergenic proteinases. From among many potential candidates, perhaps the most intriguing is the possibility such enzymes derive from airway fungi. Together, these new findings expand both our knowledge of allergic disease pathophysiology and options for therapeutic intervention. PMID:25525732

  9. Animal models of allergic airways disease: where are we and where to next?

    PubMed

    Chapman, David G; Tully, Jane E; Nolin, James D; Janssen-Heininger, Yvonne M; Irvin, Charles G

    2014-12-01

    In a complex inflammatory airways disease such as asthma, abnormalities in a plethora of molecular and cellular pathways ultimately culminate in characteristic impairments in respiratory function. The ability to study disease pathophysiology in the setting of a functioning immune and respiratory system therefore makes mouse models an invaluable tool in translational research. Despite the vast understanding of inflammatory airways diseases gained from mouse models to date, concern over the validity of mouse models continues to grow. Therefore the aim of this review is twofold; firstly, to evaluate mouse models of asthma in light of current clinical definitions, and secondly, to provide a framework by which mouse models can be continually refined so that they continue to stand at the forefront of translational science. Indeed, it is in viewing mouse models as a continual work in progress that we will be able to target our research to those patient populations in whom current therapies are insufficient.

  10. Tregs and allergic disease

    PubMed Central

    Robinson, Douglas S.; Larché, Mark; Durham, Stephen R.

    2004-01-01

    Allergic diseases such as asthma, rhinitis, and eczema are increasing in prevalence and affect up to 15% of populations in Westernized countries. The description of Tregs as T cells that prevent development of autoimmune disease led to considerable interest in whether these Tregs were also normally involved in prevention of sensitization to allergens and whether it might be possible to manipulate Tregs for the therapy of allergic disease. Current data suggest that Th2 responses to allergens are normally suppressed by both CD4+CD25+ Tregs and IL-10 Tregs. Furthermore, suppression by these subsets is decreased in allergic individuals. In animal models, Tregs could be induced by high- or low-dose inhaled antigen, and prior induction of such Tregs prevented subsequent development of allergen sensitization and airway inflammation in inhaled challenge models. For many years, allergen-injection immunotherapy has been used for the therapy of allergic disease, and this treatment may induce IL-10 Tregs, leading to both suppression of Th2 responses and a switch from IgE to IgG4 antibody production. Improvements in allergen immunotherapy, such as peptide therapy, and greater understanding of the biology of Tregs hold great promise for the treatment and prevention of allergic disease. PMID:15545986

  11. Bromelain exerts anti-inflammatory effects in an ovalbumin-induced murine model of allergic airway disease

    PubMed Central

    Secor, Eric R.; Carson, William F.; Cloutier, Michelle M.; Guernsey, Linda A.; Schramm, Craig M.; Wu, Carol A.; Thrall, Roger S.

    2008-01-01

    Objective Bromelain, a clinically used pineapple extract and natural product, has reported anti-inflammatory and immunomodulatory activities. The purpose of this study was to determine the effect of bromelain treatment in an ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). Methods To establish AAD, mice were sensitized with intraperitoneal (i.p.) OVA/alum and challenged with daily OVA aerosols. Mice were treated i.p. with either saline, 2 or 6 mg/kg bromelain, twice daily for four consecutive days. Bronchoalveolar lavage leukocytes and cytokines, lung histology, airway hyperresponsiveness, and lymphocyte populations via flow cytometry were compared between groups. Results Bromelain treatment of AAD mice resulted in reduced total BAL leukocytes, eosinophils, CD4+ and CD8+ T lymphocytes, CD4+/CD8+ T cell ratio, and IL-13. Conclusion Bromelain attenuated development of AAD while altering CD4+ to CD8+ T lymphocyte populations. The reduction in AAD outcomes suggests that bromelain may have similar effects in the treatment of human asthma and hypersensitivity disorders. PMID:16337164

  12. Global airway disease beyond allergy.

    PubMed

    Hellings, Peter W; Prokopakis, Emmanuel P

    2010-03-01

    Besides the anatomic continuity of the upper and lower airways, inflammation in one part of the airway influences the homeostasis of the other. The mechanisms underlying this interaction have been studied primarily in allergic disease, showing systemic immune activation, induction of inflammation at a distance, and a negative impact of nasal inflammation on bronchial homeostasis. In addition to allergy, other inflammatory conditions of the upper airways are associated with lower airway disease. Rhinosinusitis is frequently associated with asthma and chronic obstructive pulmonary disease. The impairment of purification, humidification, and warming up of the inspired air by the nose in rhinosinusitis may be responsible in part for bronchial pathology. The resolution of sinonasal inflammation via medical and/or surgical treatment is responsible for the beneficial effect of the treatment on bronchial disease. This article provides a comprehensive overview of the current knowledge of upper and lower airway communication beyond allergic disease.

  13. Development of allergic airway disease in mice following antibiotic therapy and fungal microbiota increase: role of host genetics, antigen, and interleukin-13.

    PubMed

    Noverr, Mairi C; Falkowski, Nicole R; McDonald, Rod A; McKenzie, Andrew N; Huffnagle, Gary B

    2005-01-01

    Lending support to the hygiene hypothesis, epidemiological studies have demonstrated that allergic disease correlates with widespread use of antibiotics and alterations in fecal microbiota ("microflora"). Antibiotics also lead to overgrowth of the yeast Candida albicans, which can secrete potent prostaglandin-like immune response modulators, from the microbiota. We have recently developed a mouse model of antibiotic-induced gastrointestinal microbiota disruption that is characterized by stable increases in levels of gastrointestinal enteric bacteria and Candida. Using this model, we have previously demonstrated that microbiota disruption can drive the development of a CD4 T-cell-mediated airway allergic response to mold spore challenge in immunocompetent C57BL/6 mice without previous systemic antigen priming. The studies presented here address important questions concerning the universality of the model. To investigate the role of host genetics, we tested BALB/c mice. As with C57BL/6 mice, microbiota disruption promoted the development of an allergic response in the lungs of BALB/c mice upon subsequent challenge with mold spores. In addition, this allergic response required interleukin-13 (IL-13) (the response was absent in IL-13(-/-) mice). To investigate the role of antigen, we subjected mice with disrupted microbiota to intranasal challenge with ovalbumin (OVA). In the absence of systemic priming, only mice with altered microbiota developed airway allergic responses to OVA. The studies presented here demonstrate that the effects of microbiota disruption are largely independent of host genetics and the nature of the antigen and that IL-13 is required for the airway allergic response that follows microbiota disruption.

  14. United airway disease: current perspectives

    PubMed Central

    Giavina-Bianchi, Pedro; Aun, Marcelo Vivolo; Takejima, Priscila; Kalil, Jorge; Agondi, Rosana Câmara

    2016-01-01

    Upper and lower airways are considered a unified morphological and functional unit, and the connection existing between them has been observed for many years, both in health and in disease. There is strong epidemiologic, pathophysiologic, and clinical evidence supporting an integrated view of rhinitis and asthma: united airway disease in the present review. The term “united airway disease” is opportune, because rhinitis and asthma are chronic inflammatory diseases of the upper and lower airways, which can be induced by allergic or nonallergic reproducible mechanisms, and present several phenotypes. Management of rhinitis and asthma must be jointly carried out, leading to better control of both diseases, and the lessons of the Allergic Rhinitis and Its Impact on Asthma initiative cannot be forgotten. PMID:27257389

  15. Silencing nociceptor neurons reduces allergic airway inflammation

    PubMed Central

    Talbot, Sébastien; Abdulnour, Raja-Elie E.; Burkett, Patrick R.; Lee, Seungkyu; Cronin, Shane J.F.; Pascal, Maud A.; Laedermann, Cedric; Foster, Simmie L.; Tran, Johnathan V.; Lai, Nicole; Chiu, Isaac M.; Ghasemlou, Nader; DiBiase, Matthew; Roberson, David; Von Hehn, Christian; Agac, Busranour; Haworth, Oliver; Seki, Hiroyuki; Penninger, Josef M.; Kuchroo, Vijay K.; Bean, Bruce P.; Levy, Bruce D.; Woolf, Clifford J.

    2015-01-01

    Summary Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8+ sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large pore ion channels to specifically block nociceptors, substantially reduced ovalbumin or house dust mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4+ and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma. PMID:26119026

  16. INHIBITION OF PAN NEUROTROPHIN RECEPTOR P75 ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAY RESPONSES IN C57/BL6J MICE

    EPA Science Inventory

    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...

  17. Integrated Innate Mechanisms Involved in Airway Allergic Inflammation to the Serine Protease Subtilisin

    PubMed Central

    Florsheim, Esther; Yu, Shuang; Bragatto, Ivan; Faustino, Lucas; Gomes, Eliane; Ramos, Rodrigo N.; Barbuto, José Alexandre M.; Medzhitov, Ruslan; Russo, Momtchilo

    2015-01-01

    Proteases are recognized environmental allergens, but little is known about the mechanisms responsible for sensing enzyme activity and initiating the development of allergic inflammation. Because usage of the serine protease subtilisin in the detergent industry resulted in an outbreak of occupational asthma in workers, we sought to develop an experimental model of allergic lung inflammation to subtilisin and to determine the immunological mechanisms involved in type 2 responses. By using a mouse model of allergic airway disease, we have defined here that subcutaneous or intranasal sensitization followed by airway challenge to subtilisin induces prototypic allergic lung inflammation, characterized by airway eosinophilia, type 2 cytokines release, mucus production, high levels of serum IgE, and airway reactivity. These allergic responses were dependent on subtilisin protease activity, protease-activated receptor (PAR)-2, IL-33 receptor ST2, and MyD88 signaling. Also, subtilisin stimulated the expression of the pro-allergic cytokines IL-1α, IL-33, TSLP, and the growth factor amphiregulin in a human bronchial epithelial cell line. Notably, acute administration of subtilisin into the airways increased lung IL-5-producing type 2 innate lymphoid cells, which required PAR-2 expression. Finally, subtilisin activity acted as a Th2 adjuvant to an unrelated airborne antigen promoting allergic inflammation to inhaled OVA. Therefore, we established a murine model of occupational asthma to a serine protease and characterized the main molecular pathways involved in allergic sensitization to subtilisin that potentially contribute to initiate allergic airway disease. PMID:25876764

  18. Macrophage/epithelial cell CCL2 contributes to rhinovirus-induced hyperresponsiveness and inflammation in a mouse model of allergic airways disease.

    PubMed

    Schneider, Dina; Hong, Jun Young; Bowman, Emily R; Chung, Yutein; Nagarkar, Deepti R; McHenry, Christina L; Goldsmith, Adam M; Bentley, J Kelley; Lewis, Toby C; Hershenson, Marc B

    2013-02-01

    Human rhinovirus (HRV) infections lead to exacerbations of lower airways disease in asthmatic patients but not in healthy individuals. However, underlying mechanisms remain to be completely elucidated. We hypothesized that the Th2-driven allergic environment enhances HRV-induced CC chemokine production, leading to asthma exacerbations. Ovalbumin (OVA)-sensitized and -challenged mice inoculated with HRV showed significant increases in the expression of lung CC chemokine ligand (CCL)-2/monocyte chemotactic protein (MCP)-1, CCL4/macrophage inflammatory protein (MIP)-1β, CCL7/MCP-3, CCL19/MIP-3β, and CCL20/MIP3α compared with mice treated with OVA alone. Inhibition of CCL2 with neutralizing antibody significantly attenuated HRV-induced airways inflammation and hyperresponsiveness in OVA-treated mice. Immunohistochemical stains showed colocalization of CCL2 with HRV in epithelial cells and CD68-positive macrophages, and flow cytometry showed increased CCL2(+), CD11b(+) cells in the lungs of OVA-treated, HRV-infected mice. Compared with lung macrophages from naïve mice, macrophages from OVA-exposed mice expressed significantly more CCL2 in response to HRV infection ex vivo. Pretreatment of mouse lung macrophages and BEAS-2B human bronchial epithelial cells with interleukin (IL)-4 and IL-13 increased HRV-induced CCL2 expression, and mouse lung macrophages from IL-4 receptor knockout mice showed reduced CCL2 expression in response to HRV, suggesting that exposure to these Th2 cytokines plays a role in the altered HRV response. Finally, bronchoalveolar macrophages from children with asthma elaborated more CCL2 upon ex vivo exposure to HRV than cells from nonasthmatic patients. We conclude that CCL2 production by epithelial cells and macrophages contributes to HRV-induced airway hyperresponsiveness and inflammation in a mouse model of allergic airways disease and may play a role in HRV-induced asthma exacerbations.

  19. Allergic airway inflammation induces a pro-secretory epithelial ion transport phenotype in mice.

    PubMed

    Anagnostopoulou, P; Dai, L; Schatterny, J; Hirtz, S; Duerr, J; Mall, M A

    2010-12-01

    The airway epithelium is a central effector tissue in allergic inflammation and T-helper cell (Th) type 2-driven epithelial responses, such as mucus hypersecretion contribute to airflow obstruction in allergic airway disease. Previous in vitro studies demonstrated that Th2 cytokines also act as potent modulators of epithelial ion transport and fluid secretion, but the in vivo effect of allergic inflammation on airway ion transport remains unknown. We, therefore, induced allergic inflammation by intratracheal instillation of Aspergillus fumigatus extract or interleukin-13 in mice and determined effects on ion transport in native tracheal and bronchial tissues. We demonstrate that allergic inflammation enhanced basal Cl(-) secretion in both airway regions and inhibited epithelial Na(+) channel (ENaC)-mediated Na(+) absorption and increased Ca²(+)-dependent Cl(-) secretion in bronchi. Allergen-induced alterations in bronchial ion transport were associated with reduced transcript levels of α-, β- and γENaC, and were largely abrogated in signal transducer and activator of transcription (Stat)6(-/-) mice. Our studies demonstrate that Th2-dependent airway inflammation produced a pro-secretory ion transport phenotype in vivo, which was largely Stat6-dependent. These results suggest that Th2-mediated fluid secretion may improve airway surface hydration and clearance of mucus that is hypersecreted in allergic airway diseases such as asthma, and identify epithelial Stat6 signalling as a potential therapeutic target to promote mucus hydration and airway clearance.

  20. Intranasal administration of a combination of choline chloride, vitamin C, and selenium attenuates the allergic effect in a mouse model of airway disease.

    PubMed

    Bansal, Preeti; Saw, Sanjay; Govindaraj, Dhanapal; Arora, Naveen

    2014-08-01

    Respiratory allergic disease is an inflammatory condition accompanied by oxidative stress. Supplementation of an anti-inflammatory agent with antioxidants may have a therapeutic effect. In this study, the effects of choline chloride in combination with antioxidants were evaluated via the intranasal route in a mouse model of allergic airway disease. Balb/c mice were sensitized on days 0, 7, and 14 and challenged on days 25-30 with cockroach extract (CE) and with a booster challenge on day 38. They were treated with choline chloride (ChCl; 1mg/kg), vitamin C (Vit C; 308.33 mg/kg), and selenium (Se; 1mg/kg) alone or in combination via the intranasal route on days 31, 33, 35, 37, and 39. The mice were sacrificed on day 40 to collect blood, bronchoalveolar lavage fluid, lungs, and spleen. Mice immunized with CE showed a significant increase in airway hyperresponsiveness (AHR), lung inflammation, Th2 cytokines, and the oxidative stress markers intracellular reactive oxygen species and 8-isoprostanes compared to the phosphate-buffered saline control group. A significant decrease was observed in these parameters with all the treatments (p<0.01). The highest decrease was noticed in the ChCl+Vit C+Se-treated group, with AHR decreased to the normal level. This group also showed the highest decrease in airway inflammation (p<0.001), IL-4 and IL-5 (p<0.001), IgE and IgG1 (p<0.001), NF-κB (p<0.001), and 8-isoprostane levels (p<0.001). Glutathione peroxidase activity, which was decreased significantly in CE-immunized mice, was restored to normal levels in this group (p<0.001). IL-10 level was decreased in CE-immunized mice and was restored to normal by combination treatment. The combination treatment induced FOXP3(+) cells in splenocyte culture, responsible for the upregulation of IL-10. In conclusion, the combination of choline chloride, vitamin C, and selenium via the intranasal route reduces AHR, inflammation, and oxidative stress, probably by causing IL-10 production by FOXP

  1. Syk Regulates Neutrophilic Airway Hyper-Responsiveness in a Chronic Mouse Model of Allergic Airways Inflammation

    PubMed Central

    Juvet, Stephen; Scott, Jeremy A.; Chow, Chung-Wai

    2017-01-01

    Background Asthma is a chronic inflammatory disease characterized by airways hyper-responsiveness (AHR), reversible airway obstruction, and airway inflammation and remodeling. We previously showed that Syk modulates methacholine-induced airways contractility in naïve mice and in mice with allergic airways inflammation. We hypothesize that Syk plays a role in the pathogenesis of AHR; this was evaluated in a chronic 8-week mouse model of house dust mite (HDM)-induced allergic airways inflammation. Methods We used the Sykflox/flox//rosa26CreERT2 conditional Syk knock-out mice to assess the role of Syk prior to HDM exposure, and treated HDM-sensitized mice with the Syk inhibitor, GSK143, to evaluate its role in established allergic airways inflammation. Respiratory mechanics and methacholine (MCh)-responsiveness were assessed using the flexiVent® system. Lungs underwent bronchoalveolar lavage to isolate inflammatory cells or were frozen for determination of gene expression in tissues. Results MCh-induced AHR was observed following HDM sensitization in the Syk-intact (Sykflox/flox) and vehicle-treated BALB/c mice. MCh responsiveness was reduced to control levels in HDM-sensitized Sykdel/del mice and in BALB/c and Sykflox/flox mice treated with GSK143. Both Sykdel/del and GSK143-treated mice mounted appropriate immune responses to HDM, with HDM-specific IgE levels that were comparable to Sykflox/flox and vehicle-treated BALB/c mice. HDM-induced increases in bronchoalveolar lavage cell counts were attenuated in both Sykdel/del and GSK143-treated mice, due primarily to decreased neutrophil recruitment. Gene expression analysis of lung tissues revealed that HDM-induced expression of IL-17 and CXCL-1 was significantly attenuated in both Sykdel/del and GSK143-treated mice. Conclusion Syk inhibitors may play a role in the management of neutrophilic asthma. PMID:28107345

  2. Epigenomics and allergic disease.

    PubMed

    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.

  3. Epigenetics in allergic diseases

    PubMed Central

    DeVries, Avery; Vercelli, Donata

    2015-01-01

    Purpose of review Allergic diseases are among the most prevalent chronic diseases of childhood, affecting more than 7 million children in the United States. Epidemiological evidence supports the idea that the inception of allergic diseases is typically before the pre-school years, even when chronic symptoms do not emerge until adulthood. The role of epigenetic mechanisms (particularly DNA methylation) in allergic disease is under active investigation because these mechanisms are known to be at the interface among gene regulation, environmental stimuli and developmental processes, all of which are essential for the pathogenesis for asthma and allergy. This article specifically reviews genome-wide DNA methylation studies in allergic disease. Recent findings Differential DNA methylation at specific regions appears to be associated with concurrent allergic disease. A few studies have identified methylation signatures predictive of disease. Summary DNA methylation signatures have been shown be associated with several allergic disease phenotypes, typically concurrently with disease. The few that have been found to precede diagnosis are especially interesting because they highlight an early trajectory to disease. PMID:26418323

  4. Notch Ligand DLL4 Alleviates Allergic Airway Inflammation via Induction of a Homeostatic Regulatory Pathway

    PubMed Central

    Huang, Miao-Tzu; Chen, Yi-Lien; Lien, Chia-I; Liu, Wei-Liang; Hsu, Li-Chung; Yagita, Hideo; Chiang, Bor-Luen

    2017-01-01

    Notch is a pleiotropic signaling family that has been implicated in pathogenesis of allergic airway diseases; however, the distinct function of individual Notch ligands remains elusive. We investigated whether Notch ligands, Jagged1 and DLL4, exert differential effects in OVA-induced allergic asthma. We found that whilst Jagged1 inhibition mitigated Th2-dominated airway inflammation, blockage of DLL4 aggravated the Th2-mediated asthma phenotypes. Additionally, Jagged1 signaling blockage enhanced IL-17 production and neutrophilic airway infiltration. In vitro, exogenous Jagged1 induced Th2-skewed responses, whereas augmented DLL4 signaling displayed a dual role by promoting expansion of both Tregs and Th17. In vivo, DLL4 blockage impaired Treg differentiation which plausibly resulted in exaggerated asthma phenotypes. On the contrary, administration of DLL4-expressing antigen-presenting cells promoted endogenous Treg expansion and ameliorated the allergic responses. Therefore, whilst Jagged1 induces Th2-skewed inflammation, DLL4 elicits an essential self-regulatory mechanism via Treg-mediated pathway that counterbalances Jagged1-induced Th2 responses and facilitates resolution of the airway inflammation to restore homeostasis. These findings uncover a disparate function of Jagged1 and DLL4 in allergic airway diseases, hinting feasibility of Notch ligand-specific targeting in therapy of allergic airway diseases. PMID:28262821

  5. Prevention of allergic airway hyperresponsiveness and remodeling in mice by Astragaliradix Antiasthmatic decoction

    PubMed Central

    2013-01-01

    Background Astragali radix Antiasthmatic Decoction (AAD), a traditional Chinese medication, is found effective in treating allergic diseases and chronic cough. The purpose of this study is to determine whether this medication could suppress allergen-induced airway hyperresponsiveness (AHR) and remodeling in mice, and its possible mechanisms. Methods A mouse model of chronic asthma was used to investigate the effects of AAD on the airway lesions. Mice were sensitized and challenged with ovalbumin (OVA), and the extent of AHR and airway remodeling were characterized. Cells and cytokines in the bronchoalveolar lavage fluid (BALF) were examined. Results AAD treatment effectively decreased OVA-induced AHR, eosinophilic airway inflammation, and collagen deposition around the airway. It significantly reduced the levels of IL-13 and TGF-β1, but exerted inconsiderable effect on INF-γ and IL-10. Conclusions AAD greatly improves the symptoms of allergic airway remodeling probably through inhibition of Th2 cytokines and TGF-β1. PMID:24367979

  6. Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE₂.

    PubMed

    Kim, Yun-Gi; Udayanga, Kankanam Gamage Sanath; Totsuka, Naoya; Weinberg, Jason B; Núñez, Gabriel; Shibuya, Akira

    2014-01-15

    Although imbalances in gut microbiota composition, or "dysbiosis," are associated with many diseases, the effects of gut dysbiosis on host systemic physiology are less well characterized. We report that gut dysbiosis induced by antibiotic (Abx) treatment promotes allergic airway inflammation by shifting macrophage polarization in the lung toward the alternatively activated M2 phenotype. Adoptive transfer of alveolar macrophages derived from Abx-treated mice was sufficient to increase allergic airway inflammation. Abx treatment resulted in the overgrowth of a commensal fungal Candida species in the gut and increased plasma concentrations of prostaglandin E₂ (PGE₂), which induced M2 macrophage polarization in the lung. Suppression of PGE₂ synthesis by the cyclooxygenase inhibitors aspirin and celecoxib suppressed M2 macrophage polarization and decreased allergic airway inflammatory cell infiltration in Abx-treated mice. Thus, Abx treatment can cause overgrowth of particular fungal species in the gut and promote M2 macrophage activation at distant sites to influence systemic responses including allergic inflammation.

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

    PubMed

    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.

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

    PubMed

    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.

  9. Iron administration reduces airway hyperreactivity and eosinophilia in a mouse model of allergic asthma.

    PubMed

    Maazi, H; Shirinbak, S; Bloksma, N; Nawijn, M C; van Oosterhout, A J M

    2011-10-01

    The prevalence of allergic diseases has increased dramatically during the last four decades and is paralleled by a striking increase in iron intake by infants in affluent societies. Several studies have suggested a link between increased iron intake and the marked increase in prevalence of allergic diseases. We hypothesized that the increased iron intake by infants offers an explanation for the increased prevalence of allergic disease in industrialized societies during the past four decades. A well-established mouse model of ovalbumin (OVA)-driven allergic asthma was used to test the effects of differences in iron intake and systemic iron levels on the manifestations of allergic asthma. Surprisingly, iron supplementation resulted in a significant decrease in airway eosinophilia, while systemic iron injections lead to a significant suppression of both allergen-induced airway eosinophilia and hyperreactivity compared to placebo. In contrast, mice fed on an iron-deprived diet did not show any difference in developing experimentally induced allergic asthma when compared to those fed on an iron-sufficient control diet. In contrast to our hypothesis, airway manifestations of allergic asthma are suppressed by both increased levels of iron intake and systemic iron administrations in the mouse model.

  10. [Apoptosis in allergic disease].

    PubMed

    Rojas Ramos, E; Martínez Jiménez, N E; Martínez Aguilar, N E; Garfias Becerra, J

    2000-01-01

    Apoptosis (cell programmed death) it is a mechanism that implicate a physiological suicide, to keep the cellular homeostasis in big amount of tissues. Fas (APO-1; CD95) system is one of the most important cellular responsible via to induce apoptosis on different tissues. Eosinophillia on peripheral blood and tissues are the main characteristics on allergic like asthma. Eosinophil apoptosis is upper regulated in those diseases by IL-5 y GM-CSF. Corticoids, teophyllin and some macrolids have been used like apoptosis inductors on eosinophills, these could be a novel mechanism to promote a better solution on inflammatory allergic diseases.

  11. Chemokines and their receptors in the allergic airway inflammatory process.

    PubMed

    Velazquez, Juan Raymundo; Teran, Luis Manuel

    2011-08-01

    The development of the allergic airway disease conveys several cell types, such as T-cells, eosinophils, mast cells, and dendritic cells, which act in a special and temporal synchronization. Cellular mobilization and its complex interactions are coordinated by a broad range of bioactive mediators known as chemokines. These molecules are an increasing family of small proteins with common structural motifs and play an important role in the recruitment and cell activation of both leukocytes and resident cells at the allergic inflammatory site via their receptors. Trafficking and recruitment of cell populations with specific chemokines receptors assure the presence of reactive allergen-specific T-cells in the lung, and therefore the establishment of an allergic inflammatory process. Different approaches directed against chemokines receptors have been developed during the last decades with promising therapeutic results in the treatment of asthma. In this review we explore the role of the chemokines and chemokine receptors in allergy and asthma and discuss their potential as targets for therapy.

  12. [Evaluation of occupational allergic diseases of the respiratory tract].

    PubMed

    Pankova, V B

    2011-01-01

    The paper presents the basic etiological and pathogenetic aspects of occupational allergic diseases of the respiratory tract, discusses the clinical course, diagnosis, and priorities of the prevention of allergic diseases of the upper airways and bronchopulmonary apparatus from the action of industrial allergens.

  13. Facilitation of Allergic Sensitization and Allergic Airway Inflammation by Pollen-Induced Innate Neutrophil Recruitment.

    PubMed

    Hosoki, Koa; Aguilera-Aguirre, Leopoldo; Brasier, Allan R; Kurosky, Alexander; Boldogh, Istvan; Sur, Sanjiv

    2016-01-01

    Neutrophil recruitment is a hallmark of rapid innate immune responses. Exposure of airways of naive mice to pollens rapidly induces neutrophil recruitment. The innate mechanisms that regulate pollen-induced neutrophil recruitment and the contribution of this neutrophilic response to subsequent induction of allergic sensitization and inflammation need to be elucidated. Here we show that ragweed pollen extract (RWPE) challenge in naive mice induces C-X-C motif ligand (CXCL) chemokine synthesis, which stimulates chemokine (C-X-C motif) receptor 2 (CXCR2)-dependent recruitment of neutrophils into the airways. Deletion of Toll-like receptor 4 (TLR4) abolishes CXCL chemokine secretion and neutrophil recruitment induced by a single RWPE challenge and inhibits induction of allergic sensitization and airway inflammation after repeated exposures to RWPE. Forced induction of CXCL chemokine secretion and neutrophil recruitment in mice lacking TLR4 also reconstitutes the ability of multiple challenges of RWPE to induce allergic airway inflammation. Blocking RWPE-induced neutrophil recruitment in wild-type mice by administration of a CXCR2 inhibitor inhibits the ability of repeated exposures to RWPE to stimulate allergic sensitization and airway inflammation. Administration of neutrophils derived from naive donor mice into the airways of Tlr4 knockout recipient mice after each repeated RWPE challenge reconstitutes allergic sensitization and inflammation in these mice. Together these observations indicate that pollen-induced recruitment of neutrophils is TLR4 and CXCR2 dependent and that recruitment of neutrophils is a critical rate-limiting event that stimulates induction of allergic sensitization and airway inflammation. Inhibiting pollen-induced recruitment of neutrophils, such as by administration of CXCR2 antagonists, may be a novel strategy to prevent initiation of pollen-induced allergic airway inflammation.

  14. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life

    PubMed Central

    Davies, Elizabeth R.; Kelly, Joanne F.C.; Howarth, Peter H.; Wilson, David I.; Holgate, Stephen T.; Davies, Donna E.; Whitsett, Jeffrey A.

    2016-01-01

    Asthma is a chronic inflammatory airways disease that usually begins in early life and involves gene-environment interactions. Although most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Here, we report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma. We show that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and plays a role in airway remodeling, independent of inflammation. Furthermore, remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. When induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps to explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, we show that sADAM33-induced airway remodeling is reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma. PMID:27489884

  15. NOX ENZYMES IN ALLERGIC AIRWAY INFLAMMATION

    PubMed Central

    van der Vliet, Albert

    2011-01-01

    Chronic airway diseases such as asthma are linked to oxidative environmental factors and are commonly associated with increased production of reactive oxygen species (ROS). Therefore, it is commonly assumed that oxidative stress is an important contributing factor to asthma disease pathogenesis and that antioxidant strategies may be useful in treatment of asthma. A primary source of ROS production in biological systems is NADPH oxidase (NOX), originally associated primarily with inflammatory cells but currently widely appreciated as an important enzyme system in many cell types, which a wide array of functional properties ranging from antimicrobial host defense to immune regulation and cell proliferation, differentiation and apoptosis. Given the complex nature of asthma disease pathology, with the involvement of many lung cell types that all express NOX homologs, it is not surprising that the contributions of NOX-derived ROS to various aspects of asthma development and progression are highly diverse and multifactorial. It is the purpose of the present review to summarize the current knowledge with respect to the functional aspects of NOX enzymes in various pulmonary cell types, and to discuss their potential importance in asthma pathogenesis. PMID:21397663

  16. Innate immunity in allergic disease.

    PubMed

    Minnicozzi, Michael; Sawyer, Richard T; Fenton, Matthew J

    2011-07-01

    The innate immune system consists of multiple cell types that express germline-encoded pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Allergens are frequently found in forms and mixtures that contain PAMPs and DAMPs. The innate immune system is interposed between the external environment and the internal acquired immune system. It is also an integral part of the airways, gut, and skin. These tissues face continuous exposure to allergens, PAMPs, and DAMPs. Interaction of allergens with the innate immune system normally results in immune tolerance but, in the case of allergic disease, this interaction induces recurring and/or chronic inflammation as well as the loss of immunologic tolerance. Upon activation by allergens, the innate immune response commits the acquired immune response to a variety of outcomes mediated by distinct T-cell subsets, such as T-helper 2, regulatory T, or T-helper 17 cells. New studies highlighted in this review underscore the close relationship between allergens, the innate immune system, and the acquired immune system that promotes homeostasis versus allergic disease.

  17. Respiratory syncytial virus predisposes mice to augmented allergic airway responses via IL-13-mediated mechanisms.

    PubMed

    Lukacs, N W; Tekkanat, K K; Berlin, A; Hogaboam, C M; Miller, A; Evanoff, H; Lincoln, P; Maassab, H

    2001-07-15

    The development of severe childhood asthma may be influenced by several factors including environmental and infectious stimuli. The causal relationship between infectious viral responses, such as respiratory syncytial virus (RSV), and severe asthma during early childhood is unclear. In these studies, the ability for an initial RSV infection to exacerbate and promote a more severe asthmatic-type response was investigated by combining established murine models of disease. We examined the ability of RSV to induce exacerbation of allergic disease over a relatively long period, leading to development of severe airway responses including airway inflammation and hyperreactivity. The preferential production of IL-13 during a primary RSV infection appears to play a critical role for the exacerbation of cockroach allergen-induced disease. The depletion of IL-13 during RSV infections inhibited the exacerbation and acceleration of severe allergen-induced airway hyperreactivity. This was indicated by decreases in airway hyperreactivity and changes in lung chemokine production. These data suggest that the airway responses during asthma can be greatly affected by a previous RSV infection, even when infection occurs before allergen sensitization. Overall, infection of the airways with RSV can induce an IL-13-dependent change in airway function and promotes an environment that contributes to the development of severe allergic asthmatic responses.

  18. Mitochondrial CaMKII inhibition in airway epithelium protects against allergic asthma

    PubMed Central

    Sebag, Sara C.; Koval, Olha M.; Paschke, John D.; Winters, Christopher J.; Jaffer, Omar A.; Dworski, Ryszard; Sutterwala, Fayyaz S.; Anderson, Mark E.; Grumbach, Isabella M.

    2017-01-01

    Excessive ROS promote allergic asthma, a condition characterized by airway inflammation, eosinophilic inflammation, and increased airway hyperreactivity (AHR). The mechanisms by which airway ROS are increased and the relationship between increased airway ROS and disease phenotypes are incompletely defined. Mitochondria are an important source of cellular ROS production, and our group discovered that Ca2+/calmodulin-dependent protein kinase II (CaMKII) is present in mitochondria and activated by oxidation. Furthermore, mitochondrial-targeted antioxidant therapy reduced the severity of allergic asthma in a mouse model. Based on these findings, we developed a mouse model of CaMKII inhibition targeted to mitochondria in airway epithelium. We challenged these mice with OVA or Aspergillus fumigatus. Mitochondrial CaMKII inhibition abrogated AHR, inflammation, and eosinophilia following OVA and A. fumigatus challenge. Mitochondrial ROS were decreased after agonist stimulation in the presence of mitochondrial CaMKII inhibition. This correlated with blunted induction of NF-κB, the NLRP3 inflammasome, and eosinophilia in transgenic mice. These findings demonstrate a pivotal role for mitochondrial CaMKII in airway epithelium in mitochondrial ROS generation, eosinophilic inflammation, and AHR, providing insights into how mitochondrial ROS mediate features of allergic asthma. PMID:28194433

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

    NASA Astrophysics Data System (ADS)

    Shipkowski, Kelly Anne

    The field of nanotechnology is continually advancing, and increasing amounts of consumer goods are being produced using engineered nanomaterials (ENMs). The health risks of occupational and/or consumer exposure to ENMs are not completely understood, although significant research indicates that pulmonary exposure to nanomaterials induces toxic effects in the lungs of exposed animals. Multi-walled carbon nanotubes (MWCNTs) are a specific category of ENMs and consist of sheets of graphene rolled into cylinders that are multiple layers thick in order to strengthen their rigidity. MWCNTs have a fiber-like shape, similar to that of asbestos, which allows for a high aspect ratio and makes them difficult to clear from the lung. Studies with rodent models have demonstrated that pulmonary exposure to ENMs, in particular MWCNTs, results in acute lung inflammation and the subsequent development of chronic fibrosis, suggesting a potential human health risk to individuals involved in the manufacturing of products utilizing these nanomaterials. Induction of IL-1beta secretion via activation of the inflammasome is a prime mechanism of MWCNT-induced inflammation. The inflammasome is a multi-protein scaffold found in a variety of cell types that forms in response to a variety of immune signals, including particulates. Sensitization with allergens, such as house dust mite (HDM), increases levels of the T helper 2 (Th2) cytokines IL-4 and IL-13 in mice and in humans, and there is particular cause for concern in cases of MWCNT exposure in individuals with pre-existing allergic airway disease, such as asthma. MWCNT exposure exacerbates airway inflammation and fibrosis in animal models of pre-existing allergic asthma, suggesting that individuals suffering from asthma are more susceptible to the toxic pulmonary effects of MWCNT exposure. Asthma is an exceptionally prominent human disease, and therefore the goal of this research was to better understand how pre-existing allergic airway

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

    PubMed Central

    de Freitas Alves, Claudiney; Angeli, Giovanna Natalia; Favarin, Daniely Cornélio; Lemos de Andrade, Edinéia; Lazo Chica, Javier Emilio; Faccioli, Lúcia Helena; Roberto da Silva, Paulo; de Paula Rogerio, Alexandre

    2013-01-01

    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. PMID:24376308

  1. Specific allergen immunotherapy attenuates allergic airway inflammation in a rat model of Alstonia scholaris pollen induced airway allergy.

    PubMed

    Datta, Ankur; Moitra, Saibal; Hazra, Iman; Mondal, Somnath; Das, Prasanta Kumar; Singh, Manoj Kumar; Chaudhuri, Suhnrita; Bhattacharya, Debanjan; Tripathi, Santanu Kumar; Chaudhuri, Swapna

    2016-01-01

    Pollen grains are well established to be an important cause of respiratory allergy. Current pharmacologic therapies for allergic asthma do not cure the disease. Allergen specific immunotherapy is the only treatment method which re-directs the immune system away from allergic response leading to a long lasting effect. The mechanism by which immunotherapy achieves this goal is an area of active research world-wide. The present experimental study was designed to develop an experimental model of allergic lung inflammation based on a relevant human allergen, Alstonia scholaris pollen, and to establish the immunological and cellular features of specific allergen immunotherapy using this same pollen extract. Our results revealed that Alstonia scholaris pollen sensitization and challenge causes eosinophilic airway inflammation with mucin hypersecretion. This is associated with increased total IgE, increased expression of FcɛRI on lung mast cells and increased levels of IL-4, IL-5 & IL-13 as confirmed by ELISA, in-situ immunofluorescence and FACS assay. Allergen specific immunotherapy reduced airway inflammation and also decreased total IgE level, FcɛRI expression, IL-4, IL-5 & IL-13 levels. It was further noted that the reduction of these levels was more by intra-nasal route than by intra-peritoneal route. Thus we present a novel animal model of Alstonia scholaris pollen allergic disease and specific allergen immunotherapy which will pave the way towards the development of better treatment modalities.

  2. [Allergic rhinitis and ashtma: 2 illnesses. The same disease?].

    PubMed

    González Díaz, Sandra N; Arias Cruz, Alfredo

    2002-01-01

    Disturbances of the upper and lower airways frequently coexist, and the association between allergic rhinitis and asthma is an example of that. The relationship between allergic rhinitis and asthma probably occurs because both, nasal and bronchial mucosas are elements of a "united airway", and on the other hand, allergic rhinitis and asthma are manifestations of a common allergic disease. Allergic rhinitis and asthma are not only statistically associated, but have pathophysiological and clinical similarities. Allergic rhinitis is itself a risk factor for the development of asthma, but additionally may confound the diagnosis of asthma and may exacerbate coexisting asthma. The management of allergic rhinitis, mainly with the use of intranasal corticosteroids, improve asthma symptoms and lung function in asthmatic patients. Several mechanisms have been proposed to link the nose and bronchi, which include: postnasal drip of inflammatory cells and pro-inflammatory molecules; a possible nasobronchial neural reflex; an increased exposure of the lower airways to dry and cold air as well as aeroallergens because the mouth breathing secondary to nasal obstruction; and an increased susceptibility to rhinovirus infection secondary to an increased ICAM-1 expression in the nasal mucosa of patients with allergic rhinitis. A better understanding of the rhinitis-asthma relationship nature might allow the creation of better strategies for the integral treatment of patients with these diseases.

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

    SciTech Connect

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

    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

  4. Allergic diseases and helminth infections

    PubMed Central

    Sitcharungsi, Raweerat; Sirivichayakul, Chukiat

    2013-01-01

    The relationships between allergic diseases and helminth infections are inconsistent. Some studies have suggested that helminth infections induce or increase the severity of atopic diseases. Other studies report that children infected with some helminths have lower prevalence and milder atopic symptoms. Expanding our knowledge on the mechanism of immunological modification as a result of helminth infection, and understanding the interaction between helminth infections and allergic diseases will be useful for developing potentially new treatments using some helminths, and for evaluating the risks and benefits of eradicating helminth infections in endemic areas. This article reviews current knowledge on the mechanisms of allergic disease, the immunological modifications that result from helminth infections, and clinical evidence of the effects of these infections on allergic diseases. PMID:23683364

  5. Allergic respiratory diseases in the elderly.

    PubMed

    Bom, A Todo; Pinto, A Mota

    2009-11-01

    In industrialized countries there has been a significant increase in life expectancy, but chronic diseases are still important causes of death and disability in the elderly. Individuals over 65 years of age have a decrease in organic functions and lungs can lose more than 40% of their capacity. Although asthma and allergic rhinitis are more common in young people their prevalence in the elderly is increasing and the mortality reported in these patients is high. Asthmatic airways show an accumulation of activated eosinophils and lymphocytes determining structural changes of the bronchi. Local allergic inflammation, changes in T cell phenotypes and in apoptosis contribute to systemic inflammation. An increased risk of respiratory infections and neoplasic diseases has been recognized. These patients have increased susceptibility to atherosclerosis and cardiovascular diseases. Metabolic diseases are associated with an impairment of lung function and with systemic inflammation. Summing up older asthmatic patients have an increased risk to premature disability and death. A proper therapeutic approach to asthma can minimize this evolution. To identify the triggers is an important goal that allows reducing medication needs. Corticosteroids dampen allergic inflammation; therefore, they are the first choice in the treatment of patients with persistent asthma and rhinitis. Second-generation H1 receptor antagonists have reduced side effects and can be used if necessary. The elderly may have difficult access to health care. They should be educated about their disease and receive a written treatment plan. This information improves the quality of life, socialization and disease outcome in older people.

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

    PubMed Central

    Kawaguchi, Akira; 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

  7. Attenuation of allergic airway inflammation and hyperresponsiveness in a murine model of asthma by silver nanoparticles

    PubMed Central

    Park, Hee Sun; Kim, Keun Hwa; Jang, Sunhyae; Park, Ji Won; Cha, Hye Rim; Lee, Jeong Eun; Kim, Ju Ock; Kim, Sun Young; Lee, Choong Sik; Kim, Joo Pyung; Jung, Sung Soo

    2010-01-01

    The use of silver in the past demonstrated the certain antimicrobial activity, though this has been replaced by other treatments. However, nanotechnology has provided a way of producing pure silver nanoparticles, and it shows cytoprotective activities and possible pro-healing properties. But, the mechanism of silver nanoparticles remains unknown. This study was aimed to investigate the effects of silver nanoparticles on bronchial inflammation and hyperresponsiveness. We used ovalbumin (OVA)-inhaled female C57BL/6 mice to evaluate the roles of silver nanoparticles and the related molecular mechanisms in allergic airway disease. In this study with an OVA-induced murine model of allergic airway disease, we found that the increased inflammatory cells, airway hyperresponsiveness, increased levels of IL-4, IL-5, and IL-13, and the increased NF-κB levels in lungs after OVA inhalation were significantly reduced by the administration of silver nanoparticles. In addition, we have also found that the increased intracellular reactive oxygen species (ROS) levels in bronchoalveolar lavage fluid after OVA inhalation were decreased by the administration of silver nanoparticles. These results indicate that silver nanoparticles may attenuate antigen-induced airway inflammation and hyperresponsiveness. And antioxidant effect of silver nanoparticles could be one of the molecular bases in the murine model of asthma. These findings may provide a potential molecular mechanism of silver nanoparticles in preventing or treating asthma. PMID:20957173

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

    PubMed Central

    Navarro-Xavier, Roberta Araujo; de Barros, Karina Vieira; de Andrade, Iracema Senna; Palomino, Zaira; Casarini, Dulce Elena; Flor Silveira, Vera Lucia

    2016-01-01

    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. PMID:27274303

  9. Therapeutic strategies for allergic diseases

    NASA Astrophysics Data System (ADS)

    Barnes, Peter J.

    1999-11-01

    Many drugs are now in development for the treatment of atopic diseases, including asthma, allergic rhinitis and atopic dermatitis. These treatments are based on improvements in existing therapies or on a better understanding of the cellular and molecular mechanisms involved in atopic diseases. Although most attention has been focused on asthma, treatments that inhibit the atopic disease process would have application to all atopic diseases, as they often coincide. Most of the many new therapies in development are aimed at inhibiting components of the allergic inflammatory response, but in the future there are real possibilities for the development of preventative and even curative treatments.

  10. G Protein βγ-subunit signaling mediates airway hyperresponsiveness and inflammation in allergic asthma.

    PubMed

    Nino, Gustavo; Hu, Aihua; Grunstein, Judith S; McDonough, Joseph; Kreiger, Portia A; Josephson, Maureen B; Choi, John K; Grunstein, Michael M

    2012-01-01

    Since the Gβγ subunit of Gi protein has been importantly implicated in regulating immune and inflammatory responses, this study investigated the potential role and mechanism of action of Gβγ signaling in regulating the induction of airway hyperresponsiveness (AHR) in a rabbit model of allergic asthma. Relative to non-sensitized animals, OVA-sensitized rabbits challenged with inhaled OVA exhibited AHR, lung inflammation, elevated BAL levels of IL-13, and increased airway phosphodiesterase-4 (PDE4) activity. These proasthmatic responses were suppressed by pretreatment with an inhaled membrane-permeable anti-Gβγ blocking peptide, similar to the suppressive effect of glucocorticoid pretreatment. Extended mechanistic studies demonstrated that: 1) corresponding proasthmatic changes in contractility exhibited in isolated airway smooth muscle (ASM) sensitized with serum from OVA-sensitized+challenged rabbits or IL-13 were also Gβγ-dependent and mediated by MAPK-upregulated PDE4 activity; and 2) the latter was attributed to Gβγ-induced direct stimulation of the non-receptor tyrosine kinase, c-Src, resulting in downstream activation of ERK1/2 and its consequent transcriptional upregulation of PDE4. Collectively, these data are the first to identify that a mechanism involving Gβγ-induced direct activation of c-Src, leading to ERK1/2-mediated upregulation of PDE4 activity, plays a decisive role in regulating the induction of AHR and inflammation in a rabbit model of allergic airway disease.

  11. TIMING OF DIESEL PARTICLE INSTILLATION AND MAGNITUDE OF DOSE INFLUENCE THE SEVERITY OF ALLERGIC AIRWAYS RESPONSES IN MICE

    EPA Science Inventory

    Exposure to diesel exhaust particulates (DEP) arising from the combustion of diesel fuel exacerbates asthma. Several studies have shown that particulate and allergen co-exposure leads to an exacerbation of the hallmark features of allergic airways disease relative to allergen exp...

  12. Asthma and Respiratory Allergic Disease

    EPA Science Inventory

    The pathogenesis of non-communicable diseases such as allergy is complex and poorly understood. The causes of chronic allergic diseases including asthma involve to a large extent, immunomodulation of the adaptive and particularly the innate immune systems and are markedly influen...

  13. Allergic diseases in the elderly

    PubMed Central

    2011-01-01

    Demographic distribution of the population is progressively changing with the proportion of elderly persons increasing in most societies. This entails that there is a need to evaluate the impact of common diseases, such as asthma and other allergic conditions, in this age segment. Frailty, comorbidities and polymedication are some of the factors that condition management in geriatric patients. The objective of this review is to highlight the characteristics of allergic diseases in older age groups, from the influence of immunosenescence, to particular clinical implications and management issues, such as drug interactions or age-related side effects. PMID:22409889

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

    PubMed

    Fenoy, Ignacio M; Chiurazzi, Romina; Sánchez, Vanesa R; Argenziano, Mariana A; Soto, Ariadna; Picchio, Mariano S; Martin, Valentina; Goldman, Alejandra

    2012-01-01

    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.

  15. Toxoplasma gondii Infection Induces Suppression in a Mouse Model of Allergic Airway Inflammation

    PubMed Central

    Fenoy, Ignacio M.; Chiurazzi, Romina; Sánchez, Vanesa R.; Argenziano, Mariana A.; Soto, Ariadna; Picchio, Mariano S.; Martin, Valentina; Goldman, Alejandra

    2012-01-01

    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. PMID:22952678

  16. Beyond Hygiene: Commensal Microbiota and Allergic Diseases.

    PubMed

    Hong, Sung-Wook; Kim, Kwang Soon; Surh, Charles D

    2017-02-01

    Complex communities of microorganisms, termed commensal microbiota, inhabit mucosal surfaces and profoundly influence host physiology as well as occurrence of allergic diseases. Perturbing factors such as the mode of delivery, dietary fibers and antibiotics can influence allergic diseases by altering commensal microbiota in affected tissues as well as in intestine. Here, we review current findings on the relationship between commensal microbiota and allergic diseases, and discuss the underlying mechanisms that contribute to the regulation of allergic responses by commensal microbiota.

  17. Beyond Hygiene: Commensal Microbiota and Allergic Diseases

    PubMed Central

    Hong, Sung-Wook; Kim, Kwang Soon

    2017-01-01

    Complex communities of microorganisms, termed commensal microbiota, inhabit mucosal surfaces and profoundly influence host physiology as well as occurrence of allergic diseases. Perturbing factors such as the mode of delivery, dietary fibers and antibiotics can influence allergic diseases by altering commensal microbiota in affected tissues as well as in intestine. Here, we review current findings on the relationship between commensal microbiota and allergic diseases, and discuss the underlying mechanisms that contribute to the regulation of allergic responses by commensal microbiota. PMID:28261020

  18. The airway microbiome and disease.

    PubMed

    Marsland, Benjamin J; Yadava, Koshika; Nicod, Laurent P

    2013-08-01

    Although traditionally thought to be sterile, accumulating evidence now supports the concept that our airways harbor a microbiome. Thus far, studies have focused upon characterizing the bacterial constituents of the airway microbiome in both healthy and diseased lungs, but what perhaps provides the greatest impetus for the exploration of the airway microbiome is that different bacterial phyla appear to dominate diseased as compared with healthy lungs. As yet, there is very limited evidence supporting a functional role for the airway microbiome, but continued research in this direction is likely to provide such evidence, particularly considering the progress that has been made in understanding host-microbe mutualism in the intestinal tract. In this review, we highlight the major advances that have been made discovering and describing the airway microbiome, discuss the experimental evidence that supports a functional role for the microbiome in health and disease, and propose how this emerging field is going to impact clinical practice.

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

    SciTech Connect

    Ribeiro-Filho, Jaime; Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana; Moraes de Carvalho, Katharinne Ingrid; Silva Mendes, Diego da; Melo, Christianne Bandeira; Martins, Marco Aurélio; Silva Dias, Celidarque da; Piuvezam, Márcia Regina; 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

  20. Respiratory responses of subjects with allergic rhinitis to ozone exposure and their relationship to nonspecific airway reactivity

    SciTech Connect

    McDonnell, W.F.; Horstman, D.H.; Abdul-Salaam, S.; Raggio, L.J.; Green, J.A.

    1987-12-01

    Ozone exposure in man produces changes in respiratory function and symptoms. There is a large degree of unexplained intersubject variability in the magnitude of these responses. There is concern that individuals with chronic respiratory diseases may also be more responsive to ozone than normal individuals. The purpose of this study was to describe the responses of subjects with allergic rhinitis to ozone exposure and to compare these responses to those previously observed in normal individuals. A further purpose was to measure the association of baseline nonspecific airway reactivity with changes in lung function and respiratory symptoms following ozone exposure. A group of 26 nonasthmatic subjects with allergic rhinitis performed a bronchial inhalation challenge with histamine and subsequently underwent two hour exposures to both clean air and to 0.18 part per million ozone with alternating periods of rest and heavy exercise. The airway reactivity of this group of subjects was no greater than that of a comparable group of subjects without allergic rhinitis. The respiratory responses of these subjects to ozone exposure were similar to those previously reported for subjects without allergic rhinitis with the exception that the allergic rhinitis subjects appeared to have a modestly increased bronchoconstrictor response compared to normals. Furthermore, we observed no significant relationships between nonspecific airway reactivity and response to ozone as measured by changes in lung function or the induction of symptoms.

  1. The Nose and the Lung: United Airway Disease?

    PubMed Central

    Licari, Amelia; Castagnoli, Riccardo; Denicolò, Chiara Francesca; Rossini, Linda; Marseglia, Alessia; Marseglia, Gian Luigi

    2017-01-01

    Epidemiologic, pathophysiologic, and clinical evidences recently revealed the link between upper and lower airways, changing the global pathogenic view of respiratory allergy. The aim of this review is to highlight the strong interaction between the upper and lower respiratory tract diseases, in particular allergic rhinitis and asthma. PMID:28316969

  2. Mastocytosis and allergic diseases.

    PubMed

    Bonadonna, P; Lombardo, C; Zanotti, R

    2014-01-01

    Mastocytosis is a clonal disorder characterized by proliferation and accumulation of mast cells in various tissues, mainly skin and bone marrow. It can cause a wide variety of clinical manifestations-other than urticaria pigmentosa-that can lead to inappropriate release of mediators by mast cells. The most severe manifestation is anaphylaxis. The triggers of anaphylaxis in adults with mastocytosis are numerous, but Hymenoptera stings seem to be the most frequent, followed by foods and drugs. Therefore, to prevent severe reactions, it is very important to recognize and avoid potential triggers; in addition, venom-allergic patients must receive lifelong immunotherapy, which has proven very effective. Given that published data on drug anaphylaxis in patients with mast cell disorders are scarce, it is not currently possible to provide clear recommendations. The risk of systemic reactions during general anesthesia can be reduced by assessing risk on an individual basis (previous reaction to a drug or reaction during surgery) and by avoiding specific trigger factors (patient temperature changes, infusion of cold solution, tissue trauma, friction, and other mechanical factors).

  3. Effect of P2X4R on airway inflammation and airway remodeling in allergic airway challenge in mice

    PubMed Central

    CHEN, HONGXIA; XIA, QINGQING; FENG, XIAOQIAN; CAO, FANGYUAN; YU, HANG; SONG, YINLI; NI, XIUQIN

    2016-01-01

    P2X4 receptor (P2X4R) is the most widely expressed subtype of the P2XRs in the purinergic receptor family. Adenosine triphosphate (ATP), a ligand for this receptor, has been implicated in the pathogenesis of asthma. ATP-P2X4R signaling is involved in pulmonary vascular remodeling, and in the proliferation and differentiation of airway and alveolar epithelial cell lines. However, the role of P2X4R in asthma remains to be elucidated. This aim of the present study was to investigate the effects of P2X4R in a murine experimental asthma model. The asthmatic model was established by the inhalation of ovalbumin (OVA) in BALB/c mice. The mice were treated with P2X4R-specific agonists and antagonists to investigate the role of this receptor in vivo. Pathological changes in the bronchi and lung tissues were examined using hematoxylin and eosin staining, Masson's trichrome staining and Alcian blue staining. The inflammatory cells in the bronchoalveolar lavage fluid were counted, and the expression levels of P2X4R, α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) were detected using western blotting. In the OVA-challenged mice, inflammation, infiltration, collagen deposition, mucus production, and the expression levels of P2X4R and PCNA were all increased; however, the expression of α-SMA was decreased, compared with the mice in the control group. Whereas treatment with the P2X4R agonist, ATP, enhanced the allergic reaction, treatment with the P2X4R antagonist, 5-BDBD, attenuated the allergic reaction. The results suggested that ATP-P2X4R signaling may not only contribute to airway inflammation, but it may also contribute to airway remodeling in allergic asthma in mice. PMID:26648454

  4. Role of cockroach proteases in allergic disease.

    PubMed

    Page, Kristen

    2012-10-01

    Allergic asthma is on the rise in developed countries, and cockroach exposure is a major risk factor for the development of asthma. In recent years, a number of studies have investigated the importance of allergen-associated proteases in modulating allergic airway inflammation. Many of the studies have suggested the importance of allergen-associated proteases as having a direct role on airway epithelial cells and dendritic cells. In most cases, activation of the protease activated receptor (PAR)-2 has been implicated as a mechanism behind the potent allergenicity associated with cockroaches. In this review, we focus on recent evidence linking cockroach proteases to activation of a variety of cells important in allergic airway inflammation and the role of PAR-2 in this process. We will highlight recent data exploring the potential mechanisms involved in the biological effects of the allergen.

  5. Cutting edge: STAT6 signaling in eosinophils is necessary for development of allergic airway inflammation.

    PubMed

    Stokes, Kindra; LaMarche, Nelson M; Islam, Nasif; Wood, Amie; Huang, Weishan; August, Avery

    2015-03-15

    Eosinophils are critical cellular mediators in allergic asthma and inflammation; however, the signals that regulate their functions are unclear. The transcription factor STAT6 regulates Th2 cytokine responses, acting downstream of IL-4 and IL-13. We showed previously that eosinophil-derived IL-13 plays an important role in the recruitment of T cells to the lung and the subsequent development of allergic asthma. However, whether eosinophils respond to Th2 signals to control allergic airway inflammation is unclear. In this report, we show that STAT6(-/-) eosinophils are unable to induce the development of allergic lung inflammation, including recruitment of CD4(+) T cells, mucus production, and development of airways hyperresponsiveness. This is likely due to the reduced migration of STAT6(-/-) eosinophils to the lung and in response to eotaxin. These data indicate that, like Th cells, eosinophils need to respond to Th2 cytokines via STAT6 during the development of allergic airway inflammation.

  6. Parasitic Nematode-Induced CD4+Foxp3+T Cells Can Ameliorate Allergic Airway Inflammation

    PubMed Central

    Kang, Shin Ae; Park, Mi-Kyung; Cho, Min Kyoung; Park, Sang Kyun; Jang, Min Seong; Yang, Bo-Gie; Jang, Myoung Ho; Kim, Dong-Hee; Yu, Hak Sun

    2014-01-01

    Background The recruitment of CD4+CD25+Foxp3+T (Treg) cells is one of the most important mechanisms by which parasites down-regulate the immune system. Methodology/Principal Findings We compared the effects of Treg cells from Trichinella spiralis-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced Treg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4+Foxp3+ cells from T. spiralis-infected [Inf(+)Foxp3+] or uninfected [Inf(-)Foxp3+] mice into the tail veins of C57BL/6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA)-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+)Foxp3+ cells [IV(inf):+(+) group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(-)Foxp3+ cells [IV(inf):+(-) group], but the effects were less distinct than those observed in the IV(inf):+(+) group. We found that Inf(+)Foxp3+ cells migrated to inflammation sites in the lung and expressed higher levels of Treg-cell homing receptors (CCR5 and CCR9) and activation markers (Klrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3+ cells. Conclusion/Significance T. spiralis infection promotes the proliferation and functional activation of Treg cells. Parasite-induced Treg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced Treg cells. The adoptive transfer of Inf(+)Foxp3+ cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment

  7. The Allergic Airway Inflammation Repository--a user-friendly, curated resource of mRNA expression levels in studies of allergic airways.

    PubMed

    Gawel, D R; Rani James, A; Benson, M; Liljenström, R; Muraro, A; Nestor, C E; Zhang, H; Gustafsson, M

    2014-08-01

    Public microarray databases allow analysis of expression levels of candidate genes in different contexts. However, finding relevant microarray data is complicated by the large number of available studies. We have compiled a user-friendly, open-access database of mRNA microarray experiments relevant to allergic airway inflammation, the Allergic Airway Inflammation Repository (AAIR, http://aair.cimed.ike.liu.se/). The aim is to allow allergy researchers to determine the expression profile of their genes of interest in multiple clinical data sets and several experimental systems quickly and intuitively. AAIR also provides quick links to other relevant information such as experimental protocols, related literature and raw data files.

  8. [Indoor air and allergic diseases].

    PubMed

    Kunkel, G; Rudolph, R; Muckelmann, R

    1982-01-01

    Allergies may be the source of a variety of clinical symptoms. With regard to indoor air, however, the subject will be limited to inhalative allergies. These are diseases which are caused and supported by allergens entering the human organism via the respiratory pathway. The fundamentals of the origin of inhalative allergies are briefly discussed as well as the antigen-antibody reaction and the differentiation between different allergic reactions (Types I and II). In addition, the importance of repetitive infects of the upper respiratory tract for the occurrence of allergies of the respiratory system is pointed out. The most common allergies develop at the mucosae of the nose (allergic rhinitis) and of the bronchiale (allergic asthma bronchiale). Their symptomatology is discussed. Out of the allergologically interesting components of indoor air the following are to be considered primarily: house dust, components of house dust (house dust mite, trogoderma angustum, tenebrio molitor), epithelia of animals, animal feeds, mildew and occupational substances. Unspecific irritants (chimico-physical irritations) which are not acting as allergens, have to be clearly separated from these most frequent allergens. As a possibility of treatment for the therapeutist and the patient, there is the allergen prophylaxis, i.e. an extensive sanitation of the patient's environment including elimination of the allergens and, in addition, an amelioration of the quality of the air with regard to unspecific irritants. To conclude, some socio-medical aspects of respiratory diseases are discussed.

  9. Ingestion of milk containing the Dp2 peptide, a dust mite allergen, protects mice from allergic airway inflammation and hyper-responsiveness

    PubMed Central

    2013-01-01

    Background Allergen-specific immunotherapy has been demonstrated to have potential for the treatment of allergic diseases. Transgenic animals are currently the best available bioreactors to produce recombinant proteins, which can be secreted in milk. It has not been clearly demonstrated whether milk from transgenic animals expressing recombinant allergens has immunomodulatory effects on allergic asthma. Methods We aimed to determine whether the oral administration of milk containing a mite allergen can down-regulate allergen-specific airway inflammation. Transgenic CD-1 mice that express a recombinant group 2 allergen from Dermatophagoides pteronyssinus (Dp2) in their milk were generated using an embryonic gene-microinjection technique. Mouse pups were fed transgenic Dp2-containing milk or wild-type milk. Subsequently, these mice were sensitized and challenged with Dp2 to induce allergic airway inflammation. Results Upon sensitization and challenge, mice fed transgenic Dp2 milk had decreased T-helper 2 (Th2) and increased T-helper 1 (Th1) responses in the airway compared with mice fed wild-type milk. Moreover, pre-treatment with transgenic Dp2 milk attenuated airway inflammation and decreased airway hyper-responsiveness. Conclusions This study provides new evidence that oral administration of transgenic milk containing the Dp2 allergen down-regulated and moderately protected against allergic airway inflammation. Milk from transgenic animals expressing allergens may have potential use in the prevention of allergic asthma. PMID:23763898

  10. Gut Microbiota and Allergic Disease. New Insights

    PubMed Central

    2016-01-01

    The rapid rise in childhood allergies (atopy) in Westernized nations has implicated associated environmental exposures and lifestyles as primary drivers of disease development. Culture-based microbiological studies indicate that atopy has demonstrable ties to altered gut microbial colonization in very early life. Infants who exhibit more severe multisensitization to food- or aero-allergens have a significantly higher risk of subsequently developing asthma in childhood. Hence an emerging hypothesis posits that environment- or lifestyle-driven aberrancies in the early-life gut microbiome composition and by extension, microbial function, represent a key mediator of childhood allergic asthma. Animal studies support this hypothesis. Environmental microbial exposures epidemiologically associated with allergy protection in humans confer protection against airway allergy in mice. In addition, gut microbiome–derived short-chain fatty acids produced from a high-fiber diet have been shown to protect against allergy via modulation of both local and remote mucosal immunity as well as hematopoietic antigen-presenting cell populations. Here we review key data supporting the concept of a gut–airway axis and its critical role in childhood atopy. PMID:27027953

  11. Gut Microbiota and Allergic Disease. New Insights.

    PubMed

    Lynch, Susan V

    2016-03-01

    The rapid rise in childhood allergies (atopy) in Westernized nations has implicated associated environmental exposures and lifestyles as primary drivers of disease development. Culture-based microbiological studies indicate that atopy has demonstrable ties to altered gut microbial colonization in very early life. Infants who exhibit more severe multisensitization to food- or aero-allergens have a significantly higher risk of subsequently developing asthma in childhood. Hence an emerging hypothesis posits that environment- or lifestyle-driven aberrancies in the early-life gut microbiome composition and by extension, microbial function, represent a key mediator of childhood allergic asthma. Animal studies support this hypothesis. Environmental microbial exposures epidemiologically associated with allergy protection in humans confer protection against airway allergy in mice. In addition, gut microbiome-derived short-chain fatty acids produced from a high-fiber diet have been shown to protect against allergy via modulation of both local and remote mucosal immunity as well as hematopoietic antigen-presenting cell populations. Here we review key data supporting the concept of a gut-airway axis and its critical role in childhood atopy.

  12. Japanese guidelines for allergic conjunctival diseases 2017.

    PubMed

    Takamura, Etsuko; Uchio, Eiichi; Ebihara, Nobuyuki; Ohno, Shigeaki; Ohashi, Yuichi; Okamoto, Shigeki; Kumagai, Naoki; Satake, Yoshiyuki; Shoji, Jun; Nakagawa, Yayoi; Namba, Kenichi; Fukagawa, Kazumi; Fukushima, Atsuki; Fujishima, Hiroshi

    2017-04-01

    The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease (Second Edition) revised in 2010. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs.

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

    PubMed Central

    Zhang, Rui; Duhl, Tiffany; Salam, Muhammad T.; House, James M.; Flagan, Richard C.; Avol, Edward L.; Gilliland, Frank D.; Guenther, Alex; Chung, Serena H.; Lamb, Brian K.; VanReken, Timothy M.

    2014-01-01

    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 WRF/CMAQ air-quality 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 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 km 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 underestimate walnut and peak oak pollen concentrations, and tends

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

    NASA Astrophysics Data System (ADS)

    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

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

    NASA Astrophysics Data System (ADS)

    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.

    2013-03-01

    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 WRF/CMAQ air-quality 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 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 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 km 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 underestimate walnut and peak oak pollen concentrations, and tends to

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

    PubMed

    Zhang, Rui; Duhl, Tiffany; Salam, Muhammad T; House, James M; Flagan, Richard C; Avol, Edward L; Gilliland, Frank D; Guenther, Alex; Chung, Serena H; Lamb, Brian K; VanReken, Timothy M

    2013-03-01

    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 WRF/CMAQ air-quality 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 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 km 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 underestimate walnut and peak oak pollen concentrations, and tends

  17. Air pollution and allergic disease.

    PubMed

    Kim, Haejin; Bernstein, Jonathan A

    2009-03-01

    Over the past several decades, there has been increased awareness of the health effects of air pollution and much debate regarding the role of global warming. The prevalence of asthma and allergic disease has risen in industrialized countries, and most epidemiologic studies focus on possible causalities between air pollution and these conditions. This review examines salient articles and summarizes findings important to the interaction between allergies and air pollution, specifically volatile organic compounds, global warming, particulate pollutants, atopic risk, indoor air pollution, and prenatal exposure. Further work is necessary to determine whether patients predisposed to developing allergic disease may be more susceptible to the health effects of air pollutants due to the direct interaction between IgE-mediated disease and air pollutants. Until we have more definitive answers, patient education about the importance of good indoor air quality in the home and workplace is essential. Health care providers and the general community should also support public policy designed to improve outdoor air quality by developing programs that provide incentives for industry to comply with controlling pollution emissions.

  18. DA-9601, Artemisia asiatica herbal extract, ameliorates airway inflammation of allergic asthma in mice.

    PubMed

    Kim, Ji Young; Kim, Dae Yong; Lee, Yun Song; Lee, Bong Ki; Lee, Kyung-Hoon; Ro, Jai Youl

    2006-08-31

    We previously reported that DA-9601, ethanol herbal extract of Artemisia asiatica, inhibited histamine and leukotriene releases in guinea pig lung mast cells activated with specific antigen/antibody reaction. This study aimed to evaluate the inhibitory effect of DA-9601 on the OVA-induced airway inflammation in allergic asthma mouse model. BALB/c mice were sensitized and challenged with OVA. DA-9601 was administered orally 1 h before every local OVA-challenge. OVA-specific serum IgE was measured by ELISA, recruitment of inflammatory cells in BAL fluids and lung tissues by Diff-Quik and H&E staining, respectively, the expressions of CD40, CD40L and VCAM-1 by immunohistochemistry, goblet cell hyperplasia by PAS staining, activities of MMPs by gelatin zymography, expressions of mRNA and proteins of cytokines by RT-PCR and ELISA, activities of MAP kinases by western blot, and activity of NF-KappaB by EMSA. DA-9601 reduced IgE level, recruitment of inflammatory cells into the BAL fluid and lung tissues, expressions of CD40, CD40L and VCAM-1 molecules, goblet cell hyperplasia, MMPs activity, expressions of mRNA and productions of various cytokines, activities of MAP kinases and NK-KappaB increased from OVA-challenged mice. These data suggest that DA-9601 may be developed as a clinical therapeutic agent in allergic diseases due to suppressing the airway allergic inflammation via regulation of various cellular molecules expressed by MAP kinases/NF-KappaB pathway.

  19. Adoptive transfer of induced-Treg cells effectively attenuates murine airway allergic inflammation.

    PubMed

    Xu, Wei; Lan, Qin; Chen, Maogen; Chen, Hui; Zhu, Ning; Zhou, Xiaohui; Wang, Julie; Fan, Huimin; Yan, Chun-Song; Kuang, Jiu-Long; Warburton, David; Togbe, Dieudonnée; Ryffel, Bernhard; Zheng, Song-Guo; Shi, Wei

    2012-01-01

    Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4(+)FoxP3(+)) and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma.

  20. Cyclooxygenase-1 overexpression decreases Basal airway responsiveness but not allergic inflammation.

    PubMed

    Card, Jeffrey W; Carey, Michelle A; Bradbury, J Alyce; Graves, Joan P; Lih, Fred B; Moorman, Michael P; Morgan, Daniel L; DeGraff, Laura M; Zhao, Yun; Foley, Julie F; Zeldin, Darryl C

    2006-10-01

    Pharmacological inhibition or genetic disruption of cyclooxygenase (COX)-1 or COX-2 exacerbates the inflammatory and functional responses of the lung to environmentally relevant stimuli. To further examine the contribution of COX-derived eicosanoids to basal lung function and to allergic lung inflammation, transgenic (Tr) mice were generated in which overexpression of human COX-1 was targeted to airway epithelium. Although no differences in basal respiratory or lung mechanical parameters were observed, COX-1 Tr mice had increased bronchoalveolar lavage fluid PGE(2) content compared with wild-type littermates (23.0 +/- 3.6 vs 8.4 +/- 1.4 pg/ml; p < 0.05) and exhibited decreased airway responsiveness to inhaled methacholine. In an OVA-induced allergic airway inflammation model, comparable up-regulation of COX-2 protein was observed in the lungs of allergic wild-type and COX-1 Tr mice. Furthermore, no genotype differences were observed in allergic mice in total cell number, eosinophil content (70 vs 76% of total cells, respectively), and inflammatory cytokine content of bronchoalveolar lavage fluid, or in airway responsiveness to inhaled methacholine (p > 0.05). To eliminate the presumed confounding effects of COX-2 up-regulation, COX-1 Tr mice were bred into a COX-2 null background. In these mice, the presence of the COX-1 transgene did not alter allergen-induced inflammation but significantly attenuated allergen-induced airway hyperresponsiveness, coincident with reduced airway leukotriene levels. Collectively, these data indicate that COX-1 overexpression attenuates airway responsiveness under basal conditions but does not influence allergic airway inflammation.

  1. Differential Activation of Airway Eosinophils Induces IL-13 Mediated Allergic Th2 Pulmonary Responses in Mice

    PubMed Central

    Jacobsen, EA; Doyle, AD; Colbert, DC; Zellner, KR; Protheroe, CA; LeSuer, WE; Lee, NA.; Lee, JJ

    2015-01-01

    Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild type or cytokine deficient (IL-13−/− or IL-4−/−) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophildeficient mice, which induced no immune/inflammatory changes either in the lung or lung draining lymph nodes (LDLNs), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLNs. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4+ T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4 and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4+ T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13 whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. PMID:26009788

  2. Psychosomatic treatment for allergic diseases.

    PubMed

    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.

  3. DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma.

    PubMed

    Habibovic, Aida; Hristova, Milena; Heppner, David E; Danyal, Karamatullah; Ather, Jennifer L; Janssen-Heininger, Yvonne M W; Irvin, Charles G; Poynter, Matthew E; Lundblad, Lennart K; Dixon, Anne E; Geiszt, Miklos; van der Vliet, Albert

    2016-11-03

    Chronic inflammation with mucous metaplasia and airway remodeling are hallmarks of allergic asthma, and these outcomes have been associated with enhanced expression and activation of EGFR signaling. Here, we demonstrate enhanced expression of EGFR ligands such as amphiregulin as well as constitutive EGFR activation in cultured nasal epithelial cells from asthmatic subjects compared with nonasthmatic controls and in lung tissues of mice during house dust mite-induced (HDM-induced) allergic inflammation. EGFR activation was associated with cysteine oxidation within EGFR and the nonreceptor tyrosine kinase Src, and both amphiregulin production and oxidative EGFR activation were diminished by pharmacologic or genetic inhibition of the epithelial NADPH oxidase dual oxidase 1 (DUOX1). DUOX1 deficiency also attenuated several EGFR-dependent features of HDM-induced allergic airway inflammation, including neutrophilic inflammation, type 2 cytokine production (IL-33, IL-13), mucous metaplasia, subepithelial fibrosis, and central airway resistance. Moreover, targeted inhibition of airway DUOX1 in mice with previously established HDM-induced allergic inflammation, by intratracheal administration of DUOX1-targeted siRNA or pharmacological NADPH oxidase inhibitors, reversed most of these outcomes. Our findings indicate an important function for DUOX1 in allergic inflammation related to persistent EGFR activation and suggest that DUOX1 targeting may represent an attractive strategy in asthma management.

  4. DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

    PubMed Central

    Habibovic, Aida; Hristova, Milena; Heppner, David E.; Danyal, Karamatullah; Ather, Jennifer L.; Janssen-Heininger, Yvonne M.W.; Irvin, Charles G.; Poynter, Matthew E.; Lundblad, Lennart K.; Dixon, Anne E.; Geiszt, Miklos

    2016-01-01

    Chronic inflammation with mucous metaplasia and airway remodeling are hallmarks of allergic asthma, and these outcomes have been associated with enhanced expression and activation of EGFR signaling. Here, we demonstrate enhanced expression of EGFR ligands such as amphiregulin as well as constitutive EGFR activation in cultured nasal epithelial cells from asthmatic subjects compared with nonasthmatic controls and in lung tissues of mice during house dust mite–induced (HDM-induced) allergic inflammation. EGFR activation was associated with cysteine oxidation within EGFR and the nonreceptor tyrosine kinase Src, and both amphiregulin production and oxidative EGFR activation were diminished by pharmacologic or genetic inhibition of the epithelial NADPH oxidase dual oxidase 1 (DUOX1). DUOX1 deficiency also attenuated several EGFR-dependent features of HDM-induced allergic airway inflammation, including neutrophilic inflammation, type 2 cytokine production (IL-33, IL-13), mucous metaplasia, subepithelial fibrosis, and central airway resistance. Moreover, targeted inhibition of airway DUOX1 in mice with previously established HDM-induced allergic inflammation, by intratracheal administration of DUOX1-targeted siRNA or pharmacological NADPH oxidase inhibitors, reversed most of these outcomes. Our findings indicate an important function for DUOX1 in allergic inflammation related to persistent EGFR activation and suggest that DUOX1 targeting may represent an attractive strategy in asthma management. PMID:27812543

  5. Toll-like Receptors, Triggering Receptor Expressed on Myeloid Cells Family Members and Receptor for Advanced Glycation End-products in Allergic Airway Inflammation

    PubMed Central

    Hall, Sannette C.; Agrawal, Devendra K.

    2016-01-01

    Asthma is a chronic disorder of the airways characterized by cellular infiltration, airway hyper-responsive and airway inflammation. Innate immune cells are the first line of defense against endogenous and exogenous signals in the airways and as such possess a diverse array of pattern recognition receptors. Toll-like receptors are crucial sentinels which when activated, can either promote or ameliorate the inflammatory response in predisposed individuals. The recently discovered triggering receptor expressed on myeloid cells family members are emerging mediators of inflammation. These receptors are believed to modulate inflammatory responses by collaborating with classic PRRs. Endogenous signals like HMGB-1, signaling through the receptor for advanced glycation end products, also promotes inflammation, however, its contribution to inflammation in the airways is not well known. Here, we discuss the role of each receptor in airway inflammation and highlight potential synergistic mechanisms, which contribute to disease pathogenesis in allergic asthma. PMID:26678062

  6. 38 CFR 3.380 - Diseases of allergic etiology.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic...

  7. 38 CFR 3.380 - Diseases of allergic etiology.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic...

  8. 38 CFR 3.380 - Diseases of allergic etiology.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic...

  9. 38 CFR 3.380 - Diseases of allergic etiology.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic...

  10. 38 CFR 3.380 - Diseases of allergic etiology.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic...

  11. Japanese Guideline for Occupational Allergic Diseases 2014.

    PubMed

    Dobashi, Kunio; Akiyama, Kazuo; Usami, Atsushi; Yokozeki, Hiroo; Ikezawa, Zenro; Tsurikisawa, Naomi; Nakamura, Yoichi; Sato, Kazuhiro; Okumura, Jiro

    2014-09-01

    In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

  12. Japanese guidelines for occupational allergic diseases 2017.

    PubMed

    Dobashi, Kunio; Akiyama, Kazuo; Usami, Atsushi; Yokozeki, Hiroo; Ikezawa, Zenro; Tsurikisawa, Naomi; Nakamura, Yoichi; Sato, Kazuhiro; Okumura, Jiro; Takayama, Kaoru

    2017-04-01

    In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

  13. Transfer of allergic airway responses with serum and lymphocytes from rats sensitized to dust mite.

    PubMed

    Lambert, A L; Winsett, D W; Costa, D L; Selgrade, M K; Gilmour, M I

    1998-06-01

    House dust mite (HDM) antigen is one of the most common allergens associated with extrinsic asthma. In a model of allergic lung disease, Brown Norway (BN) rats sensitized to HDM with alum and Bordetella pertussis adjuvants produce high levels of IgE antibody and experience bronchoconstriction, increased airway hyperresponsiveness (AHR) to acetylcholine (ACh), and pulmonary inflammation after antigen challenge. The purpose of this study was to determine whether these asthmatic symptoms could be transferred from sensitized animals to naive recipients via humoral or cellular factors. Syngeneic recipient rats were injected (intraperitoneally with 4 x 10(7) cells (precultured overnight with either HDM or bovine serum albumin [BSA]) from lymph nodes of sensitized or control rats, respectively. Other groups received a tail-vein injection of serum from either HDM-sensitized or control rats. Antigen challenge in rats injected with sensitized cells caused increases in pulmonary inflammation and in AHR, but no changes in immediate bronchoconstriction as compared with control recipients. Antigen challenge in serum recipients resulted in immediate bronchoconstriction but had no effect on AHR or on pulmonary inflammation. These data show that immune-mediated lung inflammation and AHR are promoted by antigen-specific lymphocytes, whereas immediate allergic responses are caused by serum factors.

  14. [Epigenetics in allergic diseases and asthma].

    PubMed

    Castro-Rodríguez, José A; Krause, Bernardo J; Uauy, Ricardo; Casanello, Paola

    2016-01-01

    Allergic diseases and asthma are the result of complex interactions between genetic predisposition and environmental factors. Asthma is one of the most prevalent chronic disease among children. In this article we review some environmental factors like: allergen exposition, tobacco, bacteria, microbial components, diet, obesity and stress, which influences during intrauterine and infancy life in the epigenetic regulation of asthma and allergic diseases. The review has been done in three models: in-vitro, animal and human.

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

    PubMed Central

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

    2016-01-01

    Background 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). Objective We investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms. Methods 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. Results 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. Conclusion Long-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper

  16. Bystander suppression of allergic airway inflammation by lung resident memory CD8+ T cells

    NASA Astrophysics Data System (ADS)

    Marsland, Benjamin J.; Harris, Nicola L.; Camberis, Mali; Kopf, Manfred; Hook, Sarah M.; Le Gros, Graham

    2004-04-01

    CD8+ memory T cells have recently been recognized as playing a key role in natural immunity against unrelated viral infections, a phenomenon referred to as "heterologous antiviral immunity." We now provide data that the cellular immunological interactions that underlie such heterologous immunity can play an equally important role in regulating T helper 2 immune responses and protecting mucosal surfaces from allergen-induced inflammation. Our data show that CD8+ T cells, either retained in the lung after infection with influenza virus, or adoptively transferred via the intranasal route can suppress allergic airway inflammation. The suppression is mediated by IFN-, which acts to reduce the activation level, T helper 2 cytokine production, airways hyperresponsiveness, and migration of allergen-specific CD4+ T cells into the lung, whereas the systemic and draining lymph node responses remain unchanged. Of note, adoptive transfer of previously activated transgenic CD8+ T cells conferred protection against allergic airway inflammation, even in the absence of specific-antigen. Airway resident CD8+ T cells produced IFN- when directly exposed to conditioned media from activated dendritic cells or the proinflammatory cytokines IL-12 and IL-18. Taken together these data indicate that effector/memory CD8+ T cells present in the airways produce IFN- after inflammatory stimuli, independent of specific-antigen, and as a consequence play a key role in modifying the degree and frequency of allergic responses in the lung.

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

    PubMed Central

    2012-01-01

    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 PM2.5, disparate health

  18. Air pollution and allergic diseases

    PubMed Central

    Brandt, Eric B.; Biagini Myers, Jocelyn M.; Ryan, Patrick H.; Khurana Hershey, Gurjit K.

    2015-01-01

    Purpose of review Exposure to traffic-related air pollutants (TRAP) has been implicated in asthma development, persistence, and exacerbation. This exposure is highly significant because increasingly large segments of the population worldwide reside in zones that have high levels of TRAP (1), including children since schools are often located in high traffic pollution exposure areas. Recent findings Recent findings include epidemiologic and mechanistic studies that shed new light on the impact of traffic pollution on allergic diseases and the biology underlying this impact. In addition, new innovative methods to assess and quantify traffic pollution have been developed to assess exposure and identify vulnerable populations and individuals. Summary This review will summarize the most recent findings in each of these areas. These findings will have substantial impact on clinical practice and research by development of novel methods to quantify exposure and identify at-risk individuals, as well as mechanistic studies that identify new targets for intervention for individuals most adversely affected by TRAP exposure. PMID:26474340

  19. [ENT diseases associated with allergic rhinitis: a review of the literature].

    PubMed

    Coste, A

    2000-06-01

    Various diseases of the upper airway, such as acute or chronic sinusitis, otitis media, pharyngitis or laryngitis, snoring and sleep apnea syndrom, may be associated with allergic rhinitis. The relationship between these pathologies and the allergic rhinitis has been well established from a clinical and epidemiological point of view, but the pathophysiological mechanisms remain uncertain. A good knowledge of symptoms and the performance of explorations, such as nasal endoscopy for sinusitis, are important in order to take care of these associated diseases. When upper airway diseases are associated with allergic rhinitis, treatment of rhinitis must generally be reinforced. Treament of associated disease will be specific to each disease, and sometimes surgery is required, specially in case of chronic sinusitis. In all cases, the pneumologist, allergologist and ENT physician should work in close collaboration.

  20. [Allergic rhinitis. Coexistent diseases and complications. A review and analysis].

    PubMed

    Sacre Hazouri, José Antonio

    2006-01-01

    Allergic rhinitis (AR) is rarely found in isolation and needs to be considered in the context of systemic allergic disease associated with numerous comorbid disorders, including asthma, chronic middle ear effusions, sinusitis, and lymphoid hypertrophy with obstructive sleep apnea, disordered sleep, and consequent behavioral and educational effects. The coexistence of allergic rhinitis and asthma is complex. First, the diagnosis of asthma may be confused by symptoms of cough caused by rhinitis and postnasal drip. This may lead to either inaccurate diagnosis of asthma or inappropriate assessment of asthma severity with over treatment of the patient. The term "cough variant rhinitis" is therefore proposed to describe rhinitis that manifest itself primarily as cough that results from postnasal drip. Allergic rhinitis, however, has also a causal role in asthma; it appears both to be responsible for exacerbating asthma and to have a role in its pathogenesis. Postnasal drip with nasopharyngeal inflammation leads to a number of other conditions. Thus sinusitis is a frequent extension of rhinitis and is one of the most frequently missed diagnoses. Allergen exposure in the nasopharynx with release of histamine and other mediators can cause Eustachian tube obstruction possibly leading to middle ear effusions. Chronic allergic inflammation of the upper airway causes lymphoid hypertrophy with prominence of adenoidal and tonsillar tissue. This may be associated with poor appetite, poor growth, obstructive sleep apnea, mouth breathing, pharyngeal irritation and dental abnormalities. Allergic rhinitis is therefore part of a spectrum of allergic disorders that can profoundly affect the well being and quality of life of a child. Prospective cohort studies are required to assess the disease burden caused by allergic rhinitis in childhood, its consequences due to delay in diagnosis and treatment, and to further assess the potential educational impairment that may result. Because

  1. The Lung Microbiome and Airway Disease.

    PubMed

    Lynch, Susan V

    2016-12-01

    A growing body of literature has demonstrated relationships between the composition of the airway microbiota (mixed-species communities of microbes that exist in the respiratory tract) and critical features of immune response and pulmonary function. These studies provide evidence that airway inflammatory status and capacity for repair are coassociated with specific taxonomic features of the airway microbiome. Although directionality has yet to be established, the fact that microbes are known drivers of inflammation and tissue damage suggests that in the context of chronic inflammatory airway disease, the composition and, more importantly, the function, of the pulmonary microbiome represent critical factors in defining airway disease outcomes.

  2. Respiratory responses of subjects with allergic rhinitis to ozone exposure and their relationship to nonspecific airway reactivity

    SciTech Connect

    McDonnell, W.F.; Horstman, D.H.; Abdul-Salaam, S.; Raggio, L.J.; Green, J.A.

    1987-01-01

    Ozone exposure in man produces changes in respiratory function and symptoms. There is a large degree of unexplained intersubject variability in the magnitude of these responses. There is concern that individuals with chronic respiratory diseases may also be more responsive to ozone than normal individuals. The purpose of this study was to describe the responses of subjects with allergic rhinitis to ozone exposure and to compare these responses to those previously observed in normal individuals. A further purpose was to measure the association between baseline nonspecific airway reactivity and changes in lung function and respiratory symptoms following ozone exposure.

  3. Effects of nitric acid on carbachol reactivity of the airways in normal and allergic sheep

    SciTech Connect

    Abraham, W.M.; Kim, C.S.; King, M.M.; Oliver, W. Jr.; Yerger, L.

    1982-01-01

    The airway effects of a 4-hr exposure (via a Plexiglas hood) to 1.6 ppm nitric acid vapor were evaluated in seven normal and seven allergic sheep, i.e., animals that have a history of reacting with bronchospasm to inhalation challenge with Ascaris suum antigen. The nitric acid vapor was generated by ultrasonic nebulization of a 2% nitric acid solution. Airway effects were assessed by measuring the change in specific pulmonary flow resistance before and after a standard inhalation challenge with 2.5% carbachol aerosol. Nitric acid exposure did not produce bronchoconstriction in either group. Pre-exposure increases in specific pulmonary flow resistance after carbachol inhalation were 68% (SD+/- 13%) and 82% (SD+/- 35%) for the normal and allergic sheep, respectively. Within 24 hr, the largest post-exposure increases in specific pulmonary flow resistance for the normal and allergic sheep were 108% (SD+/- 51%(P<.06)) and 175% (SD+/- 87% (p<.02)), respectively. We conclude that a short-term exposure to nitric acid vapor at levels below the industrial threshold limit (2 ppm), produces airway hyperreactivity to aerosolized carbachol in allergic sheep.

  4. DIESEL PARTICLE INSTILLATION ENHANCES INFLAMMATORY AND NEUROTROPHIN RESPONSES IN THE LUNGS OF ALLERGIC BALB/C MICE

    EPA Science Inventory

    Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airways resistance and inflammation. Antibody blockade of NGF attenuates airways resistance associated with the allergen-specific airways responses in mice. ...

  5. Early detection of allergic diseases in otorhinolaryngology

    PubMed Central

    Klimek, Ludger; Schendzielorz, Philip

    2010-01-01

    Asthmatic diseases have been reported since the ancient world. Hay fever for instance, was described for the first time in the late 18th century, and the term “allergy” was introduced about 100 years ago. Today the incidence of allergies is rising; almost one third of the Western population suffers from its side effects. Allergies are some of the most chronic medical complaints, which results in high health expenditures. Therefore, they have a large health and political relevance. Caused by genetic and environmental factors, the group of IgE mediated allergies is large. It consists of e.g. atopic dermatitis, allergic asthma or allergic rhinitis. This paper aims to emphasize the ways of early diagnosis of allergic rhinitis (AR) as AR represents the most important representative of allergic diseases in ENT. PMID:22073091

  6. Climate change and allergic disease.

    PubMed

    Bielory, Leonard; Lyons, Kevin; Goldberg, Robert

    2012-12-01

    Allergies are prevalent throughout the United States and impose a substantial quality of life and economic burden. The potential effect of climate change has an impact on allergic disorders through variability of aeroallergens, food allergens and insect-based allergic venoms. Data suggest allergies (ocular and nasal allergies, allergic asthma and sinusitis) have increased in the United States and that there are changes in allergies to stinging insect populations (vespids, apids and fire ants). The cause of this upward trend is unknown, but any climate change may induce augmentation of this trend; the subspecialty of allergy and immunology needs to be keenly aware of potential issues that are projected for the near and not so distant future.

  7. Diagnostic significance of nitric oxide concentrations in exhaled air from the airways in allergic rhinitis patients

    PubMed Central

    Krzych-Fałta, Edyta; Samoliński, Bolesław K; Zalewska, Marta

    2016-01-01

    Introduction The effect of nitric oxide (NO) on the human body is very important due its physiological regulation of the following functions of airways: modulation of ciliary movement and maintenance of sterility in sinuses. Aim To evaluate the diagnostic significance of NO concentrations in exhaled air from the upper and lower airways in patients diagnosed with allergic rhinitis (AR). Material and methods The subjects included in the study were a group of 30 people diagnosed with sensitivity to environmental allergens and a control group consisting of 30 healthy subjects. The measurement of NO in the air exhaled from the lower and upper airways was performed using an on-line method by means of Restricted Exhaled Breath (REB), as well as using the measurement procedure (chemiluminescence) set out in the guidelines prepared in 2005 by the American Thoracic Society and the European Respiratory Society. Results In the late phase of the allergic reaction, higher values of the level of exhaled NO concentration from the lower airways were observed in the groups of subjects up to the threshold values of 25.17 ppb in the group of subjects with year-round allergic rhinitis and 21.78 ppb in the group with diagnosed seasonal allergic rhinitis. The difference in the concentration of NO exhaled from the lungs between the test group and the control group in the 4th h of the test was statistically significant (p = 0.045). Conclusions Exhaled NO should be considered as a marker of airway inflammation. It plays an important role in the differential diagnosis of allergy. PMID:27279816

  8. Temporal Changes in Glutaredoxin 1 and Protein S-Glutathionylation in Allergic Airway Inflammation

    PubMed Central

    Maki, Kanako; Nagai, Katsura; Suzuki, Masaru; Inomata, Takashi; Yoshida, Takayuki; Nishimura, Masaharu

    2015-01-01

    Introduction Asthma is a chronic inflammatory disorder of the airways, involving oxidative stress. Upon oxidative stress, glutathione covalently binds to protein thiols to protect them against irreversible oxidation. This posttranslational modification, known as protein S-glutathionylation, can be reversed by glutaredoxin 1 (Glrx1) under physiological condition. Glrx1 is known to increase in the lung tissues of a murine model of allergic airway inflammation. However, the temporal relationship between levels of Glrx1, protein S-glutathionylation, and glutathione in the lungs with allergic airway inflammation is not clearly understood. Methods BALB/c mice received 3 aerosol challenges with ovalbumin (OVA) following sensitization to OVA. They were sacrificed at 6, 24, 48, or 72 h, or 8 days (5 mice per group), and the levels of Glrx1, protein S-glutathionylation, glutathione, and 25 cytokines/chemokines were evaluated in bronchoalveolar lavage fluid (BALF) and/or lung tissue. Results Levels of Glrx1 in BALF were significantly elevated in the OVA 6 h (final challenge) group compared to those in the control, with concurrent increases in protein S-glutathionylation levels in the lungs, as well as total glutathione (reduced and oxidized) and oxidized glutathione in BALF. Protein S-glutathionylation levels were attenuated at 24 h, with significant increases in Glrx1 levels in lung tissues at 48 and 72 h. Glrx1 in alveolar macrophages was induced after 6 h. Glrx1 levels concomitantly increased with Th2/NF-κB-related cytokines and chemokines in BALF. Conclusions The temporal relationships of Glrx1 with protein S-glutathionylation, glutathione, and cytokines/chemokines were observed as dynamic changes in lungs with allergic airway inflammation, suggesting that Glrx1 and protein–SSG redox status may play important roles in the development of allergic airway inflammation. PMID:25874776

  9. Absorption across the nasal airway mucosa in house dust mite perennial allergic rhinitis.

    PubMed

    Greiff, Lennart; Andersson, Morgan; Svensson, Jenny; Wollmer, Per; Lundin, Stefan; Persson, Carl G A

    2002-01-01

    House dust mite allergens express protease activity and it has been suggested that this property has pathogenic effects by increasing airway absorption. In accordance, house dust mite allergens may increase mucosal permeability in vitro. The objective of the present study was to examine nasal absorption of desmopressin (1-deamino-8-D-arginine vasopressin) in patients with perennial house dust mite allergic rhinitis and in healthy subjects in vivo. Patients with perennial allergic rhinitis were examined after a 4-week treatment withdrawal period, when symptoms of allergic rhinitis occurred, and healthy subjects were examined together with the patients. Desmopressin (20 microg ml(-1)) was moved into the nasal cavity using a nasal pool-device that contained 15 ml fluid. The fluid was kept in the nasal cavity for 15 min and then recovered. Urine was collected for 24 h after the nasal administration and the urinary excretion of desmopressin was determined as an index of nasal absorption. The urinary excretion of desmopressin was 1148+/-535 pmol 24 h(-1) in patients with perennial house dust mite allergic rhinitis and 1012+/-291 pmol 24 h(-1) in healthy subjects. We conclude that nasal airway absorption of the 1067 Da peptide desmopressin is unaffected in perennial house dust mite allergic rhinitis compared with healthy subjects.

  10. [Asthma and allergic diseases in Sweden].

    PubMed

    Lundbäck, B; Lindström, M; Forsberg, B

    1992-01-01

    Until recently the prevalence of asthma in Sweden was assessed to be 2-3 per cent. An increase in the prevalence of asthma and allergic rhinitis was noted among new conscripts undergoing health work-ups prior to military service with the most marked increase in northern Sweden, were 5 per cent of conscripts were reported to have asthma. In southern Sweden the prevalence remained about 2 per cent. More recent questionnaire studies in mid- and southern Sweden have reported similar rates of respiratory symptoms and use of anti-asthmatic drugs as in northern Sweden, suggesting that there may be no difference in asthma prevalence between the north and the south of the country. The exact prevalence of allergic diseases among Swedish adults is still not clear, but 40 per cent of adults in northern Sweden report that they often have wheezing in the chest, attacks of breathlessness, longstanding cough or sputum production. In questionnaire studies among children about 40 per cent of respondents have reported that they had asthma, allergic rhinitis or other type of hypersensitivity. The absence of generally accepted diagnostic criteria for asthma and allergic disorders in epidemiological studies makes comparison of prevalence difficult. It is thus not possible to be sure that the prevalence of asthma and allergic disorders in Sweden has recently increased. Risk factors for the development of asthma and allergic disorders are under study in Sweden. Several studies report an association in children between urban living and allergic disorders.

  11. Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1.

    PubMed

    Ge, Xiao Na; Ha, Sung Gil; Greenberg, Yana G; Rao, Amrita; Bastan, Idil; Blidner, Ada G; Rao, Savita P; Rabinovich, Gabriel A; Sriramarao, P

    2016-08-16

    Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1-expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs. In vitro, extracellular Gal-1 exerted divergent effects on eosinophils that were N-glycan- and dose-dependent. At concentrations ≤0.25 µM, Gal-1 increased eosinophil adhesion to vascular cell adhesion molecule-1, caused redistribution of integrin CD49d to the periphery and cell clustering, but inhibited ERK(1/2) activation and eotaxin-1-induced migration. Exposure to concentrations ≥1 µM resulted in ERK(1/2)-dependent apoptosis and disruption of the F-actin cytoskeleton. At lower concentrations, Gal-1 did not alter expression of adhesion molecules (CD49d, CD18, CD11a, CD11b, L-selectin) or of the chemokine receptor CCR3, but decreased CD49d and CCR3 was observed in eosinophils treated with higher concentrations of this lectin. In vivo, allergen-challenged Gal-1-deficient mice exhibited increased recruitment of eosinophils and CD3(+) T lymphocytes in the airways as well as elevated peripheral blood and bone marrow eosinophils relative to corresponding WT mice. Further, these mice had an increased propensity to develop airway hyperresponsiveness and displayed significantly elevated levels of TNF-α in lung tissue. This study suggests that Gal-1 can limit eosinophil recruitment to allergic airways and suppresses airway inflammation by inhibiting cell migration and promoting eosinophil apoptosis.

  12. Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

    PubMed Central

    Ge, Xiao Na; Ha, Sung Gil; Greenberg, Yana G.; Rao, Amrita; Bastan, Idil; Blidner, Ada G.; Rao, Savita P.; Rabinovich, Gabriel A.; Sriramarao, P.

    2016-01-01

    Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1–expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs. In vitro, extracellular Gal-1 exerted divergent effects on eosinophils that were N-glycan– and dose-dependent. At concentrations ≤0.25 µM, Gal-1 increased eosinophil adhesion to vascular cell adhesion molecule-1, caused redistribution of integrin CD49d to the periphery and cell clustering, but inhibited ERK(1/2) activation and eotaxin-1–induced migration. Exposure to concentrations ≥1 µM resulted in ERK(1/2)-dependent apoptosis and disruption of the F-actin cytoskeleton. At lower concentrations, Gal-1 did not alter expression of adhesion molecules (CD49d, CD18, CD11a, CD11b, L-selectin) or of the chemokine receptor CCR3, but decreased CD49d and CCR3 was observed in eosinophils treated with higher concentrations of this lectin. In vivo, allergen-challenged Gal-1–deficient mice exhibited increased recruitment of eosinophils and CD3+ T lymphocytes in the airways as well as elevated peripheral blood and bone marrow eosinophils relative to corresponding WT mice. Further, these mice had an increased propensity to develop airway hyperresponsiveness and displayed significantly elevated levels of TNF-α in lung tissue. This study suggests that Gal-1 can limit eosinophil recruitment to allergic airways and suppresses airway inflammation by inhibiting cell migration and promoting eosinophil apoptosis. PMID:27457925

  13. Dendritic cell-nerve clusters are sites of T cell proliferation in allergic airway inflammation.

    PubMed

    Veres, Tibor Z; Shevchenko, Marina; Krasteva, Gabriela; Spies, Emma; Prenzler, Frauke; Rochlitzer, Sabine; Tschernig, Thomas; Krug, Norbert; Kummer, Wolfgang; Braun, Armin

    2009-03-01

    Interactions between T cells and dendritic cells in the airway mucosa precede secondary immune responses to inhaled antigen. The purpose of this study was to identify the anatomical locations where dendritic cell-T cell interactions occur, resulting in T cells activation by dendritic cells. In a mouse model of allergic airway inflammation, we applied whole-mount immunohistology and confocal microscopy to visualize dendritic cells and T cells together with nerves, epithelium, and smooth muscle in three dimensions. Proliferating T cells were identified by the detection of the incorporation of the nucleotide analogue 5-ethynyl-2'-deoxyuridine into the DNA. We developed a novel quantification method that enabled the accurate determination of cell-cell contacts in a semi-automated fashion. Dendritic cell-T cell interactions occurred beneath the smooth muscle layer, but not in the epithelium. Approximately 10% of the dendritic cells were contacted by nerves, and up to 4% of T cells formed clusters with these dendritic cells. T cells that were clustered with nerve-contacting dendritic cells proliferated only in the airways of mice with allergic inflammation but not in the airways of negative controls. Taken together, these results suggest that during the secondary immune response, sensory nerves influence dendritic cell-driven T cell activation in the airway mucosa.

  14. Allergic airway inflammation decreases lung bacterial burden following acute Klebsiella pneumoniae infection in a neutrophil- and CCL8-dependent manner.

    PubMed

    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; Peebles, R Stokes

    2014-09-01

    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.

  15. [Allergic dermatitis: new concepts for old diseases].

    PubMed

    Becerril Angeles, Martín; Ayala Balboa, Julio César; Mendoza Vázquez, Victor Cristóbal

    2003-01-01

    The skin is the largest body's organ, with a well defined functional lymphoid tissue. This organ can be the target of several hypersensitivity-mediated diseases, that are both, genetically determined and influenced by environmental factors. In this paper the main clinical features and the current treatment modalities for the most frequent allergic cutaneous diseases are reviewed.

  16. Respiratory syncytial virus-induced CCL5/RANTES contributes to exacerbation of allergic airway inflammation.

    PubMed

    John, Alison E; Berlin, Aaron A; Lukacs, Nicholas W

    2003-06-01

    Severe respiratory syncytial virus (RSV) infection has a significant impact on airway function and may induce or exacerbate the response to a subsequent allergic challenge. In a murine model combining early RSV infection with later cockroach allergen (CRA) challenge, we examined the role of RSV-induced CCL5/RANTES production on allergic airway responses. RSV infection increased CCL5 mRNA and protein levels, peaking at days 8 and 12, respectively. Administration of CCL5 antiserum during days 0-14 of the RSV infection did not significantly alter viral protein expression when compared to mice treated with control serum. In mice receiving the combined RSV-allergen challenge, lungs collected on day 22 exhibited significantly increased numbers of CD4- and CD8-positive T cells. This increase in T cell numbers was not observed in mice receiving alpha-CCL5. On day 43, peribronchial eosinophilia and leukotriene levels were increased in RSV-allergen mice. Pretreatment with CCL5 antiserum resulted in decreased recruitment of inflammatory cells to bronchoalveolar and peribronchial regions of the lungs and these reductions were associated with a reduction in both T cell recruitment into the bronchoalveolar space, leukotriene release and chemokine generation. Thus, CCL5 released during RSV infection has a significant effect on the inflammatory response to subsequent allergic airway challenges.

  17. Effects of Ex Vivo y-Tocopherol on Airway Macrophage Function in Healthy and Mild Allergic Asthmatics

    EPA Science Inventory

    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-med...

  18. Trigonella foenum-graecum alleviates airway inflammation of allergic asthma in ovalbumin-induced mouse model.

    PubMed

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

    2017-01-22

    Trigonella foenum-graecum, a member oldest medicinal plant in the fabaceae (legumes) family, is used as a herb, spice, and vegetable, and known for its olfactory, laxative, and galactogogue effects. However, the inhibitory effect of Trigonella foenum-graecum on allergic inflammatory response remains unclear, therefore, we investigated the precise role of Trigonella foenum-graecum in the allergic asthma and revealed the effects of Trigonella foenum-graecum in regulating airway inflammation and its possible mechanism. Allergic asthma was initiated in BALB/c mice by sensitized with OVA emulsified in aluminum on days 1 and 14, then aerosol challenged with OVA on days 27, 28 and 29. Some mice were administered Trigonella foenum-graecum by oral gavage before challenge. Then mice were evaluated for the presence of airway inflammation, production of allergen-specific cytokine response and lung pathology. Trigonella foenum-graecum significantly ameliorated the number of inflammatory cells in BALF and alleviated lung inflammation. It also reduced the collagen deposition and goblet cells. Meanwhile, Trigonella foenum-graecum treatment evidently decreased the high expression of Th2 cytokines and increased the Th1 cytokines in BALF and lung homogenates. Trigonella foenum-graecum showed a significant inhibition of serum IgE and anti-OVA IgG1. In this study, our data suggest that Trigonella foenum-graecum has a significant anti-inflammatory effect and it may prove to be an efficacious therapeutic regent on allergic asthma.

  19. [Flexible rhinopharyngolaryngoscopy in the evaluation of patients with allergic and upper respiratory airway disorders].

    PubMed

    Sacre Hazouri, J A

    1996-01-01

    Flexible rhinofaringolaryngoscopy is a valuable diagnostic tool in our daily practice, adding up to 60% of additional information in the diagnosis and clinical approach in neonates, children and adults with pathology of the upper respiratory tract and allergic diseases. We present a practical method for office use, and review our experience with 423 patients in whom the exam was performed. 49% had an abnormal nasal mucosa and middle meatus, site related to ethmoidal and maxillary sinus drainage. In 23 patients we found abnormal turbinates, either clefting, polypoidal changes, degeneration or concha bullosa; most of these findings were not appreciated after routine speculum examination. 7% of our patients had mucosal changes in the area related to the olfactory epithelium, edema and inflammation related to taste and smell disorders. 56 patients had inflammation and hypertrophy in adenoids, 50% of these with some degree of auditory canal obstruction (Eustaquian orifice). In the inferior pharynx and larynx, 58 patients had abnormalities, inflammation in glotic area (8%) due to speech dysfunction. They required speech therapy 4% (14 patients) with abnormal vocal cords, polyps (5), paralysis (4). 2 patients with carcinoma, were referred for biopsy and specific treatment. After gaining sufficient expertise rhinofaringolaryngoscopy is a useful and safe procedure which enhances the diagnostic ability of the practicing allergist/immunologist to evaluate complains referable to the upper airways.

  20. Chrysin alleviates allergic inflammation and airway remodeling in a murine model of chronic asthma.

    PubMed

    Yao, Jing; Jiang, Mingzi; Zhang, Yunshi; Liu, Xing; Du, Qiang; Feng, Ganzhu

    2016-03-01

    Asthma is a chronic airway inflammatory disorder and progresses mainly due to airway remodeling. Chrysin, a natural flavonoid, has been reported to possess multiple biologic activities, including anti-inflammation, anti-oxidation and anti-proliferation. The present study aimed to investigate whether chrysin could relieve allergic airway inflammation and remodeling in a murine model of chronic asthma and the mechanism involved. The female BALB/c mice sensitized and challenged with ovalbumin (OVA) successfully developed airway hyperresponsiveness (AHR), inflammation and remodeling. The experimental data showed that chrysin could alleviate OVA-induced AHR. Chrysin could also reduce OVA-induced increases in the number of inflammatory cells, especially eosinophils, interleukin (IL) -4, and IL-13 in bronchoalveolar lavage fluid (BALF) and total IgE in serum. The decreased interferon-γ (IFN-γ) level in BALF was also upregulated by chrysin. In addition, inflammatory cell infiltration, goblet cell hyperplasia and the expression of α-smooth muscle actin (α-SMA) around bronchioles were suppressed by chrysin. Furthermore, the phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK) could be decreased by chrysin, which are associated with airway smooth muscle cell (ASMC) proliferation. These results indicate the promising therapeutic effect of chrysin on chronic asthma, especially the progression of airway remodeling.

  1. Occupational Respiratory Allergic Diseases in Healthcare Workers.

    PubMed

    Mazurek, Jacek M; Weissman, David N

    2016-11-01

    Healthcare workers (HCWs) are exposed to a range of high and low molecular weight agents that are allergic sensitizers or irritants including cleaners and disinfectants, natural rubber latex, and various medications. Studies have shown that exposed HCWs are at risk for work-related rhinitis and asthma (WRA). Work-related rhinitis may precede development of WRA and should be considered as an early marker of WRA. Avoidance of causative exposures through control strategies such as elimination, substitution, engineering controls, and process modification is the preferred primary prevention strategy for preventing development of work-related allergic diseases. There is limited evidence for the effectiveness of respirators in preventing occupational asthma. If sensitizer-induced WRA is diagnosed, it is important to avoid further exposure to the causative agent, preferably by more rigorous application of exposure control strategies to the workplace. This review focuses on allergic occupational respiratory diseases in HCWs.

  2. Allergen Immunotherapy in Allergic Respiratory Diseases

    PubMed Central

    Viswanathan, Ravi K.

    2012-01-01

    Allergen-specific immunotherapy (SIT) involves the repeated administration of allergenic extracts to atopic individuals over a period of 3 to 5 years either subcutaneously (SCIT) or sublingually (SLIT) for the treatment of allergic respiratory diseases, including asthma and allergic rhinitis (AR). In studies, SCIT and SLIT have been shown to improve existing symptoms of asthma and AR and to also have the capability to cause disease-modifying changes of the underlying atopic condition so as to prevent new allergic sensitization as well as arrest progression of AR to asthma. Recent evidence suggests that immunotherapy brings about these effects through actions that use T-regulatory cells and blocking antibodies such as IgG4 and IgA2, which can then result in an “immune deviation” from a T-helper (Th) 2 cell pattern to a Th1 cell pattern. Numerous meta-analyses and studies have been performed to evaluate the existing data among these studies, with the consensus recommendation favoring the use of immunotherapy because of its potential to modify existing diseases. Significant adverse reactions can occur with immunotherapy, including anaphylaxis and, very rarely, death. A primary factor in considering SIT is its potential to provide long-lasting effects that are able to be sustained well after its discontinuation. Given the significant burden these allergic diseases impose on the health-care system, SIT appears to be a cost-effective adjunctive treatment in modifying the existing disease state. PMID:22553263

  3. Effect of stress on eotaxin and expression of adhesion molecules in a murine model of allergic airway inflammation.

    PubMed

    Joachim, Ricarda A; Sagach, Viktoriya; Quarcoo, David; Dinh, Q Thai; Arck, Petra C; Klapp, Burghard F

    2007-01-01

    Recently we have shown that sound stress enhances allergic airway inflammation in a combined murine model. In the current study we investigated mediating factors and early kinetics of stress exacerbated allergic airway inflammation. Stress significantly increased allergen induced airway inflammation as identified by leukocyte numbers in BAL fluids. Eotaxin levels from stressed mice were significantly higher 24 h after stress. No differences were found for vascular or cellular adhesion molecule expression or cytokine levels. Our data indicate that the effect of stress on allergic airway inflammation might be mediated by the chemoattractant eotaxin, while Th2 cytokines and expression of adhesion molecules seem not to be differently regulated in stressed and non-stressed mice.

  4. Inhibitory effects of Pycnogenol® (French maritime pine bark extract) on airway inflammation in ovalbumin-induced allergic asthma.

    PubMed

    Shin, In-Sik; Shin, Na-Rae; Jeon, Chan-Mi; Hong, Ju-Mi; Kwon, Ok-Kyoung; Kim, Jong-Choon; Oh, Sei-Ryang; Hahn, Kyu-Woung; Ahn, Kyung-Seop

    2013-12-01

    Pycnogenol® (PYC) is a standardized extracts from the bark of the French maritime pine (Pinus maritime) and used as a herbal remedy for various diseases. In this study, we evaluated the effects of PYC on airway inflammation using a model of ovalbumin (OVA)-induced allergic asthma and RAW264.7 cells. PYC decreased nitric oxide production and reduced the interleukine (IL)-1β and IL-6 levels in LPS-stimulated RAW264.7 cells. PYC also reduced the expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase (MMP)-9 and enhanced the expression of hemeoxygenase (HO)-1. In the in vivo experiment, PYC decreased the inflammatory cell count and the levels of IL-4, IL-5, IL-13, and immunoglobulin (Ig) E in BALF or serum. These results are consistent with the histological analysis findings, which showed that PYC attenuated the airway inflammation and mucus hypersecretion induced by OVA challenge. In addition, PYC enhanced the expression of HO-1. In contrast, PYC inhibited the elevated expression of iNOS and MMP-9 proteins induced by OVA challenge. In conclusion, PYC exhibits protective effects against OVA-induced asthma and LPS-stimulated RAW264.7 cells. These results suggest that PYC has potential as a therapeutic agent for the treatment of allergic asthma.

  5. Cockroach protease allergen induces allergic airway inflammation via epithelial cell activation

    PubMed Central

    Kale, Sagar L.; Agrawal, Komal; Gaur, Shailendra Nath; Arora, Naveen

    2017-01-01

    Protease allergens are known to enhance allergic inflammation but their exact role in initiation of allergic reactions at mucosal surfaces still remains elusive. This study was aimed at deciphering the role of serine protease activity of Per a 10, a major cockroach allergen in initiation of allergic inflammation at mucosal surfaces. We demonstrate that Per a 10 increases epithelial permeability by disruption of tight junction proteins, ZO-1 and occludin, and enhances the migration of Monocyte derived dendritic cell precursors towards epithelial layer as exhibited by trans-well studies. Per a 10 exposure also leads to secretion of IL-33, TSLP and intracellular Ca2+ dependent increase in ATP levels. Further, in vivo experiments revealed that Per a 10 administration in mice elevated allergic inflammatory parameters along with high levels of IL-33, TSLP, IL-1α and uric acid in the mice lungs. We next demonstrated that Per a 10 cleaves CD23 (low affinity IgE receptor) from the surface of PBMCs and purified B cells and CD25 (IL-2 receptor) from the surface of PBMCs and purified T cells in an activity dependent manner, which might favour Th2 responses. In conclusion, protease activity of Per a 10 plays a significant role in initiation of allergic airway inflammation at the mucosal surfaces. PMID:28198394

  6. Sesamin attenuates allergic airway inflammation through the suppression of nuclear factor-kappa B activation.

    PubMed

    Li, Liangchang; Piao, Hongmei; Zheng, Mingyu; Jin, Zhewu; Zhao, Liguang; Yan, Guanghai

    2016-12-01

    The aim of the present study is to determine the role of sesamin, the most abundant lignan in sesame seed oil, on the regulation of allergic airway inflammation in a murine asthma model. A BALB/c mouse model with allergic asthma was used to evaluate the effects of sesamin on nuclear factor-kappa B (NF-κB) activation. An enzyme-linked immunosorbent assay was used to determine protein expression in bronchoalveolar lavage (BAL) fluids. Hematoxylin and eosin staining was performed to examine histological changes. Moreover, western blot analysis was used to detect the expression of proteins in tissues. Prior to administering sesamin, the mice developed the following pathophysiological features of asthma: An increase in the number of inflammatory cells, increased levels of interleukin (IL)-4, IL-5 and IL-13, decreased levels of interferon-γ in BAL fluids and lung tissues, increased immunoglobulin E (IgE) levels in the serum and an increased activation of NF-κB in lung tissues. Following treatment with sesamin, the mice had evidently reduced peribronchiolar inflammation and airway inflammatory cell recruitment, inhibited production of several cytokines in BAL fluids and lung tissues, and decreased IgE levels. Following inhalation of ovalbumin, the administration of sesamin also inhibited the activation of NF-κB. In addition, sesamin administration reduced the phosphorylation of p38 mitogen-activated protein kinases (MAPKs). The present study demonstrates that sesamin decreases the activation of NF-κB in order to attenuate allergic airway inflammation in a murine model of asthma, possibly via the regulation of phosphorylation of p38 MAPK. These observations provide an important molecular mechanism for the potential use of sesamin in preventing and/or treating asthma, as well as other airway inflammatory disorders.

  7. Sesamin attenuates allergic airway inflammation through the suppression of nuclear factor-kappa B activation

    PubMed Central

    Li, Liangchang; Piao, Hongmei; Zheng, Mingyu; Jin, Zhewu; Zhao, Liguang; Yan, Guanghai

    2016-01-01

    The aim of the present study is to determine the role of sesamin, the most abundant lignan in sesame seed oil, on the regulation of allergic airway inflammation in a murine asthma model. A BALB/c mouse model with allergic asthma was used to evaluate the effects of sesamin on nuclear factor-kappa B (NF-κB) activation. An enzyme-linked immunosorbent assay was used to determine protein expression in bronchoalveolar lavage (BAL) fluids. Hematoxylin and eosin staining was performed to examine histological changes. Moreover, western blot analysis was used to detect the expression of proteins in tissues. Prior to administering sesamin, the mice developed the following pathophysiological features of asthma: An increase in the number of inflammatory cells, increased levels of interleukin (IL)-4, IL-5 and IL-13, decreased levels of interferon-γ in BAL fluids and lung tissues, increased immunoglobulin E (IgE) levels in the serum and an increased activation of NF-κB in lung tissues. Following treatment with sesamin, the mice had evidently reduced peribronchiolar inflammation and airway inflammatory cell recruitment, inhibited production of several cytokines in BAL fluids and lung tissues, and decreased IgE levels. Following inhalation of ovalbumin, the administration of sesamin also inhibited the activation of NF-κB. In addition, sesamin administration reduced the phosphorylation of p38 mitogen-activated protein kinases (MAPKs). The present study demonstrates that sesamin decreases the activation of NF-κB in order to attenuate allergic airway inflammation in a murine model of asthma, possibly via the regulation of phosphorylation of p38 MAPK. These observations provide an important molecular mechanism for the potential use of sesamin in preventing and/or treating asthma, as well as other airway inflammatory disorders. PMID:28105144

  8. Allergic diseases in farmers' children.

    PubMed

    Braun-Fahrländer, C

    2000-01-01

    Several studies have reported lower rates of allergic sensitization and allergies in children living in rural as compared to urban communities. This has been attributed to the lower levels of air pollution in rural areas. The question arises whether other factors in the rural environment could explain the lower prevalence rates of allergic sensitization and hay fever. A first report from rural South Bavaria in Germany demonstrated that children living in a home where coal and wood were used for heating had a significantly lower risk of suffering from hay fever (odds ratio 0.57 (0.34-0.98)), of being sensitized to common allergens (OR 0.67 (0.49-0.93)) and of having bronchial hyperresponsiveness (OR 0.55 (0.34-0.90)) than their peers living in homes with other heating systems. Subsequently, the Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution (SCARPOL) tested the hypothesis that farming as parental occupation was associated with a lower risk of hay fever and atopy. A total of 1620 (86.0%) 6-15-year-old schoolchildren living in three rural communities of Switzerland were examined using a standardized questionnaire completed by the parents and IgE antibodies against six common aeroallergens in serum samples of 404 (69.3.0%) of the 13-15-year-olds. Farming as parental occupation was significantly associated with lower rates of reported hay fever symptoms and allergic sensitization. Comparing children from farming with those from non-farming environments, the adjusted OR was 0.34 (95% CI: 0.12-0.89) for sneezing attacks during the pollen season, and 0.31 (95% CI: 0.13-0.73) for a sensitization to allergens. These results have recently been confirmed in a new and much larger survey in rural South Bavaria. Several alternative explanations have to be considered when interpreting these findings, namely, selection bias, the development of tolerance, increased microbial stimulation and a more traditional lifestyle (diet and housing

  9. Aerosolized polymerized type I collagen reduces airway inflammation and remodelling in a guinea pig model of allergic asthma.

    PubMed

    Moreno-Alvarez, Paola; Sánchez-Guerrero, Edgar; Martínez-Cordero, Erasmo; Hernández-Pando, Rogelio; Campos, María G; Cetina, Lucely; Bazán-Perkins, Blanca

    2010-04-01

    Collagen-polyvinylpyrrolidone (Collagen-PVP) has been demonstrated to elicit immunomodulatory properties in different chronic inflammatory diseases. Nevertheless, its effects on asthma are still unknown. We have evaluated whether collagen-PVP could modulate airway inflammation and remodelling in a guinea pig model of allergic asthma. Sensitized guinea pigs were challenged with the allergen (ovalbumin) six times (at 10-day intervals). From the third challenge on, animals were treated every 5 days with saline aerosols containing 0.16, 0.33, or 0.66 mg/ml of collagen-PVP (n = 5, respectively). Some guinea pigs, sensitized and challenged with saline as well as treated with 0 or 0.66 mg/ml collagen-PVP, were included in the study as control (n = 7) and sham groups (n = 5), respectively. From the first challenge on, ovalbumin induced a transient airway obstruction, measured by barometric plethysmography, which was not modified by collagen-PVP treatments. After the last allergen challenge, guinea pigs were anesthetized to obtain bronchoalveolar lavage (BAL) and the left lung caudal lobe. As expected, BAL cell count from allergen-challenged guinea pigs showed abundant neutrophils and eosinophils, as well as numerous tumor necrosis factor (TNF)-alpha-expressing granulocytes and macrophages in airway wall (determined by immunohistochemical assay). Neutrophilia and TNF-alpha-expressing leukocytes, from collagen-PVP treated animals, diminished from 0.16 mg/ml, and eosinophilia from 0.66 mg/ml of collagen-PVP doses. Histological changes induced by allergen challenges include thickening of connective tissue below airway epithelium and vascular wall widening of airway adjacent vessels; these changes were reduced by collagen-PVP treatment. Collagen-PVP seems to have anti-inflammatory and antifibrotic properties in this guinea pig asthma model.

  10. Integrated care pathways for airway diseases (AIRWAYS-ICPs).

    PubMed

    Bousquet, J; Addis, A; Adcock, I; Agache, I; Agusti, A; Alonso, A; Annesi-Maesano, I; Anto, J M; Bachert, C; Baena-Cagnani, C E; Bai, C; Baigenzhin, A; Barbara, C; Barnes, P J; Bateman, E D; Beck, L; Bedbrook, A; Bel, E H; Benezet, O; Bennoor, K S; Benson, M; Bernabeu-Wittel, M; Bewick, M; Bindslev-Jensen, C; Blain, H; Blasi, F; Bonini, M; Bonini, S; Boulet, L P; Bourdin, A; Bourret, R; Bousquet, P J; Brightling, C E; Briggs, A; Brozek, J; Buhl, R; Bush, A; Caimmi, D; Calderon, M; Calverley, P; Camargos, P A; Camuzat, T; Canonica, G W; Carlsen, K H; Casale, T B; Cazzola, M; Cepeda Sarabia, A M; Cesario, A; Chen, Y Z; Chkhartishvili, E; Chavannes, N H; Chiron, R; Chuchalin, A; Chung, K F; Cox, L; Crooks, G; Crooks, M G; Cruz, A A; Custovic, A; Dahl, R; Dahlen, S E; De Blay, F; Dedeu, T; Deleanu, D; Demoly, P; Devillier, P; Didier, A; Dinh-Xuan, A T; Djukanovic, R; Dokic, D; Douagui, H; Dubakiene, R; Eglin, S; Elliot, F; Emuzyte, R; Fabbri, L; Fink Wagner, A; Fletcher, M; Fokkens, W J; Fonseca, J; Franco, A; Frith, P; Furber, A; Gaga, M; Garcés, J; Garcia-Aymerich, J; Gamkrelidze, A; Gonzales-Diaz, S; Gouzi, F; Guzmán, M A; Haahtela, T; Harrison, D; Hayot, M; Heaney, L G; Heinrich, J; Hellings, P W; Hooper, J; Humbert, M; Hyland, M; Iaccarino, G; Jakovenko, D; Jardim, J R; Jeandel, C; Jenkins, C; Johnston, S L; Jonquet, O; Joos, G; Jung, K S; Kalayci, O; Karunanithi, S; Keil, T; Khaltaev, N; Kolek, V; Kowalski, M L; Kull, I; Kuna, P; Kvedariene, V; Le, L T; Lodrup Carlsen, K C; Louis, R; MacNee, W; Mair, A; Majer, I; Manning, P; de Manuel Keenoy, E; Masjedi, M R; Melen, E; Melo-Gomes, E; Menzies-Gow, A; Mercier, G; Mercier, J; Michel, J P; Miculinic, N; Mihaltan, F; Milenkovic, B; Molimard, M; Momas, I; Montilla-Santana, A; Morais-Almeida, M; Morgan, M; N'Diaye, M; Nafti, S; Nekam, K; Neou, A; Nicod, L; O'Hehir, R; Ohta, K; Paggiaro, P; Palkonen, S; Palmer, S; Papadopoulos, N G; Papi, A; Passalacqua, G; Pavord, I; Pigearias, B; Plavec, D; Postma, D S; Price, D; Rabe, K F; Radier Pontal, F; Redon, J; Rennard, S; Roberts, J; Robine, J M; Roca, J; Roche, N; Rodenas, F; Roggeri, A; Rolland, C; Rosado-Pinto, J; Ryan, D; Samolinski, B; Sanchez-Borges, M; Schünemann, H J; Sheikh, A; Shields, M; Siafakas, N; Sibille, Y; Similowski, T; Small, I; Sola-Morales, O; Sooronbaev, T; Stelmach, R; Sterk, P J; Stiris, T; Sud, P; Tellier, V; To, T; Todo-Bom, A; Triggiani, M; Valenta, R; Valero, A L; Valiulis, A; Valovirta, E; Van Ganse, E; Vandenplas, O; Vasankari, T; Vestbo, J; Vezzani, G; Viegi, G; Visier, L; Vogelmeier, C; Vontetsianos, T; Wagstaff, R; Wahn, U; Wallaert, B; Whalley, B; Wickman, M; Williams, D M; Wilson, N; Yawn, B P; Yiallouros, P K; Yorgancioglu, A; Yusuf, O M; Zar, H J; Zhong, N; Zidarn, M; Zuberbier, T

    2014-08-01

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

  11. Toxoplasma gondii infection blocks the development of allergic airway inflammation in BALB/c mice.

    PubMed

    Fenoy, I; Giovannoni, M; Batalla, E; Martin, V; Frank, F M; Piazzon, I; Goldman, A

    2009-02-01

    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 orofaecal and foodborne microbes such as Toxoplasma gondii. Infection with T. gondii induces a strong cell-mediated immunity with a highly polarized T helper type 1 (Th1) response in early stages of infection. Using a well-known murine model of allergic lung inflammation, we sought to investigate whether T. gondii infection could modulate the susceptibility to develop respiratory allergies. Both acute and chronic infection with T. gondii before allergic sensitization resulted in a diminished allergic inflammation, as shown by a decrease in bronchoalveolar lavage (BAL) eosinophilia, mononuclear and eosinophil cell infiltration around airways and vessels and goblet cell hyperplasia. Low allergen-specific immunoglobulin (Ig)E and IgG1 and high levels of allergen-specific IgG2a serum antibodies were detected. A decreased interleukin (IL)-4 and IL-5 production by lymph node cells was observed, while no antigen-specific interferon-gamma increase was detected. Higher levels of the regulatory cytokine IL-10 were found in BAL from infected mice. These results show that both acute and chronic parasite infection substantially blocked development of airway inflammation in adult BALB/c mice. Our results support the hypothesis that T. gondii infection contributes to protection against allergy in humans.

  12. CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation

    PubMed Central

    López-Pacheco, C.; Soldevila, G.; Du Pont, G.; Hernández-Pando, R.

    2016-01-01

    Airway inflammation is the most common hallmark of allergic asthma. Chemokine receptors involved in leukocyte recruitment are closely related to the pathology in asthma. CCR9 has been described as a homeostatic and inflammatory chemokine receptor, but its role and that of its ligand CCL25 during lung inflammation remain unknown. To investigate the role of CCR9 as a modulator of airway inflammation, we established an OVA-induced allergic inflammation model in CCR9-deficient mice. Here, we report the expression of CCR9 and CCL25 as early as 6 hours post-OVA challenge in eosinophils and T-lymphocytes. Moreover, in challenged CCR9-deficient mice, cell recruitment was impaired at peribronchial and perivenular levels. OVA-administration in CCR9-deficient mice leads to a less inflammatory cell recruitment, which modifies the expression of IL-10, CCL11, and CCL25 at 24 hours after OVA challenge. In contrast, the secretion of IL-4 and IL-5 was not affected in CCR9-deficient mice compared to WT mice. These results demonstrate for the first time that CCR9 and CCL25 expressions are induced in the early stages of airway inflammation and they have an important role modulating eosinophils and lymphocytes recruitment at the first stages of inflammatory process, suggesting that they might be a potential target to regulate inflammation in asthma. PMID:27795621

  13. Oroxylin A Inhibits Allergic Airway Inflammation in Ovalbumin (OVA)-Induced Asthma Murine Model.

    PubMed

    Zhou, De-Gang; Diao, Bao-Zhong; Zhou, Wen; Feng, Jia-Long

    2016-04-01

    Oroxylin A, a natural flavonoid isolated from the medicinal herb Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory property. In this study, we aimed to investigate the protective effects and mechanism of oroxylin A on allergic inflammation in OVA-induced asthma murine model. BABL/c mice were sensitized and airway-challenged with OVA to induce asthma. Oroxylin A (15, 30, and 60 mg/kg) was administered by oral gavage 1 h before the OVA treatment on day 21 to 23. The results showed that oroxylin A attenuated OVA-induced lung histopathologic changes, airway hyperresponsiveness, and the number of inflammatory cells. Oroxylin A also inhibited the levels of IL-4, IL-5, IL-13, and OVA-specific IgE in BALF. Furthermore, oroxylin A significantly inhibited OVA-induced NF-κB activation. In conclusion, these results suggested that oroxylin A inhibited airway inflammation in OVA-induced asthma murine model by inhibiting NF-κB activation. These results suggested that oroxylin A was a potential therapeutic drug for treating allergic asthma.

  14. Down-regulation of 8-oxoguanine DNA glycosylase 1 expression in the airway epithelium ameliorates allergic lung inflammation.

    PubMed

    Bacsi, Attila; Aguilera-Aguirre, Leopoldo; Szczesny, Bartosz; Radak, Zsolt; Hazra, Tapas K; Sur, Sanjiv; Ba, Xueqing; Boldogh, Istvan

    2013-01-01

    Allergic airway inflammation is characterized by increased expression of pro-inflammatory mediators, inflammatory cell infiltration, mucus hypersecretion, and airway hyperresponsiveness, in parallel with oxidative DNA base and strand damage, whose etiological role is not understood. Our goal was to establish the role of 8-oxoguanine (8-oxoG), a common oxidatively damaged base, and its repair by 8-oxoguanine DNA glycosylase 1 (Ogg1) in allergic airway inflammatory processes. Airway inflammation was induced by intranasally administered ragweed (Ambrosia artemisiifolia) pollen grain extract (RWPE) in sensitized BALB/c mice. We utilized siRNA technology to deplete Ogg1 from airway epithelium; 8-oxoG and DNA strand break levels were quantified by Comet assays. Inflammatory cell infiltration and epithelial methaplasia were determined histologically, mucus and cytokines levels biochemically and enhanced pause was used as the main index of airway hyperresponsiveness. Decreased Ogg1 expression and thereby 8-oxoG repair in the airway epithelium conveyed a lower inflammatory response after RWPE challenge of sensitized mice, as determined by expression of Th2 cytokines, eosinophilia, epithelial methaplasia, and airway hyperresponsiveness. In contrast, 8-oxoG repair in Ogg1-proficient airway epithelium was coupled to an increase in DNA single-strand break (SSB) levels and exacerbation of allergen challenge-dependent inflammation. Decreased expression of the Nei-like glycosylases Neil1 and Neil2 that preferentially excise ring-opened purines and 5-hydroxyuracil, respectively, did not alter the above parameters of allergic immune responses to RWPE. These results show that DNA SSBs formed during Ogg1-mediated repair of 8-oxoG augment antigen-driven allergic immune responses. A transient modulation of OGG1 expression/activity in airway epithelial cells could have clinical benefits.

  15. Future treatments of allergic diseases and asthma.

    PubMed

    Stirling, R G; Chung, K F

    2000-01-01

    Recent advances in the understanding of the inflammatory and immunological mechanisms of allergic diseases have illuminated many potential therapeutic strategies that may prevent or even reverse the abnormalities of allergic inflammation. As the roles of effector cells, and of signalling and adhesion molecules are better understood, the opportunities to inhibit or prevent the inflammatory cascade have increased. In addition, there have been advances in the synthesis of proteins, monoclonal antibodies and new small molecule chemical entities, which provide further valuable flexibility in the therapeutic approach to asthma. Such new approaches are aimed at prevention of T-cell activation; redressing the imbalance of T helper cell populations thus inhibiting or preventing Th-2-derived cytokine expression; and the inhibition or blockade of the downstream actions of these cytokines such as effects on IgE and eosinophils. Approaches such as these allow both broad and highly specific targeting, and may pave the way towards the prevention and reversal of the immunological and inflammatory processes driving asthma, allergic rhinitis and atopic dermatitis. The development of effective agents with effects beyond those provided by current therapies coupled with lesser side-effects will further address the unmet needs of allergic disease.

  16. Effect of oral and intravenous heparin tetrasaccharide on allergic airway responses: critical role of N-sulfation.

    PubMed

    Ahmed, Tahir; Smith, Gregory; Abraham, William M

    2013-04-01

    We have shown that inhaled heparin (hep) oligosaccharides attenuate allergic airway responses in sheep and that this anti-allergic activity resides in a tetrasaccharide sequence. Here we determined: (a) the anti-allergic activity of oral and intravenous hep-tetrasaccharide on allergic airway responses in the sheep model of asthma; and (b) the role of N-sulfation in mediating this anti-allergic activity. Ascaris suum-induced early (EAR) and Late (LAR) airway responses and airway hyperresponsiveness (AHR) to carbachol were measured in allergic sheep without and after treatment with different doses of oral or intravenous hep-tetrasaccharide. At doses of 0.06 mg/kg, 0.125 mg/kg, and 0.25 mg/kg, oral hep-tetrasaccharide caused a dose-dependent inhibition of EAR and LAR. Post-antigen AHR was also inhibited dose dependently. The same doses of intravenous hep-tetrasaccharide yielded comparable inhibition of EAR, LAR and AHR, confirming that orally delivered hep-tetrasaccharide has good bioavailability. The protection by hep-tetrasaccharide on EAR and LAR was dependent on N-sulfation, as N-desulfated/N-acetylated tetrasaccharide had a markedly reduced effect. However, inhibition of the post-antigen AHR was independent of N-sulfation. These results demonstrate that orally administered hep-tetrasaccharide inhibits allergic airway responses in the sheep model of asthma. Hep-tetrasaccharide has good oral bioavailability and its anti-allergic activity is critically dependent on N-sulfation of the glucosamine ring.

  17. TLR2-dependent amelioration of allergic airway inflammation by parasitic nematode type II MIF in mice.

    PubMed

    Cho, M K; Park, M K; Kang, S A; Park, S K; Lyu, J H; Kim, D-H; Park, H-K; Yu, H S

    2015-04-01

    In our previous studies, the recombinant type II macrophage migration inhibitory factor homologue (rAs-MIF) secreted from Anisakis simplex suppressed experimental inflammation mouse model through IL-10 production and CD4(+)CD25(+)Foxp3(+) T-cell recruitment. Also, TLR2 gene expression was significantly increased following rAs-MIF treatment. To know the relation between TLR2 and amelioration mechanisms of rAs-MIF, we induced allergic airway inflammation by ovalbumin and alum with or without rAs-MIF under TLR2 blocking systems [anti-TLR2-specific antibody (α-mTLR2 Ab) treatment and using TLR2 knockout mice]. As a result, the amelioration effects of rAs-MIF in allergic airway inflammation model (diminished inflammation and Th2 response in the lung, increased IL-10 secretion, CD4(+)CD25(+)Foxp3(+) T-cell recruitment) were diminished under two of the TLR2 blocking model. The expression of TLR2 on the surface of lung epithelial cell was significantly elevated by rAs-MIF treatment or Pam3CSK (TLR2-specific agonist) treatment, but they might have some competition effect on the elevation of TLR2 expression. In addition, the elevation of IL-10 gene expression by rAs-MIF treatment was significantly inhibited by α-mTLR2 Ab or Pam3CSK pretreatment. In conclusion, anti-inflammatory effects of the rAs-MIF on OVA-induced allergic airway inflammation might be closely related to TLR2.

  18. Preventing atopy and allergic disease.

    PubMed

    Heine, Ralf G

    2014-01-01

    Due to the recent exponential increase in food allergies and atopic disorders, effective allergy prevention has become a public health priority in many developed regions. Important preventive strategies include the promotion of breastfeeding and vaginal deliveries, judicious use of perinatal antibiotics, as well as the avoidance of maternal tobacco smoking. Breastfeeding for at least 6 months and introduction of complementary solids from 4-6 months are generally recommended. Complex oligosaccharides in breast milk support the establishment of bifidobacteria in the neonatal gut which stimulate regulatory T lymphocyte responses and enhance tolerance development. Maternal elimination diets during pregnancy or lactation are not effective in preventing allergies. If exclusive breastfeeding is not possible, (supplemental) feeding with a partially hydrolyzed whey-based formula or extensively hydrolyzed casein-based formula may reduce the risk of cow's milk allergy and atopic dermatitis in infants with a family history of atopy. By contrast, asthma and allergic rhinitis at 4-6 years of age are not prevented by this approach. Soy formula and amino acid-based formula have no proven role in allergy prevention. Perinatal supplementation with probiotics and/or prebiotics may reduce the risk of atopic dermatitis, but no reliable effect on the prevention of food allergy or respiratory allergies has so far been found. A randomized trial on maternal fish oil supplementation during pregnancy found that atopic dermatitis and egg sensitization in the first year of life were significantly reduced, but no preventive effect for food allergies was demonstrated. The role of vitamin D deficiency or excess as a risk factor for food allergy and atopic disorders requires further study.

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

    PubMed Central

    2010-01-01

    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 < 0.01). Hierarchical regression analysis in the total study cohort indicates that the relationship between asthma and lung function could be mediated by IL-6. Among Th2 cytokines only IL-13 (p < 0.05) was also elevated in the asthmatic group, and positively correlated with IL-6 levels (rS = 0.53, p < 0.05). 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. PMID:20205953

  20. Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma

    PubMed Central

    Lee, Chen-Chen; Wang, Chien-Neng; Lai, Yu-Ting; Kang, Jaw-Jou; Liao, Jiunn-Wang; Chiang, Bor-Luen; Chen, Hui-Chen; Cheng, Yu-Wen

    2010-01-01

    BACKGROUND AND PURPOSE Shikonin exhibits a wide range of anti-inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow-derived dendritic cells (BM-DCs) and on allergic reactions in a murine model of asthma. EXPERIMENTAL APPROACH Cultured murine BM-DCs were used to investigate the effects of shikonin on expression of cell surface markers and their stimulation of T-cell proliferation and cytokine production. The therapeutic potential of shikonin was evaluated in a model of allergic airway disease. KEY RESULTS Shikonin dose-dependently inhibited expression of major histocompatibility complex class II, CD80, CD86, CCR7 and OX40L on BM-DCs, induced by a mixture of ovalbumin (OVA; 100 µg·mL−1) and thymic stromal lymphopoietin (TSLP; 20 ng·mL−1). Shikonin-treated BM-DCs were poor stimulators of CD4+ T lymphocyte and induced lower levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor (TNF)-α release by responding T-cells. After intratracheal instillation of shikonin in OVA-immunized mice, OVA challenge induced lower IL-4, IL-5, IL-13, TNF-α and eotaxin release in bronchial alveolar lavage fluid, lower IL-4 and IL-5 production in lung cells and mediastinal lymph node cells and attenuated OVA-induced lung eosinophilia and airway hyperresponsiveness. CONCLUSION AND IMPLICATIONS Shikonin effectively suppressed OVA + TSLP-induced BM-DC maturation in vitro and inhibited allergic inflammation and airway hyperresponsiveness in a murine model of asthma, showing good potential as a treatment for allergic asthma. Also, our model provides a novel platform for screening drugs for allergic diseases. PMID:20735407

  1. Self-Assembling Nanoparticles Containing Dexamethasone as a Novel Therapy in Allergic Airways Inflammation

    PubMed Central

    Kenyon, Nicholas J.; Bratt, Jennifer M.; Lee, Joyce; Luo, Juntao; Franzi, Lisa M.; Zeki, Amir A.; Lam, Kit S.

    2013-01-01

    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±0.44×105 (n = 18) vs. 5.98±1.3×105 (n = 13), P<0.05) and eosinophils (1.09±0.28×105 (n = 18) vs. 2.94±0.6×105 (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. PMID:24204939

  2. Allergen immunotherapy for allergic respiratory diseases.

    PubMed

    Cappella, Antonio; Durham, Stephen R

    2012-10-01

    Allergen specific immunotherapy involves the repeated administration of allergen products in order to induce clinical and immunologic tolerance to the offending allergen. Immunotherapy is the only etiology-based treatment that has the potential for disease modification, as reflected by longterm remission following its discontinuation and possibly prevention of disease progression and onset of new allergic sensitizations. Whereas subcutaneous immunotherapy is of proven value in allergic rhinitis and asthma there is a risk of untoward side effects including rarely anaphylaxis. Recently the sublingual route has emerged as an effective and safer alternative. Whereas the efficacy of SLIT in seasonal allergy is now well-documented in adults and children, the available data for perennial allergies and asthma is less reliable and particularly lacking in children. This review evaluates the efficacy, safety and longterm benefits of SCIT and SLIT and highlights new findings regarding mechanisms, potential biomarkers and recent novel approaches for allergen immunotherapy.

  3. Mast Cells in Allergic Diseases and Mastocytosis

    PubMed Central

    Marquardt, Diana L.; Wasserman, Stephen I.

    1982-01-01

    Mast cells with their stores of vasoactive and chemotactic mediators are central to the pathogenesis of allergic diseases. The cross-linking of receptorbound IgE molecules on the surface of mast cells initiates a complex chain of events, including calcium ion influx, phospholipid methylation and turnover and cyclic nucleotide metabolism, ultimately resulting in the release of mediators of immediate hypersensitivity. These mast cell mediators are important in smooth muscle reactivity, in the recruitment of eosinophilic and neutrophilic leukocytes and in the generation of secondary chemical mediators. Histologic evidence of mast cell degranulation, biochemical evidence of mast cell mediators in blood and tissues and clinical evidence of signs and symptoms reproducible by these mediators have strongly supported the crucial role of mast cells in asthma, urticaria, anaphylaxis, rhinitis and mastocytosis. Because of their unique location at host environment interfaces, mast cells may both participate in allergic diseases and promote homeostasis. ImagesFigure 1.Figure 2.Figure 3. PMID:6293204

  4. Allergen immunotherapy for allergic respiratory diseases

    PubMed Central

    Cappella, Antonio; Durham, Stephen R.

    2012-01-01

    Allergen specific immunotherapy involves the repeated administration of allergen products in order to induce clinical and immunologic tolerance to the offending allergen. Immunotherapy is the only etiology-based treatment that has the potential for disease modification, as reflected by longterm remission following its discontinuation and possibly prevention of disease progression and onset of new allergic sensitizations. Whereas subcutaneous immunotherapy is of proven value in allergic rhinitis and asthma there is a risk of untoward side effects including rarely anaphylaxis. Recently the sublingual route has emerged as an effective and safer alternative. Whereas the efficacy of SLIT in seasonal allergy is now well-documented in adults and children, the available data for perennial allergies and asthma is less reliable and particularly lacking in children. This review evaluates the efficacy, safety and longterm benefits of SCIT and SLIT and highlights new findings regarding mechanisms, potential biomarkers and recent novel approaches for allergen immunotherapy. PMID:23095870

  5. Genetic risk factors for the development of allergic disease identified by genome-wide association

    PubMed Central

    Portelli, M A; Hodge, E; Sayers, I

    2015-01-01

    An increasing proportion of the worldwide population is affected by allergic diseases such as allergic rhinitis (AR), atopic dermatitis (AD) and allergic asthma and improved treatment options are needed particularly for severe, refractory disease. Allergic diseases are complex and development involves both environmental and genetic factors. Although the existence of a genetic component for allergy was first described almost 100 years ago, progress in gene identification has been hindered by lack of high throughput technologies to investigate genetic variation in large numbers of subjects. The development of Genome-Wide Association Studies (GWAS), a hypothesis-free method of interrogating large numbers of common variants spanning the entire genome in disease and non-disease subjects has revolutionised our understanding of the genetics of allergic disease. Susceptibility genes for asthma, AR and AD have now been identified with confidence, suggesting there are common and distinct genetic loci associated with these diseases, providing novel insights into potential disease pathways and mechanisms. Genes involved in both adaptive and innate immune mechanisms have been identified, notably including multiple genes involved in epithelial function/secretion, suggesting that the airway epithelium may be particularly important in asthma. Interestingly, concordance/discordance between the genetic factors driving allergic traits such as IgE levels and disease states such as asthma have further supported the accumulating evidence for heterogeneity in these diseases. While GWAS have been useful and continue to identify novel genes for allergic diseases through increased sample sizes and phenotype refinement, future approaches will integrate analyses of rare variants, epigenetic mechanisms and eQTL approaches, leading to greater insight into the genetic basis of these diseases. Gene identification will improve our understanding of disease mechanisms and generate potential

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

    PubMed

    Crother, Timothy R; Schröder, Nicolas W J; Karlin, Justin; Chen, Shuang; Shimada, Kenichi; Slepenkin, Anatoly; Alsabeh, Randa; Peterson, Ellena; Arditi, Moshe

    2011-01-01

    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.

  7. IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization

    NASA Astrophysics Data System (ADS)

    Mäkelä, M. J.; Kanehiro, A.; Borish, L.; Dakhama, A.; Loader, J.; Joetham, A.; Xing, Z.; Jordana, M.; Larsen, G. L.; Gelfand, E. W.

    2000-05-01

    Cytokines play an important role in modulating inflammatory responses and, as a result, airway tone. IL-10 is a regulatory cytokine that has been suggested for treatment of asthma because of its immunosuppressive and anti-inflammatory properties. In contrast to these suggestions, we demonstrate in a model of allergic sensitization that mice deficient in IL-10 (IL-10/) develop a pulmonary inflammatory response but fail to exhibit airway hyperresponsiveness in both in vitro and in vivo assessments of lung function. Reconstitution of these deficient mice with the IL-10 gene fully restores development of airway hyperresponsiveness comparable to control mice. These results identify an important role of IL-10, downstream of the inflammatory cascade, in regulating the tone of the airways after allergic sensitization and challenge.

  8. Preventive Intra Oral Treatment of Sea Cucumber Ameliorate OVA-Induced Allergic Airway Inflammation.

    PubMed

    Lee, Da-In; Park, Mi-Kyung; Kang, Shin Ae; Choi, Jun-Ho; Kang, Seok-Jung; Lee, Jeong-Yeol; Yu, Hak Sun

    2016-01-01

    Sea cucumber extracts have potent biological effects, including anti-viral, anti-cancer, antibacterial, anti-oxidant, and anti-inflammation effects. To understand their anti-asthma effects, we induced allergic airway inflammation in mice after 7 oral administrations of the extract. The hyper-responsiveness value in mice with ovalbumin (OVA)-alum-induced asthma after oral injection of sea cucumber extracts was significantly lower than that in the OVA-alum-induced asthma group. In addition, the number of eosinophils in the lungs of asthma-induced mice pre-treated with sea cucumber extract was significantly decreased compared to that of PBS pre-treated mice. Additionally, CD4[Formula: see text]CD25[Formula: see text]Foxp3[Formula: see text]T (regulatory T; Treg) cells significantly increased in mesenteric lymph nodes after 7 administrations of the extract. These results suggest that sea cucumber extract can ameliorate allergic airway inflammation via Treg cell activation and recruitment to the lung.

  9. CD4(+) Th2 cells are directly regulated by IL-10 during allergic airway inflammation.

    PubMed

    Coomes, S M; Kannan, Y; Pelly, V S; Entwistle, L J; Guidi, R; Perez-Lloret, J; Nikolov, N; Müller, W; Wilson, M S

    2017-01-01

    Interleukin-10 (IL-10) is an important regulatory cytokine required to control allergy and asthma. IL-10-mediated regulation of T cell-mediated responses was previously thought to occur indirectly via antigen-presenting cells. However, IL-10 can act directly on regulatory T cells and T helper type 17 (Th17) cells. In the context of allergy, it is therefore unclear whether IL-10 can directly regulate T helper type 2 (Th2) cells and whether this is an important regulatory axis during allergic responses. We sought to determine whether IL-10 signaling in CD4(+) Th2 cells was an important mechanism of immune regulation during airway allergy. We demonstrate that IL-10 directly limits Th2 cell differentiation and survival in vitro and in vivo. Ablation of IL-10 signaling in Th2 cells led to enhanced Th2 cell survival and exacerbated pulmonary inflammation in a murine model of house dust mite allergy. Mechanistically, IL-10R signaling regulated the expression of several genes in Th2 cells, including granzyme B. Indeed, IL-10 increased granzyme B expression in Th2 cells and led to increased Th2 cell death, identifying an IL-10-regulated granzyme B axis in Th2 cells controlling Th2 cell survival. This study provides clear evidence that IL-10 exerts direct effects on Th2 cells, regulating the survival of Th2 cells and severity of Th2-mediated allergic airway inflammation.

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

    SciTech Connect

    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

    2012-03-01

    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.

  11. γ-Secretase Inhibitor Alleviates Acute Airway Inflammation of Allergic Asthma in Mice by Downregulating Th17 Cell Differentiation

    PubMed Central

    Zhang, Weixi; Zhang, Xueya; Sheng, Anqun; Weng, Cuiye; Zhu, Tingting; Zhao, Wei; Li, Changchong

    2015-01-01

    T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. Th17 cell differentiation requires Notch signaling. γ-Secretase inhibitor (GSI) blocks Notch signaling; thus, it may be considered as a potential treatment for allergic asthma. The aim of this study was to evaluate the effect of GSI on Th17 cell differentiation in a mouse model of allergic asthma. OVA was used to induce mouse asthma model in the presence and absence of GSI. GSI ameliorated the development of OVA-induced asthma, including suppressing airway inflammation responses and reducing the severity of clinical signs. GSI also significantly suppressed Th17-cell responses in spleen and reduced IL-17 levels in serum. These findings suggest that GSI directly regulates Th17 responses through a Notch signaling-dependent pathway in mouse model of allergic asthma, supporting the notion that GSI is a potential therapeutic agent for the treatment of allergic asthma. PMID:26339131

  12. Attenuated allergic airway hyperresponsiveness in C57BL/6 mice is associated with enhanced surfactant protein (SP)-D production following allergic sensitization

    PubMed Central

    Atochina, Elena N; Beers, Michael F; Tomer, Yaniv; Scanlon, Seth T; Russo, Scott J; Panettieri, Reynold A; Haczku, Angela

    2003-01-01

    Background C57BL/6 mice have attenuated allergic airway hyperresponsiveness (AHR) when compared with Balb/c mice but the underlying mechanisms remain unclear. SP-D, an innate immune molecule with potent immunosuppressive activities may have an important modulatory role in the allergic airway response and the consequent physiological changes. We hypothesized that an elevated SP-D production is associated with the impaired ability of C57BL/6 mice to develop allergic AHR. Methods SP-D mRNA and protein expression was investigated during development of allergic airway changes in a model of Aspergillus fumigatus (Af)-induced allergic inflammation. To study whether strain dependency of allergic AHR is associated with different levels of SP-D in the lung, Balb/c and C57BL/6 mice were compared. Results Sensitization and exposure to Af induced significant airway inflammation in both mouse strains in comparison with naïve controls. AHR to acetylcholine however was significantly attenuated in C57BL/6 mice in spite of increased eosinophilia and serum IgE when compared with Balb/c mice (p < 0.05). Af challenge of sensitized C57BL/6 mice induced a markedly increased SP-D protein expression in the SA surfactant fraction (1,894 ± 170% of naïve controls) that was 1.5 fold greater than the increase in Balb/c mice (1,234 ± 121% p < 0.01). These changes were selective since levels of the hydrophobic SP-B and SP-C and the hydrophilic SP-A were significantly decreased following sensitization and challenge with Af in both strains. Further, sensitized and exposed C57BL/6 mice had significantly lower IL-4 and IL-5 in the BAL fluid than that of Balb/c mice (p < 0.05). Conclusions These results suggest that enhanced SP-D production in the lung of C57BL/6 mice may contribute to an attenuated AHR in response to allergic airway sensitization. SP-D may act by inhibiting synthesis of Th2 cytokines. PMID:14748931

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

    PubMed Central

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

    2016-01-01

    Background: 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. Objective: To investigate whether a fiber-intake supplement is able to influence the induction of AAD and to elucidate the interactive relationship. Methods: 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. Results: 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. Conclusion: 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

  14. [Extrinsic allergic alveolitis--rarely diagnosed disease].

    PubMed

    Lauková, D; Marget, I; Plutinský, J

    2009-05-01

    Extrinsic allergic alveolitis (EAA), known as hypersensitive pneumonitis, causes interstitial lung involvement by inhaled antigen. The clinical presentation of the disease has been defined as acute, subacute and chronic. The most often symptoms of the acute form of the disease are flu-like symptoms, dyspnoe and cough. The progressive dyspnoe in particullary is characterized for the chronic form of EAA. Dyspnoe is worsed, if the disease is combinied with usual respiratory infection or reexposition of inhaled antigen. It seems the diagnostic definition of EAA should be easy and prevalence of EAA relative high. The disease belongs to the group of interstitial lung diseases and it is underestimated as a matter of fact. The clinic, radiographic, laboratory and histologic abnormalities are results of inhaled antigen contact and support the diagnosis of EAA. Specific IgG antibodies against the offending antigen along with them are consedered to be detected (established) of EAA.

  15. Hesperidin suppresses ovalbumin-induced airway inflammation in a mouse allergic asthma model.

    PubMed

    Wei, Dajun; Ci, Xinxin; Chu, Xiao; Wei, Miaomiao; Hua, Shucheng; Deng, Xuming

    2012-02-01

    Hesperidin, a flavanone glycoside comprised of the flavanone hesperetin and the disaccharide rutinose, is a plentiful and inexpensive by-product of citrus cultivation. It has been reported to exert a wide range of pharmacological effects that include antioxidant, anti-inflammatory, and anticarcinogenic properties. In this study, we attempt to determine whether hesperidin inhibits inflammatory mediators in the mouse allergic asthma model. Mice were sensitized and challenged by ovalbumin (OVA) to induce chronic airway inflammation and airway remodeling. The administration of hesperidin significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines in bronchoalveolar lavage (BAL) fluid compared with the OVA-induced group of mice. In addition, hesperidin reduced OVA-specific IgE levels in serum. Hesperidin markedly alleviated the OVA-induced airway hyperresponsiveness (AHR) to inhaled methacholine. Based on lung histopathological studies using hematoxylin and eosin and alcian blue-periodic acid-Schiff staining, hesperidin inhibited inflammatory cell infiltration and mucus hypersecretion compared with the OVA-induced group of mice. These findings provide new insight into the immunopharmacological role of hesperidin in terms of its effects in a murine model of asthma.

  16. MicroRNA in United Airway Diseases

    PubMed Central

    Liu, Zheng; Zhang, Xin-Hao; Callejas-Díaz, Borja; Mullol, Joaquim

    2016-01-01

    The concept of united airway diseases (UAD) has received increasing attention in recent years. Sustained and increased inflammation is a common feature of UAD, which is inevitably accompanied with marked gene modification and tight gene regulation. However, gene regulation in the common inflammatory processes in UAD remains unclear. MicroRNA (miRNA), a novel regulator of gene expression, has been considered to be involved in many inflammatory diseases. Although there are an increasing number of studies of miRNAs in inflammatory upper and lower airway diseases, few miRNAs have been identified that directly link the upper and lower airways. In this article, therefore, we reviewed the relevant studies available in order to improve the understanding of the roles of miRNAs in the interaction and pathogenesis of UAD. PMID:27187364

  17. Microbiology of airway disease in patients with cystic fibrosis.

    PubMed Central

    Gilligan, P H

    1991-01-01

    Individuals with cystic fibrosis have abbreviated life spans primarily due to chronic airway infection. A limited number of types of organisms are responsible for these infections, with Staphylococcus aureus and Pseudomonas aeruginosa being of primary importance. In the pre-antibiotic era, greater than 90% of deaths due to infection were caused by S. aureus and death usually occurred in the first 2 years of life. With the advent of effective antistaphylococcal therapy, life spans increased and P. aeruginosa became the pathogen of primary importance. P. aeruginosa isolates recovered from patients with cystic fibrosis have a unique phenotypic characteristic referred to as "mucoid." The mucoid phenotype is due to the production of a mucoid exopolysaccharide. A mucoid exopolysaccharide is believed to play a central role in the establishment of chronic pseudomonal lung infection in these patients. A third organism, Pseudomonas cepacia, has recently been detected in the airways of older patients with cystic fibrosis and is associated with increased mortality. The virulence of P. cepacia is not understood, but the organism is extremely refractory to antimicrobial therapy. Other bacteria, including Haemophilus influenzae and members of the family Enterobacteriaceae, appear to play a secondary role in airway infection. Aspergillus fumigatus is the most important fungal agent causing allergic bronchopulmonary disease. The role of viruses has only recently been examined. At least in some patients with cystic fibrosis, respiratory syncytial virus may be important in predisposing to subsequent bacterial infections. PMID:1900735

  18. Protective effect of curcumin on acute airway inflammation of allergic asthma in mice through Notch1-GATA3 signaling pathway.

    PubMed

    Chong, Lei; Zhang, Weixi; Nie, Ying; Yu, Gang; Liu, Liu; Lin, Li; Wen, Shunhang; Zhu, Lili; Li, Changchong

    2014-10-01

    Curcumin, a natural product derived from the plant Curcuma longa, has been found to have anti-inflammatory, antineoplastic and antifibrosis effects. It has been reported that curcumin attenuates allergic airway inflammation in mice through inhibiting NF-κB and its downstream transcription factor GATA3. It also has been proved the antineoplastic effect of curcumin through down-regulating Notch1 receptor and its downstream nuclear transcription factor NF-κB levels. In this study, we aimed to investigate the anti-inflammatory effect of curcumin on acute allergic asthma and its underlying mechanisms. 36 male BALB/c mice were randomly divided into four groups (normal, asthma, asthma+budesonide and asthma+curcumin groups). BALF (bronchoalveolar lavage fluid) and lung tissues were analyzed for airway inflammation and the expression of Notch1, Notch2, Notch3, Notch4 and the downstream transcription factor GATA3. Our findings showed that the levels of Notch1 and Notch2 receptors were up-regulated in asthma group, accompanied by the increased expression of GATA3. But the expression of Notch2 receptor was lower than Notch1 receptor. Curcumin pretreatment improved the airway inflammatory cells infiltration and reversed the increasing levels of Notch1/2 receptors and GATA3. Notch3 receptor was not expressed in all of the four groups. Notch4 receptor protein and mRNA expression level in the four groups had no significant differences. The results of the present study suggested that Notch1 and Notch2 receptor, major Notch1 receptor, played an important role in the development of allergic airway inflammation and the inhibition of Notch1-GATA3 signaling pathway by curcumin can prevent the development and deterioration of the allergic airway inflammation. This may be a possible therapeutic option of allergic asthma.

  19. Downregulation of Orai1 expression in the airway alleviates murine allergic rhinitis

    PubMed Central

    Wang, Yi; Lin, Lin

    2012-01-01

    Orai1 is the key subunit of the Ca2+-release-activated Ca2+ channel. Our previous report has demonstrated that Orai1 expression in the airway was upregulated in the ovalbumin (OVA)-induced allergic rhinitis (AR) mouse models. To observe whether inhibition of Orai1 expression in the airway could suppress symptoms in a murine model of AR and to assess the impacts of this inhibition on the responses of local and systemic immunocytes, we administered recombinant lentivirus vectors that encoded shRNA against ORAI1 (lenti-ORAI1) into the nostrils of OVA-sensitized mice before the challenges, and analyzed its effect on allergic responses, as compared with the unsensitized mice and untreated AR mice. Administration of lenti-ORAI1 into the nasal cavity successfully infected cells in the epithelial layer of the nasal mucosa, and significantly decreased the frequencies of sneezing and nasal rubbing of the mice. Protein levels of leukotriene C4, OVA-specific IgE, and IL-4 in the nasal lavage fluid and serum and eosinophil cation protein in the serum were also significantly reduced by lenti-ORAI1, as were the mRNA levels of these factors in the nasal mucosa and spleen. These data suggested that administration of lenti-ORAI1 into the nasal cavity effectively decreased Orai1 expression in the nasal mucosa, alleviated AR symptoms, and partially inhibited the hyperresponsiveness of the local and systemic immune cells including T cells, B cells, mast cells and eosinophils that are involved in the pathogenesis of AR. PMID:22170034

  20. Effects of gasoline engine emissions on preexisting allergic airway responses in mice.

    PubMed

    Day, Kimberly C; Reed, Matthew D; McDonald, Jacob D; Seilkop, Steven K; Barrett, Edward G

    2008-10-01

    Gasoline-powered vehicle emissions contribute significantly to ambient air pollution. We hypothesized that exposure to gasoline engine emissions (GEE) may exacerbate preexisting allergic airway responses. Male BALB/c mice were sensitized by injection with ovalbumin (OVA) and then received a 10-min aerosolized OVA challenge. Parallel groups were sham-sensitized with saline. Mice were exposed 6 h/day to air (control, C) or GEE containing particulate matter (PM) at low (L), medium (M), or high (H) concentrations, or to the H level with PM removed by filtration (high-filtered, HF). Immediately after GEE exposure mice received another 10-min aerosol OVA challenge (pre-OVA protocol). In a second (post-OVA) protocol, mice were similarly sensitized but only challenged to OVA before air or GEE exposure. Measurements of airway hyperresponsiveness (AHR), bronchoalveolar lavage (BAL), and blood collection were performed approximately 24 h after the last exposure. In both protocols, M, H, and HF GEE exposure significantly decreased BAL neutrophils from nonsensitized mice but had no significant effect on BAL cells from OVA-sensitized mice. In the pre-OVA protocol, GEE exposure increased OVA-specific IgG(1) but had no effect on BAL interleukin (IL)-2, IL-4, IL-13, or interferon (IFN)-gamma in OVA-sensitized mice. Nonsensitized GEE-exposed mice had increased OVA-specific IgG(2a), IgE, and IL-2, but decreased total IgE. In the post-OVA protocol, GEE exposure reduced BAL IL-4, IL-5, and IFN-gamma in nonsensitized mice but had no effect on sensitized mice. These results suggest acute exposure to the gas-vapor phase of GEE suppressed inflammatory cells and cytokines from nonsensitized mice but did not substantially exacerbate allergic responses.

  1. Allergic Diseases and Internalizing Behaviors in Early Childhood

    PubMed Central

    LeMasters, Grace K.; Levin, Linda; Rothenberg, Marc E.; Assa'ad, Amal H.; Newman, Nicholas; Bernstein, David; Khurana-Hershey, Gurjit; Lockey, James E.; Ryan, Patrick H.

    2016-01-01

    BACKGROUND AND OBJECTIVES: The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years. METHODS: Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. The association between allergic diseases at age 4, including allergic rhinitis, allergic persistent wheezing, atopic dermatitis, and allergic sensitization, and BASC-2 internalizing, anxiety, and depression T scores at age 7 was examined by logistic and linear regression, adjusting for covariates. RESULTS: The cohort included 546 children with complete information on allergic disease and BASC-2 outcomes. Allergic rhinitis at age 4 was significantly associated with elevated internalizing (adjusted odds ratio [aOR]: 3.2; 95% confidence interval [CI]: 1.8–5.8), anxiety (aOR: 2.0; 95% CI: 1.2–3.6), and depressive scores (aOR: 3.2; 95% CI: 1.7–6.5) at age 7. Allergic persistent wheezing was significantly associated with elevated internalizing scores (aOR: 2.7; 95% CI: 1.2–6.3). The presence of >1 allergic disease (aOR: 3.6; 95% CI: 1.7–7.6) and allergic rhinitis with comorbid allergic disease(s) (aOR: 4.3; 95% CI: 2.0–9.2) at age 4 had dose-dependent associations with internalizing scores. CONCLUSIONS: Children with allergic rhinitis and allergic persistent wheezing at age 4 are at increased risk of internalizing behaviors at age 7. Furthermore, multiple allergic diseases had a dose-dependent association with elevated internalizing scores. PMID:26715608

  2. Endotoxin Augments Myeloid Dendritic Cell Influx into the Airways in Patients with Allergic Asthma

    PubMed Central

    Schaumann, Frank; Müller, Meike; Braun, Armin; Luettig, Birgit; Peden, David B.; Hohlfeld, Jens M.; Krug, Norbert

    2008-01-01

    Rationale: Epidemiologic studies have shown that exacerbation of asthma is modulated by environmental endotoxin. High levels of endotoxin are associated with asthma symptoms and the current use of asthma medication. However, the underlying mechanisms by which endotoxin modulates asthma are not completely understood. Objectives: The aim of the study was to test whether endotoxin enhances the response of individuals with allergic asthma to allergen, and to determine if this interaction is associated with increased numbers of antigen-presenting cells in the airways. Methods: Seventeen subjects with mild allergic asthma underwent segmental challenge with allergen, endotoxin, and the combination of both in three different lung segments via bronchoscopy. The cellular influx including monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), as well as the level of cytokines, were assessed in bronchoalveolar lavage fluid obtained 24 hours after segmental challenge. Monocytes, mDCs, and pDCs were isolated and their capacity to induce T cell proliferation was determined. Measurements and Main Results: Endotoxin enhanced the cellular response to allergen. The combination of allergen and endotoxin resulted in increased numbers of total cells, lymphocytes, neutrophils, eosinophils, monocytes, and mDCs, as well as increased levels of lipopolysaccharide-binding protein, IL-1α, IL-6, and tumor necrosis factor–α in the bronchoalveolar lavage fluid compared with allergen alone. Isolated mDCs but not pDCs induced a strong T cell proliferation in vitro. Conclusions: Endotoxin augments the allergic inflammation in the lungs of individuals with asthma, and induces an enhanced influx of monocytes and functionally active antigen-presenting mDCs into the respiratory tract. PMID:18388357

  3. Assessment of disease control in allergic rhinitis

    PubMed Central

    2013-01-01

    The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative has had a significant impact, by raising awareness of allergic rhinitis (AR) and improving the diagnosis and treatment of AR sufferers. ARIA classifies the severity of AR as "mild" or "moderate/severe" on the basis of "yes"/"no" answers to four questions. This two-point classification has been criticized as providing little guidance on patient management; patients with "mild" AR are unlikely to consult a physician, whereas the group of patients with "moderate/severe" seen by specialists is heterogeneous. These perceived shortcomings have prompted attempts to improve the ARIA classification or, by analogy with the Global Initiative for Asthma (GINA), adopt approaches based on "disease control" in AR. Even though "disease severity", "disease control" and "responsiveness to treatment" are different (albeit related) metrics, they are not mutually exclusive. Currently, there is no single, accepted definition, but we propose that "disease control" in AR can combine (i) measurements of the severity and/or frequency of daily or nocturnal symptoms, (ii) impairments in social, physical, professional and educational activities, (iii) respiratory function monitoring and (iv) exacerbations (e.g. unscheduled medical consultations and rescue medication use). Although control-based classifications have a number of limitations (e.g. their dependence on treatment compliance and the patient's psychological status), these instruments could be used as an adjunct to the ARIA severity classification and regional practice parameters. Here, we assess the strengths and weaknesses of the current two-level ARIA classification, analyze published proposals for its modification and review the literature on instruments that measure AR control. We conclude that there is a need for research in which severity is compared with control in terms of their effects on patient management. PMID:23419058

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

    PubMed Central

    Günel, Ceren; Demirci, Buket; Eryılmaz, Aylin; Yılmaz, Mustafa; Meteoğlu, İbrahim; Ömürlü, İmran Kurt; Başal, Yeşim

    2016-01-01

    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 response

  5. Breathing hot humid air induces airway irritation and cough in patients with allergic rhinitis.

    PubMed

    Khosravi, Mehdi; Collins, Paul B; Lin, Ruei-Lung; Hayes, Don; Smith, Jaclyn A; Lee, Lu-Yuan

    2014-07-01

    We studied the respiratory responses to an increase in airway temperature in patients with allergic rhinitis (AR). Responses to isocapnic hyperventilation (40% of maximal voluntary ventilation) for 4min of humidified hot air (HA; 49°C) and room air (RA; 21°C) were compared between AR patients (n=7) and healthy subjects (n=6). In AR patients, cough frequency increased pronouncedly from 0.10±0.07 before to 2.37±0.73 during, and 1.80±0.79coughs/min for the first 8min after the HA challenge, but not during the RA challenge. In contrast, neither HA nor RA had any significant tussive effect in healthy subjects. The HA challenge also caused respiratory discomfort (mainly throat irritation) measured by the handgrip dynamometry in AR patients, but not in healthy subjects. Bronchoconstriction was not detected after the HA challenge in either group of subjects. In conclusion, hyperventilation of HA triggered vigorous cough response and throat irritation in AR patients, indicating the involvement of sensory nerves innervating upper airways.

  6. Selective, tight-binding inhibitors of integrin alpha4beta1 that inhibit allergic airway responses.

    PubMed

    Lin, K c; Ateeq, H S; Hsiung, S H; Chong, L T; Zimmerman, C N; Castro, A; Lee, W C; Hammond, C E; Kalkunte, S; Chen, L L; Pepinsky, R B; Leone, D R; Sprague, A G; Abraham, W M; Gill, A; Lobb, R R; Adams, S P

    1999-03-11

    Integrin alpha4beta1 mediates leukocyte recruitment, activation, mediator release, and apoptosis inhibition, and it plays a central role in inflammatory pathophysiology. High-affinity, selective inhibitors of alpha4beta1, based on the Leu-Asp-Val (LDV) sequence from the alternatively spliced connecting segment-1 (CS-1) peptide of cellular fibronectin, are described that employ a novel N-terminal peptide "cap" strategy. One inhibitor, BIO-1211, was approximately 10(6)-fold more potent than the starting peptide and exhibited tight-binding properties (koff = 1.4 x 10(-4) s-1, KD = 70 pM), a remarkable finding for a noncovalent, small-molecule inhibitor of a protein receptor. BIO-1211 was also 200-fold selective for the activated form of alpha4beta1, and it stimulated expression of ligand-induced epitopes on the integrin beta1 subunit, a property consistent with occupancy of the receptor's ligand-binding site. Pretreatment of allergic sheep with a 3-mg nebulized dose of BIO-1211 inhibited early and late airway responses following antigen challenge and prevented development of nonspecific airway hyperresponsiveness to carbachol. These results show that highly selective and potent small-molecule antagonists can be identified to integrins with primary specificity for peptide domains other than Arg-Gly-Asp (RGD); they confirm the generality of integrins as small molecule targets; and they validate alpha4beta1 as a therapeutic target for asthma.

  7. Loss-of-function of inositol polyphosphate-4-phosphatase reversibly increases the severity of allergic airway inflammation.

    PubMed

    Aich, Jyotirmoi; Mabalirajan, Ulaganathan; Ahmad, Tanveer; Agrawal, Anurag; Ghosh, Balaram

    2012-06-06

    Inositol polyphosphate phosphatases regulate the magnitude of phosphoinositide-3 kinase signalling output. Although inositol polyphosphate-4-phosphatase is known to regulate phosphoinositide-3 kinase signalling, little is known regarding its role in asthma pathogenesis. Here we show that modulation of inositol polyphosphate-4-phosphatase alters the severity of asthma. Allergic airway inflammation in mice led to calpain-mediated degradation of inositol polyphosphate-4-phosphatase. In allergic airway inflammation models, preventing inositol polyphosphate-4-phosphatase degradation by inhibiting calpain activity, or overexpression of inositol polyphosphate-4-phosphatase in mouse lungs, led to attenuation of the asthma phenotype. Conversely, knockdown of inositol polyphosphate-4-phosphatase severely aggravated the allergic airway inflammation and the asthma phenotype. Interestingly, inositol polyphosphate-4-phosphatase knockdown in lungs of naive mice led to spontaneous airway hyper-responsiveness, suggesting that inositol polyphosphate-4-phosphatase could be vital in maintaining the lung homeostasis. We suggest that inositol polyphosphate-4-phosphatase has an important role in modulating inflammatory response in asthma, and thus, uncover a new understanding of the complex interplay between inositol signalling and asthma, which could provide alternative strategies in asthma management.

  8. Chlamydia pneumoniae Infection Induced Allergic Airway Sensitization Is Controlled by Regulatory T-Cells and Plasmacytoid Dendritic Cells

    PubMed Central

    Crother, Timothy R.; Schröder, Nicolas W. J.; Karlin, Justin; Chen, Shuang; Shimada, Kenichi; Slepenkin, Anatoly; Alsabeh, Randa; Peterson, Ellena; Arditi, Moshe

    2011-01-01

    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. PMID:21695198

  9. The Microbiome and Development of Allergic disease

    PubMed Central

    Lynch, Susan V.; Boushey, Homer A.

    2017-01-01

    Purposes of review First, to review how the global rise in prevalence of asthma prompted studies of the relationships between microbial exposure in early infancy, the rate and pattern of development of immune function, and the development of allergic sensitization and of wheezing in childhood. And, second, to review how those studies laid the groundwork for a possible strategy for primary prevention of asthma through manipulation of the microbiome of the gastrointestinal and/or respiratory tracts. Recent findings Atopy and asthma are complex diseases thought to result from a “gene-by-environment” interaction; the rapidity of their rise in prevalence points to a change in environment as most likely causal. Epidemiologic studies noting associations between events in infancy and later development of atopic diseases have suggested that their rise in prevalence is related to a deficiency in microbial exposure in early life. The findings from birth cohort studies of humans and from interventional studies of mice converge in suggesting that a deficiency in microbial colonization of the respiratory or gastrointestinal tract by certain commensal microbes results in skewed development of systemic and/or local immune function that increases susceptibility to allergic sensitization and to viral lower respiratory infection. Recent studies are now honing in on identifying the microbes, or collection of microbes, whose collective functions are necessary for induction of immune tolerance, and thus of reduced susceptibility. Summary Atopy and asthma appear to have their roots in an insufficiency of early life exposure to the diverse environmental microbiota necessary to ensure colonization of the gastrointestinal and/or respiratory tracts with the commensal microbes necessary for induction of balanced, toleragenic immune function. Identification of the commensal bacteria necessary, now ever closer at hand, will lay the groundwork for the development of strategies for primary

  10. [Prevention of allergic diseases in childhood: from theory to reality].

    PubMed

    2016-06-01

    Allergic diseases have an increasing worldwide prevalence and a great impact on the health related costs. The research is focused on the study of etiological and risk factors of allergic diseases that can potentially be modified with primary, secondary and tertiary prevention strategies. Many of these measures do not have a definitively proven effect taking place in a controlled context different to what happens in real life. This paper aims to review the latest evidence on prevention of allergic diseases considering certainties and unresolved issues and focuses mainly on environmental, dietary, pharmacological and immunological preventive strategies for different levels of prevention. It is imperative to have a better understanding of genetic and environmental factors that cause allergic diseases to optimize preventive measures that are effective in reversing the increasing trend in the prevalence of allergic illnesses in childhood.

  11. [Cytokines and anti-cytokines in allergic diseases].

    PubMed

    Fal, Andrzej M

    2003-06-01

    Allergic inflamation is complexed phenomenon related to the activity of many mediators released from "effector cells". The role of IL-12, IL-5, IL-4 and some adhesive molecules is presented with special attention focused on therapeutical aspects in allergic diseases.

  12. NEUROTROPHIN RECEPTOR BLOCKADE ATTENUATES DIESEL EXHAUST PARTICULATE MATTER (DEP) ENHANCEMENT OF ALLERGIC RESPONSES

    EPA Science Inventory

    ABSTRACT BODY:
    Recent investigations have linked neurotrophins including NGF, NT-3, and BDNF to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance associated with allergic airway responses in mice. Mice administered an antibody against the low aff...

  13. Heme oxygenase-1 inhibits basophil maturation and activation but promotes its apoptosis in T helper type 2-mediated allergic airway inflammation.

    PubMed

    Zhong, Wenwei; Di, Caixia; Lv, Jiajia; Zhang, Yanjie; Lin, Xiaoliang; Yuan, Yufan; Lv, Jie; Xia, Zhenwei

    2016-03-01

    The anti-inflammatory role of heme oxygenase-1 (HO-1) has been studied extensively in many disease models including asthma. Many cell types are anti-inflammatory targets of HO-1, such as dendritic cells and regulatory T cells. In contrast to previous reports that HO-1 had limited effects on basophils, which participate in T helper type 2 immune responses and antigen-induced allergic airway inflammation, we demonstrated in this study, for the first time, that the up-regulation of HO-1 significantly suppressed the maturation of mouse basophils, decreased the expression of CD40, CD80, MHC-II and activation marker CD200R on basophils, blocked DQ-ovalbumin uptake and promoted basophil apoptosis both in vitro and in vivo, leading to the inhibition of T helper type 2 polarization. These effects of HO-1 were mimicked by exogenous carbon monoxide, which is one of the catalytic products of HO-1. Furthermore, adoptive transfer of HO-1-modified basophils reduced ovalbumin-induced allergic airway inflammation. The above effects of HO-1 can be reversed by the HO-1 inhibitor Sn-protoporphyrin IX. Moreover, conditional depletion of basophils accompanying hemin treatment further attenuated airway inflammation compared with the hemin group, indicating that the protective role of HO-1 may involve multiple immune cells. Collectively, our findings demonstrated that HO-1 exerted its anti-inflammatory function through suppression of basophil maturation and activation, but promotion of basophil apoptosis, providing a possible novel therapeutic target in allergic asthma.

  14. [Allergic bronchopulmonary aspergillosis].

    PubMed

    Fernández de Córdova-Aguirre, Juan Carlos; Velasco-Medina, Andrea Aída; Cariño-Cartagena, Diego Antonio; Velázquez-Sámano, Guillermo

    2014-01-01

    Allergic bronchopulmonary aspergillosis is a slowly progressive disease, caused by the fungus Aspergillus fumigatus hypersensitivity when it is found in the airway. It usually affects asthmatics and patients with cystic fibrosis. We report the case of a 20-year-old male patient, student, farmer and rancher with chronic respiratory disease. The diagnosis of allergic bronchopulmonary aspergillosis was made on the basis of the clinical symptoms and complementary studies.

  15. Inhibitory effects of l-theanine on airway inflammation in ovalbumin-induced allergic asthma.

    PubMed

    Hwang, Yong Pil; Jin, Sun Woo; Choi, Jae Ho; Choi, Chul Yung; Kim, Hyung Gyun; Kim, Se Jong; Kim, Yongan; Lee, Kyung Jin; Chung, Young Chul; Jeong, Hye Gwang

    2017-01-01

    l-theanine, a water-soluble amino acid isolated from green tea (Camellia sinensis), has anti-inflammatory activity, antioxidative properties, and hepatoprotective effects. However, the anti-allergic effect of l-theanine and its underlying molecular mechanisms have not been elucidated. In this study, we investigated the protective effects of l-theanine on asthmatic responses, particularly airway inflammation and oxidative stress modulation in an ovalbumin (OVA)-induced murine model of asthma. Treatment with l-theanine dramatically attenuated the extensive trafficking of inflammatory cells into bronchoalveolar lavage fluid (BALF). Histological studies revealed that l-theanine significantly inhibited OVA-induced mucus production and inflammatory cell infiltration in the respiratory tract and blood vessels. l-theanine administration also significantly decreased the production of IgE, monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor-alpha (TNF-α), and interferon-gamma in BALF. The lung weight decreased with l-theanine administration. l-theanine also markedly attenuated the OVA-induced generation of reactive oxygen species and the activation of nuclear factor kappa B (NF-κB) and matrix metalloprotease-9 in BALF. Moreover, l-theanine reduced the TNF-α-induced NF-κB activation in A549 cells. Together, these results suggest that l-theanine alleviates airway inflammation in asthma, which likely occurs via the oxidative stress-responsive NF-κB pathway, highlighting its potential as a useful therapeutic agent for asthma management.

  16. [Serum and secretory immunoglobulins in allergic diseases].

    PubMed

    Atovmian, O I; German, G P; Chernokhvostova, E V

    1985-07-01

    A total of 158 patients with pollinosis, bronchial asthma, urticaria and Quincke's edema were examined. The immunoglobulin and C3 levels in sera and the immunoglobulin and albumin levels in saliva were determined by the method of single radial immunodiffusion with the corresponding monospecific antisera. In all the groups of patients subjected to examination the presence of polyclonal hypergammaglobulinemia was detected, which was manifested by a rise in the levels of IgG, IgA and especially IgM; the level of IgD was low. A decrease in the level of C3 was detected in pollinosis patients in the absence of the exacerbation of the disease. No circulating immune complexes were detected. An essential increase in the level of IgG in saliva was revealed, which was due to the local synthesis of this immunoglobulin. In winter the level of salivary IgA in pollinosis patients was found to be essentially below normal, but at the period of exacerbation it increased twofold, probably in response to local stimulation with antigen-allergen. Patients with bronchial asthma and pollinosis were found to have a high level of free secretory component (SC); in pollinosis the level of free SC sharply increased during the stage of exacerbation, which was due to the increase of its synthesis and secretion by the epithelial cells of the mucous membranes. The importance of these data for the pathogenesis of allergic diseases are discussed.

  17. Phenotypic comparison of allergic airway responses to house dust mite in three rat strains.

    PubMed

    Singh, Pramila; Daniels, Mary; Winsett, Darrell W; Richards, Judy; Doerfler, Donald; Hatch, Gary; Adler, Kenneth B; Gilmour, M Ian

    2003-04-01

    Brown Norway (BN) rats develop a robust response to antigens in the lung, characterized by a large increase in allergen-specific immune function and pulmonary eosinophilia. The objective of this study was to investigate alternative models by determining whether other rat strains could be sensitized to house dust mite (HDM) antigen and whether the allergic disease process could be worsened with repeated allergen exposure. In general, BN rats sensitized by either subcutaneous or intratracheal routes exhibited increased pulmonary allergy compared with Sprague-Dawley (SD) and Lewis (L) rats. Multiple intratracheal allergen exposures incrementally increased HDM-specific immune function in BN rats but progressively decreased eosinophil recruitment and markers of lung injury. SD rats had more moderate responses, whereas L rats were relatively unresponsive. Because BN rats developed stronger clinical hallmarks of allergic asthma under various immunization regimes compared with SD and L rats, we conclude that the BN is the most appropriate strain for studying allergic asthma-like responses in rats. Phenotypic differences in response to HDM were associated with differences in the Th1/Th2 cytokine balance and antioxidant capacity.

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

    PubMed

    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.

  19. Mucoactive agents for airway mucus hypersecretory diseases.

    PubMed

    Rogers, Duncan F

    2007-09-01

    Airway mucus hypersecretion is a feature of a number of severe respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). However, each disease has a different airway inflammatory response, with consequent, and presumably linked, mucus hypersecretory phenotype. Thus, it is possible that optimal treatment of the mucus hypersecretory element of each disease should be disease-specific. Nevertheless, mucoactive drugs are a longstanding and popular therapeutic option, and numerous compounds (eg, N-acetylcysteine, erdosteine, and ambroxol) are available for clinical use worldwide. However, rational recommendation of these drugs in guidelines for management of asthma, COPD, or CF has been hampered by lack of information from well-designed clinical trials. In addition, the mechanism of action of most of these drugs is unknown. Consequently, although it is possible to categorize them according to putative mechanisms of action, as expectorants (aid and/or induce cough), mucolytics (thin mucus), mucokinetics (facilitate cough transportability), and mucoregulators (suppress mechanisms underlying chronic mucus hypersecretion, such as glucocorticosteroids), it is likely that any beneficial effects are due to activities other than, or in addition to, effects on mucus. It is also noteworthy that the mucus factors that favor mucociliary transport (eg, thin mucus gel layer, "ideal" sol depth, and elasticity greater than viscosity) are opposite to those that favor cough effectiveness (thick mucus layer, excessive sol height, and viscosity greater than elasticity), which indicates that different mucoactive drugs would be required for treatment of mucus obstruction in proximal versus distal airways, or in patients with an impaired cough reflex. With the exception of mucoregulatory agents, whose primary action is unlikely to be directed against mucus, well-designed clinical trials are required to unequivocally determine the

  20. Dectin-2 promotes house dust mite-induced T helper type 2 and type 17 cell differentiation and allergic airway inflammation in mice.

    PubMed

    Norimoto, Ayako; Hirose, Koichi; Iwata, Arifumi; Tamachi, Tomohiro; Yokota, Masaya; Takahashi, Kentaro; Saijo, Shinobu; Iwakura, Yoichiro; Nakajima, Hiroshi

    2014-08-01

    The fact that sensitization against fungi is closely related to the severity of asthma suggests that immune systems recognizing fungi are involved in the pathogenesis of severe asthma. Recently, Dectin-2 (gene symbol, Clec4n), a C-type lectin receptor, has been shown to function as not only a major pattern-recognition receptor for fungi, but also a receptor for some components of house dust mite (HDM) extract, a major allergen for asthma. However, the roles of Dectin-2 in the induction of HDM-induced allergic airway inflammation remain largely unknown. Our objective was to determine the roles of Dectin-2 in HDM-induced allergic airway inflammation. We examined the roles of Dectin-2 in the induction of HDM-induced T helper (Th) 2 and Th17 cell differentiation and subsequent allergic airway inflammation by using Clec4n-deficient (Clec4n(-/-)) mice. We also investigated Dectin-2-expressing cells in the lung and their roles in HDM-induced allergic airway inflammation. Clec4n(-/-) mice showed significantly attenuated HDM-induced allergic airway inflammation and decreased Th2 and Th17 cell differentiation. Dectin-2 mRNA, together with Dectin-3 and Fc receptor-γ mRNAs, was expressed in CD11b(+) dendritic cells (DCs), but not in CD4(+) T cells or epithelial cells in the lung. CD11b(+) DCs isolated from Clec4n(-/-) mice expressed lower amounts of proinflammatory cytokines and costimulatory molecules, which could lead to Th2 and Th17 cell differentiation than those from wild-type mice. HDM-pulsed Clec4n(-/-) DCs were less efficient for the induction of allergic airway inflammation than HDM-pulsed wild-type DCs. In conclusion, Dectin-2 expressed on CD11b(+) DCs promotes HDM-induced Th2 and Th17 cell differentiation and allergic airway inflammation.

  1. Insights into Group 2 Innate Lymphoid Cells in Human Airway Disease.

    PubMed

    Karta, Maya R; Broide, David H; Doherty, Taylor A

    2016-01-01

    Recent discoveries have led to the identification of a novel group of immune cells, the innate lymphoid cells (ILCs). The members of this group are divided into three subpopulations: ILC1s, ILC2s, and ILC3s. ILC2s produce Th2 cytokines, IL-4, IL-5, and IL-13, upon activation by epithelial cell-derived cytokines, lipid mediators (cysteinyl leukotrienes and prostaglandin D2), and TNF family member TL1A and promote structural and immune cell responses in the airways after antigen exposure. In addition, ILC2 function is also influenced by inducible T cell costimulator (ICOS)/ICOS-ligand (ICOS-L) interactions via direct contact between immune cells. The most common airway antigens are allergens and viruses which are highly linked to the induction of airway diseases with underlying type 2 inflammation including asthma and allergic rhinitis. Based on recent findings linking ILC2s and airway Th2 responses, there is intensive investigation into the role of ILC2s in human disease with the hope of a better understanding of the pathophysiology and the discovery of novel potential therapeutic targets. This review summarizes the recent advances made in elucidating ILC2 involvement in human Th2 airway disease.

  2. Dietary polyphenols in the prevention and treatment of allergic diseases.

    PubMed

    Singh, A; Holvoet, S; Mercenier, A

    2011-10-01

    Allergic disorders encompass skin, food and respiratory allergies. Sensitization to a normally harmless allergen results in the immune system being biased to a predominant T-helper type 2 response. Re-exposure to the same allergen leads to a robust secretion of allergy-related mediators that eventually triggers symptoms. Our understanding of these disorders has enabled the search of therapeutic approaches that can either modulate the sensitization process or impact on allergic mediators, thus helping manage allergic symptoms. Polyphenols are one such class of compounds that are found in foods and plant sources and have been investigated for their anti-allergic effect in different disease models and in human clinical trials. Their anti-inflammatory profile is known to impact on the recruitment of immune cells to the skin and in preventing the development of secondary infections following disruption of the skin barrier. The interaction of polyphenols with proteins can modulate the process of allergic sensitization and their direct effect on allergic effector cells such as mast cells inhibit mediator release, resulting in the alleviation of symptoms. In addition, their endogenous anti-oxidant ability limits the extent of cellular injury from free radicals during the allergic insult. Overall, polyphenols hold promise as anti-allergy agents capable of influencing multiple biological pathways and immune cell functions in the allergic immune response and deserve further investigation. The objective of the current review is to summarize the key findings and progress made in studying polyphenols as anti-allergic ingredients. Special emphasis is placed in this review to highlight key physiological, cellular and signalling pathways implicated in the mechanism of action of different polyphenols in the context of allergic disorders and their manifestations.

  3. Host-microbe interactions in distal airways: relevance to chronic airway diseases.

    PubMed

    Martin, Clémence; Burgel, Pierre-Régis; Lepage, Patricia; Andréjak, Claire; de Blic, Jacques; Bourdin, Arnaud; Brouard, Jacques; Chanez, Pascal; Dalphin, Jean-Charles; Deslée, Gaetan; Deschildre, Antoine; Gosset, Philippe; Touqui, Lhousseine; Dusser, Daniel

    2015-03-01

    This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host-microbe (mostly bacteria and viruses) interactions in healthy and diseased airways, with a special focus on distal airways.

  4. Effects of ex vivo Gamma-Tocopherol on Airway Macrophage Function in Healthy and Mild Allergic Asthmatics

    PubMed Central

    Geiser, Marianne; Lay, John C.; Bennett, William D.; Zhou, Haibo; Wang, Xiaoyan; Peden, David B.; Alexis, Neil E.

    2013-01-01

    Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate gamma-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 non-smoking healthy (n = 6) and mild house dust mite-sensitive (HDM) allergic asthmatics (n = 6) were treated ex vivo with GT (300 μM) or saline (control). Phagocytosis of opsonized Zymosan A bioparticles (S. cerevisiae) and expression of surface molecules associated with innate and adaptive immunity were assessed using flow cytometry. GT caused significantly decreased (P < 0.05) internalization of attached Zymosan bioparticles and decreased (P < 0.05) macrophage expression of CD206, CD36 and CD86 in allergic asthmatics but not in controls. Overall, GT caused down-regulation of both innate and adaptive immune response elements and atopic status appears to be an important factor. PMID:23689260

  5. Adoptive transfer of dendritic cells isolated from helminth-infected mice enhanced T regulatory cell responses in airway allergic inflammation.

    PubMed

    Liu, J-Y; Li, L-Y; Yang, X-Z; Li, J; Zhong, G; Wang, J; Li, L-J; Ji, B; Wu, Z-Q; Liu, H; Yang, X; Liu, P-M

    2011-10-01

    Our and others' previous studies have shown that Schistosoma japonicum (SJ) infection can inhibit allergic reactions. Moreover, we found that adoptive transfer of dendritic cells (DCs) from inhibited mice showed a similar inhibitory effect on allergy, suggesting a critical role of DCs in SJ-infected mediated inhibition of allergy. In this study, we further examined the mechanism by which DCs contribute to inhibition of allergy. Our results showed that DCs from SJ-infected mice (SJDCs) produced significantly higher levels of IL-10 compared to those from naive control mice (NDCs). Adoptive transfer of SJDCs, unlike NDCs, significantly increased CD4+CD25+Foxp3+ T cells and CD4+CD25+IL-10+ T cells regulatory T-cell responses in vivo. This was correlated with significantly reduced production of IL-4 and IL-5 by CD4+ T cells, eotaxin in lung tissues and reduced airway allergic inflammation in the SJDC recipients following allergen sensitization and challenge. These data suggest that helminth infection may induce tolerogenic DCs that can inhibit the development of airway allergic inflammation through enhancing T regulatory cell responses.

  6. Beta-adrenergic receptors of lymphocytes in children with allergic respiratory diseases

    SciTech Connect

    Bittera, I.; Gyurkovits, K.; Falkay, G.; Eck, E.; Koltai, M.

    1988-01-01

    The beta-adrenergic receptor binding sites on peripheral lymphocytes in children with bronchial asthma (n = 16) and seasonal allergic rhinitis (n = 8) were examined in comparison with normal controls (n = 18) by means of /sup 124/I-cyanopindolol. The number of beta-adrenergic receptors was significantly lower in the asthmatic group (858 +/- 460/lymphocyte) than in the controls (1564 +/- 983/lymphocyte). The value (1891 +/- 1502/lymphocyte in children with allergic rhinitis was slightly higher than that in healthy controls. Of the 24 patients suffering from allergic diseases of the lower or upper airways, the bronchial histamine provocation test was performed in 21; 16 gave positive results, while 5 were negative. No difference in beta-adrenergic receptor count was found between the histamine-positive and negative patients. Neither was there any correlation between the number of beta-adrenergic receptors and the high (16/24) and low (8/24) serum IgE concentrations found in allergic patients. The significant decrease in beta-adrenergic receptor count in asthmatic children lends support to Szentivanyi's concept. Further qualitative and quantitative analysis of lymphocyte beta-adrenergic receptors may provide an individual approach to the treatment of bronchial asthma with beta-sympathomimetic drugs.

  7. The role of gut microbiota in the pathogenesis and management of allergic diseases.

    PubMed

    Compare, D; Nardone, G

    2013-01-01

    Allergy is defined as a hypersensitivity reaction due to specific antibody-mediated or cell-mediated immunologic mechanisms. Epidemiological studies are showing a dramatic increase of allergies in industrialized countries in the last few decades, while remaining stable in developing countries. In 1989 Strachan, hypothesized that the increase in allergic disorders was the result of a lack of infections in early infancy, and in 1998 Wold suggested that, rather than a decrease in viral or bacterial infections, an altered normal intestinal colonization pattern in infancy, could be responsible for the increase in allergies. Germ-free mice were shown to mount an exaggerated allergic airway reaction compared with that seen in colonized mice, indicating the important role of microbe-host interactions in the development of allergic diseases. Infants with food allergies are found to exhibit an imbalance between "beneficial"and potentially harmful bacteria, i.e., decreased Lactobacilli, Bifidobacteria and Enterococcus species and increased coliforms, Staphylococcus aureus and Clostridium species, suggesting that microbial inhabitants of the human body, may play either a pathogenic or protective role in allergies. Based on this data, many clinical trial addressing the use of probiotics in the context of allergic disorders, have been conducted in children. However, currently, no conclusive item may be drawn.

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

    PubMed Central

    SHIRVAN, Sima PARANDE; BORJI, Hassan; MOVASSAGHI, Ahmadreza; KHAKZAD, Mohammadreza; FARZIN, Hamidreza; MALEKI, Mohsen; HAGHPARAST, Alireza

    2016-01-01

    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. PMID:28127363

  9. IL-33-mediated innate response and adaptive immune cells contribute to maximum responses of protease allergen-induced allergic airway inflammation.

    PubMed

    Kamijo, Seiji; Takeda, Haruna; Tokura, Tomoko; Suzuki, Mayu; Inui, Kyoko; Hara, Mutsuko; Matsuda, Hironori; Matsuda, Akira; Oboki, Keisuke; Ohno, Tatsukuni; Saito, Hirohisa; Nakae, Susumu; Sudo, Katsuko; Suto, Hajime; Ichikawa, Saori; Ogawa, Hideoki; Okumura, Ko; Takai, Toshiro

    2013-05-01

    How the innate and adaptive immune systems cooperate in the natural history of allergic diseases has been largely unknown. Plant-derived allergen, papain, and mite allergens, Der f 1 and Der p 1, belong to the same family of cysteine proteases. We examined the role of protease allergens in the induction of Ab production and airway inflammation after repeated intranasal administration without adjuvants and that in basophil/mast cell stimulation in vitro. Papain induced papain-specific IgE/IgG1 and lung eosinophilia. Der f 1 induced Der f 1-specific IgG1 and eosinophilia. Although papain-, Der f 1-, and Der p 1-stimulated basophils expressed allergy-inducing cytokines, including IL-4 in vitro, basophil-depleting Ab and mast cell deficiency did not suppress the papain-induced in vivo responses. Protease inhibitor-treated allergens and a catalytic site mutant did not induce the responses. These results indicate that protease activity is essential to Ab production and eosinophilia in vivo and basophil activation in vitro. IL-33-deficient mice lacked eosinophilia and had reduced papain-specific IgE/IgG1. Coadministration of OVA with papain induced OVA-specific IgE/IgG1, which was reduced in IL-33-deficient mice. We demonstrated IL-33 release, subsequent IL-33-dependent IL-5/IL-13 release, and activation of T1/ST2-expressing lineage(-)CD25(+)CD44(+) innate lymphoid cells in the lung after papain inhalation, suggesting the contribution of the IL-33-type 2 innate lymphoid cell-IL-5/IL-13 axis to the papain-induced airway eosinophilia. Rag2-deficient mice, which lack adaptive immune cells, showed significant, but less severe, eosinophilia. Collectively, these results suggest cooperation of adaptive immune cells and IL-33-responsive innate cells in protease-dependent allergic airway inflammation.

  10. Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation

    PubMed Central

    Elhaik Goldman, Shirin; Moshkovits, Itay; Shemesh, Avishai; Filiba, Ayelet; Tsirulsky, Yevgeny; Vronov, Elena; Shagan, Marilou; Apte, Ron N.; Benharroch, D aniel; Karo-Atar, Danielle; Dagan, Ron; Munitz, Ariel

    2016-01-01

    The function of NCR1 was studied in a model of experimental asthma, classified as a type 1 hypersensitivity reaction, in mice. IgE levels were significantly increased in the serum of OVA immunized NCR1 deficient (NCR1gfp/gfp) mice in comparison to OVA immunized wild type (NCR1+/+) and adjuvant immunized mice. Histological analysis of OVA immunized NCR1gfp/gfp mice revealed no preservation of the lung structure and overwhelming peribronchial and perivascular granulocytes together with mononuclear cells infiltration. OVA immunized NCR+/+ mice demonstrated preserved lung structure and peribronchial and perivascular immune cell infiltration to a lower extent than that in NCR1gfp/gfp mice. Adjuvant immunized mice demonstrated lung structure preservation and no immune cell infiltration. OVA immunization caused an increase in PAS production independently of NCR1 presence. Bronchoalveolar lavage (BAL) revealed NCR1 dependent decreased percentages of eosinophils and increased percentages of lymphocytes and macrophages following OVA immunization. In the OVA immunized NCR1gfp/gfp mice the protein levels of eosinophils’ (CCL24) and Th2 CD4+ T-cells’ chemoattractants (CCL17, and CCL24) in the BAL are increased in comparison with OVA immunized NCR+/+ mice. In the presence of NCR1, OVA immunization caused an increase in NK cells numbers and decreased NCR1 ligand expression on CD11c+GR1+ cells and decreased NCR1 mRNA expression in the BAL. OVA immunization resulted in significantly increased IL-13, IL-4 and CCL17 mRNA expression in NCR1+/+ and NCR1gfp/gfp mice. IL-17 and TNFα expression increased only in OVA-immunized NCR1+/+mice. IL-6 mRNA increased only in OVA immunized NCR1gfp/gfp mice. Collectively, it is demonstrated that NCR1 dampens allergic eosinophilic airway inflammation. PMID:27580126

  11. Key Mediators in the Immunopathogenesis of Allergic Asthma

    PubMed Central

    Hall, Sannette; Agrawal, Devendra K.

    2014-01-01

    Asthma is described as a chronic inflammatory disorder of the conducting airways. It is characterized by reversible airway obstruction, eosinophil and Th2 infiltration, airway hyper-responsiveness and airway remodeling. Our findings to date have largely been dependent on work done using animal models, which have been instrumental in broadening our understanding of the mechanism of the disease. However, using animals to model a uniquely human disease is not without its drawbacks. This review aims to examine some of the key mediators and cells of allergic asthma learned from animal models and shed some light on emerging mediators in the pathogenesis allergic airway inflammation in acute and chronic asthma. PMID:24933589

  12. [Prevention of asthma and allergic diseases in children].

    PubMed

    Rancé, F; de Blic, J; Scheinmann, P

    2003-03-01

    Allergic diseases have become a major public health problem in industrialized countries, justifying the development of prevention programs. A review of the literature on allergens and atopic symptoms, age of primary sensitization and other factors associated with allergic diseases development is presented and is followed by a discussion on prevention measures. The most recent physiopathological and immunological data indicate that persistent asthma and allergic diseases in adults may be associated with events in early childhood. The parallel increase in autoimmune and allergic diseases has been correlated with regulatory mechanism defects, contradicting the previous theory that involved a predominantly Th1 or Th2 pathway. The primary prevention of asthma and allergic diseases thus appear to be somewhat utopian. Indeed based on recent results, the risk of developing allergies appears to be related to modern "clean" lyfestyles. Secondary prevention is probably necessary, possibly through specific immunotherapy. Tertiary prevention must also be considered. Passive smoking must be prevented as it can alter the development of the respiratory system and promote allergen sensitization. Randomized, controlled, prospective studies are needed to evaluate the efficacy of the preventive measures.

  13. Vitamin D in Atopic Dermatitis, Asthma and Allergic Diseases

    PubMed Central

    Searing, Daniel A; Leung, Donald YM

    2010-01-01

    Synopsis This review examines the scientific evidence behind the hypothesis that vitamin D plays a role in the pathogenesis of allergic diseases, with a particular focus on emerging data regarding vitamin D and atopic dermatitis. Both elucidated molecular interactions of vitamin D with components of the immune system, as well as clinical data regarding vitamin D deficiency and atopic diseases are discussed. The rationale behind the “sunshine hypothesis,” laboratory evidence supporting links between vitamin D deficiency and allergic diseases, the clinical evidence for/and against vitamin D playing a role in allergic diseases, and the emerging evidence regarding the potential use of vitamin D in augmentation of the innate immune response in atopic dermatitis are reviewed. PMID:20670821

  14. Routes of allergic sensitization and myeloid cell IKKβ differentially regulate antibody responses and allergic airway inflammation in male and female mice.

    PubMed

    Bonnegarde-Bernard, Astrid; Jee, Junbae; Fial, Michael J; Steiner, Haley; DiBartola, Stephanie; Davis, Ian C; Cormet-Boyaka, Estelle; Tomé, Daniel; Boyaka, Prosper N

    2014-01-01

    Gender influences the incidence and/or the severity of several diseases and evidence suggests a higher rate of allergy and asthma among women. Most experimental models of allergy use mice sensitized via the parenteral route despite the fact that the mucosal tissues of the gastrointestinal and respiratory tracts are major sites of allergic sensitization and/or allergic responses. We analyzed allergen-specific Ab responses in mice sensitized either by gavage or intraperitoneal injection of ovalbumin together with cholera toxin as adjuvant, as well as allergic inflammation and lung functions following subsequent nasal challenge with the allergen. Female mice sensitized intraperitoneally exhibited higher levels of serum IgE than their male counterparts. After nasal allergen challenge, these female mice expressed higher Th2 responses and associated inflammation in the lung than males. On the other hand, male and female mice sensitized orally developed the same levels of allergen-specific Ab responses and similar levels of lung inflammation after allergen challenge. Interestingly, the difference in allergen-specific Ab responses between male and female mice sensitized by the intraperitoneal route was abolished in IKKβΔMye mice, which lack IKKβ in myeloid cells. In summary, the oral or systemic route of allergic sensitization and IKKβ signaling in myeloid cells regulate how the gender influences allergen-specific responses and lung allergic inflammation.

  15. Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA(2)LEN).

    PubMed

    Braido, F; Scichilone, N; Lavorini, F; Usmani, O S; Dubuske, L; Boulet, L P; Mosges, R; Nunes, C; Sanchez-Borges, M; Ansotegui, I J; Ebisawa, M; Levi-Schaffer, F; Rosenwasser, L J; Bousquet, J; Zuberbier, T; Canonica, G Walter; Cruz, A; Yanez, A; Yorgancioglu, A; Deleanu, D; Rodrigo, G; Berstein, J; Ohta, K; Vichyanond, P; Pawankar, R; Gonzalez-Diaz, S N; Nakajima, S; Slavyanskaya, T; Fink-Wagner, A; Loyola, C Baez; Ryan, D; Passalacqua, G; Celedon, J; Ivancevich, J C; Dobashi, K; Zernotti, M; Akdis, M; Benjaponpitak, S; Bonini, S; Burks, W; Caraballo, L; El-Sayed, Z Awad; Fineman, S; Greenberger, P; Hossny, E; Ortega-Martell, J A; Saito, H; Tang, M; Zhang, L

    2016-01-01

    Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA(2)LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 μm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect

  16. Absence of Toll-IL-1 receptor 8/single immunoglobulin IL-1 receptor-related molecule reduces house dust mite-induced allergic airway inflammation in mice.

    PubMed

    Barry, Jessica; Loh, Zhixuan; Collison, Adam; Mazzone, Stuart; Lalwani, Amit; Zhang, Vivian; Davidson, Sophia; Wybacz, Elisha; Garlanda, Cecilia; Mantovani, Alberto; Mattes, Joerg; Foster, Paul S; Phipps, Simon

    2013-09-01

    Allergic asthma is a chronic inflammatory disease predominately associated with the activation of CD4(+) T helper Type 2 (Th2) cells. Innate pattern recognition receptors are widely acknowledged to shape the adaptive immune response. For example, the activation of airway epithelial Toll-like receptor-4 (TLR4) is necessary for the generation of house dust mite (HDM)-specific Th2 responses and the development of asthma in mice. Here we sought to determine whether the absence of Toll-interleukin-1 receptor (TIR)-8, a negative regulator of TLR4 signaling that is highly expressed in airway epithelial cells, would exacerbate HDM-induced asthma in a murine model. We found that Th2 but not Th1 or Th17 cytokine expression was significantly reduced in the lung and draining lymph nodes in HDM-sensitized/challenged TIR8 gene-deleted mice. Mucus-producing goblet cells, HDM-specific IgG1, and airway hyperreactivity were also significantly reduced in HDM-exposed, TIR8-deficient mice. Consistent with the attenuated Th2 response, eotaxin-2/CCL24 expression and airway and peribronchial eosinophils were significantly reduced in the absence of TIR8. In contrast, IL-17A-responsive chemokines and neutrophil numbers were unaffected. Similar findings were obtained for cockroach allergen. HDM sensitization alone up-regulated the expression of IL-1F5, a putative TIR8 ligand and inducer of IL-4. Of note, innate IL-4, IL-5, IL-13, and IL-33 cytokine expression was reduced during HDM sensitization in the absence of TIR8, as was the recruitment of conventional dendritic cells and basophils to the draining lymph nodes. Our findings suggest that TIR8 enhances the development of HDM-induced innate and adaptive Th2, but not Th1 or Th17 type immunity.

  17. Type 2 innate lymphoid cells: friends or foes-role in airway allergic inflammation and asthma.

    PubMed

    Pishdadian, Abbas; Varasteh, Abdol-Reza; Sankian, Mojtaba

    2012-01-01

    Innate-like lymphocytes (ILLs) and innate lymphoid cells (ILCs) are two newly characterized families of lymphocytes with limited and no rearranged antigen receptors, respectively. These soldiers provide a first line of defense against foreign insults by triggering a prompt innate immune response and bridging the gap of innate and adaptive immunity. Type 2 innate lymphoid cells (ILCs2) are newly identified members of the ILC family that play a key role in type 2 immune responses by prompt production of type 2 cytokines (especially IL-5 and IL-13) in response to antigen-induced IL-25/33 and by recruiting type 2 "immune franchise." Regarding the two different roles of type 2 cytokines, helminth expulsion and type 2-related diseases, here we review the latest advances in ILC2 biology and examine the pivotal role of resident ILCs2 in allergen-specific airway inflammation and asthma.

  18. Mast cells in airway diseases and interstitial lung disease.

    PubMed

    Cruse, Glenn; Bradding, Peter

    2016-05-05

    Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease.

  19. Increase risk of allergic diseases in patients with ankylosing spondylitis

    PubMed Central

    Chang, Wei-Pin; Kuo, Chun-Nan; Kuo, Li-Na; Wang, Yao-Tung; Perng, Wuu-Tsun; Kuo, Ho-Chang; Wei, James Cheng-Chung

    2016-01-01

    Abstract Th2 and Th17 cells are both associated with developing ankylosing spondylitis (AS) and asthma. Th2 cells are also associated with allergic rhinitis and atopic dermatitis (AD). The prevalence of such allergic diseases in AS patients is unknown. In this study, we intended to study the risk of allergic diseases in a 10-year follow-up population of newly diagnosed patients with AS. We used a nationwide 10-year population-based database retrieved from the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan. The study cohort comprised 857 patients with AS who had at least 1 claim of inpatient admission or at least 2 claims of ambulatory visit. The comparison cohort consisted of 4285 randomly selected subjects matched with AS group at a ratio of 5:1. We used Cox proportional-hazards regression to determine the 10-year disease-free survival rates after adjusting for potentially confounding factors. The AS patients had a 1.31 times greater risk of developing asthma within 10 years of diagnosis when compared with non-AS age- and sex-matched subjects, after adjusting for other risk factors (95% confidence interval = 1.00–1.75). But the difference was not significantly different. The AS patients also had a 1.46 times and a 1.22 times greater risk of developing allergic rhinitis and AD significantly. AS patients also had a lower allergic disease-free survival rate compared to non-AS group. Our results showed that patients with AS had a higher risk of developing allergic diseases later in life. PMID:27828843

  20. Proteinase activated receptor-2-mediated dual oxidase-2 up-regulation is involved in enhanced airway reactivity and inflammation in a mouse model of allergic asthma.

    PubMed

    Nadeem, Ahmed; Alharbi, Naif O; Vliagoftis, Harissios; Tyagi, Manoj; Ahmad, Sheikh F; Sayed-Ahmed, Mohamed M

    2015-07-01

    Airway epithelial cells (AECs) express a variety of receptors, which sense danger signals from various aeroallergens/pathogens being inhaled constantly. Proteinase-activated receptor 2 (PAR-2) is one such receptor and is activated by cockroach allergens, which have intrinsic serine proteinase activity. Recently, dual oxidases (DUOX), especially DUOX-2, have been shown to be involved in airway inflammation in response to Toll-like receptor activation. However, the association between PAR-2 and DUOX-2 has not been explored in airways of allergic mice. Therefore, this study investigated the contribution of DUOX-2/reactive oxygen species (ROS) signalling in airway reactivity and inflammation after PAR-2 activation. Mice were sensitized intraperitoneally with intact cockroach allergen extract (CE) in the presence of aluminium hydroxide followed by intranasal challenge with CE. Mice were then assessed for airway reactivity, inflammation, oxidative stress (DUOX-2, ROS, inducible nitric oxide synthase, nitrite, nitrotyrosine and protein carbonyls) and apoptosis (Bax, Bcl-2, caspase-3). Challenge with CE led to up-regulation of DUOX-2 and ROS in AECs with concomitant increases in airway reactivity/inflammation and parameters of oxidative stress, and apoptosis. All of these changes were significantly inhibited by intranasal administration of ENMD-1068, a small molecule antagonist of PAR-2 in allergic mice. Administration of diphenyliodonium to allergic mice also led to improvement of allergic airway responses via inhibition of the DUOX-2/ROS pathway; however, these effects were less pronounced than PAR-2 antagonism. The current study suggests that PAR-2 activation leads to up-regulation of the DUOX-2/ROS pathway in AECs, which is involved in regulation of airway reactivity and inflammation via oxidative stress and apoptosis.

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

    PubMed

    Hung, Chien-Ya; Huang, Fu-Long; Shi, Li-Shian; Ka, Shuk-Man; Wang, Jing-Yao; Tsai, Yu-Cheng; Hung, Tsung-Jen; Ye, Yi-Ling

    2013-01-01

    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.

  2. Unproven diagnostic procedures in IgE-mediated allergic diseases.

    PubMed

    Niggemann, B; Grüber, C

    2004-08-01

    A considerable body of literature on therapeutic aspects of complementary and alternative medicine has been published in recent years, but little is known on diagnostic procedures. This short review lists complementary and alternative diagnostic procedures for the diagnosis of allergic diseases and presents an assessment of their usefulness for the daily practice. The review of the literature revealed that neither the determination of specific immunoglobulin G-antibodies in serum, the hair-analysis, the cytotoxic test, kinesiology, iridology, or electrodermal testing represent useful tests for the daily practice. To date, no complementary or alternative diagnostic procedure can be recommended as a meaningful element in the diagnostic work-up of allergic diseases. This is especially true for food allergy: properly performed oral food challenges still represent the gold standard for implementing specific diets in food allergic individuals. Ineffective diagnostic approaches may be costly for the consumer and delay appropriate therapy.

  3. Indoor allergens, environmental avoidance, and allergic respiratory disease.

    PubMed

    Bush, Robert K

    2008-01-01

    Indoor allergen exposure to sources such as house-dust mites, pets, fungi, and insects plays a significant role in patients with allergic rhinitis and asthma. The identification of the major allergens has led to methods that can quantitate exposure, e.g., immunoassays for Der p 1 in settled dust samples. Sensitization and the development of allergic respiratory disease result from complex genetic and environmental interactions. New paradigms that examine the role of other environmental factors, including exposure to proteases that can activate eosinophils and initiate Th2 responses, and epigenetics, are being explored. Recommendations for specific environmental allergen avoidance measures are discussed for house-dust mites, cockroaches, animal dander, and fungi. Specific measures to reduce indoor allergen exposure when vigorously applied may reduce the risk of sensitization and symptoms of allergic respiratory disease, although further research will be necessary to establish cost-effective approaches.

  4. Has the airway microbiome been overlooked in respiratory disease?

    PubMed

    Salami, Olawale; Marsland, Benjamin J

    2015-01-01

    The respiratory disease field is changing because of recent advances in our understanding of the airway microbiome. Central to this is dysbiosis, an imbalance of microbial communities that can lead to and flag inflammation in the airways. The increasing momentum of research in this area holds promise for novel treatment strategies.

  5. Impact of a Met(11)Thr single nucleotide polymorphism of surfactant protein D on allergic airway inflammation in a murine asthma model.

    PubMed

    Winkler, Carla; Bahlmann, Olaf; Viereck, Janika; Knudsen, Lars; Wedekind, Dirk; Hoymann, Heinz Gerd; Madsen, Jens; Thum, Thomas; Hohlfeld, Jens M; Ochs, Matthias

    2014-04-01

    The surfactant-associated proteins SP-A and D are pattern recognition molecules with collectin structure. A single nucleotide polymorphism (SNP) exchanging a methionine (Met) for a threonine (Thr) in the amino-terminal SP-D domain influences the oligomeric structure and function of the protein. In this study, we investigated the susceptibility of mice transgenic for the human SP-D Met(11)Thr SNP to allergic airway inflammation and consequences for microRNA (miRNA, miR) expression. Mice expressing either human Met or Thr SP-D were sensitized and challenged with ovalbumin (OVA) in an acute model of allergic asthma. The influence of the SP-D polymorphism on the allergic airway inflammation was evaluated by lung function measurement, pulmonary inflammation parameters, morphological analysis and miRNA expression. Airway hyperresponsiveness, allergic inflammation, and mucus metaplasia were not significantly different between mice expressing one or the other allelic variant of SP-D. OVA sensitization and challenge led to significant airway hyperresponsiveness in wildtype mice and significantly lower eosinophil numbers and interleukin 5 levels in Thr SP-D mice. OVA challenge induced an upregulation of miR-21 and 155 in Thr SP-D mice and a downregulation of miR-21 in Met SP-D mice. Our results show that murine expression of human polymorphic SP-D variants does not significantly influence the severity of allergic airway inflammation. MiR-21 and 155 are differentially regulated in transgenic mice in response to allergic inflammation. Further studies are required to elucidate the impact of this SNP on inflammatory conditions of the lung.

  6. Allergic diseases: the price of civilisational progress

    PubMed Central

    Sowa, Paweł; Rutkowska-Talipska, Joanna; Sulkowski, Stanisław; Rutkowski, Ryszard

    2014-01-01

    Atopic disorders are a major global health problem. The prevalence of asthma, allergic rhinitis and atopic dermatitis has been increasing over the last four decades, both in the industrialized and developing countries. It seems to be related to changes in the social structure, increasing industrialization, pollution and dietary changes. Many hypotheses link the allergy epidemic to stringent hygiene, dominance of a westernized lifestyle and an accelerated pace of life. Dietary antioxidants, lipids, sodium, vitamin D seem also to be implicated. We endeavour to review the most relevant theories with a special emphasis on the hygiene, antioxidative, lipid and air pollution hypotheses. It is however important to note that none of them explains all the aspects of unprecedented rise in the prevalence of allergic disorders. A complex interplay between host's immune response, invading pathogens, diversity of environmental factors and genetic background seems to be of a particular importance. Current allergy epidemic is multifactorial and basic and epidemiologic studies are warranted to further our understanding of this phenomenon. PMID:25097472

  7. SUBCHRONIC ENDOTOXIN INHALATION CAUSES PERSISTENT AIRWAY DISEASE

    EPA Science Inventory

    ABSTRACT

    The endotoxin component of organic dusts causes acute reversible airflow obstruction and airway inflammation. To test the hypothesis that endotoxin alone causes airway remodeling, we have compared the response of two inbred mouse strains to subchronic endotoxin ...

  8. Allergic diseases among children: nutritional prevention and intervention

    PubMed Central

    Hendaus, Mohamed A; Jomha, Fatima A; Ehlayel, Mohammad

    2016-01-01

    Allergic diseases comprise a genetically heterogeneous group of chronic, immunomediated diseases. It has been clearly reported that the prevalence of these diseases has been on the rise for the last few decades, but at different rates, in various areas of the world. This paper discusses the epidemiology of allergic diseases among children and their negative impact on affected patients, their families, and societies. These effects include the adverse effects on quality of life and economic costs. Medical interest has shifted from tertiary or secondary prevention to primary prevention of these chronic diseases among high-risk infants in early life. Being simple, practical, and cost-effective are mandatory features for any candidate methods delivering these strategies. Dietary therapy fits this model well, as it is simple, practical, and cost-effective, and involves diverse methods. The highest priority strategy is feeding these infants breast milk. For those who are not breast-fed, there should be a strategy to maintain beneficial gut flora that positively influences intestinal immunity. We review the current use of probiotics, prebiotics, and synbiotics, and safety and adverse effects. Other dietary modalities of possible potential in achieving this primary prevention, such as a Mediterranean diet, use of milk formula with modified (hydrolyzed) proteins, and the role of micronutrients, are also explored. Breast-feeding is effective in reducing the risk of asthma, allergic rhinitis, and atopic eczema among children. In addition, breast milk constitutes a major source of support for gut microbe colonization, due to its bifidobacteria and galactooligosaccharide content. The literature lacks consensus in recommending the addition of probiotics to foods for prevention and treatment of allergic diseases, while prebiotics may prove to be effective in reducing atopy in healthy children. There is insufficient evidence to support soy formulas or amino acid formulas for

  9. The ocular surface: from physiology to the ocular allergic diseases.

    PubMed

    Galicia-Carreón, Jorge; Santacruz, Concepción; Hong, Enrique; Jiménez-Martínez, María C

    2013-01-01

    Allergic conjunctivitis (AC) is an inflammation of the conjunctiva secondary to an immune response to exogenous antigens, usually called allergens. In fact, AC is a syndrome that involves the entire ocular surface, including conjunctiva, lids, cornea, and tear film. The signs and symptoms of AC have a meaningful effect on comfort and patient health, and could be influenced by environment, genetics and immune regulation mechanisms, all of which work together in a complex immunological homeostasis. Dysregulation in such immune responses could turn into a variety of ocular allergic diseases (OAD). This review describes some of the current understanding of cellular and molecular pathways involved in different OAD.

  10. Classification of pulmonary airway disease based on mucosal color analysis

    NASA Astrophysics Data System (ADS)

    Suter, Melissa; Reinhardt, Joseph M.; Riker, David; Ferguson, John Scott; McLennan, Geoffrey

    2005-04-01

    Airway mucosal color changes occur in response to the development of bronchial diseases including lung cancer, cystic fibrosis, chronic bronchitis, emphysema and asthma. These associated changes are often visualized using standard macro-optical bronchoscopy techniques. A limitation to this form of assessment is that the subtle changes that indicate early stages in disease development may often be missed as a result of this highly subjective assessment, especially in inexperienced bronchoscopists. Tri-chromatic CCD chip bronchoscopes allow for digital color analysis of the pulmonary airway mucosa. This form of analysis may facilitate a greater understanding of airway disease response. A 2-step image classification approach is employed: the first step is to distinguish between healthy and diseased bronchoscope images and the second is to classify the detected abnormal images into 1 of 4 possible disease categories. A database of airway mucosal color constructed from healthy human volunteers is used as a standard against which statistical comparisons are made from mucosa with known apparent airway abnormalities. This approach demonstrates great promise as an effective detection and diagnosis tool to highlight potentially abnormal airway mucosa identifying a region possibly suited to further analysis via airway forceps biopsy, or newly developed micro-optical biopsy strategies. Following the identification of abnormal airway images a neural network is used to distinguish between the different disease classes. We have shown that classification of potentially diseased airway mucosa is possible through comparative color analysis of digital bronchoscope images. The combination of the two strategies appears to increase the classification accuracy in addition to greatly decreasing the computational time.

  11. Microarray Technology Applied to Human Allergic Disease

    PubMed Central

    Hamilton, Robert G.

    2017-01-01

    IgE antibodies serve as the gatekeeper for the release of mediators from sensitized (IgE positive) mast cells and basophils following a relevant allergen exposure which can lead to an immediate-type hypersensitivity (allergic) reaction. Purified recombinant and native allergens were combined in the 1990s with state of the art chip technology to establish the first microarray-based IgE antibody assay. Triplicate spots to over 100 allergenic molecules are immobilized on an amine-activated glass slide to form a single panel multi-allergosorbent assay. Human antibodies, typically of the IgE and IgG isotypes, specific for one or many allergens bind to their respective allergen(s) on the chip. Following removal of unbound serum proteins, bound IgE antibody is detected with a fluorophore-labeled anti-human IgE reagent. The fluorescent profile from the completed slide provides a sensitization profile of an allergic patient which can identify IgE antibodies that bind to structurally similar (cross-reactive) allergen families versus molecules that are unique to a single allergen specificity. Despite its ability to rapidly analyze many IgE antibody specificities in a single simple assay format, the chip-based microarray remains less analytically sensitive and quantitative than its singleplex assay counterpart (ImmunoCAP, Immulite). Microgram per mL quantities of allergen-specific IgG antibody can also complete with nanogram per mL quantities of specific IgE for limited allergen binding sites on the chip. Microarray assays, while not used in clinical immunology laboratories for routine patient IgE antibody testing, will remain an excellent research tool for defining sensitization profiles of populations in epidemiological studies. PMID:28134842

  12. Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation

    PubMed Central

    2010-01-01

    Air pollutant exposure has been linked to a rise in wheezing illnesses. Clinical data highlight that exposure to mainstream tobacco smoke (MS) and environmental tobacco smoke (ETS) as well as exposure to diesel exhaust particles (DEP) could promote allergic sensitization or aggravate symptoms of asthma, suggesting a role for these inhaled pollutants in the pathogenesis of asthma. Mouse models are a valuable tool to study the potential effects of these pollutants in the pathogenesis of asthma, with the opportunity to investigate their impact during processes leading to sensitization, acute inflammation and chronic disease. Mice allow us to perform mechanistic studies and to evaluate the importance of specific cell types in asthma pathogenesis. In this review, the major clinical effects of tobacco smoke and diesel exhaust exposure regarding to asthma development and progression are described. Clinical data are compared with findings from murine models of asthma and inhalable pollutant exposure. Moreover, the potential mechanisms by which both pollutants could aggravate asthma are discussed. PMID:20092634

  13. RAPID COMMUNICATION IL-4 INDUCES IL-6 AND SIGNS OF ALLERGIC-TYPE INFLAMMATION IN THE NASAL AIRWAYS OF NONALLERGIC INDIVIDUALS

    EPA Science Inventory


    In addition to its more widely recognized role in promoting IgE synthesis, we speculate that interleukin-4 (IL-4) may modulate both allergic- and nonallergic-type inflammatory processes in the airway mucosa. We examined in vivo the effect of IL-4 on granulocyte and cytokine h...

  14. Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma

    PubMed Central

    Kim, Jin seok; Lee, Jae-Won; Park, Hyun Ah; Ryu, Hyung Won; Lee, Su Ui; Hwang, Kwang Woo; Yun, Won-Kee; Kim, Hyoung-Chin; Ahn, Kyung-Seop; Oh, Sei-Ryang

    2016-01-01

    Picroside II isolated from Pseudolysimachion rotundum var. subintegrum has been used as traditional medicine to treat inflammatory diseases. In this study, we assessed whether picroside II has inhibitory effects on airway inflammation in a mouse model of house dust mite (HDM)-induced asthma. In the HDM-induced asthmatic model, picroside II significantly reduced inflammatory cell counts in the bronchoalveolar lavage fluid (BALF), the levels of total immunoglobulin (Ig) E and HDM-specific IgE and IgG1 in serum, airway inflammation, and mucus hypersecretion in the lung tissues. ELISA analysis showed that picroside II down-regulated the levels of Th2-related cytokines (including IL-4, IL-5, and IL-13) and asthma-related mediators, but it up-regulated Th1-related cytokine, IFNγ in BALF. Picroside II also inhibited the expression of Th2 type cytokine genes and the transcription factor GATA3 in the lung tissues of HDM-induced mice. Finally, we demonstrated that picroside II significantly decreased the expression of GATA3 and Th2 cytokines in developing Th2 cells, consistent with in vivo results. Taken together, these results indicate that picroside II has protective effects on allergic asthma by reducing GATA3 expression and Th2 cytokine bias. PMID:27870920

  15. Advances in upper airway diseases and allergen immunotherapy.

    PubMed

    Nelson, Harold S

    2004-04-01

    Evidence for one airway continues to accumulate. Nasal allergen challenges increase lower airway inflammation, and nasal corticosteroid treatment reduces lower airway inflammation. Allergic respiratory inflammation might even spread systemically to involve nonrespiratory organs. Eosinophilic enteritis and eosinophilic esophagitis are reported during pollen seasons in patients with seasonal allergic rhinitis. Chronic hypertrophic sinusitis (CHS) is found in the majority of patients with asthma. Like asthma, the histology of CHS is characterized by epithelial damage, basement membrane thickening, and eosinophilic inflammation. The damaged epithelium might explain the acute bacterial exacerbations seen in patients with CHS. Studies have extended evidence of the safety and efficacy of the second- and third-generation antihistamines to younger children and to patients with perennial rhinitis but continue to show improvement of symptom scores over that seen with placebo of less than 20%. Studies on antihistamine use in the first trimester in nearly 500 women (65% taking loratadine) revealed no increase in the complications of pregnancy or congenital anomalies. Positive skin prick test responses to birch in asymptomatic young adults predicted later development of clinical allergic rhinitis. A dose response was demonstrated for immunotherapy with cat dander extract. The best results were in subjects receiving a dose containing 15 microg of the major cat allergen Fel d 1 (equivalent to approximately 2500 bioequivalent allergen units). Both topical intranasal immunotherapy and high-dose sublingual immunotherapy have been repeatedly proved to be safe and effective in double-blind, placebo-controlled studies. CD4+CD25+ regulatory T cells secreting IL-10, TGF-beta, or both appear important in normal individuals and in patients treated with allergen immunotherapy in maintaining or restoring normal T(H)1/T(H)2 balance and overall suppression of both phenotypes.

  16. Asthma: the interplay between viral infections and allergic diseases.

    PubMed

    Rowe, Regina K; Gill, Michelle A

    2015-02-01

    Respiratory viruses and allergens synergistically contribute to disease pathogenesis in asthma. Potential mechanisms underlying this clinically relevant association are the subject of intense investigation. This review summarizes current knowledge and recent advances in this area, with an emphasis on potential mechanisms involving immunoglobulin E, type I interferon antiviral responses, epithelial factors, and the role of dendritic cells and other antigen-presenting cells in linking viral and allergic inflammatory responses relevant to asthmatic disease.

  17. Allergic Diseases and Multiple Chemical Sensitivity in Korean Adults

    PubMed Central

    Jeong, Inchul; Kim, Inah; Park, Hye Jung; Roh, Jaehoon; Park, Jung-Won

    2014-01-01

    Purpose Multiple chemical sensitivity (MCS) is a clinical syndrome representing multi-organ and psychological symptoms caused by chronic exposure to various chemicals in low concentrations. We evaluated the prevalence and related factors of MCS targeting Korean adults using the Quick Environmental Exposure and Sensitivity Inventory (QEESI©). Methods A total of 446 participants were recruited from Severance Hospital. Participants underwent a questionnaire interview including questions on sociodemographic factors, occupational and environmental factors, allergic diseases, and the QEESI©. Among them, 379 participants completed the questionnaire and the QEESI©. According to the QEESI© interpretation results, participants were divided into very suggestive (VS) group and less suggestive (LS) group. Results The estimated prevalence of MCS was higher in allergic patients than non-allergic participants (19.7% and 11.3%, respectively, P=0.04). In the multivariate logistic regression analysis, ages of 30-39 (OR, 2.94; 95% CI, 1.25-6.95) and those of 40-49 (OR, 2.51; 95% CI, 1.02-6.21) were significantly related to MCS compared to those aged less than 30 years. Female sex (OR, 2.16; 95% CI, 1.11-4.18), experience of dwelling in a new house (OR, 2.05; 95% CI, 1.04-4.03), and atopic dermatitis (OR, 1.95; 95% CI, 1.04-3.69) were also significantly related to MCS. However, only age of 30-39 in the allergic group was significant in the stratified analysis. Conclusions The estimated prevalence of MCS was higher among allergic patients than non-allergic participants. People with experience of dwelling in a new house and atopic dermatitis were more at risk of being intolerant to chemicals. Further studies to provide the nationally representative prevalence data and clarify risk factors and mechanisms of MCS are required. PMID:25228997

  18. Characterization of inflammatory cell infiltration in feline allergic skin disease.

    PubMed

    Taglinger, K; Day, M J; Foster, A P

    2007-11-01

    Sixteen cats with allergic dermatitis and six control cats with no skin disease were examined. Lymphoid and histiocytic cells in skin sections were examined immunohistochemically and mast cells were identified by toluidine blue staining. The 16 allergic cats showed one or more of several features (alopecia, eosinophilic plaques or granulomas, papulocrusting lesions), and histopathological findings were diverse. In control cats there were no cells that expressed IgM or MAC387, a few that were immunolabelled for IgG, IgA or CD3, and moderate numbers of mast cells. In allergic cats, positively labelled inflammatory cells were generally more numerous in lesional than in non-lesional skin sections, and were particularly associated with the superficial dermis and perifollicular areas. There were low numbers of plasma cells expressing cytoplasmic immunoglobulin; moderate numbers of MHC II-, MAC387- and CD3-positive cells; and moderate to numerous mast cells. MHC class II expression was associated with inflammatory cells morphologically consistent with dermal dendritic cells and macrophages, and epidermal Langerhans cells. Dendritic cells expressing MHC class II were usually associated with an infiltrate of CD3 lymphocytes, suggesting that these cells participate in maintenance of the local immune response by presenting antigen to T lymphocytes. These findings confirm that feline allergic skin disease is characterized by infiltration of activated antigen-presenting cells and T lymphocytes in addition to increased numbers of dermal mast cells. This pattern mimics the dermal inflammation that occurs in the chronic phase of both canine and human atopic dermatitis.

  19. CT Metrics of Airway Disease and Emphysema in Severe COPD

    PubMed Central

    Kim, Woo Jin; Silverman, Edwin K.; Hoffman, Eric; Criner, Gerard J.; Mosenifar, Zab; Sciurba, Frank C.; Make, Barry J.; Carey, Vincent; Estépar, Raúl San José; Diaz, Alejandro; Reilly, John J.; Martinez, Fernando J.; Washko, George R.

    2009-01-01

    Background: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV1 and percent predicted value of FEV1 with CT scan measures of emphysema and airway disease. Results: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = −0.28, p = 0.0001) and SRWA (r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV1% predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV1% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema. PMID:19411295

  20. The role of bronchoscopy in the diagnosis of airway disease

    PubMed Central

    Dixon, Jennifer; Tieu, Brandon H.

    2016-01-01

    Endoscopy of the airway is a valuable tool for the evaluation and management of airway disease. It can be used to evaluate many different bronchopulmonary diseases including airway foreign bodies, tumors, infectious and inflammatory conditions, airway stenosis, and bronchopulmonary hemorrhage. Traditionally, options for evaluation were limited to flexible and rigid bronchoscopy. Recently, more sophisticated technology has led to the development of endobronchial ultrasound (EBUS) and electromagnetic navigational bronchoscopy (ENB). These technological advances, combined with increasing provider experience have resulted in a higher diagnostic yield with endoscopic biopsies. This review will focus on the role of bronchoscopy, including EBUS, ENB, and rigid bronchoscopy in the diagnosis of bronchopulmonary diseases. In addition, it will cover the anesthetic considerations, equipment, diagnostic yield, and potential complications. PMID:28149583

  1. Effects of a selective PDE4 inhibitor, D-22888, on human airways and eosinophils in vitro and late phase allergic pulmonary eosinophilia in guinea pigs.

    PubMed

    Dent, G; Poppe, H; Egerland, J; Marx, D; Szelenyi, I; Branscheid, D; Magnussen, H; Rabe, K F

    1998-02-01

    The actions of a novel selective inhibitor of type 4 cyclic nucleotide phosphodiesterase (PDE4), D-22888, on human airway smooth muscle tone and human eosinophil respiratory burst in vitro and bronchoalveolar eosinophilia in allergen-challenged sensitized guinea pigs in vivo were assessed. D-22888 was a selective inhibitor of PDE4, exhibiting an IC50 against human neutrophil PDE4 of 0.15 microM, compared to IC 50 values of 4.4 microM and 1.1 microM for human platelet PDE3 and PDE5, respectively. D-22888 relaxed inherent tone in human bronchial rings in a concentration-dependent manner with an IC50 of 5.0 microM (geometric mean, 95% ci 3.0-8.4 microM) and also caused a concentration-dependent inhibition of opsonized zymosan-induced superoxide anion generation by human eosinophils with an IC50 of 3.1 microM (1.0-9.2 microM). Treatment of actively sensitized guinea pigs with single oral doses of D-22888 2 h before or 4 h after challenge reduced bronchoalveolar lavage (BAL) eosinophil numbers, 24 h after aerosol allergen challenge, by 48% and 73% at 10 mg/kg and 30 mg/kg, respectively, 2 h pre-challenge and 68% at 30 mg/kg 4 h post-challenge. Chronic twice-daily oral dosing with D-22888 for three days caused inhibition of 24 h post-challenge BAL eosinophilia, amounting to 88% at 30 mg/kg. These in vivo actions were comparable with those achieved with other selective PDE4 inhibitors and with the corticosteroid, dexamethasone. We conclude that D-22888 exerts actions on airway smooth muscle and eosinophil recruitment and activation that suggest that D-22888 may be a promising new drug for use in the treatment of allergic obstructive airways> diseases such as bronchial asthma.

  2. Acute and Chronic Airway Disease After Human Respiratory Syncytial Virus Infection in Cotton Rats (Sigmodon hispidus).

    PubMed

    Grieves, Jessica L; Yin, Zhiwei; Durbin, Russell K; Durbin, Joan E

    2015-08-01

    Infection with respiratory syncytial virus (RSV) generally presents as a mild, upper airway disease in human patients but may cause severe lower airway disease in the very young and very old. Progress toward understanding the mechanisms of RSV pathogenesis has been hampered by a lack of relevant rodent models. Mice, the species most commonly used in RSV research, are resistant to upper respiratory infection and do not recapitulate the pattern of virus spread in the human host. To address the need for better rodent models of RSV infection, we have characterized the acute and chronic pathology of RSV infection of a relatively permissive host, cotton rats (Sigmodon hispidus). We demonstrate that virus delivered to the upper airway results in widespread RSV replication in the ciliated respiratory epithelial cells of the nasal cavity and, to a lesser extent, of the lung. Although acute inflammation is relatively mild and rapidly eliminated after viral clearance, chronic, eosinophilic lung pathology persists. These data support the use of cotton rats as a robust rodent model of human RSV disease, including the association between RSV pneumonia and subsequent development of allergic asthma.

  3. Acute and Chronic Airway Disease After Human Respiratory Syncytial Virus Infection in Cotton Rats (Sigmodon hispidus)

    PubMed Central

    Grieves, Jessica L; Yin, Zhiwei; Durbin, Russell K; Durbin, Joan E

    2015-01-01

    Infection with respiratory syncytial virus (RSV) generally presents as a mild, upper airway disease in human patients but may cause severe lower airway disease in the very young and very old. Progress toward understanding the mechanisms of RSV pathogenesis has been hampered by a lack of relevant rodent models. Mice, the species most commonly used in RSV research, are resistant to upper respiratory infection and do not recapitulate the pattern of virus spread in the human host. To address the need for better rodent models of RSV infection, we have characterized the acute and chronic pathology of RSV infection of a relatively permissive host, cotton rats (Sigmodon hispidus). We demonstrate that virus delivered to the upper airway results in widespread RSV replication in the ciliated respiratory epithelial cells of the nasal cavity and, to a lesser extent, of the lung. Although acute inflammation is relatively mild and rapidly eliminated after viral clearance, chronic, eosinophilic lung pathology persists. These data support the use of cotton rats as a robust rodent model of human RSV disease, including the association between RSV pneumonia and subsequent development of allergic asthma. PMID:26310461

  4. Non-pulmonary allergic diseases and inflammatory bowel disease: a qualitative review.

    PubMed

    Kotlyar, David S; Shum, Mili; Hsieh, Jennifer; Blonski, Wojciech; Greenwald, David A

    2014-08-28

    While the etiological underpinnings of inflammatory bowel disease (IBD) are highly complex, it has been noted that both clinical and pathophysiological similarities exist between IBD and both asthma and non-pulmonary allergic phenomena. In this review, several key points on common biomarkers, pathophysiology, clinical manifestations and nutritional and probiotic interventions for both IBD and non-pulmonary allergic diseases are discussed. Histamine and mast cell activity show common behaviors in both IBD and in certain allergic disorders. IgE also represents a key immunoglobulin involved in both IBD and in certain allergic pathologies, though these links require further study. Probiotics remain a critically important intervention for both IBD subtypes as well as multiple allergic phenomena. Linked clinical phenomena, especially sinonasal disease and IBD, are discussed. In addition, nutritional interventions remain an underutilized and promising therapy for modification of both allergic disorders and IBD. Recommending new mothers breastfeed their infants, and increasing the duration of breastfeeding may also help prevent both IBD and allergic diseases, but requires more investigation. While much remains to be discovered, it is clear that non-pulmonary allergic phenomena are connected to IBD in a myriad number of ways and that the discovery of common immunological pathways may usher in an era of vastly improved treatments for patients.

  5. Developing Primary Intervention Strategies to Prevent Allergic Disease.

    PubMed

    Rueter, Kristina; Haynes, Aveni; Prescott, Susan L

    2015-07-01

    Allergic diseases are a major cause of morbidity in the developed world, now affecting up to 40 % of the population with no evidence that this is abating. If anything, the prevalence of early onset allergic diseases such as eczema and food allergy appears to be still increasing. This is almost certainly due to the changing modern environment and lifestyle factors, acting to promote immune dysfunction through early perturbations in immune maturation, immune tolerance and regulation. This early propensity to inflammation may also have implications for the rising risk of other inflammatory non-communicable diseases (NCDs) later in life. Identifying risk factors and pathways for preventing early onset immune disease like allergy is likely to have benefits for many aspects of human health, particularly as many NCDs share similar risk factors. This review focuses on recent advances in primary intervention strategies for promoting early immune health and preventing allergic disease, highlighting the current evidence-based guidelines where applicable and areas requiring further investigation.

  6. GS143, an I{kappa}B ubiquitination inhibitor, inhibits allergic airway inflammation in mice

    SciTech Connect

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

    2008-09-26

    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-{kappa}B (NF-{kappa}B) 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 I{kappa}B ubiquitination, on antigen-induced airway inflammation and Th2 cytokine production in mice. Intranasal administration of GS143 prior to antigen challenge suppressed antigen-induced NF-{kappa}B 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 I{kappa}B ubiquitination inhibitor may have therapeutic potential against asthma.

  7. Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases.

    PubMed

    Miyata, Jun; Arita, Makoto

    2015-01-01

    Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are found naturally in fish oil and are commonly thought to be anti-inflammatory nutrients, with protective effects in inflammatory diseases including asthma and allergies. The mechanisms of these effects remain mostly unknown but are of great interest for their potential therapeutic applications. Large numbers of epidemiological and observational studies investigating the effect of fish intake or omega-3 fatty acid supplementation during pregnancy, lactation, infancy, childhood, and adulthood on asthmatic and allergic outcomes have been conducted. They mostly indicate protective effects and suggest a causal relationship between decreased intake of fish oil in modernized diets and an increasing number of individuals with asthma or other allergic diseases. Specialized pro-resolving mediators (SPM: protectins, resolvins, and maresins) are generated from omega-3 fatty acids such as EPA and DHA via several enzymatic reactions. These mediators counter-regulate airway eosinophilic inflammation and promote the resolution of inflammation in vivo. Several reports have indicated that the biosynthesis of SPM is impaired, especially in severe asthma, which suggests that chronic inflammation in the lung might result from a resolution defect. This article focuses on the beneficial aspects of omega-3 fatty acids and offers recent insights into their bioactive metabolites including resolvins and protectins.

  8. Oral administration of Enterococcus faecalis FK-23 suppresses Th17 cell development and attenuates allergic airway responses in mice.

    PubMed

    Zhang, Bei; An, Jun; Shimada, Takashi; Liu, Shuang; Maeyama, Kazutaka

    2012-08-01

    Evidence is increasing that oral administration of probiotics can attenuate asthmatic responses both in murine models and clinical trials. T-helper 17 (Th17) cells, a subset of CD4+ T cells have been implicated as having an important role in the development of several allergic disorders, but the relationship between oral administration of probiotics and Th17 development has not been well studied. BALB/c mice were given lysed Enterococcus faecalis FK-23 (LFK) orally for 28 days. After sensitization by subcutaneous injection of ovalbumin (OVA) on Days 14 and 21 and 1% OVA inhalation on Days 25, 26 and 27, they were challenged with a 5% OVA aerosol on Day 28. Twenty-four hours later, airway resistance and accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF) and lung tissues were determined. Ιnterleukin (IL)-17-expressing CD4+ lymphocytes isolated from lung, spleen and lamina propria of the intestine were detected by flow cytometry. The expression of IL-6 and TGF-β mRNA was assessed by real-time PCR. Increases in airway hyperresponsiveness, and numbers of total leukocytes and mast cells in BALF induced by OVA challenge were significantly suppressed by oral administration of LFK. The increased percentage of IL-17-expressing CD4+ cells from lung, spleen and intestine in OVA-challenged mice was reduced following LFK treatment. We conclude that the oral administration of LFK suppresses the asthmatic response and that this is associated with attenuation of Th17 cell development.

  9. So-Cheong-Ryong-Tang, a herbal medicine, modulates inflammatory cell infiltration and prevents airway remodeling via regulation of interleukin-17 and GM-CSF in allergic asthma in mice

    PubMed Central

    Kim, Hyung-Woo; Lim, Chi-Yeon; Kim, Bu-Yeo; Cho, Su-In

    2014-01-01

    Background: So-Cheong-Ryong-Tang (SCRT), herbal medicine, has been used for the control of respiratory disease in East Asian countries. However, its therapeutic mechanisms, especially an inhibitory effect on inflammatory cell infiltration and airway remodeling in allergic asthma are unclear. Objective: The present study investigated the mechanism of antiasthmatic effects of SCRT in allergic asthma in mice. Materials and Methods: We investigated the influence of SCRT on levels of interleukin-17 (IL-17), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-4, and interferon gamma (IFN-γ) in bronchoalveolar lavage fluid (BALF), ovalbumin (OVA)-specific IgE in serum, and histopathological changes in allergen-induced asthma. Results: So-Cheong-Ryong-Tang decreased levels of IL-17 and GM-CSF in BALF. IL-4, a Th2-driven cytokine, was also decreased by SCRT, but IFN-γ, a Th1-driven cytokine, was not changed. Levels of OVA-specific IgE in serum were also decreased by SCRT. With SCRT treatment, histopathological findings showed reduced tendency of inflammatory cell infiltration, and prevention from airway remodeling such as epithelial hyperplasia. Conclusion: In this study, we firstly demonstrated that regulation of IL-17 and GM-CSF production may be one of the mechanism contributed to a reduction of inflammatory cell infiltration and prevention from airway remodeling. PMID:25298667

  10. Small airways involvement in coal mine dust lung disease.

    PubMed

    Long, Joshua; Stansbury, Robert C; Petsonk, Edward L

    2015-06-01

    Inhalation of coal mine dust results in a spectrum of symptoms, dysfunction, and pathological changes in the respiratory tract that collectively have been labeled coal mine dust lung disease. Recent reports from periodic health surveillance among underground and surface coal miners in the United States have demonstrated an increasing prevalence and severity of dust diseases, and have also documented that some miners experience rapid disease progression. The coal macule is an inflammatory lesion associated with deposited dust, and occurs in the region of the most distal conducting airways and proximal respiratory bronchioles. Inflammatory changes in the small airways have long been recognized as the signature lung pathology among coal miners. Human and laboratory studies have suggested oxidant injury, and increased recruitment and activity of macrophages play important roles in dust-induced lung injury. However, the functional importance of the small airway changes was debated for many years. We reviewed published literature that documents a pervasive occurrence of both physiologic and structural abnormalities in small airways among coal miners and other workers exposed to airborne particulates. There is increasing evidence supporting an important association of abnormalities in the small peripheral airways with the development of respiratory symptoms, deficits in spirometry values, and accelerated declines in ventilatory lung function. Pathologic changes associated with mineral dust deposition in the small airways may be of particular importance in contemporary miners with rapidly progressive respiratory impairment.

  11. Occupational Exposure to Urban Air Pollution and Allergic Diseases

    PubMed Central

    Vimercati, Luigi; Gatti, Maria Franca; Baldassarre, Antonio; Nettis, Eustachio; Favia, Nicola; Palma, Marco; Martina, Gabriella Lucia Maria; Di Leo, Elisabetta; Musti, Marina

    2015-01-01

    Exposure to air pollution is associated with increased morbidity from cardiovascular diseases, lung cancer, respiratory and allergic diseases. The aim of this study was to investigate allergic diseases in 111 traffic wardens compared to a control group of 101 administrative employees. All participating subjects underwent a physical examination, in which a complete medical history was taken and a dedicated allergological questionnaire administered. Spirometry, Specific IgE dosage (RAST) and skin prick tests (SPT) were done. Diagnostic investigations such as the nasal cytology, a specific nasal provocation test and rhinomanometry were also performed. Statistical analyses were performed using STATA version 11. The percentage of subjects with a diagnosis of allergy was higher in the exposed workers than in the controls. As regards the clinical tests, the positivity was higher for the group of exposed subjects. Among the exposed workers, those who worked on foot or motorcycle had a higher positivity in clinical trials compared to the traffic wardens who used the car. Our study showed a higher percentage of allergic subjects in the group of workers exposed to outdoor pollutants than in the controls. These results suggest that allergological tests should be included in the health surveillance protocols for workers exposed to outdoor pollutants. PMID:26501303

  12. European Symposium on Precision Medicine in Allergy and Airways Diseases: Report of the European Union Parliament Symposium (October 14, 2015).

    PubMed

    Muraro, A; Fokkens, W J; Pietikainen, S; Borrelli, D; Agache, I; Bousquet, J; Costigliola, V; Joos, G; Lund, V J; Poulsen, L K; Price, D; Rolland, C; Zuberbier, T; Hellings, P W

    2016-05-01

    The European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS), and the European Medical Association (EMA) organized, on October 14, 2015, a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP David Borrelli, and with active participation of the EU Commissioner for Health and Food Safety Vytenis Andriukaitis, MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, the European Respiratory Society (ERS), the European Federations of Allergy and Airways Diseases Patients Associations (EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma (ARIA), and the Respiratory Effectiveness Group (REG). The socioeconomic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic noncommunicable diseases in the EU; 30% of the total European population is suffering from allergies and asthma, and more than half are deprived from adequate diagnosis and treatment. Precision medicine represents a novel approach, embracing four key features: personalized care based on molecular, immunologic, and functional endotyping of the disease, with participation of the patient in the decision-making process of therapeutic actions, and considering predictive and preventive aspects of the treatment. Implementation of precision medicine into clinical practice may help to achieve the arrest of the epidemic of allergies and chronic airways diseases. Participants underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient empowerment, and cost-effective treatment strategies.

  13. The Diacetyl-exposed Human Airway Epithelial Secretome: New Insights Into Flavoring Induced Airways Disease.

    PubMed

    Brass, David M; Gwinn, William M; Valente, Ashlee M; Kelly, Francine L; Brinkley, Christie D; Nagler, Andrew E; Moseley, M Arthur; Morgan, Daniel L; Palmer, Scott M; Foster, Matthew W

    2017-03-01

    Bronchiolitis obliterans (BO) is an increasingly important lung disease characterized by fibroproliferative airway lesions and decrements in lung function. Occupational exposure to the artificial food flavoring ingredient diacetyl, commonly used to impart a buttery flavor to microwave popcorn, has been associated with BO development. In the occupational setting, diacetyl vapor is first encountered by the airway epithelium. To better understand the effects of diacetyl vapor on the airway epithelium we used an unbiased proteomic approach to characterize both the apical and basolateral secretomes of air liquid interface cultures of primary human airway epithelial cells from four unique donors after exposure to an occupationally relevant ~1100 ppm of diacetyl vapor or PBS as a control on alternating days. Basolateral and apical supernatants collected 48 hours after the third exposure were analyzed using one-dimensional liquid chromatography tandem mass spectrometry. Paired t-tests adjusted for multiple comparisons were used to assess differential expression between diacetyl and PBS exposure. Of the significantly differentially expressed proteins identified, 61 were unique to the apical secretome, 81 were unique to the basolateral secretome and there were an additional 11 present in both. Pathway enrichment analysis using publicly available databases reveals that proteins associated with matrix remodeling including degradation, assembly and new matrix organization were over-represented in the data sets. Similarly, protein modifiers of epidermal growth factor receptor signaling were significantly altered. The ordered changes in protein expression suggest that the airway epithelial response to diacetyl may contribute to BO pathogenesis.

  14. The possible mechanisms of the human microbiome in allergic diseases.

    PubMed

    Ipci, Kagan; Altıntoprak, Niyazi; Muluk, Nuray Bayar; Senturk, Mehmet; Cingi, Cemal

    2017-02-01

    In the present paper, we discuss the importance of the microbiome in allergic disease. In this review paper, the data from the Medline (PubMed) and search engine of Kirikkale University were systematically searched for all relevant articles in June 15th, 2015 for the past 30 years. The keywords of "microbiome", "dysbiosis", "allergy", "allergic rhinitis", "allergic disease", "mechanisms" and "treatment" were used alone or together. In this paper, microbiomes were presented in terms of "Definition", "Influence of \\the human microbiome on health", "The microbiome and allergic diseases", and "Modulation of the gut microbiota in terms of treatment and prevention". Microbiological dysbiosis is also reviewed. The microbiome is the genetic material of all microbes (bacteria, fungi, protozoa, and viruses) that live on or in the human body. Microbes outnumber human cells in a 10:1 ratio. Most microbes live in the gut, particularly the large intestine. Changes in the immune function of the respiratory tract are (at least in theory) linked to the immunomodulatory activity of the gut microbiota via the concept of a "common mucosal response". The gut microbiota shapes systemic immunity, thus affecting the lung mucosa. Alternatively, changes in the gut microbiota may reflect alterations in the oropharyngeal microbiota, which may in turn directly affect the lung microbiota and host immune responses via microaspiration. Dysbiosis is defined as qualitative and quantitative changes in the intestinal flora; and modern diet and lifestyle, antibiotics, psychological and physical stress result in alterations in bacterial metabolism, as well as the overgrowth of potentially pathogenic microorganisms. All immune system components are directly or indirectly regulated by the microbiota. The nature of microbial exposure early in life appears to be important for the development of robust immune regulation; disruption of either the microbiota or the host response can trigger chronic

  15. [Histamine H₁ receptor gene as an allergic diseases-sensitive gene and its impact on therapeutics for allergic diseases].

    PubMed

    Mizuguchi, Hiroyuki; Kitamura, Yoshiaki; Kondo, Yuto; Kuroda, Wakana; Yoshida, Haruka; Miyamoto, Yuko; Hattori, Masashi; Takeda, Noriaki; Fukui, Hiroyuki

    2011-02-01

    Therapeutics targeting disease-sensitive genes are required for the therapy of multifactorial diseases. There is no clinical report on therapeutics for allergic disease-sensitive genes. We are focusing on the histamine H₁ receptor (H1R) as a sensitive gene. H1R mediates allergy histamine signals. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression level. We discovered that the stimulation of H1R induced H1R gene expression through PKCδ activation, resulting in receptor upregulation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Preseasonal prophylactic treatment with antihistamines is recommended for the therapy of pollinosis. However, the mechanism of the therapy remains to be elucidated. We demonstrated that repeated pretreatment treatment with antihistamines in the allergic rhinitis model rats resulted not only in improvement of symptoms but also in suppressed elevation of H1R mRNA levels in the nasal mucosa. A clinical trial was then initiated. When symptoms and H1R mRNA levels in the nasal mucosa of pollinosis patients with or without preseasonal prophylactic treatment with antihistamines were examined, both symptoms and high levels of H1R mRNA were significantly improved in treated compared with untreated patients. These results strongly suggest that H1R is an allergic disease-sensitive gene.

  16. SENSITIZATION AND EXACERBATION OF ALLERGIC DISEASES BY DIESEL ENGINE PARTICLES

    SciTech Connect

    Diaz-Sanchez, David

    2000-08-20

    Most studies of the health effects of diesel exhaust have focused on the controversial issue of its role in cancer. However, recently the role of combustion products such as diesel exhaust particles (DEP) in modulating the immune response has garnered much attention. In particular the effect of DEP on allergic and asthmatic diseases has been the focus of many studies. A link between industrialization and allergic disease has long been presumed. Indeed, only 50 years after the first recorded reported case of allergy in 1819, Charles Blackely wrote that the ''hay-fever epidemic'' was associated with the movement of people from the country into the cities. Ishizaki et al. (1987) found that people in Japan living on busy roads lined with cedar trees have more allergies to cedar than residents living on similar streets with much less traffic. Since that time other epidemiological studies have reported similar findings. Kramer, et al., showed that hay fever is greater in residential areas with heavy truck traffic, while Weiland, et al., reported that allergic symptoms correlate with the distance of residences to roads with heavy traffic.

  17. Distinct clinical phenotypes of airways disease defined by cluster analysis.

    PubMed

    Weatherall, M; Travers, J; Shirtcliffe, P M; Marsh, S E; Williams, M V; Nowitz, M R; Aldington, S; Beasley, R

    2009-10-01

    Airways disease is currently classified using diagnostic labels such as asthma, chronic bronchitis and emphysema. The current definitions of these classifications may not reflect the phenotypes of airways disease in the community, which may have differing disease processes, clinical features or responses to treatment. The aim of the present study was to use cluster analysis to explore clinical phenotypes in a community population with airways disease. A random population sample of 25-75-yr-old adults underwent detailed investigation, including a clinical questionnaire, pulmonary function tests, nitric oxide measurements, blood tests and chest computed tomography. Cluster analysis was performed on the subgroup with current respiratory symptoms or obstructive spirometric results. Subjects with a complete dataset (n = 175) were included in the cluster analysis. Five clusters were identified with the following characteristics: cluster 1: severe and markedly variable airflow obstruction with features of atopic asthma, chronic bronchitis and emphysema; cluster 2: features of emphysema alone; cluster 3: atopic asthma with eosinophilic airways inflammation; cluster 4: mild airflow obstruction without other dominant phenotypic features; and cluster 5: chronic bronchitis in nonsmokers. Five distinct clinical phenotypes of airflow obstruction were identified. If confirmed in other populations, these findings may form the basis of a modified taxonomy for the disorders of airways obstruction.

  18. Barrier function of the nasal mucosa in health and type-2 biased airway diseases.

    PubMed

    Zhang, N; Van Crombruggen, K; Gevaert, E; Bachert, C

    2016-03-01

    The mucosal lining of the upper airways represents the outer surface of the body to the ambient air and its contents and is prepared for it as the first line of defense. Apart from the well-described physical barrier and the mucociliary clearance, a variety of systems, including the airway microbiome, antimicrobial proteins, damage-associated molecular patterns, innate lymphoid cells, epithelial-derived cytokines and chemokines, and finally the adaptive immune system, as well as eosinophils as newly appreciated defense cells form different levels of protection against and response to any possible intruder. Of interest especially for allergic airway disease, mucosal germs might not just elicit a classical Th1/Th17-biased inflammatory response, but may directly induce a type-2 mucosal inflammation. Innovative therapeutic interventions may be possible at different levels also; however, whether modulations of the innate or adaptive immune responses will finally be more successful, and how the correction of the adaptive immune response might impact on the innate side, will be determined in the near future.

  19. [Personalised medicine for the diagnosis and treatment of allergic diseases].

    PubMed

    Vieths, S; Bieber, T

    2013-11-01

    Immunoglobulin E (IgE) mediated allergic diseases are characterised by heterogeneous clinical phenotypes and a large variety of different sensitisation patterns. Apart from genetic predisposition several environmental factors play a role in sensitisation and elicitation of symptoms. Since the majority of clinically relevant allergens are now available as purified recombinant allergens component-resolved in vitro diagnosis allows the sensitization profile of allergic patients to be determined at the molecular level. Such data may allow physicians to draw conclusions on the severity and persistence of a given allergic disease and to predict the outcome of allergen-specific immunotherapy (SIT) However, the potential of this approach needs to be demonstrated in controlled clinical trials. Moreover, in the context of atopic dermatitis, allergic rhinitis, allergic bronchial asthma as well as the atopic march several screening-biomarkers, diagnostic and prognostic biomarkers, biomarkers of severity and predictive biomarkers are presented and discussed in this article. Traditionally a relevant proportion of allergen-specific immunotherapies is performed in a personalised manner using named patient products manufactured on the basis of an individual prescription. Such named patient products are often mixtures containing several allergen extracts from different sources. However, there is no proven evidence for the safety and efficacy of this approach. In Germany the Therapy Allergen Ordinance ("Therapieallergene-Verordnung", TAV) regulates that in the future allergen products for SIT of insect venom allergies, allergies to pollen of early flowering trees and grass pollen and house dust mite allergies cannot be marketed as named patient products, but always require a marketing authorisation. Thus personalised SIT with named patient products is restricted to the treatment of less prevalent allergies, for which the generation of state-of-the-art clinical data is more difficult

  20. IL-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease.

    PubMed

    Mukherjee, Sumanta; Lindell, Dennis M; Berlin, Aaron A; Morris, Susan B; Shanley, Thomas P; Hershenson, Marc B; Lukacs, Nicholas W

    2011-07-01

    Severe respiratory syncytial virus (RSV) infections are characterized by airway epithelial cell damage, mucus hypersecretion, and Th2 cytokine production. Less is known about the role of IL-17. We observed increased IL-6 and IL-17 levels in tracheal aspirate samples from severely ill infants with RSV infection. In a mouse model of RSV infection, time-dependent increases in pulmonary IL-6, IL-23, and IL-17 expression were observed. Neutralization of IL-17 during infection and observations from IL-17(-/-) knockout mice resulted in significant inhibition of mucus production during RSV infection. RSV-infected animals treated with anti-IL-17 had reduced inflammation and decreased viral load, compared with control antibody-treated mice. Blocking IL-17 during infection resulted in significantly increased RSV-specific CD8 T cells. Factors associated with CD8 cytotoxic T lymphocytes, T-bet, IFN-γ, eomesodermin, and granzyme B were significantly up-regulated after IL-17 blockade. Additionally, in vitro analyses suggest that IL-17 directly inhibits T-bet, eomesodermin, and IFN-γ in CD8 T cells. The role of IL-17 was also investigated in RSV-induced exacerbation of allergic airway responses, in which neutralization of IL-17 led to a significant decrease in the exacerbated disease, including reduced mucus production and Th2 cytokines, with decreased viral proteins. Taken together, our data demonstrate that IL-17 plays a pathogenic role during RSV infections.

  1. Self-expandable metallic stents in nonmalignant large airway disease.

    PubMed

    Fortin, Marc; MacEachern, Paul; Hergott, Christopher A; Chee, Alex; Dumoulin, Elaine; Tremblay, Alain

    2015-01-01

    Airway self-expandable metallic stents (SEMS) were initially studied in malignant airway obstruction; however, their use in benign airway diseases has become progressively more frequent. This may be explained by their ease of insertion compared with silicone stents, which require rigid bronchoscopy for insertion. While initial experience with SEMS in benign disease suggested efficacy and promising short-term safety profile, long-term follow-up revealed significant complication rates. In addition to a high complication rate, the management of these complications is made more difficult by the semipermanent nature of these devices. Reported complications include infection, granulation tissue formation, stent migration, stent fracture, airway perforation and fistula formation, as well as extension of the initial injury, potentially eliminating other therapeutic options such as surgical resection. Therefore, SEMS should only be used in nonmalignant large airway disease as a last resort for patients in whom other endoscopic methods, including silicone stents and dilations, as well as surgical options have failed or are technically not feasible.

  2. Update on epigenetics in allergic disease.

    PubMed

    Harb, Hani; Renz, Harald

    2015-01-01

    Chronic inflammatory diseases, including allergies and asthma, are the result of complex gene-environment interactions. One of the most challenging questions in this regard relates to the biochemical mechanism of how exogenous environmental trigger factors modulate and modify gene expression, subsequently leading to the development of chronic inflammatory conditions. Epigenetics comprises the umbrella of biochemical reactions and mechanisms, such as DNA methylation and chromatin modifications on histones and other structures. Recently, several lifestyle and environmental factors have been investigated in terms of such biochemical interactions with the gene expression-regulating machinery: allergens; microbes and microbial compounds; dietary factors, including vitamin B12, folic acid, and fish oil; obesity; and stress. This article aims to update recent developments in this context with an emphasis on allergy and asthma research.

  3. Neurophenotypes in Airway Diseases. Insights from Translational Cough Studies

    PubMed Central

    Birrell, Mark A.; Khalid, Saifudin; Wortley, Michael A.; Dockry, Rachel; Coote, Julie; Holt, Kimberley; Dubuis, Eric; Kelsall, Angela; Maher, Sarah A.; Bonvini, Sara; Woodcock, Ashley

    2016-01-01

    Rationale: Most airway diseases, including chronic obstructive pulmonary disease (COPD), are associated with excessive coughing. The extent to which this may be a consequence of increased activation of vagal afferents by pathology in the airways (e.g., inflammatory mediators, excessive mucus) or an altered neuronal phenotype is unknown. Understanding whether respiratory diseases are associated with dysfunction of airway sensory nerves has the potential to identify novel therapeutic targets. Objectives: To assess the changes in cough responses to a range of inhaled irritants in COPD and model these in animals to investigate the underlying mechanisms. Methods: Cough responses to inhaled stimuli in patients with COPD, healthy smokers, refractory chronic cough, asthma, and healthy volunteers were assessed and compared with vagus/airway nerve and cough responses in a cigarette smoke (CS) exposure guinea pig model. Measurements and Main Results: Patients with COPD had heightened cough responses to capsaicin but reduced responses to prostaglandin E2 compared with healthy volunteers. Furthermore, the different patient groups all exhibited different patterns of modulation of cough responses. Consistent with these findings, capsaicin caused a greater number of coughs in CS-exposed guinea pigs than in control animals; similar increased responses were observed in ex vivo vagus nerve and neuron cell bodies in the vagal ganglia. However, responses to prostaglandin E2 were decreased by CS exposure. Conclusions: CS exposure is capable of inducing responses consistent with phenotypic switching in airway sensory nerves comparable with the cough responses observed in patients with COPD. Moreover, the differing profiles of cough responses support the concept of disease-specific neurophenotypes in airway disease. Clinical trial registered with www.clinicaltrials.gov (NCT 01297790). PMID:26741046

  4. NF-kappaB Signaling in Chronic Inflammatory Airway Disease

    PubMed Central

    Schuliga, Michael

    2015-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments. In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression. The redox-sensitive transcription factor, nuclear factor (NF)-kappaB (NF-κB), is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology. The anti-inflammatory actions of glucocorticoids (GCs), a mainstay treatment for asthma, involve inhibition of NF-κB induced gene transcription. Ligand bound GC receptors (GRs) bind NF-κB to suppress the transcription of NF-κB responsive genes (i.e., transrepression). However, in severe asthma and COPD, the transrepression of NF-κB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling. Therapeutics which target NF-κB activation, including inhibitors of IκB kinases (IKKs) are potential treatments for asthma and COPD. Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-κB transrepression. This review examines NF-κB signaling in airway inflammation and its potential as target for treatment of asthma and COPD. PMID:26131974

  5. Phloretin Attenuates Allergic Airway Inflammation and Oxidative Stress in Asthmatic Mice

    PubMed Central

    Huang, Wen-Chung; Fang, Li-Wen; Liou, Chian-Jiun

    2017-01-01

    Phloretin (PT), isolated from the apple tree, was previously demonstrated to have antioxidative and anti-inflammatory effects in macrophages and anti-adiposity effects in adipocytes. Inflammatory immune cells generate high levels of reactive oxygen species (ROS) for stimulated severe airway hyperresponsiveness (AHR) and airway inflammation. In this study, we investigated whether PT could reduce oxidative stress, airway inflammation, and eosinophil infiltration in asthmatic mice, and ameliorate oxidative and inflammatory responses in tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin (OVA) to induce asthma symptoms. Mice were randomly assigned to the five experimental groups: normal controls; OVA-induced asthmatic mice; and OVA-induced mice injected intraperitoneally with one of the three PT doses (5, 10, or 20 mg/kg). In addition, we treated inflammatory human tracheal epithelial cells (BEAS-2B cells) with PT to assess oxidative responses and the levels of proinflammatory cytokines and chemokines. We found that PT significantly reduced goblet cell hyperplasia and eosinophil infiltration, which decreased AHR, inflammation, and oxidative responses in the lungs of OVA-sensitized mice. PT also decreased malondialdehyde levels in the lung and reduced Th2 cytokine production in bronchoalveolar lavage fluids. Furthermore, PT reduced ROS, proinflammatory cytokines, and eotaxin production in BEAS-2B cells. PT also suppressed monocyte cell adherence to inflammatory BEAS-2B cells. These findings suggested that PT alleviated pathological changes, inflammation, and oxidative stress by inhibiting Th2 cytokine production in asthmatic mice. PT showed therapeutic potential for ameliorating asthma symptoms in the future. PMID:28243240

  6. Air pollution and respiratory allergic diseases in schoolchildren

    PubMed Central

    Nicolussi, Francine Heloisa; dos Santos, Ana Paula Milla; André, Sílvia Carla da Silva; Veiga, Tatiane Bonametti; Takayanagui, Angela Maria Magosso

    2014-01-01

    Study on the prevalence of allergic respiratory diseases in schoolchildren between six and seven years old, associated with indicators of air pollution. A questionnaire based on the International Study of Asthma and Allergies in Childhood was administered to parents of students from public schools, located in urban areas with differing vehicle flows. There was a positive correlation between monthly frequency of rhinitis and concentration of pollutants, and negative with relative air humidity. Even with levels of air pollutants below that allowed by law, the prevalence of asthma, rhinitis and associated symptoms tended to be higher in the central region school, where there is heavy vehicular traffic. PMID:24897055

  7. Oral administration of Lactobacillus paracasei L9 attenuates PM2.5-induced enhancement of airway hyperresponsiveness and allergic airway response in murine model of asthma

    PubMed Central

    Zhao, Liang; Hao, Yanling; Guo, Huiyuan; Ren, Fazheng

    2017-01-01

    This study investigated allergy immunotherapy potential of Lactobacillus paracasei L9 to prevent or mitigate the particulate matter 2.5 (PM2.5) enhanced pre-existing asthma in mice. Firstly, we used a mouse model of asthma (a 21-day ovalbumin (OVA) sensitization and challenge model) followed by PM2.5 exposure twice on the same day of the last challenge. PM2.5 was collected from the urban area of Beijing and underwent analysis for metals and polycyclic aromatic hydrocarbon contents. The results showed that PM2.5 exposure enhanced airway hyper-responsiveness (AHR) and lead to a mixed Th2/ IL-17 response in asthmatic mice. Secondly, the PM2.5 exposed asthmatic mice were orally administered with L9 (4×107, 4×109 CFU/mouse, day) from the day of first sensitization to the endpoint, for 20 days, to investigate the potential mitigative effect of L9 on asthma. The results showed that L9 ameliorated PM2.5 exposure enhanced AHR with an approximate 50% decrease in total airway resistance response to methacholine (48 mg/ml). L9 also prevented the exacerbated eosinophil and neutrophil infiltration in bronchoalveolar lavage fluid (BALF), and decreased the serum level of total IgE and OVA-specific IgG1 by 0.44-fold and 0.3-fold, respectively. Additionally, cytokine production showed that L9 significantly decreased T-helper cell type 2 (Th2)–related cytokines (IL-4, -5, -13) and elevated levels of Th1 related IFN-γ in BALF. L9 also reduced the level of IL-17A and increased the level of TGF-β. Taken together, these results indicate that L9 may exert the anti-allergic benefit, possibly through rebalancing Th1/Th2 immune response and modulating IL-17 pro-inflammatory immune response. Thus, L9 is a promising candidate for preventing PM exposure enhanced pre-existing asthma. PMID:28199353

  8. Oral administration of Lactobacillus paracasei L9 attenuates PM2.5-induced enhancement of airway hyperresponsiveness and allergic airway response in murine model of asthma.

    PubMed

    Wang, Xifan; Hui, Yan; Zhao, Liang; Hao, Yanling; Guo, Huiyuan; Ren, Fazheng

    2017-01-01

    This study investigated allergy immunotherapy potential of Lactobacillus paracasei L9 to prevent or mitigate the particulate matter 2.5 (PM2.5) enhanced pre-existing asthma in mice. Firstly, we used a mouse model of asthma (a 21-day ovalbumin (OVA) sensitization and challenge model) followed by PM2.5 exposure twice on the same day of the last challenge. PM2.5 was collected from the urban area of Beijing and underwent analysis for metals and polycyclic aromatic hydrocarbon contents. The results showed that PM2.5 exposure enhanced airway hyper-responsiveness (AHR) and lead to a mixed Th2/ IL-17 response in asthmatic mice. Secondly, the PM2.5 exposed asthmatic mice were orally administered with L9 (4×107, 4×109 CFU/mouse, day) from the day of first sensitization to the endpoint, for 20 days, to investigate the potential mitigative effect of L9 on asthma. The results showed that L9 ameliorated PM2.5 exposure enhanced AHR with an approximate 50% decrease in total airway resistance response to methacholine (48 mg/ml). L9 also prevented the exacerbated eosinophil and neutrophil infiltration in bronchoalveolar lavage fluid (BALF), and decreased the serum level of total IgE and OVA-specific IgG1 by 0.44-fold and 0.3-fold, respectively. Additionally, cytokine production showed that L9 significantly decreased T-helper cell type 2 (Th2)-related cytokines (IL-4, -5, -13) and elevated levels of Th1 related IFN-γ in BALF. L9 also reduced the level of IL-17A and increased the level of TGF-β. Taken together, these results indicate that L9 may exert the anti-allergic benefit, possibly through rebalancing Th1/Th2 immune response and modulating IL-17 pro-inflammatory immune response. Thus, L9 is a promising candidate for preventing PM exposure enhanced pre-existing asthma.

  9. Primary prevention of allergic disease through nutritional interventions.

    PubMed

    Fleischer, David M; Spergel, Jonathan M; Assa'ad, Amal H; Pongracic, Jacqueline A

    2013-01-01

    With the rising prevalence of atopic disease, primary prevention may play a role in reducing its burden, especially in high-risk infants. With this in mind, the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology was charged with the task of developing recommendations for primary care physicians and specialists about the primary prevention of allergic disease through nutritional interventions according to current available literature and expert opinion. Recommendations that are supported by data are as follows. Avoidance diets during pregnancy and lactation are not recommended at this time, but more research is necessary for peanut. Exclusive breast-feeding for at least 4 and up to 6 months is endorsed. For high-risk infants who cannot be exclusively breast-fed, hydrolyzed formula appears to offer advantages to prevent allergic disease and cow's milk allergy. Complementary foods can be introduced between 4 and 6 months of age. Because no formal recommendations have been previously provided about how and when to introduce the main allergenic foods (cow's milk, egg, soy, wheat, peanut, tree nuts, fish, shellfish), these are now provided, and reasons to consider allergy consultation for development of a personalized plan for food introduction are also presented.

  10. European symposium on precision medicine in allergy and airways diseases: report of the European Union parliament symposium (October 14, 2015).

    PubMed

    Muraro, A; Fokkens, W J; Pietikainen, S; Borrelli, D; Agache, I; Bousquet, J; Costigliola, V; Joos, G; Lund, V J; Poulsen, L K; Price, D; Rolland, C; Zuberbier, T; Hellings, P W

    2015-12-01

    On 14 October 2015, the European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS) and the European Medical Association (EMA) organized a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP David Borrelli and with active participation of the European Respiratory Society (ERS), the European Federations of Allergy and Airways Diseases Patients Associations (EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma (ARIA) and the Respiratory Effectiveness Group (REG). MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, underlined the importance of the need for a better diagnostic and therapeutic approach for patients with Allergies and Chronic Airways Diseases, and encouraged a joint initiative to control the epidemic of Allergy and Asthma in Europe. The socio-economic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic non-communicable diseases in the EU. Despite the fact that 30% of the total European population is nowadays suffering from allergies and asthma, more than half of these patients are deprived from adequate diagnosis and treatment. Precision Medicine represents a novel approach in medicine, embracing 4 key features: personalized care based on molecular, immunologic and functional endotyping of the disease, with participation of the patient in the decision making process of therapeutic actions, and taking into account predictive and preventive aspects of the treatment. Implementation of Precision Medicine into clinical practice may help to achieve the arrest of the Epidemic of Allergies and Chronic Airways Diseases. This report summarizes the key messages delivered during the symposium by the speakers, including the EU Commissioner for Health and Food Safety Vitenys Andriukaitis. The

  11. Aquaporin-3 potentiates allergic airway inflammation in ovalbumin-induced murine asthma.

    PubMed

    Ikezoe, Kohei; Oga, Toru; Honda, Tetsuya; Hara-Chikuma, Mariko; Ma, Xiaojun; Tsuruyama, Tatsuaki; Uno, Kazuko; Fuchikami, Jun-Ichi; Tanizawa, Kiminobu; Handa, Tomohiro; Taguchi, Yoshio; Verkman, Alan S; Narumiya, Shuh; Mishima, Michiaki; Chin, Kazuo

    2016-05-11

    Oxidative stress plays a pivotal role in the pathogenesis of asthma. Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel that may facilitate the membrane uptake of hydrogen peroxide (H2O2). Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma by mediating both chemokine production from alveolar macrophages and T cell trafficking. AQP3 deficient (AQP3(-/-)) mice exhibited significantly reduced airway inflammation compared to wild-type mice. Adoptive transfer experiments showed reduced airway eosinophilic inflammation in mice receiving OVA-sensitized splenocytes from AQP3(-/-) mice compared with wild-type mice after OVA challenge, consistently with fewer CD4(+) T cells from AQP3(-/-) mice migrating to the lung than from wild-type mice. Additionally, in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic target.

  12. Epithelial barrier function: at the frontline of asthma immunology and allergic airway inflammation

    PubMed Central

    Georas, Steve N.; Rezaee, Fariba

    2014-01-01

    Airway epithelial cells form a barrier to the outside world, and are at the frontline of mucosal immunity. Epithelial apical junctional complexes are multi-protein subunits that promote cell-cell adhesion and barrier integrity. Recent studies in the skin and GI tract suggest that disruption of cell-cell junctions is required to initiate epithelial immune responses, but how this applies to mucosal immunity in the lung is not clear. Increasing evidence indicates that defective epithelial barrier function is a feature of airway inflammation in asthma. One challenge in this area is that barrier function and junctional integrity are difficult to study in the intact lung, but innovative approaches should provide new knowledge in this area in the near future. In this article, we review the structure and function of epithelial apical junctional complexes, emphasizing how regulation of the epithelial barrier impacts innate and adaptive immunity. We discuss why defective epithelial barrier function may be linked to Th2 polarization in asthma, and propose a rheostat model of barrier dysfunction that implicates the size of inhaled allergen particles as an important factor influencing adaptive immunity. PMID:25085341

  13. Aquaporin-3 potentiates allergic airway inflammation in ovalbumin-induced murine asthma

    PubMed Central

    Ikezoe, Kohei; Oga, Toru; Honda, Tetsuya; Hara-Chikuma, Mariko; Ma, Xiaojun; Tsuruyama, Tatsuaki; Uno, Kazuko; Fuchikami, Jun-ichi; Tanizawa, Kiminobu; Handa, Tomohiro; Taguchi, Yoshio; Verkman, Alan S.; Narumiya, Shuh; Mishima, Michiaki; Chin, Kazuo

    2016-01-01

    Oxidative stress plays a pivotal role in the pathogenesis of asthma. Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel that may facilitate the membrane uptake of hydrogen peroxide (H2O2). Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma by mediating both chemokine production from alveolar macrophages and T cell trafficking. AQP3 deficient (AQP3−/−) mice exhibited significantly reduced airway inflammation compared to wild-type mice. Adoptive transfer experiments showed reduced airway eosinophilic inflammation in mice receiving OVA-sensitized splenocytes from AQP3−/− mice compared with wild-type mice after OVA challenge, consistently with fewer CD4+ T cells from AQP3−/− mice migrating to the lung than from wild-type mice. Additionally, in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic target. PMID:27165276

  14. Schistosome-induced pulmonary B cells inhibit allergic airway inflammation and display a reduced Th2-driving function.

    PubMed

    van der Vlugt, L E; Obieglo, K; Ozir-Fazalalikhan, A; Sparwasser, T; Haeberlein, S; Smits, H H

    2017-04-04

    Chronic schistosome infections protect against allergic airway inflammation (AAI) via the induction of IL-10-producing splenic regulatory B (Breg) cells. Previous experiments have demonstrated that schistosome-induced pulmonary B cells can also reduce AAI, but act independently of IL-10. We have now further characterized the phenotype and inhibitory activity of these protective pulmonary B cells. We excluded a role for regulatory T (Treg) cell induction as putative AAI-protective mechanisms. Schistosome-induced B cells showed increased CD86 expression and reduced cytokine expression in response to Toll-like receptor (TLR) ligands compared with control B cells. To investigate the consequences for T cell activation we cultured ovalbumin (OVA)-pulsed, schistosome-induced B cells with OVA-specific transgenic T cells and observed less Th2 cytokine expression and T cell proliferation compared with control conditions. This suppressive effect was preserved even under optimal T cell stimulation by anti-CD3/28. Blocking of the inhibitory cytokines IL-10 or TGF-β only marginally restored Th2 cytokine induction. These data suggest that schistosome-induced pulmonary B cells are impaired in their capacity to produce cytokines to TLR ligands and to induce Th2 cytokine responses independent of their antigen-presenting function. These findings underline the presence of distinct B cell subsets with different stimulatory or inhibitory properties even if induced by the same type of helminth.

  15. Microbiota abnormalities in inflammatory airway diseases - Potential for therapy.

    PubMed

    Gollwitzer, Eva S; Marsland, Benjamin J

    2014-01-01

    Increasingly the development of novel therapeutic strategies is taking into consideration the contribution of the intestinal microbiota to health and disease. Dysbiosis of the microbial communities colonizing the human intestinal tract has been described for a variety of chronic diseases, such as inflammatory bowel disease, obesity and asthma. In particular, reduction of several so-called probiotic species including Lactobacilli and Bifidobacteria that are generally considered to be beneficial, as well as an outgrowth of potentially pathogenic bacteria is often reported. Thus a tempting therapeutic approach is to shape the constituents of the microbiota in an attempt to restore the microbial balance towards the growth of 'health-promoting' bacterial species. A twist to this scenario is the recent discovery that the respiratory tract also harbors a microbiota under steady-state conditions. Investigators have shown that the microbial composition of the airway flora is different between healthy lungs and those with chronic lung diseases, such as asthma, chronic obstructive pulmonary disease as well as cystic fibrosis. This is an emerging field, and thus far there is very limited data showing a direct contribution of the airway microbiota to the onset and progression of disease. However, should future studies provide such evidence, the airway microbiota might soon join the intestinal microbiota as a target for therapeutic intervention. In this review, we highlight the major advances that have been made describing the microbiota in chronic lung disease and discuss current and future approaches concerning manipulation of the microbiota for the treatment and prevention of disease.

  16. Multidetector computed tomography of pediatric large airway diseases: state-of-the-art.

    PubMed

    Lee, Edward Y; Greenberg, S Bruce; Boiselle, Phillip M

    2011-09-01

    Advances in multidetector computed tomography (MDCT) technology have given rise to improvements in the noninvasive and comprehensive assessment of the large airways in pediatric patients. Superb two-dimensional and three-dimensional reconstruction MDCT images have revolutionized the display of large airways and enhanced the ability to diagnose large airway diseases in children. The 320-MDCT scanner, which provides combined detailed anatomic and dynamic functional information assessment of the large airways, is promising for the assessment of dynamic large airway disease such as tracheobronchomalacia. This article discusses imaging techniques and clinical applications of MDCT for assessing large airway diseases in pediatric patients.

  17. Airway Reflux, Cough and Respiratory Disease

    PubMed Central

    Molyneux, Ian D.; Morice, Alyn H.

    2011-01-01

    It is increasingly accepted that the effects of gastro-oesophageal reflux are not limited to the gastrointestinal tract. The adjacent respiratory structures are also at risk from material ejected from the proximal oesophagus as a result of the failure of anatomical and physiological barriers. There is evidence of the influence of reflux on several respiratory and otorhinological conditions and although in many cases the precise mechanism has yet to be elucidated, the association alone opens potential novel avenues of therapy to clinicians struggling to treat patients with apparently intractable respiratory complaints. This review provides a description of the airway reflux syndrome, its effects on the lung and current and future therapeutic options. PMID:23251752

  18. Role of interleukin-18 in the pathophysiology of allergic diseases.

    PubMed

    Sanders, Nathan L; Mishra, Anil

    2016-12-01

    Interleukin (IL)-18 is an IL-1 family cytokine expressed by macrophages, dendritic cells, epithelial cells, and keratinocytes and is implicated in various aspects of both the innate and adaptive immune systems. IL-18 signals similar to IL-1β intracellularly to activate gene transcription. Since its discovery, IL-18 has been demonstrated to play a key role in pathogen defense from helminths and some bacteria. Recently however, evidence has accumulated that IL-18 expression is increased in many presentations of allergic disease. A pathologic role for IL-18 includes stimulating mast cell and basophil degranulation, recruiting granulocytes to sites of inflammation, increasing cytotoxic activity of natural killer (NK) and NK-T cells, inducing Immunoglobulin (Ig)E production and isotype switching, and affecting a broad range of T cells to promote a type II helper T cell (Th2) response. Evidence and importance of these effects are presented, including novel results from our lab implicating IL-18 in the direct expansion of mast cells, basophils, and other myeloid-lineage cells from bone-marrow precursors. The development of urticaria, asthma, dermatitis, rhinitis, and eosinophilic disorders all have demonstrated correlations to increased IL-18 levels either in the tissue or systemically. IL-18 represents a novel site of immune regulation in not only allergic conditions, but also autoimmune diseases and other instances of aberrant immune functioning. Diagrammatic summarized abstract for readers convinance is presented in Fig. 1.

  19. Inflammatory mechanisms and treatment of obstructive airway diseases with neutrophilic bronchitis.

    PubMed

    Simpson, Jodie L; Phipps, Simon; Gibson, Peter G

    2009-10-01

    Obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major global health issues. Although considered as distinct diseases, airway inflammation is a key underlying pathophysiological process in asthma, COPD and bronchiectasis. Persistent neutrophilic airway inflammation (neutrophilic bronchitis) occurs with innate immune activation and is a feature of each of these airway diseases. Little is known about the mechanisms leading to neutrophilic bronchitis and few treatments are effective in reducing neutrophil accumulation in the airways. There is a similar pattern of inflammatory mediator release and toll like receptor 2 expression in asthma, COPD and bronchiectasis. We propose the existence of an active amplification mechanism, an effector arm of the innate immune system, involving toll like receptor 2, operating in persistent neutrophilic bronchitis. Neutrophil persistence in the airways can occur through a number of mechanisms such as impaired apoptosis, efferocytosis and mucus hypersecretion, all of which are impaired in airways disease. Impairment of neutrophil clearance results in a reduced ability to respond to bacterial infection. Persistent activation of airway neutrophils may result in the persistent activation of the innate immune system resulting in further airway insult. Current therapies are limited for the treatment of neutrophilic bronchitis; possible treatments being investigated include theophylline, statins, antagonists of pro-inflammatory cytokines and macrolide antibiotics. Macrolides have shown great promise in their ability to reduce airway inflammation, and can reduce airway neutrophils, levels of CXCL8 and neutrophil proteases in the airways. Studies also show improvements in quality of life and exacerbation rates in airways diseases.

  20. Oxidant-mediated ciliary dysfunction. Possible role in airway disease

    SciTech Connect

    Burman, W.J.; Martin, W.J. 2d.

    1986-03-01

    The effects of reactive species of oxygen on the airway are not well known. This study examined the effects of hydrogen peroxide (H2O2) on the structure and function of the airway epithelium. Tracheal rings were prepared from 200 g male rats. Damage to the airway epithelium was assayed by monitoring the ciliary beat frequency, the release of 51Cr, and histology. H2O2 at concentrations of 1.0 mM and above caused a very rapid decrease in ciliary beat frequency. After ten minutes' exposure to 1.0 mM, the ciliary beat frequency was 72 +/- 20 percent of control. Release of 51Cr was a less sensitive measure with significant release occurring after four hours of exposure to ciliotoxic concentrations of H2O2. Histologic changes were not evident within the experimental time period. All toxic effects of H2O2 were completely blocked by catalase. This study shows that H2O2 causes a rapid decline in ciliary activity and suggests that oxidant-mediated ciliary dysfunction could play a role in the pathogenesis of airway disease. The ciliary beat frequency provides a sensitive, physiologically relevant parameter for the in vitro study of these diseases.

  1. Parental allergic disease before and after child birth poses similar risk for childhood allergies.

    PubMed

    Fuertes, E; Standl, M; von Berg, A; Lehmann, I; Hoffmann, B; Bauer, C-P; Koletzko, S; Berdel, D; Heinrich, J

    2015-07-01

    Whether the strength of associations between parental and child allergic diseases differs by whether the first onset of the parental disease is before or after a child's birth has never been examined and is the aim of this study. Yearly childhood asthma, allergic rhinitis, and eczema diagnoses were longitudinally regressed against the effect of a parental disease (pre- vs post-child birth) of the same type separately for each parent using generalized estimation equations. Both a maternal and paternal history of asthma were associated with childhood asthma prevalence up to 15 years of age. Effect estimates were similar for parental asthma with first onset before and after the birth of the child. The results for allergic rhinitis and eczema were less consistent. Parental allergic diseases with first onsets before and after the birth of a child both pose risks to childhood allergic disease in the offspring, especially for asthma.

  2. Neutrophil recruitment by allergens contribute to allergic sensitization and allergic inflammation

    PubMed Central

    Hosoki, Koa; Boldogh, Istvan; Sur, Sanjiv

    2016-01-01

    Purpose of review To discuss the presence and role of neutrophils in asthma and allergic diseases, and outline importance of pollen and cat dander-induced innate neutrophil recruitment in induction of allergic sensitization and allergic inflammation. Recent findings Uncontrolled asthma is associated with elevated numbers of neutrophils, and levels of neutrophil-attracting chemokine IL-8 and IL-17 in BAL fluids. These parameters negatively correlate with lung function. Pollen allergens and cat dander recruit neutrophils to the airways in a TLR4, MD2 and CXCR2-dependent manner. Repeated recruitment of activated neutrophils by these allergens facilitates allergic sensitization and airway inflammation. Inhibition of neutrophil recruitment with CXCR2 inhibitor, disruption of TLR4, or siRNA against MD2 also inhibits allergic inflammation. The molecular mechanisms by which neutrophils shift the inflammatory response of the airways to inhaled allergens to an allergic phenotype is an area of active research. Summary Recent studies have revealed that neutrophil recruitment is important in development of allergic sensitization and inflammation. Inhibition of neutrophils recruitment may be strategy to control allergic inflammation. PMID:26694038

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

    DTIC Science & Technology

    2006-03-01

    diseases, such as experimental autoimmune encephalomyelitis, neuritis, uveitis , thyroiditis, orchitis, and adjuvant arthritis [4, 5]. The adjuvants...have been widely used to establish animal models of autoimmune diseases, such as experimental autoimmune encephalomyelitis, neuritis, uveitis ...models of autoimmune diseases, such as experimental autoimmune encephalomyelitis, neuritis, uveitis , thyroiditis, orchitis, and adjuvant arthritis

  4. Notch ligand delta-like 4 regulates development and pathogenesis of allergic airway responses by modulating IL-2 production and Th2 immunity.

    PubMed

    Jang, Sihyug; Schaller, Matthew; Berlin, Aaron A; Lukacs, Nicholas W

    2010-11-15

    Activation of the canonical Notch pathways has been implicated in Th cell differentiation, but the role of specific Notch ligands in Th2-mediated allergic airway responses has not been completely elucidated. In this study, we show that delta-like ligand 4 (Dll4) was upregulated on dendritic cells in response to cockroach allergen. Blocking Dll4 in vivo during either the primary or secondary response enhanced allergen-induced pathogenic consequences including airway hyperresponsiveness and mucus production via increased Th2 cytokines. In vitro assays demonstrated that Dll4 regulates IL-2 in T cells from established Th2 responses as well as during primary stimulation. Notably, Dll4 blockade during the primary, but not the secondary, response increased IL-2 levels in lung and lymph node of allergic mice. The in vivo neutralization of Dll4 was associated with increased expansion and decreased apoptosis during the primary allergen sensitization. Moreover, Dll4-mediated Notch activation of T cells during primary stimulation in vitro increased apoptosis during the contraction/resting phase of the response, which could be rescued by exogenous IL-2. Consistent with the role for Dll4-mediated IL-2 regulation in overall T cell function, the frequency of IL-4-producing cells was also significantly altered by Dll4 both in vivo and in vitro. These data demonstrate a regulatory role of Dll4 both in initial Th2 differentiation and in Th2 cytokine production in established allergic responses.

  5. Divers' lung function: small airways disease?

    PubMed Central

    Thorsen, E; Segadal, K; Kambestad, B; Gulsvik, A

    1990-01-01

    Pulmonary function was measured in 152 professional saturation divers and in a matched control group of 106 subjects. Static lung volumes, dynamic lung volumes and flows, transfer factor for carbon monoxide (T1CO), transfer volume per unit alveolar volume (KCO), delta-N2, and closing volume (CV) were measured and compared with reference values from recent Scandinavian studies, British submariners, and the European Community for Coal and Steel (ECCS) recommended reference values. Diving exposure was assessed as years of diving experience, total number of days in saturation and depth, and as the product of days in saturation and mean depth. Divers had significantly lower values for forced expired volume in one second (FEV1), FEV1/forced vital capacity (FVC) ratio, FEF25-75%, FEF75-85%, FEF50%, FEF75%, T1CO, and KCO compared with the controls and a significantly higher CV. There was a positive correlation between diving exposure and CV, whereas the other variables had negative correlations with diving exposure. Values for the control group were not different from the predictive values of Scandinavian reference studies or British submariners, although the ECCS standard predicted significantly lower values for the lung function variables both in divers and the control group. The pattern of the differences in lung function variables between the divers and controls is consistent with small airways dysfunction and with the transient changes in lung function found immediately after a single saturation dive. The association between reduced pulmonary function and previous diving exposure further indicates the presence of cumulative long term effects of diving on pulmonary function. PMID:2393630

  6. Contribution of anaphylatoxin C5a to late airway responses after repeated exposure of antigen to allergic rats.

    PubMed

    Abe, M; Shibata, K; Akatsu, H; Shimizu, N; Sakata, N; Katsuragi, T; Okada, H

    2001-10-15

    We attempted to elucidate the contribution of complement to allergic asthma. Rat sensitized to OVA received repeated intratracheal exposures to OVA for up to 3 consecutive days, and pulmonary resistance was then estimated for up to 6 h after the last exposure. Whereas the immediate airway response (IAR) in terms of R(L) tended to decrease in proportion to the number of OVA exposures, late airway response (LAR) became prominent only after three. Although premedication with two kinds of complement inhibitors, soluble complement receptor type 1 (sCR1) or nafamostat mesylate, resulted in inhibition of the IAR after either a single or a double exposure, the LAR was inhibited after the triple. Premedication with a C5a receptor antagonist (C5aRA) before every exposure to OVA also inhibited the LAR after three. Repeated OVA exposure resulted in eosinophil and neutrophil infiltration into the bronchial submucosa which was suppressed by premedication with sCR1 or C5aRA. Up-regulation of C5aR mRNA was shown in lungs after triple OVA exposure, but almost no up-regulation of C3aR. Pretreatment with sCR1 or C5aRA suppressed the up-regulation of C5aR expression as well as cytokine messages in the lungs. The suppression of LAR by pretreatment with sCR1 was reversed by intratracheal instillation of rat C5a desArg the action of which was inhibited by C5aRA. In contrast, rat C3a desArg or cytokine-induced neutrophil chemoattractant-1 induced cellular infiltration into the bronchial submucosa by costimulation with OVA, but these had no influence on the LAR. These differences might be explained by the fact that costimulation with OVA and C5a synergistically potentiated IAR, whereas that with OVA and either C3a or cytokine-induced neutrophil chemoattractant-1 did not. C5a generated by Ag-Ab complexes helps in the production of cytokines and contributes to the LAR after repeated exposure to Ag.

  7. Intranasal administration of CpG oligodeoxynucleotides reduces lower airway inflammation in a murine model of combined allergic rhinitis and asthma syndrome.

    PubMed

    Li, Hong-Tao; Zhang, Tian-Tuo; Chen, Zhuang-Gui; Ye, Jin; Liu, Hui; Zou, Xiao-Ling; Wang, Yan-Hong; Yang, Hai-Ling

    2015-09-01

    Given the relationship between allergic rhinitis (AR) and asthma, it can be hypothesized that reducing upper airway inflammation by targeting oligodeoxynucleotides with CpG motifs (CpG-ODN) specifically to the upper airway via intranasal administration in a small volume (10 μL) might improve lower airway (asthma) outcomes. The goal of this study was to investigate the therapeutic efficacy of 10 μL of intranasal versus intradermal administration of CpG-ODN in suppressing lower airway inflammation and methacholine-induced airway hyperreactivity (AHR) in mice subjected to ovalbumin (OVA)-induced combined allergic rhinitis and asthma syndrome (CARAS). OVA-sensitized BALB/c mice were subjected to upper-airway intranasal OVA exposure three times per week for 3 weeks. Then, CpG-ODN was administered to a subset of these mice 1h after intranasal OVA exposure, followed by five days of OVA aerosol challenges, thereby targeting OVA to the lower airways. Immunologic variables and nasal symptoms were evaluated. The results showed that the CARAS mice exhibited significant increases in bronchoalveolar lavage fluid (BALF) and splenocytes Th2-associated cytokine production, OVA-specific serum IgE, and AHR, as well as nose and lung pathologies. Intranasal administration of CpG-ODN significantly reduced Th2-associated cytokine production, the percentage of eosinophils in the BALF, the IL-4 and IL-5 concentrations in the supernatants of cultured OVA-challenged splenic lymphocytes, the serum OVA-specific IgE levels, the peribronchial inflammation score in the lungs, and the severity of nose pathology and nasal symptoms. However, intradermal administration of CpG-ODN did not significantly reduce the aforementioned parameters. In conclusion, intranasal treatment with CpG-ODN attenuated AR and significantly alleviated lower airway inflammation and AHR in the CARAS model. CpG-ODN therapy was more effective when administered intranasally than when administered intradermally. The current

  8. Allergic rhinitis, bronchial asthma and other allergies in patients with Alzheimer’s disease: unnoticed issue

    PubMed Central

    Bednarski, Piotr; Jarzab, Jerzy

    2016-01-01

    Introduction Allergic diseases are becoming more prevalent in elderly patients. Allergic diseases have been observed in patients with Alzheimer’s disease (AD). The prevalence of atopic bronchial asthma, allergic rhinitis and atopic dermatitis was analyzed in such elderly Polish population. Aim Analysis of the presence of allergic diseases in the patients with AD in Poland, including asthma, allergic rhinoconjunctivitis and atopic dermatitis. Material and methods The recruitment of subjects with AD was conducted at 6 sites representative of Polish rural and urban areas, and 1060 subjects with a mean age of 69.2 ±5.1 years were screened. Medical examinations, an original questionnaire, skin prick testing for common aeroallergens and appropriate serum-specific IgE assays were performed. Results Probable atopy was diagnosed in 234 (22.1%) analyzed patients, including 127 women (21.5% of women) and 234 men (22.8% of men). The average prevalence associated with age and sex in this population for bronchial asthma was 2.9%, atopic dermatitis/eczema was 0.6%, seasonal allergic rhinitis was 6.6%, perennial allergic rhinitis was 11.1% and polymorphous atopic disease was 4.4%. The most frequent positive results were recorded for the following allergens: mixed grass, Dermatophagoides pteronyssinus, Dermatophagoides farinae and Alternaria. Conclusions One-fifth of diagnosed patients with AD have allergic disease requiring treatment. PMID:27881942

  9. Repurposing tromethamine as inhaled therapy to treat CF airway disease

    PubMed Central

    Alaiwa, Mahmoud H. Abou; Launspach, Janice L.; Sheets, Kelsey A.; Rivera, Jade A.; Gansemer, Nicholas D.; Taft, Peter J.; Thorne, Peter S.; Welsh, Michael J.; Stoltz, David A.

    2016-01-01

    In cystic fibrosis (CF), loss of CF transmembrane conductance regulator (CFTR) anion channel activity causes airway surface liquid (ASL) pH to become acidic, which impairs airway host defenses. One potential therapeutic approach is to correct the acidic pH in CF airways by aerosolizing HCO3– and/or nonbicarbonate pH buffers. Here, we show that raising ASL pH with inhaled HCO3– increased pH. However, the effect was transient, and pH returned to baseline values within 30 minutes. Tromethamine (Tham) is a buffer with a long serum half-life used as an i.v. formulation to treat metabolic acidosis. We found that Tham aerosols increased ASL pH in vivo for at least 2 hours and enhanced bacterial killing. Inhaled hypertonic saline (7% NaCl) is delivered to people with CF in an attempt to promote mucus clearance. Because an increased ionic strength inhibits ASL antimicrobial factors, we added Tham to hypertonic saline and applied it to CF sputum. We found that Tham alone and in combination with hypertonic saline increased pH and enhanced bacterial killing. These findings suggest that aerosolizing the HCO3–-independent buffer Tham, either alone or in combination with hypertonic saline, might be of therapeutic benefit in CF airway disease. PMID:27390778

  10. [An association of the occupational risk factors from greenhouses with allergic diseases in their female workers' children: results of analysis].

    PubMed

    Imamov, A A; Troshina, I V; Fomicheva, G B; Zamalieva, M A

    2010-01-01

    The paper analyzes an association between occupational risk factors in the female workers of greenhouses and allergic diseases in their children. The major factors contributing to the occurrence of allergic disease in children are their maternal employment in greenhouses with harmful working conditions, much dust in an apartment, a family history of allergic diseases, and unfavorable family lifestyle.

  11. Treatment of mice with fenbendazole attenuates allergic airways inflammation and Th2 cytokine production in a model of asthma.

    PubMed

    Cai, Yeping; Zhou, Jiansheng; Webb, Dianne C

    2009-01-01

    Mouse models have provided a significant insight into the role of T-helper (Th) 2 cytokines such as IL-5 and IL-13 in regulating eosinophilia and other key features of asthma. However, the validity of these models can be compromised by inadvertent infection of experimental mouse colonies with pathogens such as oxyurid parasites (pinworms). While the benzimidazole derivative, fenbendazole (FBZ), is commonly used to treat such outbreaks, the effects of FBZ on mouse models of Th2 disease are largely unknown. In this investigation, we show that mice fed FBZ-supplemented food during the in utero and post-weaning period developed attenuated lung eosinophilia, antigen-specific IgG1 and Th2 cytokine responses in a model of asthma. Treatment of the mediastinal lymph node cells from allergic mice with FBZ in vitro attenuated cell proliferation, IL-5 and IL-13 production and expression of the early lymphocyte activation marker, CD69 on CD4(+) T cells and CD19(+) B cells. In addition, eosinophilia and Th2 responses remained attenuated after a 4-week withholding period in allergic mice treated preweaning with FBZ. Thus, FBZ modulates the amplitude of Th2 responses both in vivo and in vitro.

  12. Relationship between gastro-oesophageal reflux and airway diseases: the airway reflux paradigm.

    PubMed

    Pacheco-Galván, Adalberto; Hart, Simon P; Morice, Alyn H

    2011-04-01

    Our understanding of the relationship between gastro-oesophageal reflux and respiratory disease has recently undergone important changes. The previous paradigm of airway reflux as synonymous with the classic gastro-oesophageal reflux disease (GORD) causing heartburn has been overturned. Numerous epidemiological studies have shown a highly significant association of the acid, liquid, and gaseous reflux of GORD with conditions such as laryngeal diseases, chronic rhinosinusitis, treatment resistant asthma, COPD and even idiopathic pulmonary fibrosis. However, it has become clear from studies on cough hypersensitivity syndrome that much reflux of importance in the airways has been missed, since it is either non- or weakly acid and gaseous in composition. The evidence for such a relationship relies on the clinical history pointing to symptom associations with known precipitants of reflux. The tools for the diagnosis of extra-oesophageal reflux, in contrast to the oesophageal reflux of GORD, lack sensitivity and reproducibility. Unfortunately, methodology for detecting such reflux is only just becoming available and much additional work is required to properly delineate its role.

  13. Synthesis and evaluation of airway targeted PLGA nanoparticles for drug delivery in obstructive lung diseases.

    PubMed

    Vij, Neeraj

    2012-01-01

    Chronic airway inflammation is a hallmark of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease), and CF (cystic fibrosis). It is also a major challenge in delivery and therapeutic efficacy of nano-based delivery systems in these chronic airway conditions as nanoparticle (NP) need to bypass airways defense mechanisms as we recently discussed. NPs which are capable of overcoming airways defense mechanisms should allow targeted drug delivery to disease cells. Over the last decade there has been increasing interest in development of targeted NPs for cancer but relatively little effort on designing novel systems for treating chronic inflammatory and obstructive airway conditions. Here we describe methods for preparing drug loaded multifunctional nanoparticles for targeted delivery to specific cell types in airways. The formulations and methods for selective drug delivery, discussed here are currently under preclinical development in our laboratory for treating chronic airway conditions such as COPD, CF, and asthma.

  14. The role bronchoscopy in the diagnosis of airway disease in children

    PubMed Central

    Soyer, Tutku

    2016-01-01

    Bronchoscopy is endoscopic examination of airways that allows both diagnostic and interventional procedures in the evaluation of airway disease in children. It can be performed with either rigid or flexible instruments, depending on the particular needs of patients and skills of bronchoscopist. In addition to visualization of airways, bronchoscopy enables to obtain specimens from lungs and distal airways. Bronchoalveolar lavage (BAL) yields samples from surfaces of the alveoli and aids differential diagnosis of various pulmonary disease. Foreign body removal and examination of anatomy and dynamics of airways are also common indications of bronchoscopy in children. Improvement in the technology, endoscopic instrumentation allows detailed evaluation and interventional manipulation of airway lesions in small children. Although bronchoscopy is considered as a safe procedure, obstruction of airway may challenge and require special endoscopic skills with appropriate instrumentation. This review is aimed to outline the role of bronchoscopy in diagnosis airway disease in children. PMID:28066622

  15. Scientists find link between allergic and autoimmune diseases in mouse study

    Cancer.gov

    Scientists at the National Institutes of Health, and their colleagues, have discovered that a gene called BACH2 may play a central role in the development of diverse allergic and autoimmune diseases, such as multiple sclerosis, asthma, Crohn's disease, ce

  16. Inflammatory Signalings Involved in Airway and Pulmonary Diseases

    PubMed Central

    Lee, I-Ta; Yang, Chuen-Mao

    2013-01-01

    In respiratory diseases, there is an increased expression of multiple inflammatory proteins in the respiratory tract, including cytokines, chemokines, and adhesion molecules. Chemokines have been shown to regulate inflammation and immune cell differentiation. Moreover, many of the known inflammatory target proteins, such as matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A2 (cPLA2), are associated with airway and lung inflammation in response to various stimuli. Injuriously environmental stimuli can access the lung through either the airways or the pulmonary and systemic circulations. The time course and intensity of responses by resident and circulating cells may be regulated by various inflammatory signalings, including Src family kinases (SFKs), protein kinase C (PKC), growth factor tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species (ROS), PI3K/Akt, MAPKs, nuclear factor-kappa B (NF-κB), activator protein-1 (AP-1), and other signaling molecules. These signaling molecules regulate both key inflammatory signaling transduction pathways and target proteins involved in airway and lung inflammation. Here, we discuss the mechanisms involved in the expression of inflammatory target proteins associated with the respiratory diseases. Knowledge of the mechanisms of inflammation regulation could lead to the pharmacological manipulation of anti-inflammatory drugs in the respiratory diseases. PMID:23690670

  17. Impact of perinatal environmental tobacco smoke on the development of childhood allergic diseases

    PubMed Central

    2016-01-01

    Allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy, are most common chronic, noncommunicable diseases in childhood. In the past few decades, the prevalence has increased abruptly worldwide. There are 2 possible explanations for the rising prevalence of allergic diseases worldwide, that an increased disease-awareness of physician, patient, or caregivers, and an abrupt exposure to unknown hazards. Unfortunately, the underlying mechanisms remain largely unknown. Despite the continuing efforts worldwide, the etiologies and rising prevalence remain unclear. Thus, it is important to identify and control risk factors in the susceptible individual for the best prevention and management. Genetic susceptibility or environments may be a potential background for the development of allergic disease, however they alone cannot explain the rising prevalence worldwide. There is growing evidence that epigenetic change depends on the gene, environment, and their interactions, may induce a long-lasting altered gene expression and the consequent development of allergic diseases. In epigenetic mechanisms, environmental tobacco smoke (ETS) exposure during critical period (i.e., during pregnancy and early life) are considered as a potential cause of the development of childhood allergic diseases. However, the causal relationship is still unclear. This review aimed to highlight the impact of ETS exposure during the perinatal period on the development of childhood allergic diseases and to propose a future research direction. PMID:27610180

  18. TLR-7 agonist attenuates airway reactivity and inflammation through Nrf2-mediated antioxidant protection in a murine model of allergic asthma.

    PubMed

    Nadeem, Ahmed; Siddiqui, Nahid; Al-Harbi, Naif O; Al-Harbi, Mohammed M; Ahmad, Sheikh F

    2016-04-01

    Toll-like receptors (TLRs) through innate immune system recognize pathogen associated molecular patterns and play an important role in host defense against bacteria, fungi and viruses. TLR-7 is responsible for sensing single stranded nucleic acids of viruses but its activation has been shown to be protective in mouse models of asthma. The NADPH oxidase (NOX) enzymes family mainly produces reactive oxygen species (ROS) in the lung and is involved in regulation of airway inflammation in response to TLRs activation. However, NOX-4 mediated signaling in response to TLR-7 activation in a mouse model of allergic asthma has not been explored previously. Therefore, this study investigated the role TLR-7 activation and downstream oxidant-antioxidant signaling in a murine model of asthma. Mice were sensitized with ovalbumin (OVA) intraperitoneally and treated with TLR-7 agonist, resiquimod (RSQ) intranasally before each OVA challenge from days 14 to 16. Mice were then assessed for airway reactivity, inflammation, and NOX-4 and nuclear factor E2-related factor 2 (Nrf2) related signaling [inducible nitric oxide synthase (iNOS), nitrotyrosine, lipid peroxides and copper/zinc superoxide dismutase (Cu/Zn SOD)]. Treatment with RSQ reduced allergen induced airway reactivity and inflammation. This was paralleled by a decrease in ROS which was due to induction of Nrf2 and Cu/Zn SOD in RSQ treated group. Inhibition of MyD88 reversed RSQ-mediated protective effects on airway reactivity/inflammation due to reduction in Nrf2 signaling. SOD inhibition produced effects similar to MyD88 inhibition. The current study suggests that TLR-7 agonist is beneficial and may be developed into a therapeutic option in allergic asthma.

  19. Crosscultural communication in those with airway diseases.

    PubMed

    Car, J; Partridge, M R

    2004-01-01

    Transcultural consultations are becoming commonplace. Such consultations arise because patients from ethnic groups consult doctors, but also because patients consult doctors from other ethnic backgrounds. Such consultations require a cultural awareness and sensitivity which may be particularly necessary when concerning those with respiratory illnesses which are often long-term and about which there may be considerable stigma. The prevalence of respiratory disease can vary between ethnic groups, most noticeably in tuberculosis and smoking; and in diseases such as asthma, health service usage and treatment can vary significantly with ethnicity. Some of this may represent cultural, rather than disease specific differences. Good communication is essential throughout medical practice, but in transcultural consultations it is especially important that the doctor pays appropriate attention to likely patient beliefs and approaches to shared decision making. Usual negotiation regarding goals and outcomes first requires the clinician to understand how a patient's understanding of illness may vary from a traditional western scientific approach. Special attention needs to be paid to the optimal way of using interpreters and more time is often needed for crosscultural consultations. Specific training is necessary for health practitioners to enable them to acquire the skills for crosscultural care and this involves learning about other cultures and an appreciation of how a change in attitude often needs to be incorporated into the clinical approach. Acquiring these skills and understandings to facilitate optimal transcultural consultation enables transfer of these skills to other similar clinical scenarios such as the approach to those with disability. The global burden of long-term respiratory disease, both infectious and noncommunicable, coupled with increased migration and geographical mobility means that a successful crosscultural approach is now a priority area for

  20. Airway Epithelial Cell Cilia and Obstructive Lung Disease

    PubMed Central

    Yaghi, Asma; Dolovich, Myrna B.

    2016-01-01

    Airway epithelium is the first line of defense against exposure of the airway and lung to various inflammatory stimuli. Ciliary beating of airway epithelial cells constitutes an important part of the mucociliary transport apparatus. To be effective in transporting secretions out of the lung, the mucociliary transport apparatus must exhibit a cohesive beating of all ciliated epithelial cells that line the upper and lower respiratory tract. Cilia function can be modulated by exposures to endogenous and exogenous factors and by the viscosity of the mucus lining the epithelium. Cilia function is impaired in lung diseases such as COPD and asthma, and pharmacologic agents can modulate cilia function and mucus viscosity. Cilia beating is reduced in COPD, however, more research is needed to determine the structural-functional regulation of ciliary beating via all signaling pathways and how this might relate to the initiation or progression of obstructive lung diseases. Additionally, genotypes and how these can influence phenotypes and epithelial cell cilia function and structure should be taken into consideration in future investigations. PMID:27845721

  1. Current management of allergic rhinitis in children.

    PubMed

    Georgalas, Christos; Terreehorst, Ingrid; Fokkens, Wytske

    2010-02-01

    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 therapeutic modalities. These new insights have been documented in the Allergic Rhinitis and its Impact on Asthma guidelines and have led to the creation of evidence-based management algorithms. We now understand the importance of a common strategy for treating allergic inflammation of the upper and lower airway as a way of improving outcome, reducing hospital admissions, providing better quality of life and perhaps, altering the natural course of the 'allergic march'. A therapeutic ladder is suggested: Whereas for mild intermittent allergic rhinitis, allergen avoidance should be the first line of treatment with subsequent addition of a second generation topical or oral antihistamine, nasal saline or cromoglycate, in cases of moderate to severe allergic rhinitis, a nasal steroid is the treatment of choice. If a patient with moderate/severe persistent allergic rhinitis fails to improve after 4 wk of adequate treatment, patient compliance or the diagnosis must be re-assessed. In such cases, when the diagnosis is in doubt, a careful clinical examination including nasal endoscopy is mandatory to assess for other potential causes of nasal obstruction. In children who suffer from concomitant allergic rhinitis and asthma, a management algorithm that addresses concurrently asthma and allergic rhinitis is vital, both from a theoretical and from a practical point of view: Parents overwhelmingly prefer a single strategy for the treatment of their child's upper and lower airway symptoms; however, the overall quality of life in children with severe asthma can be significantly improved if rhinitis is adequately addressed.

  2. Targeted therapy of bronchitis in obstructive airway diseases.

    PubMed

    Dasgupta, Angira; Neighbour, Helen; Nair, Parameswaran

    2013-12-01

    Guidelines for the management of obstructive airway diseases do not emphasize the measurement of bronchitis to indicate appropriate treatments or monitor response to treatment. Bronchitis is the central component of airway diseases and contributes to symptoms, physiological and structural abnormalities. It can be measured directly and reliably by quantitative assay of spontaneous or induced sputum. The measurement is reproducible, valid, and responsive to treatment and to changes in disease status. Bronchitis may be eosinophilic, neutrophilic, mixed, or paucigranulocytic (eosinophils and neutrophils not elevated). Eosinophilic bronchitis is usually a Th2 driven process and therefore a sputum eosinophilia of greater than 3% usually indicates a response to treatment with corticosteroids or novel therapies directed against Th2 cytokines such as IL-4, IL-5 and IL-13. Neutrophilic bronchitis which is a non-Th2 driven disease is generally a predictor of response to antibiotics and may be a predictor to therapies targeted at pathways that lead to neutrophil recruitment such as IL-8 (eg anti-CXCR2), IL-17 (eg anti-IL17) etc. Paucigranulocytic disease may not warrant anti-inflammatory therapy. Several novel monoclonals and small molecule antagonists have been evaluated in clinical trials with variable results and several more are likely to be discovered in the near future. The success of these agents will depend on appropriate patient selection by accurate phenotyping or characterization of bronchitis.

  3. Hyperleukotrieneuria in patients with allergic and inflammatory disease.

    PubMed

    Taniguchi, Masami; Higashi, Noritaka; Ono, Emiko; Mita, Haruhisa; Akiyama, Kazuo

    2008-12-01

    Cysteinyl leukotrienes (CysLTs: leukotrienes C(4), D(4), and E(4)) have long been implicated in the pathogenesis of asthma and several allergic diseases. LTE(4) has been identified as a major metabolite of LTC(4), and urinary LTE(4) (U-LTE(4)) is considered as the most reliable analytic parameter for monitoring the endogenous synthesis of CysLTs. From recent studies on the U-LTE(4) associated with adult stable asthma we identified four factors for hyperleukotrieneuria, namely, aspirin intolerance, eosinophilic nasal polyposis (ENP), vasculitis, and severe asthma. In ENP, there is prominent infiltration of eosinophils in the sinus and polyp tissues, which is linked to adult asthma and aspirin sensitivity, and ENP is the most important factor for the overproduction of CysLTs in asthmatics. We also demonstrated that anaphylaxis and eosinophilic pneumonia (EP) are associated with a marked increase in the U-LTE(4) concentration. Under these disease conditions, U-LTE(4) may be one of the candidate biomarkers. Moreover, the changes in U-LTE(4) concentrations may provide valuable information concerning therapeutic targets.

  4. [Swimming pool lung -- extrinsic allergic alveolitis or mycobacterial disease?].

    PubMed

    Koschel, D; Pietrzyk, C; Sennekamp, J; Müller-Wening, D

    2006-05-01

    There have been several recent reports of pulmonary disease resulting from exposure to Mycobacterium avium complex in indoor hot tubs. The disease is thought to be due either to infection or extrinsic allergic alveolitis (EAA). In this report we describe the case of a patient who developed episodes of fever, dyspnea and cough 4-6 hours after cleaning his indoor swimming pool. A diagnosis of EAA was made on finding a restrictive lung function pattern with gas exchange abnormalities, a predominant lymphocytosis in the bronchoalveolar lavage, diffuse ground-glass opacities in the lower lobes on high-resolution computer tomography, and specific IgG antibody activity to the swimming pool water. There was no precipitin reaction or specific IgG antibody activity to microbes extracted from the water. Interestingly, the water contained Mycobacterium avium complex (MAC) in huge amounts and in this case the histopathological features of the lung biopsy specimens differed from those seen in typical EAA, but were similar to those described in "hot tub lung" caused by mycobacteria. Solely by avoidance of cleaning the swimming pool, without any pharmacological treatment, the patient recovered completely within three months. To the best of our knowledge, this is the first report of EAA possibly associated with MAC exposure in a swimming pool environment.

  5. Systems biology of asthma and allergic diseases: a multiscale approach.

    PubMed

    Bunyavanich, Supinda; Schadt, Eric E

    2015-01-01

    Systems biology is an approach to understanding living systems that focuses on modeling diverse types of high-dimensional interactions to develop a more comprehensive understanding of complex phenotypes manifested by the system. High-throughput molecular, cellular, and physiologic profiling of populations is coupled with bioinformatic and computational techniques to identify new functional roles for genes, regulatory elements, and metabolites in the context of the molecular networks that define biological processes associated with system physiology. Given the complexity and heterogeneity of asthma and allergic diseases, a systems biology approach is attractive, as it has the potential to model the myriad connections and interdependencies between genetic predisposition, environmental perturbations, regulatory intermediaries, and molecular sequelae that ultimately lead to diverse disease phenotypes and treatment responses across individuals. The increasing availability of high-throughput technologies has enabled system-wide profiling of the genome, transcriptome, epigenome, microbiome, and metabolome, providing fodder for systems biology approaches to examine asthma and allergy at a more holistic level. In this article we review the technologies and approaches for system-wide profiling, as well as their more recent applications to asthma and allergy. We discuss approaches for integrating multiscale data through network analyses and provide perspective on how individually captured health profiles will contribute to more accurate systems biology views of asthma and allergy.

  6. Cystic fibrosis lung disease starts in the small airways: can we treat it more effectively?

    PubMed

    Tiddens, Harm A W M; Donaldson, Scott H; Rosenfeld, Margaret; Paré, Peter D

    2010-02-01

    The aims of this article are to summarize existing knowledge regarding the pathophysiology of small airways disease in cystic fibrosis (CF), to speculate about additional mechanisms that might play a role, and to consider the available or potential options to treat it. In the first section, we review the evidence provided by pathologic, physiologic, and imaging studies suggesting that obstruction of small airways begins early in life and is progressive. In the second section we discuss how the relationships between CF transmembrane conductance regulator (CFTR), ion transport, the volume of the periciliary liquid layer and airway mucus might lead to defective mucociliary clearance in small airways. In addition, we discuss how chronic endobronchial bacterial infection and a chronic neutrophilic inflammatory response increase the viscosity of CF secretions and exacerbate the clearance problem. Next, we discuss how the mechanical properties of small airways could be altered early in the disease process and how remodeling can contribute to small airways disease. In the final section, we discuss how established therapies impact small airways disease and new directions that may lead to improvement in the treatment of small airways disease. We conclude that there are many reasons to believe that small airways play an important role in the pathophysiology of (early) CF lung disease. Therapy should be aimed to target the small airways more efficiently, especially with drugs that can correct the basic defect at an early stage of disease.

  7. X-Ray based Lung Function measurement–a sensitive technique to quantify lung function in allergic airway inflammation mouse models

    PubMed Central

    Dullin, C.; Markus, M. A.; Larsson, E.; Tromba, G.; Hülsmann, S.; Alves, F.

    2016-01-01

    In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy. PMID:27805632

  8. X-Ray based Lung Function measurement-a sensitive technique to quantify lung function in allergic airway inflammation mouse models.

    PubMed

    Dullin, C; Markus, M A; Larsson, E; Tromba, G; Hülsmann, S; Alves, F

    2016-11-02

    In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy.

  9. X-Ray based Lung Function measurement–a sensitive technique to quantify lung function in allergic airway inflammation mouse models

    NASA Astrophysics Data System (ADS)

    Dullin, C.; Markus, M. A.; Larsson, E.; Tromba, G.; Hülsmann, S.; Alves, F.

    2016-11-01

    In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy.

  10. Gut Microbiome and the Development of Food Allergy and Allergic Disease

    PubMed Central

    Prince, Benjamin T.; Mandel, Mark J.; Nadeau, Kari; Singh, Anne Marie

    2015-01-01

    The prevalence of food allergy and other allergic diseases continues to rise within the industrialized world, yet the cause of this epidemic remains elusive. Environmental factors such as microbial exposures have more recently been implicated as one possible driving factor behind the increasing burden of allergic disease. The impact of gut microbiome on human development, nutritional needs, and disease has become evident with advances in our ability to study these complex communities of microorganisms, and there is a growing appreciation for the role of the microbiome in immune regulation. Several studies have examined associations between changes in the commensal microbiota and the development of asthma, allergic rhinitis, and asthma, but far less have evaluated the impact of the microbiome on the development of food allergy. In this article we review the human gastrointestinal microbiome, focusing on the theory and evidence for its role in the development of IgE-mediated food allergy and other allergic diseases. PMID:26456445

  11. The Treatment of Allergic Respiratory Disease During Pregnancy.

    PubMed

    Namazy, Jai; Schatz, M

    2016-01-01

    Pregnancy may be complicated by new-onset or preexisting asthma and allergic rhinitis.This article reviews the recognition and management of asthma and allergic rhinitis during pregnancy, paying close attention to the general principles of allergy and use of asthma medication during pregnancy. Both allergic rhinitis and asthma can adversely affect both maternal quality of life and, in the case of maternal asthma, perinatal outcomes. Optimal management is thus important for both mother and baby. This article reviews the safety of asthma and allergy medications commonly used during pregnancy.

  12. [Non-allergic type of atopic dermatitis among patients of Allergic Diseases Diagnostic Center, University of Medical Sciences in Poznań].

    PubMed

    Czarnecka-Operacz, Magdalena; Jenerowicz, Dorota; Silny, Wojciech

    2005-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease of unclear etiopathogenesis. It belongs to the group of atopic diseases and an IgE-mediated uptake and antigen focusing of environmental allergens by IgE-bearing dendritic cells is assumed to be a central immunopathogenetic event resulting in clinical appearance of AD. In case of non-allergic (intrinsic) type of AD, non IgE-related factors are involved in the process. Potential immunological and clinical differences between allergic and non-allergic type of the disease are still being investigated. The aim of our study was to evaluate prevalence of non-allergic and allergic type of AD among patients of Allergic Diseases Diagnostic Center, University of Medical Sciences in Poznań between 2001 and 2002. We investigated 161 patients with AD and selected factors influencing course of the disease such as age, gender, month of birth, population of the region and characteristics of sensitizing allergens were analyzed. Allergological diagnostics consisted of skin prick tests and measurements of total and antigen specific IgE concentrations in sera of investigated patients (FEIA CAP). Non-allergic type of AD was registered in 38.5% of the investigated population. There was no significant difference between allergic and non-allergic type of AD in terms of month of birth and living conditions (urban areas or countryside). Especially in the case of children evaluations of total and antigen specific IgE serum concentrations were helpful in verification of skin prick test results. In the group of patients with allergic type of AD grass pollen allergens were sensitizing most frequently and finally type of sensitizing airborne allergens may be at least partially related to the environmental characteristics of the region.

  13. Curcumin attenuates allergic airway inflammation by regulation of CD4+CD25+ regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice.

    PubMed

    Ma, Chunhua; Ma, Zhanqiang; Fu, Qiang; Ma, Shiping

    2013-06-01

    The present study aimed to determine the protective effects and the underlying mechanisms of curcumin on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Asthma mice model was established by ovalbumin. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg), and curcumin (50 mg/kg, 100 mg/kg, 200 mg/kg). Airway resistance (Raw) was measured by the forced oscillation technique, differential cell count in BAL fluid (BALF) was measured by Wright-Giemsa staining, histological assessment was measured by hematoxylin and eosin (HE) staining, BALF levels of Treg/Th17 cytokines were measured by enzyme-linked immunosorbent assay, Treg cells and Th17 cells were evaluated by flow cytometry (FCM). Our study demonstrated that curcumin inhibited OVA-induced increases in eosinophil count; interleukin (IL)-17A level were recovered in bronchoalveolar lavage fluid increased IL-10 level in bronchoalveolar lavage fluid. Histological studies demonstrated that curcumin substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry (FCM) studies demonstrated that curcumin remarkably inhibited Th17 cells and significantly increased Treg cells. The results in vivo show ovalbumin-induced significantly broke Treg/Th17 balance; curcumin treatments markedly attenuated the inflammatory in asthma model by regulating Treg/Th17 balance. Our findings support the possible use of curcumin as a therapeutic drug for patients with allergic asthma.

  14. Prevalence of allergic diseases and risk factors of wheezing in Korean military personnel.

    PubMed

    Lee, Sang Min; Ahn, Jong Seong; Noh, Chang Suk; Lee, Sei Won

    2011-02-01

    The objective of this study was to evaluate the prevalence of asthma, allergic rhinitis, and atopic dermatitis, as well as the risk factors of wheezing among young adults in the Korean military. Young military conscripts in five areas completed a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. For subjects with current wheeze in one sample area, baseline spirometry and bronchodilator response were measured. For subjects without a significant response to bronchodilator (improvement in FEV1 of more than 200 mL and 12%), methacholine challenge tests (MCT) were also performed. Of 3,359 subjects that completed the questionnaire, 354 (10.5%) had current wheeze, 471 (14.0%) had current allergic rhinitis, and 326 (9.7%) had current eczema. Current wheeze was associated with family history of allergic disease, overweight, current smoking, allergic rhinitis, and atopic dermatitis. Of 36 subjects with current wheeze who underwent PFT with or without MCT in the Anyang area, 24 (66.7%) were confirmed to have current asthma. In conclusion, the prevalence of allergic disease in young adults of Korean military is not low, and the risk factors of wheezing include family history of allergic disease, overweight, current smoking, allergic rhinitis, and atopic dermatitis.

  15. Pathway Reconstruction of Airway Remodeling in Chronic Lung Diseases: A Systems Biology Approach

    PubMed Central

    Najafi, Ali; Masoudi-Nejad, Ali; Ghanei, Mostafa; Nourani, Mohamad-Reza; Moeini, Ali

    2014-01-01

    Airway remodeling is a pathophysiologic process at the clinical, cellular, and molecular level relating to chronic obstructive airway diseases such as chronic obstructive pulmonary disease (COPD), asthma and mustard lung. These diseases are associated with the dysregulation of multiple molecular pathways in the airway cells. Little progress has so far been made in discovering the molecular causes of complex disease in a holistic systems manner. Therefore, pathway and network reconstruction is an essential part of a systems biology approach to solve this challenging problem. In this paper, multiple data sources were used to construct the molecular process of airway remodeling pathway in mustard lung as a model of airway disease. We first compiled a master list of genes that change with airway remodeling in the mustard lung disease and then reconstructed the pathway by generating and merging the protein-protein interaction and the gene regulatory networks. Experimental observations and literature mining were used to identify and validate the master list. The outcome of this paper can provide valuable information about closely related chronic obstructive airway diseases which are of great importance for biologists and their future research. Reconstructing the airway remodeling interactome provides a starting point and reference for the future experimental study of mustard lung, and further analysis and development of these maps will be critical to understanding airway diseases in patients. PMID:24978043

  16. [Recommendations for the management of the child with allergic diseases at school].

    PubMed

    Saranz, Ricardo J; Lozano, Alejandro; Mariño, Andrea; Boudet, Raúl V; Sarraquigne, María Paula; Cáceres, María Elena; Bandín, Gloria; Lukin, Alicia; Skrie, Víctor; Cassaniti, María Cristina; Agüero, Claudio; Chorny, Marta; Reichbach, Débora S; Arnolt, Roque Gustavo; Cavallo, Aldo

    2015-06-01

    Allergic diseases cause great impact on the health related quality of life in children and adolescents, resulting in increased school absenteeism and deficiencies in school performance. Although the bibliographic framework on allergic diseases is wide, in our country, there are no guidelines for proper management of the allergic child at school. It is necessary to establish guidelines for coordinated action among the educational community, the families, the pediatrician, the health team and governmental and non-governmental authorities. This position paper aims to provide information about the impact of allergic diseases on school activities, establish standards of competence of the various stakeholders at school and consider the legal framework for the intervention of the school staff about the child with allergies at school.

  17. Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of airway allergic inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The epithelium lining the airway tract and allergen-specific IgE are considered essential controllers of inflammatory responses to allergens. The human IgE receptor, CD23 (Fc'RII), is capable of transporting IgE or IgE-allergen complexes across the polarized human airway epithelial cell (AEC) monola...

  18. Using biomarkers in the assessment of airways disease.

    PubMed

    Taylor, D Robin

    2011-11-01

    A biomarker provides a window on underlying disease activity. This is helpful when the pathology, treatment response, or both are heterogeneous or when trying to interpret nonspecific respiratory symptoms in patients with comorbidities. The successful application of a biomarker result is critically dependent on the specific question being addressed and the performance characteristics of the biomarker in relation to that question in the context of pretest probabilities. Negative prediction might be the best way to use a biomarker, such as a D-dimer, pro-brain natriuretic peptide, and exhaled nitric oxide. In this review the role of biomarkers in airways disease (notably induced sputum eosinophils and exhaled nitric oxide) is considered in relation to risk stratification, identification of treatment responders, identification of a clinical phenotype, monitoring of disease, and new drug development.

  19. The emerging relationship between the airway microbiota and chronic respiratory disease: clinical implications

    PubMed Central

    Huang, Yvonne J; Lynch, Susan V

    2012-01-01

    Until recently, relationships between evidence of colonization or infection by specific microbial species and the development, persistence or exacerbation of pulmonary disease have informed our opinions of airway microbiology. However, recent applications of culture-independent tools for microbiome profiling have revealed a more diverse microbiota than previously recognized in the airways of patients with chronic pulmonary disease. New evidence indicates that the composition of airway microbiota differs in states of health and disease and with severity of symptoms and that the microbiota, as a collective entity, may contribute to pathophysiologic processes associated with chronic airway disease. Here, we review the evolution of airway microbiology studies of chronic pulmonary disease, focusing on asthma, chronic obstructive pulmonary disease and cystic fibrosis. Building on evidence derived from traditional microbiological approaches and more recent culture-independent microbiome studies, we discuss the implications of recent findings on potential microbial determinants of respiratory health or disease. PMID:22082166

  20. The emerging relationship between the airway microbiota and chronic respiratory disease: clinical implications.

    PubMed

    Huang, Yvonne J; Lynch, Susan V

    2011-12-01

    Until recently, relationships between evidence of colonization or infection by specific microbial species and the development, persistence or exacerbation of pulmonary disease have informed our opinions of airway microbiology. However, recent applications of culture-independent tools for microbiome profiling have revealed a more diverse microbiota than previously recognized in the airways of patients with chronic pulmonary disease. New evidence indicates that the composition of airway microbiota differs in states of health and disease and with severity of symptoms and that the microbiota, as a collective entity, may contribute to pathophysiologic processes associated with chronic airway disease. Here, we review the evolution of airway microbiology studies of chronic pulmonary disease, focusing on asthma, chronic obstructive pulmonary disease and cystic fibrosis. Building on evidence derived from traditional microbiological approaches and more recent culture-independent microbiome studies, we discuss the implications of recent findings on potential microbial determinants of respiratory health or disease.

  1. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Huang, Yvonne J; Sethi, Sanjay; Murphy, Timothy; Nariya, Snehal; Boushey, Homer A; Lynch, Susan V

    2014-08-01

    Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥ 2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome.

  2. Osteopontin and allergic disease: pathophysiology and implications for diagnostics and therapy.

    PubMed

    Frenzel, Denis F; Weiss, Johannes M

    2011-01-01

    Osteopontin (OPN) is a phosphoglycoprotein that is expressed by various immune cells in a secreted and intracellular form. It has cytokine, chemotactic and cell signaling functions enhancing Th1 and Th17 immunity and protects against apoptosis. Recent studies found OPN to be modulatory in cell-mediated and immediate-type allergic diseases. In allergic asthma, OPN enhances sensitization but downmodulates Th2-driven IL-4-dominated inflammation. The finding that OPN expression is augmented during specific immunotherapy supports a Th2 suppressive effect of OPN. In Th1-driven delayed-type allergy, such as allergic contact dermatitis, OPN supports dendritic cell migration and IL-12 expression and is secreted by T effector cells and keratinocytes, augmenting Th1-mediated allergy and supporting disease chronification. There are numerous missing links as to how OPN variants modulate allergic inflammation through different OPN receptors. OPN research in allergy is an interesting, rapidly expanding field that has high potential for translational research.

  3. The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods

    PubMed Central

    2014-01-01

    Background This paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases. Methods/Design The participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child’s neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child’s genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim. The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6 months and every year until 10 years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child’s exposure to environmental factors, maternal pre

  4. Off-label prescribing for allergic diseases in children

    PubMed Central

    2014-01-01

    The majority of drugs prescribed have not been tested in children and safety and efficacy of children’s medicines are frequently supported by low quality of evidence. Therefore, a large percentage of prescriptions for children in the clinical daily practice are used off label. Despite the several recent legislation and regulatory efforts performed worldwide, they have not been successful in increasing availability of medicines adapted to children. Moreover, if we consider that 30% of the prescribed drugs for children are for the respiratory field and only 4% of new investigation projects for children research were proposed to access drugs for respiratory and allergy treatment, there is a clear imbalance of the children needs in this therapeutic area. This narrative review aimed to describe and discuss the off-label use of medicines in the treatment and control of respiratory and allergic diseases in children. It was recognized that a large percentage of prescriptions performed for allergy treatment in daily clinical practice are off label. The clinicians struggle on a daily basis with the responsibility to balance risk-benefits of an off-label prescription while involving the patients and their families in this decision. It is crucial to increase awareness of this reality not only for the clinician, but also to the global organizations and competent authorities. New measures for surveillance of off-label use should be established, namely through population databases implementation. There is a need for new proposal to correct the inconsistency between the priorities for pediatric drug research, frequently dependent on commercial motivations, in order to comply to the true needs of the children, especially on the respiratory and allergy fields. PMID:24528848

  5. [Anticholinergic drugs in the therapy of obstructive airway diseases].

    PubMed

    Windt, Roland

    2011-04-01

    The anticholinergic effects from botanical preparations of the deadly nightshade family have been used for hundreds of years for the treatment of obstructive airway diseases. Nowadays, derivatives of the plant alkaloids with quaternary ammonium structure, ipratropium bromide and tiotropium bromide, are used, which retain the bronchodilator properties of the parent compounds but are much safer since they are poorly absorbed across biologic membranes. They are the bronchodilators of choice in the management of chronic obstructive pulmonary disease (COPD). However, ipratropium is considered a second-line agent in the treatment of asthma as the bronchodilatory effects seen with ipratropium are less than those seen with beta-adrenergic drugs. Tiotropium is only approved for use in COPD. Though, a recent study provides some evidence that this agent may be an alternative to long-acting beta agonists as an add-on therapy to inhaled glucocorticoids for asthma.

  6. Systems physiology of the airways in health and obstructive pulmonary disease.

    PubMed

    Bates, Jason H T

    2016-09-01

    Fresh air entering the mouth and nose is brought to the blood-gas barrier in the lungs by a repetitively branching network of airways. Provided the individual airway branches remain patent, this airway tree achieves an enormous amplification in cross-sectional area from the trachea to the terminal bronchioles. Obstructive lung diseases such as asthma occur when airway patency becomes compromised. Understanding the pathophysiology of these obstructive diseases thus begins with a consideration of the factors that determine the caliber of an individual airway, which include the force balance between the inward elastic recoil of the airway wall, the outward tethering forces of its parenchymal attachments, and any additional forces due to contraction of airway smooth muscle. Other factors may also contribute significantly to airway narrowing, such as thickening of the airway wall and accumulation of secretions in the lumen. Airway obstruction becomes particularly severe when these various factors occur in concert. However, the effect of airway abnormalities on lung function cannot be fully understood only in terms of what happens to a single airway because narrowing throughout the airway tree is invariably heterogeneous and interdependent. Obstructive lung pathologies thus manifest as emergent phenomena arising from the way in which the airway tree behaves a system. These emergent phenomena are studied with clinical measurements of lung function made by spirometry and by mechanical impedance measured with the forced oscillation technique. Anatomically based computational models are linking these measurements to underlying anatomic structure in systems physiology terms. WIREs Syst Biol Med 2016, 8:423-437. doi: 10.1002/wsbm.1347 For further resources related to this article, please visit the WIREs website.

  7. How changes in nutrition have influenced the development of allergic diseases in childhood

    PubMed Central

    2012-01-01

    The increasing prevalence of allergic diseases in childhood in the last decades could be linked to concomitant dietary changes, especially with the modified and lower consumption of fruit, vegetables and minerals. The consumption of these foods by pregnant women and children in the first years of life seems to be associated with a reduced risk of asthma and related symptoms. Foods that can prevent the development of wheezing through their antioxidant effects contain vitamin C and selenium; blood levels of these elements correlate negatively with the risk of wheezing. Intake of vitamin E during pregnancy also appears to be correlated with a reduced risk of wheezing for the unborn child. Similarly, low intake of zinc and carotenoids by pregnant women is associated with an increased risk of wheezing and asthma in childhood. Fiber also has anti-inflammatory properties and protective effects against allergic diseases such as atopic dermatitis and asthma. The consumption of fat influences the development of the airways. Populations in Western countries have increased their consumption of n-6 PUFAs and, in parallel, reduced n-3 PUFAs. This has led to decreased production of PGE2, which is believed to have a protective effect against inflammation of the airways. Conflicting hypotheses also concern vitamin D; both an excess and a deficiency of vitamin D, in fact, have been associated with an increased risk of asthma. Further studies on the role of these substances are necessary before any conclusions can be drawn on a clinical level. Astratto La crescente prevalenza negli ultimi decenni delle malattie allergiche in età pediatrica potrebbe essere legata a concomitanti cambiamenti nella dieta, in particolare alla minore e modificata introduzione di frutta, verdura e minerali. Il consumo di questi alimenti da parte delle donne in gravidanza e dei bambini nei primi anni di vita sembra essere associato ad un ridotto rischio di asma e di sintomi correlati. Gli alimenti che

  8. Spi2 gene polymorphism is not associated with recurrent airway obstruction and inflammatory airway disease in thoroughbred horses

    PubMed Central

    da Silva, Aline Correa; Brass, Karin Erica; da Silva Loreto, Elgion; Vinocur, Myriam Elizabeth; Pozzobon, Ricardo; da Silva Azevedo, Marcos

    2011-01-01

    The aim was to detect the presence of polymorphisms at exons 1, 2, 3 and 4 of the Spi2 gene, and evaluate a possible association between them and recurrent airway obstruction (RAO) or inflammatory airway disease (IAD) in thoroughbred horses, through single-strand conformational-polymorphism (SSCP) screening. Although polymorphism was not detected in exons 1, 2 and 3, three alleles and six genotypes were identified in exon 4. The frequencies of allele A (0.6388) and genotype AA (0.3888) were higher in horses affected by RAO, although no association was found between polymorphism and horses with either RAO or IAD. PMID:21931519

  9. Effects of prior oral exposure to combinations of environmental immunosuppressive agents on ovalbumin allergen-induced allergic airway inflammation in Balb/c mice.

    PubMed

    Fukuyama, Tomoki; Nishino, Risako; Kosaka, Tadashi; Watanabe, Yuko; Kurosawa, Yoshimi; Ueda, Hideo; Harada, Takanori

    2014-08-01

    Abstract Humans are exposed daily to multiple environmental chemicals in the atmosphere, in food, and in commercial products. Therefore, hazard identification and risk management must account for exposure to chemical mixtures. The objective of the study reported here was to investigate the effects of combinations of three well-known environmental immunotoxic chemicals - methoxychlor (MXC), an organochlorine compound; parathion (PARA), an organophosphate compound; and piperonyl butoxide (PBO), an agricultural insecticide synergist - by using a mouse model of ovalbumin (OVA)-induced allergic airway inflammation. Four-week-old Balb/c mice were exposed orally to either one or two of the environmental immunotoxic chemicals for five consecutive days, prior to intraperitoneal sensitization with OVA and an inhalation challenge. We assessed IgE levels in serum, B-cell counts, and cytokine production in hilar lymph nodes, and differential cell counts and levels of related chemokines in bronchoalveolar lavage fluid (BALF). Mice treated with MXC + PARA or PBO + MXC showed marked increases in serum IgE, IgE-positive B-cells and cytokines in lymph nodes, and differential cell counts and related chemokines in BALF compared with mice that received the vehicle control or the corresponding individual test substances. These results suggest that simultaneous exposure to multiple environmental chemicals aggravates allergic airway inflammation more than exposure to individual chemicals. It is expected that the results of this study will help others in their evaluation of immunotoxic combinational effects when conducting assessments of the safety of environmental/occupational chemicals.

  10. Diet and Allergic Diseases among Population Aged 0 to 18 Years: Myth or Reality?

    PubMed Central

    Saadeh, Danielle; Salameh, Pascale; Baldi, Isabelle; Raherison, Chantal

    2013-01-01

    Allergic diseases are an important health problem. However, epidemiological studies concerning childhood diet-related allergic diseases are scarce. This review examines published articles dealing with diet, dietary patterns and nutrition in relation with allergic diseases among population aged 0 to 18 years. Studies and trials were identified using MEDLINE/PubMed and Cochrane Database of Systematic Reviews and were limited to those published in English or French from 1992 until 2012. This manuscript also reviews the evidence for maternal diet during pregnancy and diet during early childhood and their association with childhood atopic diseases, taking into account the methodology used to evaluate dietary patterns. The evidence reviewed is derived from large epidemiological studies exploring the effects of different food categories on asthma, atopic dermatitis, and allergic rhinitis in children. Overall, maternal diet during pregnancy and a childhood diet rich in antioxidants and omega-3 fatty acids are considered as healthy diets that could be protective for allergic diseases in childhood. PMID:23995043

  11. β-Glucans in the treatment and prevention of allergic diseases.

    PubMed

    Jesenak, Milos; Banovcin, Peter; Rennerova, Zuzana; Majtan, Juraj

    2014-01-01

    β-glucans are a group of biologically active polysaccharides of natural origin with a proven pleiotropic immunomodulation effect. Their efficacy has been confirmed in the therapeutic treatment and prevention of various infectious diseases, secondary immune defects and also of oncologic disorders. Allergic diseases are one of the most frequent diseases and their prevalence continues to increase. They develop as a consequence of dysregulation of the immune system, especially when there is failure in the equilibrium of the response of TH1/TH2 lymphocytes towards TH2. New therapeutic approaches in the treatment of immunopathological conditions (e.g. allergic or oncologic) are directed to restoring the equilibrium among different T lymphocyte subpopulations. Based on in vitro experiments, and also on animal and human clinical studies, there is much evidence for the importance of β-glucans in the treatment and also prevention of allergic diseases; this opens new perspectives on the use of this widespread and popular group of natural substances.

  12. Comparative study of aural microflora in healthy cats, allergic cats and cats with systemic disease.

    PubMed

    Pressanti, Charline; Drouet, Clémence; Cadiergues, Marie-Christine

    2014-12-01

    Twenty healthy cats (group 1) with clinically normal ears, 15 cats with systemic disease (group 2) and 15 allergic cats (group 3) were included in a prospective study. The experimental unit was the ear. A clinical score was established for each ear canal after otoscopic examination. Microbial population was assessed on cytological examination of smears performed with the cotton-tipped applicator smear technique. Fungal population was significantly more prominent in allergic cats (P <0.001) and in diseased cats compared with healthy cats (P <0.02). Bacterial population was significantly higher in allergic cats than in healthy cats (P <0.001) and cats suffering from systemic disease (P <0.001). Bacterial overgrowth was also higher in cats with systemic disease than healthy cats. In cats from group 2, only fungal overgrowth was associated with otitis severity. In group 3, only bacterial overgrowth was associated with otitis severity.

  13. THE SPONTANEOUSLY HYPERTENSIVE RAT: AN EXPERIMENTAL MODEL OF SULFUR DIOXIDE-INDUCED AIRWAYS DISEASE

    EPA Science Inventory

    Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction, inflammation and mucus hypersecretion; features that capture bronchitis, emphysema and often asthma. However, current rodent models do not reflect this human disease. Because genetically predisp...

  14. Socio-epidemiological Aspects of Respiratory Allergic Diseases in Southern Africa

    PubMed Central

    Taborda-Barata, Luís

    2012-01-01

    Abstract The prevalence of respiratory allergic diseases has been increasing in Southern Africa both in urban and in rural environments. Various factors may contribute toward this situation, namely, exposure to aeroallergens, such as grass pollens and house dust mites. However, other irritant environmental triggers, such as exposure to tobacco smoke and certain indoor and outdoor fumes, may also play a relevant part. Furthermore, certain parasitic and mycobacterial infections may act as allergic disease risk modifiers, although such an influence should be confirmed. Finally, certain cultural and socioeconomic factors may also influence accessibility to healthcare and adherence to treatment of these diseases. PMID:23268464

  15. Titanium dioxide nanoparticles augment allergic airway inflammation and Socs3 expression via NF-κB pathway in murine model of asthma.

    PubMed

    Mishra, Vani; Baranwal, Vikas; Mishra, Rohit K; Sharma, Shivesh; Paul, Bholanath; Pandey, Avinash C

    2016-06-01

    Titanium dioxide nanoparticles (nTiO2) previously considered to possess relatively low toxicity both in vitro and in vivo, although classified as possibly carcinogenic to humans. Also, their adjuvant potential has been reported to promote allergic sensitization and modulate immune responses. Previously, in OVA induced mouse model of asthma we found high expression of Socs3 and low expression of Stat3 and IL-6. However, a clear understanding regarding the signaling pathways associated with nTiO2 adjuvant effect in mouse model of asthma is lacking. In the present study we investigated the status of Stat3/IL-6 and Socs3 and their relationship with NF-κB, with nTiO2 as an adjuvant in mouse model of asthma. nTiO2 when administered with ovalbumin (OVA) during sensitization phase augmented airway hyper-responsiveness (AHR), biochemical markers of lung damage and a mixed Th2/Th1 dependent immune response. At the same time, we observed significant elevation in the levels of Stat3, Socs3, NF-κB, IL-6 and TNF-α. Furthermore, transient in vivo blocking of NF-κB by NF-κB p65 siRNA, downregulated the expression of Socs3, IL-6 and TNF-α. Our study, thus, shows that nTiO2 exacerbate the inflammatory responses in lungs of pre-sensitized allergic individuals and that these changes are regulated via NF-κB pathway.

  16. Low frequency of filaggrin null mutations in Croatia and their relation with allergic diseases.

    PubMed

    Sabolić Pipinić, I; Varnai, V M; Turk, R; Breljak, D; Kezić, S; Macan, J

    2013-06-01

    Filaggrin gene (FLG) null mutations are considered associated with atopic dermatitis. This study was conducted to determine the prevalence of FLG null mutations R501X, 2282del4, R2447X and S3247X in the Croatian population and their role in the occurrence of allergic diseases including atopic dermatitis, allergic rhinitis, asthma and allergic contact dermatitis (ACD). Study enrolled 440 freshmen with defined allergic diseases by means of both present symptoms in International Study of Asthma and Allergies in Childhood questionnaire (relevant respiratory and/or skin symptoms) and markers of allergic sensitization (positive skin prick and/or patch test). FLG null mutations were successfully genotyped in 423 students of which 11 (2.6%) were carriers of FLG null mutation: 1/423 (0.2%) was heterozygous for R501X and 10/423 (2.4%) were heterozygous for 2282del4. No carriers of R2447X and S3247X mutations were identified. In wild-type FLG carriers (412 subjects), atopic dermatitis was present in 45 (11%), allergic rhinitis in 70 (17%) and allergic asthma in 29 (7%) students. Twenty-five of 393 (7%) patch-tested wild-type FLG carriers had ACD. Among 11 FLG null mutation carriers, four had one or more allergic diseases, and five had reported skin symptoms without defined allergic sensitization (positive skin prick test and/or patch test). FLG null mutations were not confirmed as a predictor of analysed allergic diseases, but were confirmed as an independent predictor of skin symptoms (OR 17.19, 95% CI 3.41-86.6, P < 0.001). Our results in general indicate a low frequency of FLG null mutations in the studied Croatian population supporting a theory of a latitude-dependent distribution of FGL null mutations in Europe, with a decreasing north-south gradient of R501X and 2282del4 mutation frequency. The relation between FLG null mutations and skin disorders was confirmed.

  17. Proallergic cytokines and group 2 innate lymphoid cells in allergic nasal diseases.

    PubMed

    Matsushita, Kazufumi; Kato, Yukinori; Akasaki, Shoko; Yoshimoto, Tomohiro

    2015-07-01

    Recent advances in our understanding of proallergic cytokines and group 2 innate lymphoid cells (ILC2s) indicate their critical roles in type 2 immunity-mediated disorders. Proallergic cytokines, interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin, are released from epithelial cells in inflamed tissues and drive type 2 inflammation by acting on innate and acquired immune systems. ILC2s are an innate immune population that responds to proallergic cytokines by producing type 2 cytokines. In line with allergic disorders in the lung, skin, and intestine, emerging evidence suggests the involvement of proallergic cytokines and ILC2s in allergic nasal diseases such as chronic rhinosinusitis with polyps (CRSwNP), allergic fungal rhinosinusitis, and allergic rhinitis (AR). In CRSwNP patients, both proallergic cytokine levels and ILC2s frequency are increased in the nasal mucosa. Increased proallergic cytokine levels correlate with poorer disease outcomes in CRSwNP. Levels of nasal proallergic cytokines are also elevated in AR patients. In addition, animal studies demonstrate that cytokines are essential for the development of AR. It is becoming clear that the proallergic cytokine/ILC2s axis participates in allergic diseases by multiple mechanisms dependent upon the inflammatory context. Thus, a thorough understanding of these cytokines and ILC2s including their tissue- and disease-specific roles is essential for targeting the pathways to achieve therapeutic applications.

  18. IgE sensitization to inhalant allergens and the risk of airway infection and disease: A population-based study

    PubMed Central

    Husemoen, Lise Lotte Nystrup; Thuesen, Betina Heinsbæk; Fenger, Runa Vavia; Linneberg, Allan

    2017-01-01

    Background Immunoglobulin E (IgE) sensitization, which is the propensity to develop IgE antibodies against common environmental allergens, is associated with a lymphocyte T-helper type 2 (Th2) skewed immune response and a high risk of allergic respiratory disease. Little is known about whether IgE sensitization confers an increased risk of respiratory infections in adults. We investigated the association between IgE sensitization and the incidence of acute airway infections, other infections and chronic lower airway disease events as recorded in nation-wide registries. Methods We included 14,849 persons from five population-based studies with measurements of serum specific IgE positivity against inhalant allergens. Participants were followed by linkage to Danish national registries (median follow-up time 11.3 years). The study-specific relative risks were estimated by Cox regression analysis, meta-analysed, and expressed as hazard ratios, HRs (95% confidence intervals, CIs). Results The relative risks for IgE sensitized vs. non-sensitized were: for pneumonia (HR = 1.20, 95% CI: 1.01, 1.41), other acute airway infection (HR = 0.86, 95% CI: 0.60, 1.22), infection (HR = 1.06, 95% CI: 0.90, 1.24), asthma (HR = 2.26, 95% CI: 1.79, 2.86), and other chronic lower airway disease (HR = 1.31, 95% CI: 1.08, 1.58). In never smokers, the higher risk of pneumonia (HR = 1.73, 95% CI: 1.23, 2.44) and asthma (HR = 3.17, 95% CI: 2.10, 4.76) among IgE sensitized was more pronounced. Conclusions IgE sensitization was associated with a higher risk of asthma, other chronic lower airway diseases, and pneumonia. However, the association between IgE sensitization and pneumonia may be explained by undiagnosed asthma causing the pneumonia. Further studies are needed for confirmation. PMID:28182643

  19. Naturally occurring lung CD4(+)CD25(+) T cell regulation of airway allergic responses depends on IL-10 induction of TGF-beta.

    PubMed

    Joetham, Anthony; Takeda, Katsuyuki; Takada, Katsuyuki; Taube, Christian; Miyahara, Nobuaki; Matsubara, Shigeki; Matsubara, Satoko; Koya, Toshiyuki; Rha, Yeong-Ho; Dakhama, Azzeddine; Gelfand, Erwin W

    2007-02-01

    Peripheral tolerance to allergens is mediated in large part by the naturally occurring lung CD4(+)CD25(+) T cells, but their effects on allergen-induced airway responsiveness have not been well defined. Intratracheal, but not i.v., administration of naive lung CD4(+)CD25(+) T cells before allergen challenge of sensitized mice, similar to the administration of the combination of rIL-10 and rTGF-beta, resulted in reduced airway hyperresponsiveness (AHR) and inflammation, lower levels of Th2 cytokines, higher levels of IL-10 and TGF-beta, and less severe lung histopathology. Significantly, CD4(+)CD25(+) T cells isolated from IL-10(-/-) mice had no effect on AHR and inflammation, but when incubated with rIL-10 before transfer, suppressed AHR, and inflammation, and was associated with elevated levels of bronchoalveolar lavage TGF-beta levels. By analogy, anti-TGF-beta treatment reduced regulatory T cell activity. These data identify naturally occurring lung CD4(+)CD25(+) T cells as capable of regulating lung allergic responses in an IL-10- and TGF-beta-dependent manner.

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

    PubMed Central

    Matheu, Victor; Treschow, Alexandra; Teige, Ingrid; Navikas, Vaidrius; Issazadeh-Navikas, Shohreh

    2005-01-01

    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-β in the immunomodulatory effects of CpG-ODN is not known. Objective Here, we aimed to elucidate the role of IFN-β in the anti-allergic effect of CpG motifs. Methods We assessed the immune response in OVA-primed/OVA-challenged IFN-β knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment with synthetic CpG motifs. Results Vaccination with CpG-ODN reduced the number of cells in airways of OVA-sensitized WT but not IFN-β-/- mice. Although airway eosinophilia was reduced in both treated groups, they were significantly higher in IFN-β-/- mice. Other inflammatory cells, such as lymphocytes and macrophages were enhanced in airways by CpG treatment in IFN-β-/- mice. The ratio of IFN-γ/IL-4 cytokines in airways was significantly skewed to a Th1 response in WT compared to IFN-β-/- group. In contrast, IL-4 and IgE were reduced with no differences between groups. Ag-specific T-cell proliferation, Th1-cytokines such as IFN-γ, IL-2 and also IL-12 were significantly lower in IFN-β-/- mice. Surprisingly, we discovered that intranasal treatment of mice with CpG-ODN results in mild synovitis particularly in IFN-β-/- mice. Conclusion Our results indicate that induction of Th1 response by therapy with CpG-ODN is only slightly and partially dependent on IFN-β, while IFN-β 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. PMID:15748290

  1. [Aeroallergens, skin tests and allergic diseases in 1091 patients].

    PubMed

    Enríquez Palomec, O; Hernández Chávez, L; Sarrazola Sanjuan, D M; Segura Méndez, N H; Hernández Colín, D D; Martínez-Cairo, S

    1997-01-01

    To know the frequency of positively of several skin tests, data cards from patients, of the Allergy and Clinic Immunology Service of the Hospital de Especialidades del Centro Medico Nacional Siglo XXI (Mexico City), between January, 1989 and March, 1995, were reviewed. Aqueous extracts manufactures by our laboratory were applied, in a dilution of 1:1000 weight-volume. 1091 from 5,651 skin tests patients were positive. Asthma and rhinitis were diagnosed in 492, allergic rhinitis in 289, allergic asthma in 111, and other diagnosis in 199 cases. The most frequent inhalable aeroallergens were house dust and perennial Dermatophagoides p and f1 with predominance in the rainy season, followed by pollens from Fraxinus a. Quercus a and Capriola, with predominance in the rainy season. The most frequent fungi were Candida and Fusarium, with predominance in the dry season.

  2. Exposure to cats: update on risks for sensitization and allergic diseases.

    PubMed

    Dharmage, Shyamali C; Lodge, Caroline L; Matheson, Melanie C; Campbell, Brittany; Lowe, Adrian J

    2012-10-01

    Cats are the pets most commonly implicated in the etiology of asthma and allergic disease. However, systematic reviews have concluded that there is a lack of evidence to support the idea that cat exposure in early life increases the risk of allergic disease. Indeed, it appears most likely that cat exposure is protective against allergic diseases. Recent large prospective studies have shown that living with a cat during childhood, especially during the first year of a child's life, could be protective. However, any advice given to the parents should also incorporate how new acquisition of cats can affect other family members, especially those who are already sensitized. Research is urgently needed to determine whether the suggested impact of acquisition of cats in adult life is modified by the person's childhood pet ownership, to help parents who seek advice on whether or not to get a cat.

  3. Airway gene expression of IL-1 pathway mediators predicts exacerbation risk in obstructive airway disease

    PubMed Central

    Baines, Katherine J; Fu, Juan-juan; McDonald, Vanessa M; Gibson, Peter G

    2017-01-01

    Background Exacerbations of asthma and COPD are a major cause of morbidity and mortality and are responsible for significant health care costs. This study further investigates interleukin (IL)-1 pathway activation and its relationship with exacerbations of asthma and COPD. Methods In this prospective cohort study, 95 participants with stable asthma (n=35) or COPD (n=60) were recruited and exacerbations recorded over the following 12 months. Gene expressions of IL-1 pathway biomarkers, including the IL-1 receptors (IL1R1, IL1R2, and IL1RN), and signaling molecules (IRAK2, IRAK3, and PELI1), were measured in sputum using real-time quantitative polymerase chain reaction. Mediators were compared between the frequent (≥2 exacerbations in the 12 months) and infrequent exacerbators, and the predictive relationships investigated using receiver operating characteristic curves and area under the curve (AUC) values. Results Of the 95 participants, 89 completed the exacerbation follow-up, where 30 participants (n=22 COPD, n=8 asthma) had two or more exacerbations. At the baseline visit, expressions of IRAK2, IRAK3, PELI1, and IL1R1 were elevated in participants with frequent exacerbations of both asthma and COPD combined and separately. In the combined population, sputum gene expression of IRAK3 (AUC=75.4%; P<0.001) was the best predictor of future frequent exacerbations, followed by IL1R1 (AUC=72.8%; P<0.001), PELI1 (AUC=71.2%; P<0.001), and IRAK2 (AUC=68.6; P=0.004). High IL-1 pathway gene expression was associated with frequent prior year exacerbations and correlated with the number and severity of exacerbations. Conclusion The upregulation of IL-1 pathway mediators is associated with frequent exacerbations of obstructive airway disease. Further studies should investigate these mediators as both potential diagnostic biomarkers predicting at-risk patients and novel treatment targets. PMID:28223794

  4. Omega-6 and omega-3 polyunsaturated fatty acids and allergic diseases in infancy and childhood.

    PubMed

    Miles, Elizabeth A; Calder, Philip C

    2014-01-01

    There may be a causal relationship between intake of n-6 polyunsaturated fatty acids (PUFAs) and childhood allergic diseases. This can be explained by plausible biological mechanisms involving eicosanoid mediators produced from the n-6 PUFA arachidonic acid. Long chain n-3 PUFAs are found in fish and fish oils. These fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will lower the risk of developing allergic diseases. In support of this, protective associations have been reported between maternal fish intake during pregnancy and allergic outcomes in infants and children from those pregnancies. However, studies of fish intake during infancy and childhood and allergic outcomes in those infants or children are inconsistent, although some reported a protective association. Supplementing pregnant women with fish oil can induce immunologic changes in cord blood. This supplementation has been reported in some studies to decrease sensitisation to common food allergens and to lower the prevalence and severity of atopic dermatitis in the first year of life. The protective effect of maternal n-3 PUFAs may last until adolescence of the offspring. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, although this benefit may not persist. Whether fish oil is a useful therapy in children with asthma receiving standard therapy is not clear from studies performed to date and this requires further exploration.

  5. Gut Microbiome and the Development of Food Allergy and Allergic Disease.

    PubMed

    Prince, Benjamin T; Mandel, Mark J; Nadeau, Kari; Singh, Anne Marie

    2015-12-01

    The impact of gut microbiome on human development, nutritional needs, and disease has become evident with advances in the ability to study these complex communities of microorganisms, and there is growing appreciation for the role of the microbiome in immune regulation. Several studies have examined associations between changes in the commensal microbiota and the development of asthma, allergic rhinitis, and asthma, but far less have evaluated the impact of the microbiome on the development of food allergy. This article reviews the human gastrointestinal microbiome, focusing on the theory and evidence for its role in the development of IgE-mediated food allergy and other allergic diseases.

  6. Lyn regulates mucus secretion and MUC5AC via the STAT6 signaling pathway during allergic airway inflammation

    PubMed Central

    Wang, Xiaoyun; Li, Yin; Luo, Deyu; Wang, Xing; Zhang, Yun; Liu, Zhigang; Zhong, Nanshan; Wu, Min; Li, Guoping

    2017-01-01

    Hypersecretion of mucus is an important component of airway remodeling and contributes to the mucus plugs and airflow obstruction associated with severe asthma phenotypes. Lyn has been shown to down-regulate allergen-induced airway inflammation. However, the role of Lyn in mucin gene expression remains unresolved. In this study, we first demonstrate that Lyn overexpression decreased the mucus hypersecretion and levels of the muc5ac transcript in mice exposed to ovalbumin (OVA). Lyn overexpression also decreased the infiltration of inflammatory cells and the levels of IL-13 and IL-4 in OVA-challenged airways. Whereas Lyn knockdown increased the IL-4 or IL-13-induced MUC5AC transcript and protein levels in the human bronchial epithelial cell line, 16HBE, Lyn overexpression decreased IL-4- or IL-13-induced MUC5AC transcript and protein levels. Overexpression of Lyn also decreased the expression and phosphorylation of STAT6 in OVA-exposed mice, whereas Lyn knockdown increased STAT6 and MUC5AC levels in 16HBE cells. Finally, chromatin immunoprecipitation analysis confirmed that Lyn overexpression decreased the binding of STAT6 to the promoter region of Muc5ac in mice exposed to OVA. Collectively, these findings demonstrated that Lyn overexpression ameliorated airway mucus hypersecretion by down-regulating STAT6 and its binding to the MUC5AC promoter. PMID:28205598

  7. Airway Epithelial Expression Quantitative Trait Loci Reveal Genes Underlying Asthma and Other Airway Diseases

    PubMed Central

    Luo, Wei; Obeidat, Ma’en; Di Narzo, Antonio Fabio; Chen, Rong; Sin, Don D.; Paré, Peter D.

    2016-01-01

    Genome-wide association studies (GWASs) have identified loci that are robustly associated with asthma and related phenotypes; however, the molecular mechanisms underlying these associations need to be explored. The most relevant tissues to study the functional consequences of asthma are the airways. We used publically available data to derive expression quantitative trait loci (eQTLs) for human epithelial cells from small and large airways and applied the eQTLs in the interpretation of GWAS results of asthma and related phenotypes. For the small airways (n = 105), we discovered 660 eQTLs at a 10% false discovery rate (FDR), among which 315 eQTLs were not previously reported in a large-scale eQTL study of whole lung tissue. A large fraction of the identified eQTLs is supported by data from Encyclopedia of DNA Elements (ENCODE) showing that the eQTLs reside in regulatory elements (57.5 and 67.6% of cis- and trans-eQTLs, respectively). Published pulmonary GWAS hits were enriched as airway epithelial eQTLs (9.2-fold). Further, genes regulated by asthma GWAS loci in epithelium are significantly enriched in immune response pathways, such as IL-4 signaling (FDR, 5.2 × 10−4). The airway epithelial eQTLs described in this study are complementary to previously reported lung eQTLs and represent a powerful resource to link GWAS-associated variants to their regulatory function and thus elucidate the molecular mechanisms underlying asthma and airway-related conditions. PMID:26102239

  8. [. Oсumethyl in the treatment of allergic diseases of eyelids and conjunctiva].

    PubMed

    Marchenko, N R

    Treatment of allergic diseases of eyelids and conjunctiva (conjunctivites and blepharoconjunctivites) often presents difficulties due to peculiarities of their pathogenesis - allergic and vascular reactions, disorder of lacrimal production, meibomian gland dysfunction, and possible bacterial contamination. It has been suggested to use Ocumethyl, which contains zinc sulfate (binding, drying, anti-inflammatory, and antiseptic effect), diphenhydamine hydrochloride (an Н1-antihistamine that decreases capillary permeability and helps resolve conjunctival and eyelid edema), naphazoline hydrochloride (a sympathomimetic notable for its strong, rapid, and long-lasting vasoconstrictive effect), and methylene blue (antiseptic effect, disintoxication, and antioxidant activity). A total of 80 patients with chronic allergic conjunctivitis, blepharoconjuntivitis, or giant papillary conjunctivitis associated with contact lens wearing were treated with Ocumethyl instillations (3 times daily for 15-30 days). A clinically significant effect was obtained in 77-91% of patients depending on the disease entity.

  9. Occupational rhinitis and occupational asthma; one airway two diseases?

    NASA Astrophysics Data System (ADS)

    Seed, M. J.; Gittins, M.; DeVocht, F.; Agius, R. M.

    2009-02-01

    The concept of 'one airway, one disease' refers to the frequent comorbidity of asthma and rhinitis. However, only limited research has been done on this association for the diverse range of occupational respiratory sensitisers. The relative frequency of rhinitis was determined for the 15 respiratory sensitisers reported to cause at least 10 cases of rhinitis or asthma to The Health and Occupation Reporting (THOR) network between 1997 and 2006. Of 1408 cases, 1190 were sole diagnoses of asthma, 138 sole diagnoses of rhinitis and in 80 cases asthma coexisted with rhinitis. The six sensitisers for which rhinitis featured in over 15% of cases were all particulates and known to cause release of mast cell mediators, either directly or through IgE antibodies. Four of the other nine sensitisers often exist as vapours and only two have been consistently associated with IgE-mediated disease mechanisms. Particle size did not appear to correlate with the relative frequency of rhinitis. Despite its limitations this study would support the hypothesis that there are at least two mechanistic categories of respiratory sensitisation with rhinitis being relatively more common where the mechanism is IgE-mediated. Particulate nature may be another important factor to consider in future studies.

  10. Clinical application of expectorant therapy in chronic inflammatory airway diseases (Review)

    PubMed Central

    ZHANG, TING; ZHOU, XIANGDONG

    2014-01-01

    Airway mucus hypersecretion is a significant clinical and pathological feature of chronic inflammatory airway diseases. Its clinical presentations include recurrent coughing and phlegm. Airway mucus is closely associated with the occurrence, development and prognosis of chronic inflammatory airway diseases and critically affects the lung function, quality of life, hospitalization rate and mortality of patients with chronic inflammatory airway diseases. Therefore, expectorant therapies targeting the potential mechanisms of mucus hypersecretion have been the focus of numerous studies. Conventional expectorants are mainly mucoactive medicines, including nausea-stimulating expectorants, mucolytics, mucokinetics, and proteases and nucleases. In addition, certain traditional Chinese herbal medicines and non-mucoactive agents, including muscarinic acetylcholine receptor antagonists, corticosteroids, leukotriene receptor antagonists and macrolide antibiotics, have also shown expectorant effects. Several novel medicines for expectorant therapy have emerged, including cholesterol-lowering statins, epidermal growth factor receptor tyrosine kinase inhibitors, phosphodiesterase-4 inhibitors, stanozolol, surfactants, flavonoids, tachykinin receptor antagonists, protease inhibitors, cytokine antagonists and purinergic agonists. With the increasing number of multidisciplinary studies, the effectiveness of expectorant therapy for the treatment of chronic inflammatory airway diseases has been confirmed. Therefore, the development of novel expectorants and the standardization of expectorant therapy are the direction and focus of future studies, thus benefiting patients who have a chronic inflammatory airway disease. PMID:24660026

  11. Sinobronchial allergic aspergillosis with allergic bronchopulmonary aspergillosis: a less common co-existence.

    PubMed

    Upadhyay, Rashmi; Kant, Surya; Prakash, Ved; Saheer, S

    2014-11-04

    Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder that is characterised by a hyper-responsiveness of the airways to Aspergillus fumigatus. Although several other fungi may also present with similar clinical conditions, Aspergillus remains the most common fungal pathogen causing airway infections. Co-existence of ABPA with allergic Aspergillus sinusitis (AAS) is an uncommon presentation. The concept of one airway/one disease justifies the co-existence of ABPA with AAS, but it does not always hold true. We report a case of a 35-year-old woman who presented with symptoms suggestive of bronchial asthma. On further investigation, the radiological pattern showed fleeting shadows and CT scan showed central cystic bronchiectatic changes characteristic of ABPA. The nasal secretions were investigated for the presence of Aspergillus and were found to be positive. Hence a diagnosis of ABPA with AAS was established. The patient was treated with oral steroids and antifungal drugs.

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

    PubMed

    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.

  13. [The pilot study of type Ⅰ allergic reaction in Meniere's disease patients].

    PubMed

    Pan, T; Zhao, Y; Ding, Y J; Lu, Z Y; Ma, F R

    2017-02-07

    Objective: To evaluate the correlation between type Ⅰ allergic reaction and pathogenesis of Meniere's disease. Methods: A total of 35 (10 male vs. 25 female) patients aged between 21-66 years diagnosed with Meniere's disease were recruited to this study, mean age of them was (47.3±13.6) years. The control group consisted of 15 inpatients (5 male vs. 10 female) with pharyngolaryngeal diseases but without otologic and rhinologic abnormity, mean age was 45.4±12.8 years. Allergic prevalence, serous total immunoglobulin E( tIgE ) levels, serous specific immunoglobulin E( sIgE ) levels and subtypes of T lymphocytes were measured and compared in patients with Meniere's disease and the control group. Severity of vertigo, tinnitus and sensation of fullness were compared between Meniere's disease patients with or without allergy. Results: Allergic prevalence were significantly different (Pearson chi-square 5.832, P<0.05) between patients with Meniere's disease and the control group(57.1% vs. 20.0%). Patients with Meniere's disease report higher level of serous tIgE compared with controls, the difference is statistically significant (Z=168.000, P<0.05). However, positive rates of sIgE of food allergens and inhalant allergens were not significantly different between patients with Meniere's disease and the control group. Scores of vertiginous severity, dizziness handicap inventory (DHI) and tinnitus handicap inventory (THI) were significantly different between Meniere's disease patients with or without allergy (P<0.05). Treg and Treg/Th17 levels (Z=26.000) were much higher in Meniere's disease patients with allergy than in the controls(P<0.05). Conclusions: Patients with Meniere's disease report higher rate of allergy than the control group. Type Ⅰ allergic reaction is thought to be one of the possible reasons that may induce endolymphatic hydrops and lead to Meniere's disease.

  14. Nonspecific provocation of target organs in allergic diseases: EAACI-GA(2)LEN consensus report.

    PubMed

    Bonini, S; Rasi, G; Brusasco, V; Carlsen, K-H; Crimi, E; Popov, T; Schultze-Werninghaus, G; Gramiccioni, C; Bonini, M; Passali, D; Bachert, C; van Cauwenberge, P B; Bresciani, M; Bonini, S; Calonge, M; Montan, P G; Serapiao Dos Santos, M; Belfort, R; Lambiase, A; Sacchetti, M

    2007-06-01

    It is widely accepted that nonspecific tissue reactivity is a distinct pathophysiological hallmark of allergic diseases, influenced by genetic and environmental factors different from those involved in causing sensitization and allergen response of target organs. This consensus document aims at reviewing procedures currently used for nonspecific provocation of the bronchi, nose and eye and for measuring their responsiveness to nonspecific stimuli.

  15. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    DTIC Science & Technology

    2016-01-01

    selection of more suitable animal models for studying various airway diseases in humans. A continuing growth of our knowledge about the physiological and...rats, but not in control rats. Chronic airway inflammation in sensitized animals is likely a major contributing factor in causing this response. 3) A...C-fibers. 4) In an animal model of asthma (Brown-Norway rats sensitized by ovalbumin), chronic allergic inflammation sensitization increases the

  16. Overweight/Obesity and Respiratory and Allergic Disease in Children: International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two

    PubMed Central

    Weinmayr, Gudrun; Forastiere, Francesco; Büchele, Gisela; Jaensch, Andrea; Strachan, David P.; Nagel, Gabriele

    2014-01-01

    Background Childhood obesity and asthma are increasing worldwide. A possible link between the two conditions has been postulated. Methods Cross-sectional studies of stratified random samples of 8–12-year-old children (n = 10 652) (16 centres in affluent and 8 centres in non-affluent countries) used the standardized methodology of ISAAC Phase Two. Respiratory and allergic symptoms were ascertained by parental questionnaires. Tests for allergic disease were performed. Height and weight were measured, and overweight and obesity were defined according to international definitions. Prevalence rates and prevalence odds ratios were calculated. Results Overweight (odds ratio = 1.14, 95%-confidence interval: 0.98; 1.33) and obesity (odds ratio = 1.67, 95%-confidence interval: 1.25; 2.21) were related to wheeze. The relationship was stronger in affluent than in non-affluent centres. Similar results were found for cough and phlegm, rhinitis and eczema but the associations were mostly driven by children with wheeze. There was a clear association of overweight and obesity with airways obstruction (change in FEV1/FVC, −0.90, 95%-confidence interval: −1.33%; −0.47%, for overweight and −2.46%, 95%-confidence interval: −3.84%; −1.07%, for obesity) whereas the results for the other objective markers, including atopy, were null. Conclusions Our data from a large international child population confirm that there is a strong relation of body mass index with wheeze especially in affluent countries. Moreover, body mass index is associated with an objective marker of airways obstruction (FEV1/FVC) but no other objective markers of respiratory and allergic disorders. PMID:25474308

  17. Anti-allergic activity of a Kampo (Japanese herbal) medicine "Sho-seiryu-to (Xiao-Qing-Long-Tang)" on airway inflammation in a mouse model.

    PubMed

    Nagai, Takayuki; Arai, Yumiko; Emori, Michiko; Nunome, Shin-Yu; Yabe, Takeshi; Takeda, Tadahiro; Yamada, Haruki

    2004-10-01

    Effects of a Kampo (Japanese herbal) medicine "Sho-seiryu-to (SST, Xiao-Qing-Long-Tang in Chinese)", which has been used for the treatment of allergic bronchial asthma clinically, were examined on ovalbumin (OVA)-sensitized allergic airway inflammation model (i.e., bronchial asthma) in a mouse. When SST was orally administered at 0.5 g/kg/day from day 1 to 6 days after OVA inhalation, SST reduced the OVA-specific IgE antibody titer in bronchoalveolar lavage (BAL) fluids at 7 days after the OVA inhalation. CD4(+) T cells obtained from the mouse lung produced more interleukin (IL)-4 and IL-5 but less interferon (IFN)-gamma than T cells from nonsensitized control animals. However, oral administration of SST reduced the production of IL-4 and IL-5 and the production of IFN-gamma returned to the control level. In addition, the IL-4 level was increased in the BAL fluid of the OVA-sensitized animals compared to the nonsensitized control, while the IFN-gamma levels decreased. SST reduced the IL-4 levels in the BAL fluids and returned the IFN-gamma level to control levels. Nerve growth factor (NGF) was increased in the BAL fluids of the OVA-sensitized mice over that of nonsensitized mice, but oral administration of SST augmented the NGF levels to approximately 2 times higher than in the sensitized mice. Although lung cells obtained from sensitized mice produced higher levels of NGF than nonsensitized mice, oral administration of SST augmented the production of NGF by the lung cells even higher ( approximately 2 times more than cells from sensitized mice). Administration of anti-NGF antibody to the airway blocked the effects of SST. These results suggest that SST modulates Th1/Th2 balance in the lungs and augmentation of NGF in the lungs may be related to the effects of SST. Pinellic acid (9S, 12S, 13S-trihydroxy-10E-octadecenoic acid), one component of the herbs of SST [Int. Immunopharmacol. 2 (2002) 1183], was purified from the tuber of Pinellia ternata Breitenbach. Oral

  18. A Persistent and Diverse Airway Microbiota Present during Chronic Obstructive Pulmonary Disease Exacerbations

    PubMed Central

    Huang, Yvonne J.; Kim, Eugenia; Cox, Michael J.; Brodie, Eoin L.; Brown, Ron; Wiener-Kronish, Jeanine P.

    2010-01-01

    Abstract Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major source of morbidity and contribute significantly to healthcare costs. Although bacterial infections are implicated in nearly 50% of exacerbations, only a handful of pathogens have been consistently identified in COPD airways, primarily by culture-based methods, and the bacterial microbiota in acute exacerbations remains largely uncharacterized. The aim of this study was to comprehensively profile airway bacterial communities using a culture-independent microarray, the 16S rRNA PhyloChip, of a cohort of COPD patients requiring ventilatory support and antibiotic therapy for exacerbation-related respiratory failure. PhyloChip analysis revealed the presence of over 1,200 bacterial taxa representing 140 distinct families, many previously undetected in airway diseases; bacterial community composition was strongly influenced by the duration of intubation. A core community of 75 taxa was detected in all patients, many of which are known pathogens. Bacterial community diversity in COPD airways is substantially greater than previously recognized and includes a number of potential pathogens detected in the setting of antibiotic exposure. Comprehensive assessment of the COPD airway microbiota using high-throughput, culture-independent methods may prove key to understanding the relationships between airway bacterial colonization, acute exacerbation, and clinical outcomes in this and other chronic inflammatory airway diseases. PMID:20141328

  19. The Contribution of Small Airway Obstruction to the Pathogenesis of Chronic Obstructive Pulmonary Disease.

    PubMed

    Hogg, James C; Paré, Peter D; Hackett, Tillie-Louise

    2017-04-01

    The hypothesis that the small conducting airways were the major site of obstruction to airflow in normal lungs was introduced by Rohrer in 1915 and prevailed until Weibel introduced a quantitative method of studying lung anatomy in 1963. Green repeated Rohrer's calculations using Weibels new data in 1965 and found that the smaller conducting airways offered very little resistance to airflow. This conflict was resolved by seminal experiments conducted by Macklem and Mead in 1967, which confirmed that a small proportion of the total lower airways resistance is attributable to small airways <2 mm in diameter. Shortly thereafter, Hogg, Macklem, and Thurlbeck used this technique to show that small airways become the major site of obstruction in lungs affected by emphysema. These and other observations led Mead to write a seminal editorial in 1970 that postulated the small airways are a silent zone within normal lungs where disease can accumulate over many years without being noticed. This review provides a progress report since the 1970s on methods for detecting chronic obstructive pulmonary disease, the structural nature of small airways' disease, and the cellular and molecular mechanisms that are thought to underlie its pathogenesis.

  20. A persistent and diverse airway microbiota present during chronic obstructive pulmonary disease exacerbations.

    PubMed

    Huang, Yvonne J; Kim, Eugenia; Cox, Michael J; Brodie, Eoin L; Brown, Ron; Wiener-Kronish, Jeanine P; Lynch, Susan V

    2010-02-01

    Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major source of morbidity and contribute significantly to healthcare costs. Although bacterial infections are implicated in nearly 50% of exacerbations, only a handful of pathogens have been consistently identified in COPD airways, primarily by culture-based methods, and the bacterial microbiota in acute exacerbations remains largely uncharacterized. The aim of this study was to comprehensively profile airway bacterial communities using a culture-independent microarray, the 16S rRNA PhyloChip, of a cohort of COPD patients requiring ventilatory support and antibiotic therapy for exacerbation-related respiratory failure. PhyloChip analysis revealed the presence of over 1,200 bacterial taxa representing 140 distinct families, many previously undetected in airway diseases; bacterial community composition was strongly influenced by the duration of intubation. A core community of 75 taxa was detected in all patients, many of which are known pathogens. Bacterial community diversity in COPD airways is substantially greater than previously recognized and includes a number of potential pathogens detected in the setting of antibiotic exposure. Comprehensive assessment of the COPD airway microbiota using high-throughput, culture-independent methods may prove key to understanding the relationships between airway bacterial colonization, acute exacerbation, and clinical outcomes in this and other chronic inflammatory airway diseases.

  1. Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease.

    PubMed

    Puchelle, Edith; Zahm, Jean-Marie; Tournier, Jean-Marie; Coraux, Christelle

    2006-11-01

    In chronic obstructive pulmonary disease (COPD), exacerbations are generally associated with several causes, including pollutants, viruses, bacteria that are responsible for an excess of inflammatory mediators, and proinflammatory cytokines released by activated epithelial and inflammatory cells. The normal response of the airway surface epithelium to injury includes a succession of cellular events, varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even complete denudation of the basement membrane. The epithelium then has to repair and regenerate to restore its functions, through several mechanisms, including basal cell spreading and migration, followed by proliferation and differentiation of epithelial cells. In COPD, the remodeling of the airway epithelium, such as squamous metaplasia and mucous hyperplasia that occur during injury, may considerably disturb the innate immune functions of the airway epithelium. In vitro and in vivo models of airway epithelial wound repair and regeneration allow the study of the spatiotemporal modulation of cellular and molecular interaction factors-namely, the proinflammatory cytokines, the matrix metalloproteinases and their inhibitors, and the intercellular adhesion molecules. These factors may be markedly altered during exacerbation periods of COPD and their dysregulation may induce remodeling of the airway mucosa and a leakiness of the airway surface epithelium. More knowledge of the mechanisms involved in airway epithelium regeneration may pave the way to cytoprotective and regenerative therapeutics, allowing the reconstitution of a functional, well-differentiated airway epithelium in COPD.

  2. Long chain N-3 polyunsaturated fatty acids in the prevention of allergic and cardiovascular disease.

    PubMed

    van den Elsen, Lieke; Garssen, Johan; Willemsen, Linette

    2012-01-01

    The diet is considered to have a major impact on human health. Dietary lipids including long chain polyunsaturated fatty acids (LCPUFA) possess potent immunomodulatory activities. Over the last decades the incidence of inflammatory disorders including allergic and cardiovascular diseases (CVD) has been rising. This phenomenon is associated with deficiencies in N-3 LCPUFA, found in fatty fish, and increased content of N-6 LCPUFA in the Western diet. LCPUFA act via different mechanisms including membrane fluidity, raft composition, lipid mediator formation, signaling pathways and transmembrane receptors. N-3 LCPUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce the development of allergic disease by affecting both the innate and adaptive immune system involved in the initiation and persistence of allergic disease. Fish oil has been shown to be effective in the primary prevention of allergic disease in infants at risk when supplemented during pregnancy and lactation. Subtle effects of N-3 LCPUFA on the outcome of the immune response may underlie these protective effects. This review describes the currently reported effects of LCPUFA on dendritic cells, T cells, B cells and mast cells. Also CVD are positively affected by N-3 LCPUFA. Populations consuming high amounts of oily fish are protected against CVD. Moreover N-3 LCPUFA are effective in the secondary prevention of cardiovascular events. Amongst other effects, EPA and DHA have been shown to suppress endothelial cell activation hereby reducing adhesion molecule expression and endothelial cell - leukocyte interactions. This review describes the mechanistic basis of the preventive role for N-3 LCPUFA in allergic disease and CVD.

  3. High proportion of CD5+ B cells in infants predicts development of allergic disease.

    PubMed

    Lundell, Anna-Carin; Johansen, Susanne; Adlerberth, Ingegerd; Wold, Agnes E; Hesselmar, Bill; Rudin, Anna

    2014-07-15

    Delayed maturation of the immune system has been proposed to be a risk factor for development of allergy, but B cell maturation in relation to allergic disease has not been examined. B cells lose CD5 and acquire CD27 during maturation from immature via mature/naive to Ig-secreting cells and memory cells. We sought to investigate B cell maturation in relation to development of allergic disease and sensitization in the FARMFLORA birth cohort including 65 Swedish children. Total B cell numbers, proportions of CD5(+) and CD27(+) B cells, and levels of IgM, IgG, IgA, and IgE were measured in blood on repeated occasions from birth to 36 mo of age, and related to allergic disease and sensitization at 18 and 36 mo of age with multivariate discriminant analysis. We also compared the expression of CD24 and CD38 within CD5(+) and CD5(neg) B cells in children and in adults. We found that infants with a high proportion of CD5(+) B cells at birth and at 1 mo of age had an increased risk for having allergic disease at 18 and 36 mo of life. Further, the proportions of CD5(+) B cells at 1 mo of age were inversely correlated with total IgG levels at 18 and 36 mo of age. The majority of the CD5(+) B cells were of a CD24(hi/+)CD38(hi/+) immature/naive phenotype at birth (97%), 7 y of age (95%), and in adults (86%). These results suggest that development of allergic disease is preceded by an immaturity in neonatal B cell phenotype.

  4. TGFβ Receptor Mutations Impose a Strong Predisposition for Human Allergic Disease

    PubMed Central

    Frischmeyer-Guerrerio, Pamela A.; Guerrerio, Anthony L.; Oswald, Gretchen; Chichester, Kristin; Myers, Loretha; Halushka, Marc K.; Oliva-Hemker, Maria; Wood, Robert A.; Dietz, Harry C.

    2013-01-01

    Transforming growth factor–β (TGFβ) is a multifunctional cytokine that plays diverse roles in physiologic processes as well as human disease, including cancer, heart disease, and fibrotic disorders. In the immune system, TGFβ regulates regulatory T cell (Treg) maturation and immune homeostasis. Although genetic manipulation of the TGFβ pathway modulates immune tolerance in mouse models, the contribution of this pathway to human allergic phenotypes is not well understood. We demonstrate that patients with Loeys-Dietz syndrome (LDS), an autosomal dominant disorder caused by mutations in the genes encoding receptor subunits for TGFβ, TGFBR1 and TGFBR2, are strongly predisposed to develop allergic disease, including asthma, food allergy, eczema, allergic rhinitis, and eosinophilic gastrointestinal disease. LDS patients exhibited elevated immunoglobulin E levels, eosinophil counts, and T helper 2 (TH2) cytokines in their plasma. They had an increased frequency of CD4+ T cells that expressed both Foxp3 and interleukin-13, but retained the ability to suppress effector T cell proliferation. TH2 cytokine–producing cells accumulated in cultures of naïve CD4+ T cells from LDS subjects, but not controls, after stimulation with TGFβ, suggesting that LDS mutations support TH2 skewing in naïve lymphocytes in a cell-autonomous manner. The monogenic nature of LDS demonstrates that altered TGFβ signaling can predispose to allergic phenotypes in humans and underscores a prominent role for TGFβ in directing immune responses to antigens present in the environment and foods. This paradigm may be relevant to nonsyndromic presentations of allergic disease and highlights the potential therapeutic benefit of strategies that inhibit TGFβ signaling. PMID:23884466

  5. [An increase in allergic diseases in childhood--current hypotheses and possible prevention].

    PubMed

    Kurz, Herbert; Riedler, Jose

    2003-01-01

    During the last few decades there has ben a significant rise in the prevalence of allergic diseases such as asthma, hay fever and atopic dermatitis. Epidemiological studies strongly suggest that this increase is real and not due to changes in diagnostic labelling. It has become increasingly clear that a complex interplay between genetic and environmental factors account for this phenomenon. Genetically predisposed individuals are at an increased susceptibility to develop asthma or other allergic diseases when exposed to certain environmental or lifestyle factors. Particularly passive smoking has been shown to increase the risk for asthma in many studies and for atopy at least in some studies. This association is less clear for the exposure to sulfur dioxide, particulate matter, diesel exhaust and ozone. Lifestyle factors like socioeconomic status, sib-ship size, early childhood infections, dietary habits, growing up in antroposophic families or on a farm are more and more realised to be of great relevance for the development of allergic conditions. At the moment, there is a lot of uncertainty about which recommendations should be given for primary prevention. Recent studies have challenged the old paradigma that avoidance of early allergen contact could prevent the development of allergic disease. However, there is consensus that avoidance of smoking during pregnancy and avoidance of passive smoking during childhood should be recommended for primary prevention of asthma.

  6. Influence of Socioeconomic Factors on Self-Reported Prevalence of Allergic Diseases Among Female University Students.

    PubMed

    Kliś, K; Żurawiecka, M; Suder, A; Teul, I; Borowska-Strugińska, B; Suliga, E; Wronka, I

    2017-02-25

    Until recently, most studies report an increasing prevalence of allergy and asthma. The research suggests that the increase may have to do with changes in lifestyle and living conditions. This study seeks to determine the prevalence and changes in allergic diseases in relation to socioeconomic status (SES) 6 years apart. The research material consisted of data collected in two cross-sectional surveys conducted among university female students in 2009 and 2015 (respectively, 702 and 1305 subjects). The surveys evaluated the incidence of allergic conditions and socio-economic status. The occurrence of allergy was determined on the basis of answers to the questions whether the allergy and specific allergens were defined on the basis of medical work-up. The prevalence of allergic diseases increased from 14.0% to 22.3% over a 6-year period. In both cohorts, allergic diseases were more prevalent among females with high SES than with low SES. In 2009, significant differences were noted in relation to urbanization of the place of living and the number of siblings. In 2015, all socioeconomics factors significantly bore on the prevalence of allergy.

  7. The Relationship between Vitamin D Status and Allergic Diseases in New Zealand Preschool Children

    PubMed Central

    Cairncross, Carolyn; Grant, Cameron; Stonehouse, Welma; Conlon, Cath; McDonald, Barry; Houghton, Lisa; Eyles, Darryl; Camargo, Carlos A.; Coad, Jane; von Hurst, Pamela

    2016-01-01

    Recent research on vitamin D in young children has expanded from bone development to exploring immunomodulatory effects. Our aim was to investigate the relationship of vitamin D status and allergic diseases in preschool-aged children in New Zealand. Dried capillary blood spots were collected from 1329 children during late-winter to early-spring for 25(OH)D measurement by LC-MS/MS. Caregivers completed a questionnaire about their child’s recent medical history. Analysis was by multivariable logistic regression. Mean 25(OH)D concentration was 52(SD19) nmol/L, with 7% of children <25 nmol/L and 49% <50 nmol/L. Children with 25(OH)D concentrations ≥75 nmol/L (n = 29) had a two-fold increased risk for parent-report of doctor-diagnosed food allergy compared to children with 25(OH)D 50–74.9 nmol/L (OR = 2.21, 1.33–3.68, p = 0.002). No associations were present between 25(OH)D concentration and presence of parent-reported eczema, allergic rhinoconjunctivitis or atopic asthma. Vitamin D deficiency was not associated with several allergic diseases in these New Zealand preschool children. In contrast, high 25(OH)D concentrations were associated with a two-fold increased risk of parental-report food allergy. This increase supports further research into the association between vitamin D status and allergic disease in preschool children. PMID:27258306

  8. The Relationship between Vitamin D Status and Allergic Diseases in New Zealand Preschool Children.

    PubMed

    Cairncross, Carolyn; Grant, Cameron; Stonehouse, Welma; Conlon, Cath; McDonald, Barry; Houghton, Lisa; Eyles, Darryl; Camargo, Carlos A; Coad, Jane; von Hurst, Pamela

    2016-06-01

    Recent research on vitamin D in young children has expanded from bone development to exploring immunomodulatory effects. Our aim was to investigate the relationship of vitamin D status and allergic diseases in preschool-aged children in New Zealand. Dried capillary blood spots were collected from 1329 children during late-winter to early-spring for 25(OH)D measurement by LC-MS/MS. Caregivers completed a questionnaire about their child's recent medical history. Analysis was by multivariable logistic regression. Mean 25(OH)D concentration was 52(SD19) nmol/L, with 7% of children <25 nmol/L and 49% <50 nmol/L. Children with 25(OH)D concentrations ≥75 nmol/L (n = 29) had a two-fold increased risk for parent-report of doctor-diagnosed food allergy compared to children with 25(OH)D 50-74.9 nmol/L (OR = 2.21, 1.33-3.68, p = 0.002). No associations were present between 25(OH)D concentration and presence of parent-reported eczema, allergic rhinoconjunctivitis or atopic asthma. Vitamin D deficiency was not associated with several allergic diseases in these New Zealand preschool children. In contrast, high 25(OH)D concentrations were associated with a two-fold increased risk of parental-report food allergy. This increase supports further research into the association between vitamin D status and allergic disease in preschool children.

  9. General anesthesia exposure in early life reduces the risk of allergic diseases

    PubMed Central

    Kuo, Ho-Chang; Yang, Ya-Ling; Ho, Shu-Chen; Guo, Mindy Ming-Huey; Jiang, Jyun-Hong; Huang, Ying-Hsien

    2016-01-01

    Abstract General anesthesia (GA) has been used for second line treatment strategy for status asthmaticus in pediatric patients. The association between GA in children and risk of followed-up allergic diseases is unclear. This study aims to assess the risk of allergic diseases after GA in children. We did a nationwide retrospective cohort study by analyzing data from the National Health Insurance Research Database (NHIRD) in Taiwan. The subsequent risks for allergic diseases, including asthma (ICD-9: 493.X), allergic rhinitis (AR; ICD-9 CM code 477.X), and atopic dermatitis (AD; ICD-9-CM code 691.X), were compared between exposure to GA and none before 1 year of age throughout the follow-up period using the Cox proportional hazards model. Insurance claims data for 32,742 children younger than 1 year old from all insured children in the NHIRD. Of those, 2358 subjects were exposed to GA; 414 and 1944 children exposed to mask and intubation ventilation, respectively, served as the study cohort, whereas the remaining 30,384 children made up the comparison cohort. Children in the GA group were at a lower risk of developing asthma, AR and AD, with adjusted hazard ratios of 0.67 (0.62–0.72, 95%CI), 0.72 (0.68–0.77, 95%CI), 0.60 (0.56–0.64, 95%CI), respectively. Children who were exposed to GA in early life before 1 year of age had reduced risk of subsequently developing allergic diseases such as asthma, AD, and AR, when compared with general population. PMID:27428241

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

    PubMed

    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.

  11. Clinical significance of airway mucus hypersecretion in chronic obstructive pulmonary disease

    PubMed Central

    Tian, Pan-wen; Wen, Fu-qiang

    2015-01-01

    Airway mucus hypersecretion is one of the most important features of chronic obstructive pulmonary disease (COPD). Airway mucus hypersecretion in COPD patients results in outcomes such as rapid decline of lung function, poor quality of life, and high rate of acute exacerbation, hospitalization and mortality. Nonpharmacologic treatments for airway mucus hypersecretion in COPD include smoking cessation and physical rehabilitation. Pharmacologic therapies include expectorants, mucolytics, methylxanthines, beta-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. Novel drugs with promising prospects are currently under clinical trials. PMID:27847895

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

    PubMed Central

    Lee, Chen-Chen; Wang, Ching-Chiung; Huang, Huei-Mei; Lin, Chu-Lun; Leu, Sy-Jye; Lee, Yueh-Lun

    2015-01-01

    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. PMID:26495021

  13. Duration of breast-feeding and the risk of childhood allergic diseases in a developing country.

    PubMed

    Ehlayel, Mohammad S; Bener, Abdulbari

    2008-01-01

    Exclusive breast-feeding (EBF) seems to reduce risk of allergies in the western countries, but there are few reports from developing countries. The purpose of this study was to assess the effect of EBF on the development of allergic diseases and eczema in a developing country. This is a cross-sectional survey done at the well-baby clinics of 11 primary health centers, Hamad Medical Corporation, Qatar. A multistage sampling design was used and a representative sample of 1500 children (0-5 years old) and mothers (18-47 years old) were surveyed between October 2006 and September 2007. Of them, 1278 mothers (85.2%) participated in the study. A confidential, anonymous questionnaire assessing breast-feeding and allergic diseases was completed by mothers bringing children for immunization. Questionnaire included allergic rhinitis, wheezing, eczema, type and duration of breast-feeding, parental smoking habits, number of siblings, family income, maternal education, and parental allergies. Univariate and multivariate statistical methods were performed for statistical analysis. More than one-half of the infants (59.3%) were on EBF. Length of breast-feeding was associated with maternal age. Prevalence of eczema (19.4%), allergic rhinitis (22.6%), and wheezing (12.7%) were significantly less frequent in those with prolonged (>6 months) compared with short-term fed infants. The association between EBF and eczema tended to be similar in children with a positive family history of atopy (p < 0.001) and eczema (p < 0.001) compared with those without. In children of developing countries, prolonged breast-feeding reduces the risk of developing allergic diseases and eczema even in the presence of maternal allergy, where it might be a practical, effective preventive measure.

  14. The Microbiome, Timing, and Barrier Function in the Context of Allergic Disease.

    PubMed

    Wesemann, Duane R; Nagler, Cathryn R

    2016-04-19

    Allergic disease affects millions. Despite many advances in our understanding of the immune system in the past century, the physiologic underpinning for the existence of allergy remains largely mysterious. Food allergies, in particular, have increased dramatically in recent years, adding a new sense of urgency to unraveling this mystery. The concurrence of significant lifestyle changes in Western societies with increasing disease prevalence implies a causal link. Demographic variables that influence the composition and function of the commensal microbiota early in life seem to be most important. Identifying the evolutionary and physiologic foundations of allergic disease and defining what about our modern environment is responsible for its increased incidence will provide insights critical to the development of new approaches to prevention and treatment.

  15. The prevalence and risk factors of asthma and allergic diseases among working adolescents.

    PubMed

    Cakir, Erkan; Ersu, Refika; Uyan, Zeynep Seda; Oktem, Sedat; Varol, Nezih; Karakoc, Fazilet; Karadag, Bulent; Akyol, Mesut; Dagli, Elif

    2010-01-01

    Certain occupational groups are known to be at particularly high risk of developing allergic diseases. The objective of the present study was to evaluate the prevalence of allergic diseases among working adolescents. The International Study of Asthma and Allergies in Childhood questionnaire was used. Four hundred and thirty six adolescents working in motor, lathe-finish, coiffure and textile and 366 high school students as control group were enrolled to the study. Mean age was 16.8 +/- 1.2 years and 82.9% of them were male. There was no significant difference among groups for ever and current wheezing while doctor diagnosed asthma was higher in lathe- finish group (p = 0.036). Family history of allergy, history of allergic rhinitis, and active smoking were found to be risk factors for asthma and related symptoms. Working in coiffure (p = 0.054), and textile (p = 0.003) were significant risk factors for ever allergic rhinitis. Working in lathe finish (p = 0.023), coiffure (p = .002), and textile (p < 0.001) were associated with a higher risk for current allergic rhinitis. Working in coiffure was a risk factor for ever eczema (p = 0.008) and doctor diagnosed eczema (p = 0.014). It was concluded that working in lathe-finish was associated with doctor diagnosed asthma and active smoking was a risk factor for asthma and related symptoms. Working in coiffure, textile and lathe- finish were risk factors for rhinitis, and working in coiffure was a risk factor for eczema. Preventive measures should be taken at the onset of employment in order to prevent or reduce the detrimental effects of exposures in these occupational groups.

  16. Effects of inhaled budesonide on spirometric values, reversibility, airway responsiveness, and cough threshold in smokers with chronic obstructive lung disease.

    PubMed Central

    Auffarth, B; Postma, D S; de Monchy, J G; van der Mark, T W; Boorsma, M; Koëter, G H

    1991-01-01

    Inhaled corticosteroids are known to reduce respiratory symptoms and airway responsiveness in allergic patients with asthma. The aim of the present randomised, double blind study was to assess the effect of eight weeks' treatment with inhaled budesonide in non-allergic smokers with chronic obstructive lung disease. Twenty four subjects (23 male) entered the study. Their ages ranged from 40 to 70 (mean 57) years, with a mean of 35 (range 9-80) pack years of smoking; the mean FEV1 was 53% (range 32-74%) predicted and geometric mean PC20 (histamine concentration causing a 20% fall in FEV1) 0.96 (range 0.07-7.82) mg/ml. After a two week washout, single blind, placebo period, 12 patients were allocated to treatment with budesonide 1600 microgram/day and 12 to placebo for eight weeks. The only additional drug to be taken was ipratropium bromide "if needed." Twenty one patients completed the study, 10 in the budesonide group and 11 in the placebo group. The standard deviation of the difference between duplicate measurements of PC20 histamine and citric acid cough threshold made two weeks apart was below one doubling dose step. There was a significant reduction in dyspnoea in the budesonide group, but otherwise no change in symptom scores or use of ipratropium bromide over the eight weeks of treatment within or between the two groups. No significant differences in spirometric values, peak expiratory flow, PC20 histamine, or citric acid cough threshold were found between the groups. Although differences were not significant, some of the changes showed a trend in favour of budesonide. Whether a longer observation period would show a significant influence of inhaled corticosteroids in patients with chronic obstructive lung disease remains to be determined. Images PMID:2068695

  17. Airway smooth muscle in airway reactivity and remodeling: what have we learned?

    PubMed Central

    2013-01-01

    It is now established that airway smooth muscle (ASM) has roles in determining airway structure and function, well beyond that as the major contractile element. Indeed, changes in ASM function are central to the manifestation of allergic, inflammatory, and fibrotic airway diseases in both children and adults, as well as to airway responses to local and environmental exposures. Emerging evidence points to novel signaling mechanisms within ASM cells of different species that serve to control diverse features, including 1) [Ca2+]i contractility and relaxation, 2) cell proliferation and apoptosis, 3) production and modulation of extracellular components, and 4) release of pro- vs. anti-inflammatory mediators and factors that regulate immunity as well as the function of other airway cell types, such as epithelium, fibroblasts, and nerves. These diverse effects of ASM “activity” result in modulation of bronchoconstriction vs. bronchodilation relevant to airway hyperresponsiveness, airway thickening, and fibrosis that influence compliance. This perspective highlights recent discoveries that reveal the central role of ASM in this regard and helps set the stage for future research toward understanding the pathways regulating ASM and, in turn, the influence of ASM on airway structure and function. Such exploration is key to development of novel therapeutic strategies that influence the pathophysiology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. PMID:24142517

  18. Mechanistic impact of outdoor air pollution on asthma and allergic diseases

    PubMed Central

    Zhang, Qingling; Qiu, Zhiming; Chung, Kian Fan

    2015-01-01

    Over the past decades, asthma and allergic diseases, such as allergic rhinitis and eczema, have become increasingly common, but the reason for this increased prevalence is still unclear. It has become apparent that genetic variation alone is not sufficient to account for the observed changes; rather, the changing environment, together with alterations in lifestyle and eating habits, are likely to have driven the increase in prevalence, and in some cases, severity of disease. This is particularly highlighted by recent awareness of, and concern about, the exposure to ubiquitous environmental pollutants, including chemicals with oxidant-generating capacities, and their impact on the human respiratory and immune systems. Indeed, several epidemiological studies have identified a variety of risk factors, including ambient pollutant gases and airborne particles, for the prevalence and the exacerbation of allergic diseases. However, the responsible pollutants remain unclear and the causal relationship has not been established. Recent studies of cellular and animal models have suggested several plausible mechanisms, with the most consistent observation being the direct effects of particle components on the generation of reactive oxygen species (ROS) and the resultant oxidative stress and inflammatory responses. This review attempts to highlight the experimental findings, with particular emphasis on several major mechanistic events initiated by exposure to particulate matters (PMs) in the exposure-disease relationship. PMID:25694815

  19. Roles of histamine and its receptors in allergic and inflammatory bowel diseases

    PubMed Central

    Xie, Hua; He, Shao-Heng

    2005-01-01

    Mast cell has a long history of being recognized as an important mediator-secreting cell in allergic diseases, and has been discovered to be involved in IBD in last two decades. Histamine is a major mediator in allergic diseases, and has multiple effects that are mediated by specific surface receptors on target cells. Four types of histamine receptors have now been recognized pharmacologically and the first three are located in the gut. The ability of histamine receptor antagonists to inhibit mast cell degranulation suggests that they might be developed as a group of mast cell stabilizers. Recently, a series of experiments with dispersed colon mast cells suggested that there should be at least two pathways in man for mast cells to amplify their own activation-degranulation signals in an autocrine or paracrine manner. In a word, histamine is an important mediator in allergic diseases and IBD, its antagonists may be developed as a group of mast cell stabilizers to treat these diseases. PMID:15902718

  20. Barrier dysfunction caused by environmental proteases in the pathogenesis of allergic diseases.

    PubMed

    Takai, Toshiro; Ikeda, Shigaku

    2011-03-01

    Skin barrier dysfunction has emerged as a critical driving force in the initiation and exacerbation of atopic dermatitis and the "atopic march" in allergic diseases. The genetically determined barrier deficiency and barrier disruption by environmental and endogenous proteases in skin and epithelium are considered to increase the risk of sensitization to allergens and contribute to the exacerbation of allergic diseases. Sources of allergens such as mites, cockroaches, fungi, and pollen, produce or contain proteases, which are frequently themselves allergens. Staphylococcus aureus, which heavily colonizes the lesions of atopic dermatitis patients and is known to trigger a worsening of the disease, also produces extracellular proteases. Environmental proteases can cause barrier breakdown in the skin, not only in the epithelium, and stimulate various types of cells through IgE-independent mechanisms. Endogenous protease inhibitors control the functions of environmental and endogenous proteases. In this review, we focus on the barrier dysfunction caused by environmental proteases and roles of endogenous protease inhibitors in the pathogenesis of allergic diseases. Additionally, we examine the subsequent innate response to Th2-skewed adaptive immune reactions.

  1. Environmental protection from allergic diseases: From humans to mice and back.

    PubMed

    Schaub, Bianca; Vercelli, Donata

    2015-10-01

    Allergic diseases have a strong environmental component, illustrated by the rapid rise of their prevalence in the Western world. Environmental exposures have been consistently shown to either promote or protect against allergic disease. Here we focus on protective exposures and the pathways they regulate. Traditional farming, natural environments with high biodiversity, and pets in the home (particularly dogs) have the most potent and consistent allergy-protective effects and are actively investigated to identify the environmental and host-based factors that confer allergy protection. Recent work emphasizes the critical protective role of microbial diversity and its interactions with the gut/lung and skin/lung axes-a cross-talk through which microbial exposure in the gut or skin powerfully influences immune responses in the lung.

  2. Dissimilar allergic disease in identical twins; a study of psychosomatic aspects.

    PubMed

    CREDE, R H; CARMAN, C T; WHALEY, R D; SCHUMACHER, I C

    1953-01-01

    Identical twins with bronchial asthma were studied. One had the first attack of the disease in late adolescence, the other not until he was adult. Both were demonstrated by immunologic means to be sensitive to house dust and certain foods. Yet, of itself, the factor of exposure to a known allergen seemed not enough to precipitate clinical allergic reaction in either of them. It is believed that emotional stress is accompanied by physiologic changes which facilitate increased reactions to antigenic agents that in normal circumstances would not cause clinical disease.The twins were widely different with regard to emotional development and in their reaction to situations of stress. In both of them allergic manifestations were associated with periods of emotional conflict.The dissimilar clinical manifestations of allergy in these identical twins may be explained by differences in personality and therefore in reactions to stress situations.

  3. Human airway organoid engineering as a step toward lung regeneration and disease modeling.

    PubMed

    Tan, Qi; Choi, Kyoung Moo; Sicard, Delphine; Tschumperlin, Daniel J

    2017-01-01

    Organoids represent both a potentially powerful tool for the study cell-cell interactions within tissue-like environments, and a platform for tissue regenerative approaches. The development of lung tissue-like organoids from human adult-derived cells has not previously been reported. Here we combined human adult primary bronchial epithelial cells, lung fibroblasts, and lung microvascular endothelial cells in supportive 3D culture conditions to generate airway organoids. We demonstrate that randomly-seeded mixed cell populations undergo rapid condensation and self-organization into discrete epithelial and endothelial structures that are mechanically robust and stable during long term culture. After condensation airway organoids generate invasive multicellular tubular structures that recapitulate limited aspects of branching morphogenesis, and require actomyosin-mediated force generation and YAP/TAZ activation. Despite the proximal source of primary epithelium used in the airway organoids, discrete areas of both proximal and distal epithelial markers were observed over time in culture, demonstrating remarkable epithelial plasticity within the context of organoid cultures. Airway organoids also exhibited complex multicellular responses to a prototypical fibrogenic stimulus (TGF-β1) in culture, and limited capacity to undergo continued maturation and engraftment after ectopic implantation under the murine kidney capsule. These results demonstrate that the airway organoid system developed here represents a novel tool for the study of disease-relevant cell-cell interactions, and establishes this platform as a first step toward cell-based therapy for chronic lung diseases based on de novo engineering of implantable airway tissues.

  4. Broncho-Vaxom Attenuates Allergic Airway Inflammation by Restoring GSK3β-Related T Regulatory Cell Insufficiency

    PubMed Central

    Zhong, Hua; Yu, Dehong; Zeng, Xianping; Deng, Mengxia; Sun, Yueqi; Wen, Weiping; Li, Huabin

    2014-01-01

    Background Oral administration of bacterial extracts (eg, Broncho-Vaxom (BV)) has been proposed to attenuate asthma through modulating Treg cells. However, the underlying mechanism has not been fully characterized. This study sought to assess the effects of oral administration of BV on GSK-3β expression and Treg cells in ovalbumin (OVA)-induced asthmatic mice models. Method Asthmatic mice models were established with OVA challenge and treated with oral administration of BV. Next, infiltration of inflammatory cells including eosinophil and neutrophils, mucous metaplasia, levels of Th1/Th2/Treg-typed cytokines and expression of GSK3β and Foxp3 were examined in asthmatic mice models by histological analysis, Bio-Plex and western blot, respectively. Moreover, the frequencies of Treg cells were evaluated in cultured splenocytes by flow cytometry in the presence of BV or GSK3β siRNA interference. Results We found significant decrease of infiltrated inflammatory cells in bronchoalveolar lavage fluid (BALF) in asthmatic mice models after oral administration of BV. Oral administration of BV was shown to significantly suppress mucus metaplasia, Th2-typed cytokine levels and GSK3β expression while increasing Foxp3 production in asthmatic mice models. Moreover, BV significantly enhanced GSK3β-related expansion of Treg cells in cultured spleen cells in vitro. Conclusion Our findings provide evidence that oral administration of BV is capable of attenuating airway inflammation in asthmatic mice models, which may be associated with GSK3β-related expansion of Treg cells. PMID:24667347

  5. Air Pollution and Prevalence of Allergic Diseases in Georgian Adolescent Population

    DTIC Science & Technology

    2004-06-01

    adolescent and young population in Tbilisi a prospective epidemiological investigation has been carried out. During the last decades special attention...unified methods including a screening-questionnaire, a detailed map of epidemiological analysis. 11073 adolescent and young population of 12 to 20...in Georgian Adolescent Population 4 - 6 RTO-MP-HFM-108 Table 1: Relationship Between the Prevalence Rate of Allergic Diseases in Young Population and

  6. Breastfeeding and the prevalence of allergic diseases in schoolchildren: Does reverse causation matter?

    PubMed

    Kusunoki, Takashi; Morimoto, Takeshi; Nishikomori, Ryuta; Yasumi, Takahiro; Heike, Toshio; Mukaida, Kumiko; Fujii, Tatsuya; Nakahata, Tatsutoshi

    2010-02-01

    Infants at higher risk of allergic diseases might be breastfed for longer periods compared with infants at lower risk in the hope that breastfeeding might reduce the risk of atopic disorders. Therefore, this intention could manifest as an apparent allergy-promoting effect of breastfeeding or reverse causation. To analyze the effect of breast feeding on the prevalence of allergic diseases at school age, a large questionnaire survey was administered to the parents of schoolchildren aged 7-15 yrs. 13,215 parents responded (response rate, 90.1%). Prevalence rates of allergic diseases were compared according to the type of feeding in infancy (either complete breastfeeding, mixed feeding or complete artificial feeding). In both univariate and multivariate analysis, compared with those with complete artificial feeding, those with mixed and complete breastfeeding showed a significantly lower prevalence of bronchial asthma (BA) (p = 0.01 and 0.003, respectively). On the other hand, in univariate analysis, the prevalence of atopic dermatitis (AD) and food allergy (FA) were significantly higher in those with complete breastfeeding (p = 0.04 and 0.01, respectively). There was a significantly higher proportion of complete breastfeeding among those with greater risk of allergic diseases (presence of family history, either eczema or wheeze within 6 months after birth, or FA in infancy). Therefore, our multivariate analysis included these risks as confounding factors, and we found that the promoting effects of breastfeeding on AD and FA disappeared. In conclusion, our data clearly showed the inhibitory effect of breastfeeding on the prevalence of BA at school age. The apparent promoting effect of breastfeeding on the prevalence of AD and FA is most likely because of reverse causation.

  7. [Leukotrien antagonists in the treatment of allergic rhinitis and comorbidities].

    PubMed

    Sacre Hazouri, José Antonio

    2008-01-01

    Leukotrienes comprise a family of products of the 5-lipoxigenase pathway of arachidonic acid metabolism. The cysteinil leukotrienes C4, D4 and E4 account for the biologic activity that was previously termed "slow-reacting substance of anaphylaxis". The proinflammatory effects of cysteinil leukotrienes (cys LTs) have been well described in asthma and rhinitis. The cys LTs induce broncospasm (1,000 times more potent than histamine), edema, mucus, hypersecretion, attract inflammatory cells like eosinophils, increase airway hyperreactivity, vascular leakage, and stimulate takikinins. The leukotriene synthesis can be inhibited in two different places; through inhibition of 5 lipooxigenase activating protein (FLAP) in the 5 lipooxigenase pathway, with the drug Zyleuton, or blocking the cysLT1 receptor with the drugs Montelukast, Pranlukast, Zafirlukast. The cysLTs play an important role in pathophysiology of allergic rhinitis and comorbid diseases like rhinosinusitis and nasal polyposis. Antileukotrienes are prescribed in the treatment of allergic rhinitis. Allergic rhinitis is a complex IgE inflammatory disease of the upper airways. It is the most common allergic disease ocurring in 10 to 20% of adults and up to 30% of children. It may be seasonal or perennial, intermittent or persistent. Sneezing, itching, watery rhinorrea and nasal obstruction are classic symptoms. Ocular itching, lacrimation and redness also occur frequently as almost 50% of the patients also have allergic conjunctivitis. Allergic rhinitis may be mild, moderate or severe disease. It may impair cognition, school and work performance. It affects productivity, behavior and mood changes, causes sleep disturbance and diminish the patient's quality of life. Allergic rhinitis is a common comorbid condition with asthma, sinusitis, otitis media, nasal polyposis and recurrent respiratory infections. The purpose of this rewiew article is to know the importante of leukotrienes, its receptors and the clinical

  8. Grass pollen allergens globally: the contribution of subtropical grasses to burden of allergic respiratory diseases.

    PubMed

    Davies, J M

    2014-06-01

    types of subtropical grass pollens to achieve optimal diagnosis and treatment of patients with allergic respiratory disease in subtropical regions of the world.

  9. The role of partially hydrolyzed whey formula for the prevention of allergic disease: evidence and gaps.

    PubMed

    Lowe, Adrian J; Dharmage, Shyamali C; Allen, Katrina J; Tang, Mimi L K; Hill, David J

    2013-01-01

    Hydrolyzed formulae are created by using enzymatic processes to break native proteins into smaller fragments. They may prevent development of allergic diseases by reducing exposure to intact allergens. Partially hydrolyzed whey formula (pHWF) is particularly promising for allergy prevention, as it is cheap to manufacture and palatable. Scientific organizations have recommended the use of hydrolyzed formula in the first 4-6 months of life for the prevention of allergic disease based on a limited number of trials. Three recent developments challenge these recommendations: our growing understanding of the importance of allergen exposure for induction of immune tolerance, recently published evidence that failed to identify a protective effect of pHWF, which the authors and other experts believe will necessitate updating of systematic reviews, and methodological limitations of available trials and systematic reviews on which these recommendations are based. Until more definitive evidence is obtained, the authors recommend continuing to advocate that 'breast is best', and caution against overstating the potential for pHWF to prevent allergic disease.

  10. Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis

    PubMed Central

    Ierodiakonou, Despo; Khan, Tasnia; Chivinge, Jennifer; Robinson, Zoe; Geoghegan, Natalie; Jarrold, Katharine; Afxentiou, Thalia; Reeves, Tim; Cunha, Sergio; Trivella, Marialena; Garcia-Larsen, Vanessa; Leonardi-Bee, Jo

    2016-01-01

    Objective To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease. Design Systematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool. Data sources Medline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015. Eligibility criteria for selecting studies Prospective intervention trials of hydrolysed cows’ milk formula compared with another hydrolysed formula, human breast milk, or a standard cows’ milk formula, which reported on allergic or autoimmune disease or allergic sensitisation. Results 37 eligible intervention trials of hydrolysed formula were identified, including over 19 000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall there was no consistent evidence that partially or extensively hydrolysed formulas reduce risk of allergic or autoimmune outcomes in infants at high pre-existing risk of these outcomes. Odds ratios for eczema at age 0-4, compared with standard cows’ milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I2=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I2=74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I2=0%) for extensively hydrolysed whey based formula. There was no evidence to support the health claim approved by the US Food and Drug Administration that a partially hydrolysed formula could reduce the risk of eczema nor the conclusion of the Cochrane review that hydrolysed formula could prevent allergy to cows’ milk. Conclusion These findings do not support current guidelines

  11. Overview on the pathomechanisms of allergic rhinitis.

    PubMed

    Pawankar, Ruby; Mori, Sachiko; Ozu, Chika; Kimura, Satoko

    2011-10-01

    Allergic rhinitis a chronic inflammatory disease of the upper airways that has a major impact on the quality of life of patients and is a socio-economic burden. Understanding the underlying immune mechanisms is central to developing better and more targeted therapies. The inflammatory response in the nasal mucosa includes an immediate IgE-mediated mast cell response as well as a latephase response characterized by recruitment of eosinophils, basophils, and T cells expressing Th2 cytokines including interleukin (IL)-4, a switch factor for IgE synthesis, and IL-5, an eosinophil growth factor and on-going allergic inflammation. Recent advances have suggested new pathways like local synthesis of IgE, the IgE-IgE receptor mast cell cascade in on-going allergic inflammation and the epithelial expression of cytokines that regulate Th2 cytokine responses (i.e., thymic stromal lymphopoietin, IL-25, and IL-33). In this review, we briefly review the conventional pathways in the pathophysiology of allergic rhinitis and then elaborate on the recent advances in the pathophysiology of allergic rhinitis. An improved understanding of the immune mechanisms of allergic rhinitis can provide a better insight on novel therapeutic targets.

  12. Effects of Educational Interventions for Chronic Airway Disease on Primary Care.

    PubMed

    Lee, Jung Yeon; Yoo, Kwang Ha; Kim, Deog Kyeom; Kim, Sang-Ha; Kim, Tae-Eun; Kim, Tae-Hyung; Rhee, Chin Kook; Park, Yong Bum; Yoon, Hyoung Kyu; Yum, Ho-Kee

    2016-07-01

    Education has been known to essential for management of chronic airway diseases. However the real benefits remain unclear. We evaluated the effectiveness of an organized educational intervention for chronic airway diseases directed at primary care physicians and patients. The intervention was a 1-month education program of three visits, during which subjects were taught about their disease, an action plan in acute exacerbation and inhaler technique. Asthma control tests (ACT) for asthma and, chronic obstructive pulmonary disease (COPD) assessment tests (CAT) for COPD subjects were compared before and after education as an index of quality of life. Educational effectiveness was also measured associated with improvement of their knowledge for chronic airway disease itself, proper use of inhaler technique, and satisfaction of the subjects and clinicians before and after education. Among the 285 participants, 60.7% (n = 173) were men and the mean age was 62.2 ± 14.7. ACT for asthma and CAT in COPD patients were significantly improved by 49.7% (n = 79) and 51.2% (n = 65) more than MCID respectively after education (P < 0.05). In all individual items, knowledge about their disease, inhaler use and satisfaction of the patients and clinicians were also improved after education (P < 0.05). This study demonstrates the well-organized education program for primary care physicians and patients is a crucial process for management of chronic airway diseases.

  13. Epigenetics in immune development and in allergic and autoimmune diseases.

    PubMed

    Martino, David; Kesper, Dörthe A; Amarasekera, Manori; Harb, Hani; Renz, Harald; Prescott, Susan

    2014-10-01

    Epigenetic mechanisms such as DNA methylation, histone modification, and micro RNA signaling regulate the activity of the genome. Virtually all aspects of immunity involve some level of epigenetic regulation, whether it be host defense or in mediating tolerance. These processes are critically important in mediating dynamic responses to the environment over the life course of the individual, yet we are only just beginning to understand how dysregulation in these pathways may play a role in immune disease. Here, we give a brief chronological overview of epigenetic processes during immune development in health and disease.

  14. TGF-β-dependent dendritic cell chemokinesis in murine models of airway disease

    PubMed Central

    Hashimoto, Mitsuo; Yanagisawa, Haruhiko; Minagawa, Shunsuke; Sen, Debasish; Ma, Royce; Murray, Lynne A.; Tsui, Ping; Lou, Jianlong; Marks, James D.; Baron, Jody L.; Krummel, Matthew F.; Nishimura, Stephen L.

    2015-01-01

    Small airway chronic inflammation is a major pathologic feature of chronic obstructive pulmonary disease (COPD) and is refractory to current treatments. Dendritic cells (DCs) accumulate around small airways in COPD. DCs are critical mediators of antigen surveillance and antigen presentation and amplify adaptive immune responses. How DCs accumulate around airways remains largely unknown. We use 2-photon DC imaging of living murine lung sections to directly visualize the dynamic movement of living DCs around airways in response to either soluble mediators (IL-1β) or environmental stimuli (cigarette smoke or TLR3 ligands) implicated in COPD pathogenesis. We find that DCs accumulate around murine airways primarily by increasing velocity (chemokinesis) rather than directional migration (chemotaxis) in response to all three stimuli. DC accumulation maximally occurs in a specific zone located 26-50 μm from small airways, which overlaps with zones of maximal DC velocity. Our data suggest that increased accumulation of DCs around airways results from increased numbers of highly chemokinetic DCs entering the lung from the circulation with balanced rates of immigration and emigration. Increases in DC accumulation and chemokinesis are partially dependent on ccr6, a crucial DC chemokine receptor, and fibroblast expression of the integrin αvβ8, a critical activator of TGF-β αvβ8-mediated TGF-β activation is known to enhance IL-1β-dependent fibroblast expression of the only known endogenous ccr6 chemokine ligand, ccl20. Taken together, these data suggest a mechanism by which αvβ8, ccl20 and ccr6 interact to lead to DC accumulation around airways in response to COPD-relevant stimuli. PMID:26109638

  15. Allergen-encoded signals that control allergic responses

    PubMed Central

    Tung, Hui-Ying; Landers, Cameron; Li, Evan; Porter, Paul; Kheradmand, Farrah; Corry, David B.

    2016-01-01

    Purpose of review The purpose is to review the important recent advances made in how innate immune cells, microbes, and the environment contribute to the expression of allergic disease, emphasizing the allergen-related signals that drive allergic responses. Recent findings The last few years have seen crucial advances in how innate immune cells such as innate lymphoid cells group 2 and airway epithelial cells and related molecular pathways through organismal proteinases and innate immune cytokines, such as thymic stromal lymphopoietin, IL-25, and IL-33 contribute to allergy and asthma. Simultaneously with these advances, important progress has been made in our understanding of how the environment, and especially pathogenic organisms, such as bacteria, viruses, helminths, and especially fungi derived from the natural and built environments, either promote or inhibit allergic inflammation and disease. Of specific interest are how lipopolysaccharide mediates its antiallergic effect through the ubiquitin modifying factor A20 and the antiallergic activity of both helminths and protozoa. Summary Innate immune cells and molecular pathways, often activated by allergen-derived proteinases acting on airway epithelium and macrophages as well as additional unknown factors, are essential to the expression of allergic inflammation and disease. These findings suggest numerous future research opportunities and new opportunities for therapeutic intervention in allergic disease. PMID:26658015

  16. New Allergic and Hypersensitivity Conditions Section in the International Classification of Diseases-11.

    PubMed

    Tanno, Luciana K; Calderon, Moises A; Demoly, Pascal

    2016-07-01

    Allergy and hypersensitivity, originally perceived as rare and secondary disorders, are one of the fastest growing conditions worldwide, but not adequately tracked in international information systems, such as the International Classification of Diseases (ICD). Having allergic and hypersensitivity conditions classification able to capture conditions in health international information systems in a realistic manner is crucial to the identification of potential problems, and in a wider system, can identify contextually specific service deficiencies and provide the impetus for changes. Since 2013, an international collaboration of Allergy Academies has spent tremendous efforts to have a better and updated classification of allergies in the forthcoming International Classification of Diseases (ICD)-11 version, by providing scientific and technical evidences for the need for changes. The following bilateral discussions with the representatives of the ICD-11 revision, a simplification process was carried out. The new parented "Allergic and hypersensitivity conditions" section has been built under the "Disorders of the Immune System" chapter through the international collaboration of Allergy Academies and upon ICD WHO representatives support. The classification of allergic and hypersensitivity conditions has been updated through the ICD-11 revision and will allow the aggregation of reliable data to perform positive quality-improvements in health care systems worldwide.

  17. Maternal Folic Acid Supplementation during Pregnancy and Childhood Allergic Disease Outcomes: A Question of Timing?

    PubMed Central

    McStay, Catrina L.; Prescott, Susan L.; Bower, Carol; Palmer, Debra J.

    2017-01-01

    Since the early 1990s, maternal folic acid supplementation has been recommended prior to and during the first trimester of pregnancy, to reduce the risk of infant neural tube defects. In addition, many countries have also implemented the folic acid fortification of staple foods, in order to promote sufficient intakes amongst women of a childbearing age, based on concerns surrounding variable dietary and supplementation practices. As many women continue to take folic acid supplements beyond the recommended first trimester, there has been an overall increase in folate intakes, particularly in countries with mandatory fortification. This has raised questions on the consequences for the developing fetus, given that folic acid, a methyl donor, has the potential to epigenetically modify gene expression. In animal studies, folic acid has been shown to promote an allergic phenotype in the offspring, through changes in DNA methylation. Human population studies have also described associations between folate status in pregnancy and the risk of subsequent childhood allergic disease. In this review, we address the question of whether ongoing maternal folic acid supplementation after neural tube closure, could be contributing to the rise in early life allergic diseases. PMID:28208798

  18. Nutrition in early life and the risk of asthma and allergic disease.

    PubMed

    Wyness, Laura

    2014-07-01

    The prevalence of reported cases of asthma and allergic disease has seen a marked increase throughout the world since the 1960s, particularly in more developed, westernised countries. A key focus of research in this area has been the possible adverse effects of foetal and infant exposure to food allergens. There is some evidence that foetal and infant exposure to a range of allergens via the mother and her breast milk is important in the development of normal immune tolerance. Current advice is that pregnant and breastfeeding women do not need to avoid potential food allergens unless they are allergic themselves, or are advised to modify their diet by a health professional. Delaying the introduction of common food allergies beyond 6 months is unlikely to reduce the likelihood of food allergy and allergic disease. The findings of current ongoing trials investigating the potential benefits of early introduction on allergenic foods into the diet of children-as well as the comprehensive review of complementary and young-child feeding advice currently being conducted by the Scientific Advisory Committee on Nutrition-will help inform guidance in this area.

  19. The Role of Thymic Stromal Lymphopoietin (TSLP) in Allergic Disorders

    PubMed Central

    Ziegler, Steven F.

    2010-01-01

    Summary The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergens contact first occurs at mucosal sites in exposed to the external environment such as the skin, airways and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies, in both humans and mouse models, have implicated TSLP in the development and progression of atopy and atopic diseases. This review will discuss this work and place TSLP in the inflammatory cascade that leads to allergic disease. PMID:21109412

  20. Takes your breath away--the immunology of allergic alveolitis.

    PubMed

    McSharry, C; Anderson, K; Bourke, S J; Boyd, G

    2002-04-01

    Extrinsic allergic alveolitis (synonym: hypersensitivity pneumonitis) is caused by inhaling antigenic aerosols which induce hypersensitivity responses in susceptible individuals. It is an interstitial inflammatory disease affecting the distal, gas-exchanging parts of the lung, in contrast to allergic asthma where the inflammation is more proximal, affecting the conducting airways. The aims of this review are to describe current concepts of the immunology of this model of lung inflammation, to describe some of the constitutional and environmental characteristics which affect disease susceptibility and development, and to describe topics for prospective study.

  1. Epicutaneous immunity and onset of allergic diseases - per-"eczema"tous sensitization drives the allergy march.

    PubMed

    Matsumoto, Kenji; Saito, Hirohisa

    2013-09-01

    Results from recent epidemiological studies strongly suggest that ingestion of food promotes immune tolerance to food antigens, whereas exposure to food antigens through skin leads to allergic sensitization. A "dual-allergen-exposure hypothesis" has been proposed to explain those findings. However, several other recent studies have demonstrated that some allergic diseases can be successfully treated by recurrent epicutaneous exposure to allergens. At a glance, these two sets of findings seem to be contradictory, but we think they provide important clues for understanding the mechanisms behind the allergy march. Here, we propose that per-"eczema"tous sensitization drives the allergy march, and we introduce results from several published studies in support of this hypothesis. We hope that this review may help in establishment of new strategies for preventing the allergy march in the near future.

  2. Toward precision medicine and health: Opportunities and challenges in allergic diseases.

    PubMed

    Galli, Stephen Joseph

    2016-05-01

    Precision medicine (also called personalized, stratified, or P4 medicine) can be defined as the tailoring of preventive measures and medical treatments to the characteristics of each patient to obtain the best clinical outcome for each person while ideally also enhancing the cost-effectiveness of such interventions for patients and society. Clearly, the best clinical outcome for allergic diseases is not to get them in the first place. To emphasize the importance of disease prevention, a critical component of precision medicine can be referred to as precision health, which is defined herein as the use of all available information pertaining to specific subjects (including family history, individual genetic and other biometric information, and exposures to risk factors for developing or exacerbating disease), as well as features of their environments, to sustain and enhance health and prevent the development of disease. In this article I will provide a personal perspective on how the precision health-precision medicine approach can be applied to the related goals of preventing the development of allergic disorders and providing the most effective diagnosis, disease monitoring, and care for those with these prevalent diseases. I will also mention some of the existing and potential challenges to achieving these ambitious goals.

  3. [Allergic disease--pollen allergy and climate change].

    PubMed

    Sommer, Janne; Plaschke, Peter; Poulsen, Lars K

    2009-10-26

    Pollen allergy currently affects a fifth of the population. A warmer climate will lead to a longer pollen season and more days with high pollen counts. In addition, a warmer climate increases the risk of proliferation of new plants with well-known allergenic pollens like ragweed, plane tree and wall pellitory, which have not previously caused allergy in Denmark. The consequences will be more people with hay fever and pollen asthma, longer allergy seasons and an increase in the severity of symptoms, disease-related costs and demands on health care for diagnosis and treatment of more complex allergies.

  4. [Environmental causes of the distal airways disease. Hypersensitivity pneumonitis and rare causes].

    PubMed

    Dalphin, J-C; Didier, A

    2013-10-01

    Hypersensitivity pneumonitis is one of the most frequent causes of distal airways disease. It is associated with inflammation of the bronchioles, predominantly by lymphocytic infiltrates, and with granuloma formation causing bronchial obstruction. This inflammation explains the clinical manifestations and the airways obstruction seen on pulmonary function tests, most often in the distal airways but proximal in almost 20%. CT scan abnormalities reflect the lymphocytic infiltrates and air trapping and, in some cases, the presence of emphysema. Bronchiolitis induced by chronic inhalation of mineral particles or acute inhalation of toxic gases (such as NO2) are other examples of small airways damage due to environmental exposure. The pathophysiological mechanisms are different and bronchiolar damage is either exclusive or predominant. Bronchiolitis induced by tobacco smoke exposure, usually classified as interstitial pneumonitis, is easily diagnosed thanks to broncho-alveolar lavage. Its prognosis is linked to the other consequences of tobacco smoke exposure including respiratory insufficiency. Finally, the complex lung exposure observed in some rare cases (such as the World Trade Center fire or during wars) may lead to a less characteristic pattern of small airways disease.

  5. Constructing a classification of hypersensitivity/allergic diseases for ICD-11 by crowdsourcing the allergist community.

    PubMed

    Tanno, L K; Calderon, M A; Goldberg, B J; Gayraud, J; Bircher, A J; Casale, T; Li, J; Sanchez-Borges, M; Rosenwasser, L J; Pawankar, R; Papadopoulos, N G; Demoly, P

    2015-06-01

    The global allergy community strongly believes that the 11th revision of the International Classification of Diseases (ICD-11) offers a unique opportunity to improve the classification and coding of hypersensitivity/allergic diseases via inclusion of a specific chapter dedicated to this disease area to facilitate epidemiological studies, as well as to evaluate the true size of the allergy epidemic. In this context, an international collaboration has decided to revise the classification of hypersensitivity/allergic diseases and to validate it for ICD-11 by crowdsourcing the allergist community. After careful comparison between ICD-10 and 11 beta phase linearization codes, we identified gaps and trade-offs allowing us to construct a classification proposal, which was sent to the European Academy of Allergy and Clinical Immunology (EAACI) sections, interest groups, executive committee as well as the World Allergy Organization (WAO), and American Academy of Allergy Asthma and Immunology (AAAAI) leaderships. The crowdsourcing process produced comments from 50 of 171 members contacted by e-mail. The classification proposal has also been discussed at face-to-face meetings with experts of EAACI sections and interest groups and presented in a number of business meetings during the 2014 EAACI annual congress in Copenhagen. As a result, a high-level complex structure of classification for hypersensitivity/allergic diseases has been constructed. The model proposed has been presented to the WHO groups in charge of the ICD revision. The international collaboration of allergy experts appreciates bilateral discussion and aims to get endorsement of their proposals for the final ICD-11.

  6. A critical role for dendritic cells in the evolution of IL-1β-mediated murine airway disease

    PubMed Central

    Hashimoto, Mitsuo; Yanagisawa, Haruhiko; Minagawa, Shunsuke; Sen, Debasish; Goodsell, Amanda; Ma, Royce; Moermans, Catherine; McKnelly, Kate J.; Baron, Jody L.; Krummel, Matthew F.; Nishimura, Stephen L.

    2015-01-01

    Chronic airway inflammation and fibrosis, known as airway remodeling, are defining features of chronic obstructive pulmonary disease (COPD) and are refractory to current treatments. How and if chronic inflammation contributes to airway fibrosis remains controversial. Here, we use a model of COPD airway disease utilizing adenoviral (Ad) delivery of IL-1β to determine that adaptive T-cell immunity is required for airway remodeling since mice deficient in α/β T-cells (tcra −/−) are protected. Dendritic cells (DCs) accumulate around COPD airways and are critical to prime adaptive immunity, but have not been shown to directly influence airway remodeling. We show that DC depletion or deficiency in the crucial DC chemokine receptor, ccr6, both protect from Ad-IL-1β-induced airway adaptive T-cell immune responses, and fibrosis in mice. These results provide evidence that chronic airway inflammation, mediated by accumulation of α/β T-cells and driven by DCs, is critical to airway fibrosis. PMID:25786688

  7. The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease.

    PubMed

    Hoffmann, H J; Santos, A F; Mayorga, C; Nopp, A; Eberlein, B; Ferrer, M; Rouzaire, P; Ebo, D G; Sabato, V; Sanz, M L; Pecaric-Petkovic, T; Patil, S U; Hausmann, O V; Shreffler, W G; Korosec, P; Knol, E F

    2015-11-01

    The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross-linking IgE on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food-, insect venom-, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases.

  8. Invariant natural killer T (iNKT) cells in asthma: a novel insight into the pathogenesis of asthma and the therapeutic implication of glycolipid ligands for allergic diseases.

    PubMed

    Oki, Shinji; Miyake, Sachiko

    2007-03-01

    Allergic bronchial asthma is a complex inflammatory diseases originated from dysregulated immune responses in the respiratory mucosa. The inflammatory state in asthmatic lung is characterized by massive infiltration with eosinophils, lymphocytes, and mast cells in the airway mucosa leading to airway hyperseisitivity, goblet cell hyperplasia and mucus overproduction. The inflammatory process is thought to be the result of intensive T helper (Th) 2-biased immune response. Over the past several years, there has been enormous progress in understanding the mechanisms for development of Th2-biased responses after inhaled exposure to allergens and the characteristics of CD4+ T cells prominently involved in this process. Recently, a new population of T cells, invariant natural killer T (iNKT) cells has been shown to play an important role in the pathogenesis of mouse model of allergic airway inflammation. iNKT cells are one of the most potent immune modulators through a massive production of a various cytokines including IL-4 and IFN-gamma upon activation, and are involved in a variety of immunoregulations including infection, autoimmunity, and tumor surveillance. The potent pathogenic role of iNKT cells in the development of bronchial asthma is due to their ability to produce predominant Th2 cytokines in a given condition. The involvement of iNKT cells in the pathogenesis of asthma might have been underestimated in the past studies demonstrating the involvement of CD4+ T cells in asthma because of the difficulty in the detection of iNKT cells. Meanwhile, growing evidences have demonstrated that iNKT cells could be a promising target for immune-based therapies for autoimmune diseases, tumor, and infection due to the invariance of their TCR usage, the restriction to the evolutionally-conserved non-polymorphic antigen-presenting molecule CD1d, and their outstanding ability to produce both Th1- and Th2-cytokines. In this review, we will overview current understanding of the

  9. NEUTROPHILS PLAY A CRITICAL ROLE IN THE DEVELOPMENT OF LPS-INDUCED AIRWAY DISEASE

    EPA Science Inventory

    ETD-02-045 (GAVETT) GPRA # 10108

    Neutrophils Play a Critical Role in the Development of LPS-Induced Airway Disease.
    Jordan D. Savov, Stephen H. Gavett*, David M. Brass, Daniel L. Costa*, and David A. Schwartz

    ABSTRACT
    We investigated the role of neutrophils...

  10. EFFECTS OF SYSTEMIC NEUTROPHIL DEPLETION ON LPS-INDUCED AIRWAY DISEASE

    EPA Science Inventory

    Effects of Systemic Neutrophil Depletion on LPS-induced Airway Disease
    Jordan D. Savov, Stephen H. Gavett*, David M. Brass, Daniel L. Costa*, David A. Schwartz
    Pulmonary and Critical Care Division, Dept of Medicine ? Duke University Medical Center
    * National Health and E...

  11. Within-breath respiratory impedance and airway obstruction in patients with chronic obstructive pulmonary disease

    PubMed Central

    da Silva, Karla Kristine Dames; Faria, Alvaro Camilo Dias; Lopes, Agnaldo José; de Melo, Pedro Lopes

    2015-01-01

    OBJECTIVE: Recent work has suggested that within-breath respiratory impedance measurements performed using the forced oscillation technique may help to noninvasively evaluate respiratory mechanics. We investigated the influence of airway obstruction on the within-breath forced oscillation technique in smokers and chronic obstructive pulmonary disease patients and evaluated the contribution of this analysis to the diagnosis of chronic obstructive pulmonary disease. METHODS: Twenty healthy individuals and 20 smokers were assessed. The study also included 74 patients with stable chronic obstructive pulmonary disease. We evaluated the mean respiratory impedance (Zm) as well as values for the inspiration (Zi) and expiration cycles (Ze) at the beginning of inspiration (Zbi) and expiration (Zbe), respectively. The peak-to-peak impedance (Zpp=Zbe-Zbi) and the respiratory cycle dependence (ΔZrs=Ze-Zi) were also analyzed. The diagnostic utility was evaluated by investigating the sensitivity, the specificity and the area under the receiver operating characteristic curve. ClinicalTrials.gov: NCT01888705. RESULTS: Airway obstruction increased the within-breath respiratory impedance parameters that were significantly correlated with the spirometric indices of airway obstruction (R=−0.65, p<0.0001). In contrast to the control subjects and the smokers, the chronic obstructive pulmonary disease patients presented significant expiratory-inspiratory differences (p<0.002). The adverse effects of moderate airway obstruction were detected based on the Zpp with an accuracy of 83%. Additionally, abnormal effects in severe and very severe patients were detected based on the Zm, Zi, Ze, Zbe, Zpp and ΔZrs with a high degree of accuracy (>90%). CONCLUSIONS: We conclude the following: (1) chronic obstructive pulmonary disease introduces higher respiratory cycle dependence, (2) this increase is proportional to airway obstruction, and (3) the within-breath forced oscillation technique may

  12. Newly Recognized Occupational and Environmental Causes of Chronic Terminal Airways and Parenchymal Lung Disease

    PubMed Central

    Sauler, Maor; Gulati, Mridu

    2012-01-01

    Synopsis With the introduction of new materials and changes in manufacturing practices, occupational health investigators continue to uncover associations between novel exposures and chronic forms of diffuse parenchymal lung disease and terminal airways disease. In order to discern exposure disease relationships, clinicians must maintain a high index of suspicion for the potential toxicity of occupational and environmental exposures. This article details several newly recognized chronic parenchymal and terminal airways. Diseases related to exposure to Indium, Nylon Flock, Diacetyl used in the flavorings industry, nanoparticles, and the World Trade Center disaster are reviewed. Additionally, this article will review methods in worker surveillance as well as the potential use of biomarkers in the evaluation of exposure disease relationships. PMID:23153608

  13. Evaluation of IgE serum level by radial immunodiffusion and radioimmunoassay in allergic diseases.

    PubMed

    Palma-Carlos, M L; Escaja, D; Palma-Carlos, A G

    1975-01-01

    Sensitive radioactive methods are usually required for assay of low or normal serum levels of IgE up to 1.000 I.U./ml. However radioimmunoassay or other radioactive techniques are not always available or practical in routine diagnosis of allergic patients. Therefore, some modifications of the conventional radial immunodiffusion techniques have been tried for IgE. We have studied the comparative results of radioimmunoassay (RIST) and a modified radial immunodiffusion for IgE evaluation in allergic diseases. In 18 subjects a solid phase radio-immunoassay for IgE has been done. In 14 no allergic subjects total IgE serum level determined by the RIST method was 248 +/- 210 (I.U./ml--m +/- 2SD). A double precipitation or a intensification method of immunodiffusion employing Partigen plates (Behring-Werke) has been applied for global IgE assay in routine laboratory work in the last months. Serum IgE levels were studied by this method in 20 normal subjects and 206 patients referred for diagnosis of allergic disease. A modification of the double precipitation technique allowed us to measure IgE levels above 260 I.U. In normal subjects IgE serum level was 355 +/- 182 I.U. (M +/- 2SD). In 120 extrinsic asthmas the range was 9.580--260 I.U. and mean value 2.120 +/- 627 I.I. and the range 1.760--300 I.U. 14 cases of pollinosis were studied during the grass pollen season. Mean values were 1.840 +/- 1.270 I.U. and range 2.760--600 I.U. 18 cases of perennial allergic rhinitis the mean value was 1.868 +/- 1.301 I.U. and the range 2.600--260 I.U. In 12 urticarias the mean value was 1.730 +/- 1.252 I.U. and the range 2.300--260 I.U. Highest IgE serum levels occurred in atopic asthmatics with mite sensitivity. A general positive relationship was observed between the intensity of skin reactivity and elevated serum IgE level. However some exceptions to this rule have been observed. A simultaneous assay of serum immunoglobulins IgG, IgA and IgM by radial immunodiffusion has been done in

  14. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update

    PubMed Central

    Okada, H; Kuhn, C; Feillet, H; Bach, J-F

    2010-01-01

    According to the ‘hygiene hypothesis’, the decreasing incidence of infections in western countries and more recently in developing countries is at the origin of the increasing incidence of both autoimmune and allergic diseases. The hygiene hypothesis is based upon epidemiological data, particularly migration studies, showing that subjects migrating from a low-incidence to a high-incidence country acquire the immune disorders with a high incidence at the first generation. However, these data and others showing a correlation between high disease incidence and high socio-economic level do not prove a causal link between infections and immune disorders. Proof of principle of the hygiene hypothesis is brought by animal models and to a lesser degree by intervention trials in humans. Underlying mechanisms are multiple and complex. They include decreased consumption of homeostatic factors and immunoregulation, involving various regulatory T cell subsets and Toll-like receptor stimulation. These mechanisms could originate, to some extent, from changes in microbiota caused by changes in lifestyle, particularly in inflammatory bowel diseases. Taken together, these data open new therapeutic perspectives in the prevention of autoimmune and allergic diseases. PMID:20415844

  15. Pluripotent allospecific CD8+ effector T cells traffic to lung in murine obliterative airway disease.

    PubMed

    West, Erin E; Lavoie, Tera L; Orens, Jonathan B; Chen, Edward S; Ye, Shui Q; Finkelman, Fred D; Garcia, Joe G N; McDyer, John F

    2006-01-01

    Long-term success in lung transplantation is limited by obliterative bronchiolitis, whereas T cell effector mechanisms in this process remain incompletely understood. Using the mouse heterotopic allogeneic airway transplant model, we studied T cell effector responses during obliterative airways disease (OAD). Allospecific CD8+ IFN-gamma+ T cells were detected in airway allografts, with significant coexpression of TNF-alpha and granzyme B. Therefore, using IFN-gamma as a surrogate marker, we assessed the distribution and kinetics of extragraft allo-specific T cells during OAD. Robust allospecific IFN-gamma was produced by draining the lymph nodes, spleen, and lung mononuclear cells from allograft, but not isograft recipients by Day 14, and significantly decreased by Day 28. Although the majority of allospecific T cells were CD8+, allospecific CD4+ T cells were also detected in these compartments, with each employing distinct allorecognition pathways. An influx of pluripotent CD8+ effector cells with a memory phenotype were detected in the lung during OAD similar to those seen in the allografts and secondary lymphoid tissue. Antibody depletion of CD8+ T cells markedly reduced airway lumen obliteration and fibrosis at Day 28. Together, these data demonstrate that allospecific CD8+ effector T cells play an important role in OAD and traffic to the lung after heterotopic airway transplant, suggesting that the lung is an important immunologic site, and perhaps a reservoir, for effector cells during the rejection process.

  16. METAL COMPOSITION OF AMBIENT PM2.5 INFLUENCES SEVERITY OF ALLERGIC AIRWAYS DISEASE IN MICE

    EPA Science Inventory


    ABSTRACT

    Children living in Hettstedt in eastern Germany were reported to have a higher prevalence of sensitization to common aeroallergens than another cohort living in the neighboring city of Zerbst; these differences correlated with the presence of industrial air ...

  17. Presence of other allergic disease modifies the effect of early childhood traffic-related air pollution exposure on asthma prevalence.

    PubMed

    Dell, Sharon D; Jerrett, Michael; Beckerman, Bernard; Brook, Jeffrey R; Foty, Richard G; Gilbert, Nicolas L; Marshall, Laura; Miller, J David; To, Teresa; Walter, Stephen D; Stieb, David M

    2014-04-01

    Nitrogen dioxide (NO2), a surrogate measure of traffic-related air pollution (TRAP), has been associated with incident childhood asthma. Timing of exposure and atopic status may be important effect modifiers. We collected cross-sectional data on asthma outcomes from Toronto school children aged 5-9years in 2006. Lifetime home, school and daycare addresses were obtained to derive birth and cumulative NO2 exposures for a nested case-control subset of 1497 children. Presence of other allergic disease (a proxy for atopy) was defined as self-report of one or more of doctor-diagnosed rhinitis, eczema, or food allergy. Generalized estimating equations were used to adjust for potential confounders, and examine hypothesized effect modifiers while accounting for clustering by school. In children with other allergic disease, birth, cumulative and 2006 NO2 were associated with lifetime asthma (OR 1.46, 95% CI 1.08-1.98; 1.37, 95% CI 1.00-1.86; and 1.60, 95% CI 1.09-2.36 respectively per interquartile range increase) and wheeze (OR 1.44, 95% CI 1.10-1.89; 1.31, 95% CI 1.02-1.67; and 1.60, 95% CI 1.16-2.21). No or weaker effects were seen in those without allergic disease, and effect modification was amplified when a more restrictive algorithm was used to define other allergic disease (at least 2 of doctor diagnosed allergic rhinitis, eczema or food allergy). The effects of modest NO2 levels on childhood asthma were modified by the presence of other allergic disease, suggesting a probable role for allergic sensitization in the pathogenesis of TRAP initiated asthma.

  18. Evolution in immunological methods used in research and in the clinical diagnosis and management of human allergic diseases.

    PubMed

    Hamilton, Robert G

    2012-09-28

    Since the discovery of IgE in 1967, there has been an evolution in design and quality of immunological methods used to research allergic disease mechanisms, to diagnose allergic disease in the clinic, and to monitor allergic patients on various therapeutic regimens. This issue of the Journal of Immunological Methods highlights recent methodological developments in three areas: (1) understanding of the interactions between T-cells, dendritic cella and B-cells and various signaling mediators in the induction phase of sensitization, (2) developments in the definitive diagnosis of allergic disease with a focus on food allergy and eosinophil related diseases, and (3) enhancements in allergy patient management through improved methods for monitoring allergen levels in the environment and documenting changes in IgE in patients on therapeutic anti-IgE (Omalizumab). This special issue of the Journal of Immunological Methods examines each of these three areas and provides a compendium on state-of-the-art immunological methods used to assess human allergic disease.

  19. Induction of Oral Tolerance with Transgenic Plants Expressing Antigens for Prevention/Treatment of Autoimmune, Allergic and Inflammatory Diseases.

    PubMed

    Ma, Shengwu; Liao, Yu-Cai; Jevnikar, Anthony M

    2015-01-01

    The prevalence and incidence of autoimmune and allergic diseases have increased dramatically over the last several decades, especially in the developed world. The treatment of autoimmune and allergic diseases is typically with the use of non-specific immunosuppressive agents that compromise the integrity of the host immune system and therefore, increase the risk of infections. Antigenspecific immunotherapy by reinstating immunological tolerance towards self antigens without compromising immune functions is a much desired goal for the treatment of autoimmune and allergic diseases. Mucosal administration of antigen is a long-recognized method of inducing antigen-specific immune tolerance known as oral tolerance, which is viewed as having promising potential in the treatment of autoimmune and allergic diseases. Plant-based expression and delivery of recombinant antigens provide a promising new platform to induce oral tolerance, having considerable advantages including reduced cost and increased safety. Indeed, in recent years the use of tolerogenic plants for oral tolerance induction has attracted increasing attention, and considerable progress has been made. This review summarizes recent advances in using plants to deliver tolerogens for induction of oral tolerance in the treatment of autoimmune, allergic and inflammatory diseases.

  20. Adaptation to impacts of climate change on aeroallergens and allergic respiratory diseases.

    PubMed

    Beggs, Paul J

    2010-08-01

    Climate change has the potential to have many significant impacts on aeroallergens such as pollen and mould spores, and therefore related diseases such as asthma and allergic rhinitis. This paper critically reviews this topic, with a focus on the potential adaptation measures that have been identified to date. These are aeroallergen monitoring; aeroallergen forecasting; allergenic plant management; planting practices and policies; urban/settlement planning; building design and heating, ventilating, and air-conditioning (HVAC); access to health care and medications; education; and research.

  1. The nervous system of airways and its remodeling in inflammatory lung diseases.

    PubMed

    Audrit, Katrin Julia; Delventhal, Lucas; Aydin, Öznur; Nassenstein, Christina

    2017-03-01

    Inflammatory lung diseases are associated with bronchospasm, cough, dyspnea and airway hyperreactivity. The majority of these symptoms cannot be primarily explained by immune cell infiltration. Evidence has been provided that vagal efferent and afferent neurons play a pivotal role in this regard. Their functions can be altered by inflammatory mediators that induce long-lasting changes in vagal nerve activity and gene expression in both peripheral and central neurons, providing new targets for treatment of pulmonary inflammatory diseases.

  2. Allergic rhinitis and chronic suppurative otitis media.

    PubMed

    Bakhshaee, Mehdi; Rajati, Mohsen; Fereidouni, Mohammad; Khadivi, Ehsan; Varasteh, Abdolreza

    2011-01-01

    Allergic inflammation in upper airways can act as a predisposing factor for infectious ear diseases. There are some evidences about the role of allergic rhinitis in chronic otitis media with effusion, but its role in establishing chronic suppurative otitis media (CSOM) has not been clearly shown. 68 adult patients with established CSOM, who were candidates for ear surgery, and 184 age- and sex-matched controls were evaluated for the presence of allergic rhinitis. Standard questionnaire was filled out for all participants. All patients and controls underwent skin prick test for 28 common regional aeroallergens, and serum total IgE was measured by means of ELISA method. Allergic rhinitis were defined as a positive responses to the questionnaire, positive skin prick test to at least one allergen, and/or high level of serum total IgE. Allergic rhinitis was diagnosed in 20 (29.41%) and 41 (22.28%) of patients and controls, respectively (P = 0.241) (OR = 1.28, CI = 0.69-2.36). Outdoor allergens, especially grass pollen, were the most prevalent allergens among both groups, but indoor allergens like mites and molds have a low prevalence. The study did not show a significant difference in the prevalence of AR in the CSOM patients compared to the controls. The intermittent nature of allergy and other less known intervening factors in the etiopathogenesis of CSOM make such a conclusion difficult.

  3. Application of statistical mining in healthcare data management for allergic diseases

    NASA Astrophysics Data System (ADS)

    Wawrzyniak, Zbigniew M.; Martínez Santolaya, Sara

    2014-11-01

    The paper aims to discuss data mining techniques based on statistical tools in medical data management in case of long-term diseases. The data collected from a population survey is the source for reasoning and identifying disease processes responsible for patient's illness and its symptoms, and prescribing a knowledge and decisions in course of action to correct patient's condition. The case considered as a sample of constructive approach to data management is a dependence of allergic diseases of chronic nature on some symptoms and environmental conditions. The knowledge summarized in a systematic way as accumulated experience constitutes to an experiential simplified model of the diseases with feature space constructed of small set of indicators. We have presented the model of disease-symptom-opinion with knowledge discovery for data management in healthcare. The feature is evident that the model is purely data-driven to evaluate the knowledge of the diseases` processes and probability dependence of future disease events on symptoms and other attributes. The example done from the outcomes of the survey of long-term (chronic) disease shows that a small set of core indicators as 4 or more symptoms and opinions could be very helpful in reflecting health status change over disease causes. Furthermore, the data driven understanding of the mechanisms of diseases gives physicians the basis for choices of treatment what outlines the need of data governance in this research domain of discovered knowledge from surveys.

  4. A Novel Nonhuman Primate Model of Cigarette Smoke–Induced Airway Disease

    PubMed Central

    Polverino, Francesca; Doyle-Eisele, Melanie; McDonald, Jacob; Wilder, Julie A.; Royer, Christopher; Laucho-Contreras, Maria; Kelly, Emer M.; Divo, Miguel; Pinto-Plata, Victor; Mauderly, Joe; Celli, Bartolome R.; Tesfaigzi, Yohannes; Owen, Caroline A.

    2016-01-01

    Small animal models of chronic obstructive pulmonary disease (COPD) have several limitations for identifying new therapeutic targets and biomarkers for human COPD. These include a pulmonary anatomy that differs from humans, the limited airway pathologies and lymphoid aggregates that develop in smoke-exposed mice, and the challenges associated with serial biological sampling. Thus, we assessed the utility of cigarette smoke (CS)–exposed cynomolgus macaque as a nonhuman primate (NHP) large animal model of COPD. Twenty-eight NHPs were exposed to air or CS 5 days per week for up to 12 weeks. Bronchoalveolar lavage and pulmonary function tests were performed at intervals. After 12 weeks, we measured airway pathologies, pulmonary inflammation, and airspace enlargement. CS-exposed NHPs developed robust mucus metaplasia, submucosal gland hypertrophy and hyperplasia, airway inflammation, peribronchial fibrosis, and increases in bronchial lymphoid aggregates. Although CS-exposed NHPs did not develop emphysema over the study time, they exhibited pathologies that precede emphysema development, including increases in the following: i) matrix metalloproteinase-9 and proinflammatory mediator levels in bronchoalveolar lavage fluid, ii) lung parenchymal leukocyte counts and lymphoid aggregates, iii) lung oxidative stress levels, and iv) alveolar septal cell apoptosis. CS-exposed NHPs can be used as a model of airway disease occurring in COPD patients. Unlike rodents, NHPs can safely undergo longitudinal sampling, which could be useful for assessing novel biomarkers or therapeutics for COPD. PMID:25542772

  5. Smokers with emphysema and small airway disease on computed tomography have lower bone density.

    PubMed

    Pompe, Esther; de Jong, Pim A; van Rikxoort, Eva M; Gallardo Estrella, Leticia; de Jong, Werner U; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; van der Aalst, Carlijn M; van Ginneken, Bram; Lammers, Jan-Willem J; Mohamed Hoesein, Firdaus Aa

    2016-01-01

    Osteoporosis is more common in patients with COPD and in smokers. The aim of this study was to assess whether measures of emphysema and airway disease on computed tomography (CT) were associated with lower bone density or vertebral fractures in smokers with and without COPD. For this purpose, we included participants from the NELSON lung cancer screening trial. Bone density was measured as Hounsfield Units in the first lumbar vertebra, and vertebral fractures were assessed semiquantitatively. The 15th percentile method (Perc15) was used to assess emphysema, and the airway lumen perimeter (Pi10) was used for airway wall thickness. Expiratory/inspiratory-ratiomean lung density (E/I-ratioMLD) was used as a measure for air trapping and tracheal index to assess tracheal deformity. Linear regression models and logistic regression models were used to assess associations between CT biomarkers, bone density, and presence of fractures. Exactly 1,093 male participants were eligible for analysis. Lower Perc15 and higher E/I-ratioMLD were significantly associated with lower bone density (b=-1.27, P=0.02 and b=-0.37, P=0.02, respectively). Pi10 and tracheal index were not associated with bone density changes. CT-derived biomarkers were not associated with fracture prevalence. Bone density is lower with increasing extent of emphysema and small airway disease but is not associated with large airway disease and tracheal deformity. This may indicate the necessity to measure bone density early in smokers with emphysema and air trapping to prevent vertebral fractures.

  6. Environmental risk factors and allergic bronchial asthma.

    PubMed

    D'Amato, G; Liccardi, G; D'Amato, M; Holgate, S

    2005-09-01

    The prevalence of allergic respiratory diseases such as bronchial asthma has increased in recent years, especially in industrialized countries. A change in the genetic predisposition is an unlikely cause of the increase in allergic diseases because genetic changes in a population require several generations. Consequently, this increase may be explained by changes in environmental factors, including indoor and outdoor air pollution. Over the past two decades, there has been increasing interest in studies of air pollution and its effects on human health. Although the role played by outdoor pollutants in allergic sensitization of the airways has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases observed in most industrialized countries, and there is considerable evidence that asthmatic persons are at increased risk of developing asthma exacerbations with exposure to ozone, nitrogen dioxide, sulphur dioxide and inhalable particulate matter. However, it is not easy to evaluate the impact of air pollution on the timing of asthma exacerbations and on the prevalence of asthma in general. As concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of allergic respiratory allergy and bronchial asthma. Pollinosis is frequently used to study the interrelationship between air pollution and respiratory allergy. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc) can affect both components (biological and chemical) of this interaction. By attaching to the surface of pollen grains and of plant-derived particles of paucimicronic size, pollutants could modify not only the morphology of these antigen-carrying agents but also their allergenic

  7. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2012-01-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.

  8. Probiotic lactic acid bacteria and their potential in the prevention and treatment of allergic diseases

    PubMed Central

    Wróblewska, Paula; Adamczuk, Piotr; Silny, Wojciech

    2014-01-01

    Allergy is one of the most important and very common health problems worldwide. To reduce the proportion of people suffering from allergy, alternative methods of prevention and treatment are sought. The aim of this paper is to present the possibilities of probiotics in the prevention and treatment of allergic diseases. Probiotics are live microorganisms belonging mainly to the lactic acid bacteria. They modify the microflora of the human digestive system, especially the intestinal microflora. Prophylactic administration of probiotics in the early stages of life (naturally in breast milk or milk substitute synthetic compounds) is very important because intestinal microflora plays a huge role in the development of the immune system. Prevention of allergies as early as in the prenatal and postnatal periods provides huge opportunities for inhibiting the growing problem of allergy in emerging and highly developed societies. Effects of probiotic therapy depend on many factors such as the species of the microorganism used, the dose size and characteristics of the bacteria such as viability and capacity of adhesion to the intestinal walls. Authors of several studies showed beneficial effects of probiotics in the perinatal period, infancy, and also in adults in the prevention of atopic dermatitis or allergic rhinitis. Probiotics, due to their immunomodulatory properties and safety of use are a good, natural alternative for the prevention and treatment of many diseases including allergies. It is therefore important to explore the knowledge about their use and to carry out further clinical trials. PMID:26155109

  9. Exogenous surfactant therapy and mucus rheology in chronic obstructive airway diseases.

    PubMed

    Banerjee, R; Puniyani, R R

    2000-01-01

    Exogenous surfactant is a specialized biomaterial used for substitution of the lipoprotein mixture normally present in the lungs-pulmonary surfactant. Respiratory Distress Syndrome is a disease of preterm infants mainly caused by pulmonary immaturity as evidenced by a deficiency of mature lung surfactant. Pulmonary surfactant is known to stabilize small alveoli and prevent them from collapsing during expiration. However, apart from alveoli, surfactant also lines the narrow conducting airways of the tracheobronchial tree. This paper reviews the role of this surfactant in the airways and its effect on mucus rheology and mucociliary clearance. Its potential role as a therapeutic biomaterial in chronic obstructive airway diseases, namely asthma, chronic bronchitis, and respiratory manifestations of cystic fibrosis, are discussed. This paper also attempts to elucidate the exact steps in the pathogenic pathway of these diseases which could be reversed by supplementation of exogenous surfactant formulations. It is shown that there is great potential for the use of present day surfactants (which are actually formulated for use in Respiratory Disease Syndrome) as therapy in the aforementioned diseases of altered mucus viscoelasticity and mucociliary clearance. However, for improved effectiveness, specific surfactant formulations satisfying certain specific criteria should be tailor-made for the clinical condition for which they are intended. The properties required to be fulfilled by the optimal exogenous surfactant in each of the above clinical conditions are enumerated in this paper.

  10. Effects of allergic diseases and age on the composition of serum IgG glycome in children

    PubMed Central

    Pezer, Marija; Stambuk, Jerko; Perica, Marija; Razdorov, Genadij; Banic, Ivana; Vuckovic, Frano; Gospic, Adrijana Miletic; Ugrina, Ivo; Vecenaj, Ana; Bakovic, Maja Pucic; Lokas, Sandra Bulat; Zivkovic, Jelena; Plavec, Davor; Devereux, Graham; Turkalj, Mirjana; Lauc, Gordan

    2016-01-01

    It is speculated that immunoglobulin G (IgG) plays a regulatory role in allergic reactions. The glycans on the Fc region are known to affect IgG effector functions, thereby possibly having a role in IgG modulation of allergic response. This is the first study investigating patients’ IgG glycosylation profile in allergic diseases. Subclass specific IgG glycosylation profile was analyzed in two cohorts of allergen sensitized and non-sensitized 3- to 11-year-old children (conducted at University of Aberdeen, UK and Children’s Hospital Srebrnjak, Zagreb, Croatia) with 893 subjects in total. IgG was isolated from serum/plasma by affinity chromatography on Protein G. IgG tryptic glycopeptides were analyzed by liquid chromatography electrospray ionization mass spectrometry. In the Zagreb cohort IgG glycome composition changed with age across all IgG subclasses. In both cohorts, IgG glycome composition did not differ in allergen sensitized subjects, nor children sensitized to individual allergens, single allergen mean wheal diameter or positive wheal sum values. In the Zagreb study the results were also replicated for high total serum IgE and in children with self-reported manifest allergic disease. In conclusion, our findings demonstrate no association between serum IgG glycome composition and allergic diseases in children. PMID:27616597

  11. Climate change and air pollution: Effects on pollen allergy and other allergic respiratory diseases.

    PubMed

    D'Amato, Gennaro; Bergmann, Karl Christian; Cecchi, Lorenzo; Annesi-Maesano, Isabella; Sanduzzi, Alessandro; Liccardi, Gennaro; Vitale, Carolina; Stanziola, Anna; D'Amato, Maria

    The observational evidence indicates that recent regional changes in climate, particularly temperature increases, have already affected a diverse set of physical and biological systems in many parts of the world. Allergens patterns are also changing in response to climate change and air pollution can modify the allergenic potential of pollen grains especially in the presence of specific weather conditions. Although genetic factors are important in the development of asthma and allergic diseases, their rising trend can be explained only by changes occurring in the environment and urban air pollution by motor vehicles has been indicated as one of the major risk factors responsible for this increase. Despite some differences in the air pollution profile and decreasing trends of some key air pollutants, air quality is an important concern for public health in the cities throughout the world. Due to climate change, air pollution patterns are changing in several urbanized areas of the world with a significant effect on respiratory health. The underlying mechanisms of all these interactions are not well known yet. The consequences on health vary from decreases in lung function to allergic diseases, new onset of diseases, and exacerbation of chronic respiratory diseases. In addition, it is important to recall that an individual's response to pollution exposure depends on the source and components of air pollution, as well as meteorological conditions. Indeed, some air pollution-related incidents with asthma aggravation do not depend only on the increased production of air pollution, but rather on atmospheric factors that favor the accumulation of air pollutants at ground level. Associations between thunderstorms and asthma morbidity of pollinosis-affected people have also been identified in multiple locations around the world (Fig.1). Cite this as D'Amato G, Bergmann KC, Cecchi L, Annesi-Maesano I, Sanduzzi A, Liccardi G, Vitale C, Stanziola A, D'Amato M. Climate change

  12. Increased Epicardial Adipose Tissue Is Associated with the Airway Dominant Phenotype of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Higami, Yuichi; Ogawa, Emiko; Ryujin, Yasushi; Goto, Kenichi; Seto, Ruriko; Wada, Hiroshi; Tho, Nguyen Van; Lan, Le Thi Tuyet; Paré, Peter D.; Nakano, Yasutaka

    2016-01-01

    Background Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD). It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD). However, little is known about which phenotypes of COPD are associated with increased EAT. Methods One hundred and eighty smokers who were referred to the clinic were consecutively enrolled. A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT. These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively. The same measurements were made on 225 Vietnamese COPD patients to replicate the results. Results Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70. The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients. The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001). These results were replicated in the Vietnamese population. Conclusions The EAT area is independently associated with airway wall thickness. Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD. PMID:26866482

  13. The Global Epidemiologic Transition: Noncommunicable Diseases and Emerging Health Risk of Allergic Disease in Sub-Saharan Africa.

    PubMed

    Atiim, George A; Elliott, Susan J

    2016-04-01

    Globally, there has been a shift in the causes of illness and death from infectious diseases to noncommunicable diseases. This changing pattern has been attributed to the effects of an (ongoing) epidemiologic transition. Although researchers have applied epidemiologic transition theory to questions of global health, there have been relatively few studies exploring its relevance especially in the context of emerging allergic disorders in sub-Saharan Africa (SSA). In this article, we address the growing burden of noncommunicable diseases in sub-Saharan Africa through the lens of epidemiologic transition theory. After a brief review of the literature on the evolution of the epidemiologic transition with a particular emphasis on sub-Saharan Africa, we discuss existing frameworks designed to help inform our understanding of changing health trends in the developing world. We subsequently propose a framework that privileges "place" as a key construct informing our understanding. In so doing, we use the example of allergic disease, one of the fastest growing chronic conditions in most parts of the world.

  14. Antenatal Dexamethasone Exposure in Preterm Infants Is Associated with Allergic Diseases and the Mental Development Index in Children

    PubMed Central

    Tseng, Wan-Ning; Chen, Chih-Cheng; Yu, Hong-Ren; Huang, Li-Tung; Kuo, Ho-Chang

    2016-01-01

    Background: Antenatal steroid administration may benefit fetal lung maturity in preterm infants. Although some studies have shown that this treatment may increase asthma in childhood, the correlation between antenatal dexamethasone exposure and allergic diseases remains unclear. The purpose of this study is to investigate the association between antenatal dexamethasone and T cell expression in childhood allergic diseases. Methods: We recruited a cohort of preterm infants born at Kaohsiung Chang Gung Memorial Hospital between 2007 and 2010 with a gestational age of less than 35 weeks and body weight at birth of less than 1500 g. The status of antenatal exposure to steroids and allergic diseases were surveyed using a modified ISAAC questionnaire for subjects aged 2–5 years old. We analyzed Th1/Th2/Th17 expression of mRNA, cytokines (using the Magpix® my-system), and mental development index (MDI). Results: Among the 40 patients that were followed, the data showed that the antenatal dexamethasone exposure group (N = 24) had a significantly higher incidence of allergic diseases (75.0% vs. 18.8%, p < 0.0001) when compared to the non-dexamethasone exposure group (N = 16), especially with regard to asthma (41.7% vs. 0.0%, p = 0.003) and allergic rhinitis (58.3% vs. 18.8%, p = 0.013), but not atopic dermatitis. No statistical difference was observed in the mRNA expression levels of total white blood cell count between the dexamethasone exposure and non-exposure groups (p > 0.05). However, the asthma group had higher IL-5 levels (p = 0.009), and the MDI was shown to be significantly higher in the dexamethasone exposure group (90.38 ± 3.31 vs. 79.94 ± 3.58, p = 0.043) while no significant difference was found between the PDI of the two groups. Conclusions: Exposure to antenatal dexamethasone in preterm infants will increase their susceptibility to allergic diseases, particularly asthma and allergic rhinitis. Preterm infants’ exposure to antenatal dexamethasone also

  15. Complementary and alternative medicine for the treatment and diagnosis of asthma and allergic diseases.

    PubMed

    Passalacqua, G; Compalati, E; Schiappoli, M; Senna, G

    2005-03-01

    The use of Complementary/Alternative Medicines (CAM) is largely diffused and constantly increasing, especially in the field of allergic diseases and asthma. Homeopathy, acupuncture and phytotherapy are the most frequently utilised treatments, whereas complementary diagnostic techniques are mainly used in the field of food allergy-intolerance. Looking at the literature, the majority of clinical trials with CAMS are of low methodological quality, thus difficult to interpret. There are very few studies performed in a rigorously controlled fashion, and those studies provided inconclusive results. In asthma, none of the CAM have thus far been proved more effective than placebo or equally effective as standard treatments. Some herbal products, containing active principles, have displayed some clinical effect, but the herbal remedies are usually not standardised and not quantified, thus carry the risk of toxic effects or interactions. None of the alternative diagnostic techniques (electrodermal testing, kinesiology, leukocytotoxic test, iridology, hair analysis) have been proved able to distinguish between healthy and allergic subjects or to diagnose sensitizations. Therefore these tests must not be used, since they can lead to delayed or incorrect diagnosis and therapy.

  16. Modulation of the immune response by infection with Cryptosporidium spp. in children with allergic diseases.

    PubMed

    Guangorena-Gómez, J O; Maravilla-Domínguez, A; García-Arenas, G; Cervantes-Flores, M; Meza-Velázquez, R; Rivera-Guillén, M; Acosta-Saavedra, L C; Goytia-Acevedo, R C

    2016-08-01

    It has been demonstrated that the allergic response can be ameliorated by the administration of pathogen derivatives that activate Toll-like receptors and induce a Th1-type immune response (IR). Cryptosporidium is a parasite that promotes an IR via Toll-like receptors and elicits the production of Th1-type cytokines, which limit cryptosporidiosis. The aim of this study was to investigate allergy-related immune markers in children naturally infected with Cryptosporidium. In a cross-sectional study, 49 children with or without clinical diagnosis of allergies, oocysts of Cryptosporidium spp. in the faeces were screened microscopically. We microscopically screened for leucocytes, examined T and B cells for allergy-related activation markers using flow cytometry and evaluated serum for total IgE using chemiluminescence. Children with allergies and Cryptosporidium in the faeces had significantly lower levels of total IgE, B cells, CD19(+) CD23(+) and CD19(+) CD124(+) cells as well as a greater percentage of interferon-gamma (IFN-γ(+) ) and IL-4(+) CD4(+) cells than children with allergies without Cryptosporidium. This is the first description of the modulation of the IR in children with allergic diseases in the setting of natural Cryptosporidium infection. Our findings suggest the involvement of CD4(+) cells producing IL-4 and IFN-γ in the IR to Cryptosporidium in naturally infected children.

  17. Multi-dimensional phenotyping: towards a new taxonomy for airway disease.

    PubMed

    Wardlaw, A J; Silverman, M; Siva, R; Pavord, I D; Green, R

    2005-10-01

    All the real knowledge which we possess, depends on methods by which we distinguish the similar from the dissimilar. The greater the number of natural distinctions this method comprehends the clearer becomes our idea of things. The more numerous the objects which employ our attention the more difficult it becomes to form such a method and the more necessary. Classification is a fundamental part of medicine. Diseases are often categorized according to pre-20th century descriptions and concepts of disease based on symptoms, signs and functional abnormalities rather than on underlying pathogenesis. Where the aetiology of disease has been revealed (for example in the infectious diseases) a more precise classification has become possible, but in the chronic inflammatory diseases, and in the inflammatory airway diseases in particular, where pathogenesis has been stubbornly difficult to elucidate, we still use broad descriptive terms such as asthma and chronic obstructive pulmonary disease, which defy precise definition because they encompass a wide spectrum of presentations and physiological and cellular abnormalities. It is our contention that these broad-brush terms have outlived their usefulness and that we should be looking to create a new taxonomy of airway disease-a taxonomy that more closely reflects the spectrum of phenotypes that are encompassed within the term airway inflammatory diseases, and that gives full recognition to late 20th and 21st century insights into the disordered physiology and cell biology that characterizes these conditions in the expectation that these will map more closely to both aetiology and response to treatment. Development of this taxonomy will require a much more complete and sophisticated correlation of the many variables that make up a condition than has been usual to employ in an approach that encompasses multi-dimensional phenotyping and uses complex statistical tools such as cluster analysis.

  18. Th2 Allergic Immune Response to Inhaled Fungal Antigens is Modulated By TLR-4-Independent Bacterial Products

    PubMed Central

    Allard, Jenna B.; Rinaldi, Lisa; Wargo, Matt; Allen, Gilman; Akira, Shizuo; Uematsu, Satoshi; Poynter, Matthew E.; Hogan, Deborah A.; Rincon, Mercedes; Whittaker, Laurie A.

    2009-01-01

    SUMMARY Allergic airway disease is characterized by eosinophilic inflammation, mucus hypersecretion and increased airway resistance. Fungal antigens are ubiquitous within the environment and are well know triggers of allergic disease. Bacterial products are also frequently encountered within the environment and may alter the immune response to certain antigens. The consequence of simultaneous exposure to bacterial and fungal products on the lung adaptive immune response has not been explored. Here we show that oropharyngeal aspiration of fungal lysates (Candida albicans, Aspergillus fumigatus) promotes airway eosinophilia, secretion of Th2 cytokines and mucus cell metaplasia. In contrast, oropharyngeal exposure to bacterial lysates (Pseudomonas aeruginosa) promotes airway inflammation characterized by neutrophils, Th1 cytokine secretion and no mucus production. More importantly, administration of bacterial lysates together with fungal lysates deviates the adaptive immune response to a Th1 type associated with neutrophilia and diminished mucus production. The immunomodulatory effect that bacterial lysates have on the response to fungi is TLR4-independent but MyD88 dependent. Thus, different types of microbial products within the airway can alter the host's adaptive immune response, and potentially impact the development of allergic airway disease to environmental fungal antigens. PMID:19224641

  19. Pulmonary iron overload in thalassemia major presenting as small airway disease.

    PubMed

    Ooi, G C; Khong, P L; Lam, W K; Trendell-Smith, N J; Tsang, K W T

    2002-01-01

    Lung function abnormalities that are associated with thalassemia major are variable with etiology that is yet undetermined. Some studies have suggested that pulmonary iron deposition is a probable cause for these lung defects although there has been no antemortem histopathological and radiological evidence for this. We report a case of thalassemia major with biopsy-proven pulmonary iron overload, in which thoracic high-resolution computed tomography revealed a morphological-functional correlation consistent with small airway disease.

  20. Expression of airway remodeling proteins in mast cell activated by TGF-β released in OVA-induced allergic responses and their inhibition by low-dose irradiation or 8-oxo-dG.

    PubMed

    Hong, Gwan Ui; Kim, Nam Goo; Ro, Jai Youl

    2014-04-01

    Allergic asthma is characterized by chronic airway remodeling, which is associated with the expression of extracellular matrix proteins (ECM) by TGF-β. However, to date there are no reports demonstrating that structural proteins are directly expressed in mast cells. This study aimed to investigate whether ECM proteins are expressed in mast cells activated with antigen/antibody reaction, and whether the resolution effects of irradiation or 8-oxo-dG may contribute to allergic asthma prevention. Bone marrow-derived mast cells (BMMCs) were activated with DNP-HSA/anti-DNP IgE antibody (act-BMMCs). C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce allergic asthma. Mice were treated orally with 8-oxo-dG or exposed to whole body irradiation (using (137)Cs gamma ray at a dose of 0.5 Gy) for three consecutive days 24 h after OVA challenge. Expression of extracellular matrix (ECM) proteins, TGF-β signaling molecules an