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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. 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.

  3. Prevention of House Dust Mite Induced Allergic Airways Disease in Mice through Immune Tolerance

    PubMed Central

    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. PMID:21818308

  4. Engineered silica nanoparticles act as adjuvants to enhance allergic airway disease in mice

    PubMed Central

    2013-01-01

    Background With the increase in production and use of engineered nanoparticles (NP; ≤ 100 nm), safety concerns have risen about the potential health effects of occupational or environmental NP exposure. Results of animal toxicology studies suggest that inhalation of NP may cause pulmonary injury with subsequent acute or chronic inflammation. People with chronic respiratory diseases like asthma or allergic rhinitis may be even more susceptible to toxic effects of inhaled NP. Few studies, however, have investigated adverse effects of inhaled NP that may enhance the development of allergic airway disease. Methods We investigated the potential of polyethylene glycol coated amorphous silica NP (SNP; 90 nm diameter) to promote allergic airway disease when co-exposed during sensitization with an allergen. BALB/c mice were sensitized by intranasal instillation with 0.02% ovalbumin (OVA; allergen) or saline (control), and co-exposed to 0, 10, 100, or 400 μg of SNP. OVA-sensitized mice were then challenged intranasally with 0.5% OVA 14 and 15 days after sensitization, and all animals were sacrificed a day after the last OVA challenge. Blood and bronchoalveolar lavage fluid (BALF) were collected, and pulmonary tissue was processed for histopathology and biochemical and molecular analyses. Results Co-exposure to SNP during OVA sensitization caused a dose-dependent enhancement of allergic airway disease upon challenge with OVA alone. This adjuvant-like effect was manifested by significantly greater OVA-specific serum IgE, airway eosinophil infiltration, mucous cell metaplasia, and Th2 and Th17 cytokine gene and protein expression, as compared to mice that were sensitized to OVA without SNP. In saline controls, SNP exposure did cause a moderate increase in airway neutrophils at the highest doses. Conclusions These results suggest that airway exposure to engineered SNP could enhance allergen sensitization and foster greater manifestation of allergic airway disease upon

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

    PubMed

    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

  6. 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...

  7. Characterization of NLRP12 during the Development of Allergic Airway Disease in Mice

    PubMed Central

    Allen, Irving C.; Lich, John D.; Arthur, Janelle C.; Jania, Corey M.; Roberts, Reid A.; Callaway, Justin B.; Tilley, Stephen L.; Ting, Jenny P.-Y.

    2012-01-01

    Among the 22 members of the nucleotide binding-domain, leucine rich repeat-containing (NLR) family, less than half have been functionally characterized. Of those that have been well studied, most form caspase-1 activating inflammasomes. NLRP12 is a unique NLR that has been shown to attenuate inflammatory pathways in biochemical assays and mediate the lymph node homing of activated skin dendritic cells in contact hypersensitivity responses. Since the mechanism between these two important observations remains elusive, we further evaluated the contribution of NLRP12 to organ specific adaptive immune responses by focusing on the lung, which, like skin, is exposed to both exogenous and endogenous inflammatory agents. In models of allergic airway inflammation induced by either acute ovalbumin (OVA) exposure or chronic house dust mite (HDM) antigen exposure, Nlrp12−/− mice displayed subtle differences in eosinophil and monocyte infiltration into the airways. However, the overall development of allergic airway disease and airway function was not significantly altered by NLRP12 deficiency. Together, the combined data suggest that NLRP12 does not play a vital role in regulating Th2 driven airway inflammation using common model systems that are physiologically relevant to human disease. Thus, the allergic airway inflammation models described here should be appropriate for subsequent studies that seek to decipher the contribution of NLRP12 in mediating the host response to agents associated with asthma exacerbation. PMID:22291998

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

    PubMed

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

    2016-01-01

    Fungi cause a wide spectrum of fungal diseases of the upper and lower airways. There are three main phyla involved in allergic fungal disease: (1) Ascomycota (2) Basidiomycota (3) Zygomycota. Allergic fungal rhinosinusitis (AFRS) causes chronic rhinosinusitis symptoms and is caused predominantly by Aspergillus fumigatus in India and Bipolaris in the United States. The recommended treatment approach for AFRS is surgical intervention and systemic steroids. Allergic bronchopulmonary aspergillosis (APBA) is most commonly diagnosed in patients with asthma or cystic fibrosis. Long term systemic steroids are the mainstay treatment option for ABPA with the addition of an antifungal medication. Fungal sensitization or exposure increases a patient's risk of developing severe asthma and has been termed severe asthma associated with fungal sensitivity (SAFS). Investigating for triggers and causes of a patient's asthma should be sought to decrease worsening progression of the disease. PMID:26776889

  9. 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 ...

  10. Neonatal Streptococcus pneumoniae Infection May Aggravate Adulthood Allergic Airways Disease in Association with IL-17A

    PubMed Central

    Yang, Ting; Jiang, Xiaoli; Zhang, Liqun; Wang, Lijia; Wang, Qinghong; Luo, Zhengxiu; Liu, Enmei; Fu, Zhou

    2015-01-01

    Epidemiologic studies have demonstrated that some bacteria colonization or infections in early-life increased the risk for subsequent asthma development. However, little is known about the mechanisms by which early-life bacterial infection increases this risk. The aim of this study was to investigate the effect of neonatal Streptococcus pneumoniae infection on the development of adulthood asthma, and to explore the possible mechanism. A non-lethal S. pneumoniae lung infection was established by intranasal inoculation of neonatal (1-week-old) female mice with D39. Mice were sensitized and challenged with ovalbumin in adulthood to induce allergic airways disease (AAD). Twenty-four hours later, the lungs and bronchoalveolar lavage fluid (BALF) were collected to assess AAD. Neonatal S. pneumoniae infection exacerbated adulthood hallmark features of AAD, with enhanced airway hyperresponsiveness and increased neutrophil recruitment into the airways, increased Th17 cells and interleukin (IL)-17A productions. Depletion of IL-17A by i.p. injection of a neutralizing monoclonal antibody reduced neutrophil recruitment into the airways, alleviated airway inflammation and decreased airway hyperresponsiveness. Furthermore, IL-17A depletion partially restored levels of inteferon-γ, but had no effect on the release of IL-5 or IL-13. Our data suggest that neonatal S. pneumoniae infection may promote the development of adulthood asthma in association with increased IL-17A production. PMID:25816135

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

    PubMed Central

    Das, Rashmi Ranjan; Naik, Sushree Samiksha; Singh, Meenu

    2013-01-01

    Background. We conducted a systematic review to find out the role of probiotics in treatment of allergic airway diseases.  Methods. A comprehensive search of the major electronic databases was done till March 2013. Trials comparing the effect of probiotics versus placebo were included. A predefined set of outcome measures were assessed. Continuous data were expressed as standardized mean difference with 95% CI. Dichotomous data were expressed as odds ratio with 95% CI. P value < 0.05 was considered as significant. Results. A total of 12 studies were included. Probiotic intake was associated with a significantly improved quality of life score in patients with allergic rhinitis (SMD −1.9 (95% CI −3.62, −0.19); P = 0.03), though there was a high degree of heterogeneity. No improvement in quality of life score was noted in asthmatics. Probiotic intake also improved the following parameters: longer time free from episodes of asthma and rhinitis and decrease in the number of episodes of rhinitis per year. Adverse events were not significant. Conclusion. As the current evidence was generated from few trials with high degree of heterogeneity, routine use of probiotics as an additive on therapy in subjects with allergic airway diseases cannot be recommended. PMID:23956972

  12. Acetaminophen Attenuates House Dust Mite-Induced Allergic Airway Disease in Mice.

    PubMed

    Smith, Gregory J; Thrall, Roger S; Cloutier, Michelle M; Manautou, Jose E; Morris, John B

    2016-09-01

    Epidemiologic evidence suggests that N-acetyl-para-aminophenol (APAP) may play a role in the pathogenesis of asthma, likely through pro-oxidant mechanisms. However, no studies have investigated the direct effects of APAP on the development of allergic inflammation. To determine the likelihood of a causal relationship between APAP and asthma pathogenesis, we explored the effects of APAP on inflammatory responses in a murine house dust mite (HDM) model of allergic airway disease. We hypothesized that APAP would enhance the development of HDM-induced allergic inflammation. The HDM model consisted of once daily intranasal instillations for up to 2 weeks with APAP or vehicle administration 1 hour prior to HDM during either week 1 or 2. Primary assessment of inflammation included bronchoalveolar lavage (BAL), cytokine expression in lung tissue, and histopathology. Contrary to our hypothesis, the effects of HDM treatment were substantially diminished in APAP-treated groups compared with controls. APAP-treated groups had markedly reduced airway inflammation: including decreased inflammatory cells in the BAL fluid, lower cytokine expression in lung tissue, and less perivascular and peribronchiolar immune cell infiltration. The anti-inflammatory effect of APAP was not abrogated by an inhibitor of cytochrome P450 (P450) metabolism, suggesting that the effect was due to the parent compound or a non-P450 generated metabolite. Taken together, our studies do not support the biologic plausibility of the APAP hypothesis that APAP use may contribute to the causation of asthma. Importantly, we suggest the mechanism by which APAP modulates airway inflammation may provide novel therapeutic targets for asthma. PMID:27402277

  13. Interaction of vitamin E isoforms on asthma and allergic airway disease.

    PubMed

    Cook-Mills, Joan; Gebretsadik, Tebeb; Abdala-Valencia, Hiam; Green, Jeremy; Larkin, Emma K; Dupont, William D; Shu, Xiao Ou; Gross, Myron; Bai, Chunxue; Gao, Yu-Tang; Hartman, Terryl J; Rosas-Salazar, Christian; Hartert, Tina

    2016-10-01

    Prospective epidemiological studies, observational cross-sectional studies and some randomised prevention trials have demonstrated inconsistent findings of the impact of vitamin E on asthma risk. The goals of this study were to explore whether this differing association of vitamin E on asthma risk is due to an interaction of vitamin E isoforms. To address this question, in a population-based asthma incidence study we assessed the interaction between the plasma concentrations of vitamin E isoforms α-tocopherol and γ-tocopherol on asthma risk. Second, to understand the mechanisms of any interaction of these isoforms, we conducted experimental supplementation of α-tocopherol and γ-tocopherol isoforms in mice on the outcome of allergic airway inflammation. We found that in the highest γ-tocopherol tertile, low levels of α-tocopherol were associated with increased asthma risk, while highest tertile α-tocopherol levels trended to be protective. Similarly, in a mouse model of asthma, diet supplementation with α-tocopherol decreased lung inflammation in response to house dust mite (HDM) challenge. In contrast, diet supplementation with γ-tocopherol increased lung inflammation in response to HDM. These human and animal studies provide evidence for the competing effects of the vitamin E isoforms, in physiological concentrations, on asthma and allergic airway disease.

  14. Interaction of vitamin E isoforms on asthma and allergic airway disease.

    PubMed

    Cook-Mills, Joan; Gebretsadik, Tebeb; Abdala-Valencia, Hiam; Green, Jeremy; Larkin, Emma K; Dupont, William D; Shu, Xiao Ou; Gross, Myron; Bai, Chunxue; Gao, Yu-Tang; Hartman, Terryl J; Rosas-Salazar, Christian; Hartert, Tina

    2016-10-01

    Prospective epidemiological studies, observational cross-sectional studies and some randomised prevention trials have demonstrated inconsistent findings of the impact of vitamin E on asthma risk. The goals of this study were to explore whether this differing association of vitamin E on asthma risk is due to an interaction of vitamin E isoforms. To address this question, in a population-based asthma incidence study we assessed the interaction between the plasma concentrations of vitamin E isoforms α-tocopherol and γ-tocopherol on asthma risk. Second, to understand the mechanisms of any interaction of these isoforms, we conducted experimental supplementation of α-tocopherol and γ-tocopherol isoforms in mice on the outcome of allergic airway inflammation. We found that in the highest γ-tocopherol tertile, low levels of α-tocopherol were associated with increased asthma risk, while highest tertile α-tocopherol levels trended to be protective. Similarly, in a mouse model of asthma, diet supplementation with α-tocopherol decreased lung inflammation in response to house dust mite (HDM) challenge. In contrast, diet supplementation with γ-tocopherol increased lung inflammation in response to HDM. These human and animal studies provide evidence for the competing effects of the vitamin E isoforms, in physiological concentrations, on asthma and allergic airway disease. PMID:27257004

  15. Metal composition of ambient PM2.5 influences severity of allergic airways disease in mice.

    PubMed Central

    Gavett, Stephen H; Haykal-Coates, Najwa; Copeland, Lisa B; Heinrich, Joachim; Gilmour, M Ian

    2003-01-01

    Children living in Hettstedt in eastern Germany have been 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 pollution. Samples of fine particulate matter (< 2.5 micro m aerodynamic diameter; PM(2.5)) collected in Hettstedt in 1999 had several-fold higher levels of zinc, magnesium, lead, copper, and cadmium than samples from Zerbst. To determine if the results from epidemiologic studies could be repeated in an animal model, we administered PM(2.5) from Hettstedt and Zerbst to ovalbumin-allergic mice. In Balb/c mice, PM(2.5) from Hettstedt, but not PM(2.5) from Zerbst or control filter extract, caused a significant increase in immediate responses to ovalbumin challenge when aspirated 2 hr before challenge, but not when aspirated immediately before sensitization 2 weeks earlier. Antigen-specific IgE was increased by Hettstedt PM(2.5) whether administered before sensitization or challenge. Airway responsiveness to methacholine aerosol and lung inflammatory cell numbers were significantly increased only in allergic mice exposed to Hettstedt PM(2.5) before challenge. Both Hettstedt and Zerbst PM(2.5) significantly increased lung injury parameters and proinflammatory cytokines. These results are consistent with epidemiologic findings and show that metal composition of ambient PM(2.5) influences the severity of allergic respiratory disease. PMID:12948886

  16. Ultrafine carbon black particles cause early airway inflammation and have adjuvant activity in a mouse allergic airway disease model.

    PubMed

    de Haar, Colin; Hassing, Ine; Bol, Marianne; Bleumink, Rob; Pieters, Raymond

    2005-10-01

    To gain more insight into the mechanisms of particulate matter (PM)-induced adjuvant activity, we studied the kinetics of airway toxicity/inflammation and allergic sensitization to ovalbumin (OVA) in response to ultrafine carbon black particles (CBP). Mice were exposed intranasally to OVA alone or in combination with different concentrations of CBP. Airway toxicity and inflammation were assessed at days 4 and 8. Immune adjuvant effects were studied in the lung draining peribronchial lymph nodes (PBLN) at day 8. Antigen-specific IgE was measured at days 21 and 28, whereas allergic airway inflammation was studied after OVA challenges (day 28). Results show that a total dose of 200 microg CBP per mouse, but not 20 microg or 2 microg, induced immediate airway inflammation. This 200 microg CBP was the only dose that had immune adjuvant activity, by inducing enlargement of the PBLN and increasing OVA-specific production of Th2 cytokines (IL-4, IL-5, and IL-10). The immune adjuvant activity of 200 microg CBP dosing was further examined. Whereas increased OVA-specific IgE levels in serum on day 21 confirms systemic sensitization, this was further supported by allergic airway inflammation after challenges with OVA. Our data show a link between early airway toxicity and adjuvant effects of CBP. In addition, results indicate that local cytokine production early after exposure to CBP is predictive of allergic airway inflammation. In addition this model appears suitable for studying the role of airway toxicity, inflammation and other mechanisms of particle adjuvant activity, and predicting the adjuvant potential of different particles.

  17. 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...

  18. 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

  19. 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.

  20. 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. PMID:18160846

  1. 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.

  2. Programmed Death Ligand 1 Promotes Early-Life Chlamydia Respiratory Infection-Induced Severe Allergic Airway Disease.

    PubMed

    Starkey, Malcolm R; Nguyen, Duc H; Brown, Alexandra C; Essilfie, Ama-Tawiah; Kim, Richard Y; Yagita, Hideo; Horvat, Jay C; Hansbro, Philip M

    2016-04-01

    Chlamydia infections are frequent causes of respiratory illness, particularly pneumonia in infants, and are linked to permanent reductions in lung function and the induction of asthma. However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incompletely understood. In the current study, we investigated the role of programmed death (PD)-1 and its ligands PD-L1 and PD-L2 in promoting early-life Chlamydia respiratory infection, and infection-induced airway hyperresponsiveness (AHR) and severe allergic airway disease in later life. Infection increased PD-1 and PD-L1, but not PD-L2, mRNA expression in the lung. Flow cytometric analysis of whole lung homogenates identified monocytes, dendritic cells, CD4(+), and CD8(+) T cells as major sources of PD-1 and PD-L1. Inhibition of PD-1 and PD-L1, but not PD-L2, during infection ablated infection-induced AHR in later life. Given that PD-L1 was the most highly up-regulated and its targeting prevented infection-induced AHR, subsequent analyses focused on this ligand. Inhibition of PD-L1 had no effect on Chlamydia load but suppressed infection-induced pulmonary inflammation. Infection decreased the levels of the IL-13 decoy receptor in the lung, which were restored to baseline levels by inhibition of PD-L1. Finally, inhibition of PD-L1 during infection prevented subsequent infection-induced severe allergic airways disease in later life by decreasing IL-13 levels, Gob-5 expression, mucus production, and AHR. Thus, early-life Chlamydia respiratory infection-induced PD-L1 promotes severe inflammation during infection, permanent reductions in lung function, and the development of more severe allergic airway disease in later life.

  3. Natural antibody repertoires: development and functional role in inhibiting allergic airway disease.

    PubMed

    Kearney, John F; Patel, Preeyam; Stefanov, Emily K; King, R Glenn

    2015-01-01

    In this review we discuss the effects of microbial exposure on the B cell repertoire. Neonatal exposure to conserved bacterial carbohydrates and phospholipids permanently reprograms the natural antibody repertoire directed toward these antigens by clonal expansion, alterations in clonal dominance, and increased serum antibody levels. These epitopes are present not only in bacterial cell walls, but also in common environmental allergens. Neonatal immunization with bacterial polysaccharide vaccines results in attenuated allergic airway responses to fungi-, house dust mite-, and cockroach-associated allergens in mouse models. The similarities between mouse and human natural antibody repertoires suggest that reduced microbial exposure in children may have the opposite effect, providing a potential mechanistic explanation for the hygiene hypothesis. We propose that understanding the effects of childhood infections on the natural antibody repertoire and the mechanisms of antibody-mediated immunoregulation observed in allergy models will lead to the development of prevention/interventional strategies for treatment of allergic asthma. PMID:25622195

  4. [Recent advances in DNA vaccines against allergic airway disease: a review].

    PubMed

    Ou, Jin; Xu, Yu; Shi, Wendan

    2013-12-01

    DNA vaccine is used in infectious diseases initially, and later is applied in neoplastic diseases, allergic diseases and other fields with the further understanding of DNA vaccine and the development of genetic engineering. DNA vaccine transfers the genes encoding exogenous antigens to plasmid vector and then is introduced into organism. It controls the antigen proteins synthesis, thus induces specific humoral and cellular immune responses. So it has a broad application prospect in allergic diseases. Compared with the traditional protein vaccines used in specific immunotherapy, DNA vaccine has many advantages, including high purity and specificity, and improvement of patients' compliance etc. However, there are still two unsolved problems. First, the transfection rate of unmodified naked DNA plasmid is not high, Second, it's difficult to induce ideal immune response. In this study, we will review the progress of DNA vaccine applications in respiratory allergic diseases and its various optimization strategies.

  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. 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

  8. Animal Models of Allergic Airways Disease: Where Are We and Where to Next?

    PubMed Central

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

    2014-01-01

    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 two-fold; 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. PMID:25043224

  9. Amelioration of ovalbumin-induced allergic airway disease following Der p 1 peptide immunotherapy is not associated with induction of IL-35.

    PubMed

    Moldaver, D M; Bharhani, M S; Wattie, J N; Ellis, R; Neighbour, H; Lloyd, C M; Inman, M D; Larché, M

    2014-03-01

    In the present study, we show therapeutic amelioration of established ovalbumin (OVA)-induced allergic airway disease following house dust mite (HDM) peptide therapy. Mice were sensitized and challenged with OVA and HDM protein extract (Dermatophagoides species) to induce dual allergen sensitization and allergic airway disease. Treatment of allergic mice with peptides derived from the major allergen Der p 1 suppressed OVA-induced airway hyperresponsiveness, tissue eosinophilia, and goblet cell hyperplasia upon rechallenge with allergen. Peptide treatment also suppressed OVA-specific T-cell proliferation. Resolution of airway pathophysiology was associated with a reduction in recruitment, proliferation, and effector function of T(H)2 cells and decreased interleukin (IL)-17⁺ T cells. Furthermore, peptide immunotherapy induced the regulatory cytokine IL-10 and increased the proportion of Fox p3⁺ cells among those expressing IL-10. Tolerance to OVA was not associated with increased IL-35. In conclusion, our results provide in vivo evidence for the creation of a tolerogenic environment following HDM peptide immunotherapy, leading to the therapeutic amelioration of established OVA-induced allergic airway disease.

  10. Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life

    PubMed Central

    Lee, Debbie C P; Walker, Simone A; Byrne, Adam J; Gregory, Lisa G; Buckley, James; Bush, Andrew; Shaheen, Seif O; Saglani, Sejal; Lloyd, Clare M

    2015-01-01

    Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model. Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age. Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels. Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma. PMID:25841236

  11. BLOCKADE OF TRKA OR P75 NEUROTROPHIN RECEPTORS ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAYS RESPONSES IN BALB/C MICE

    EPA Science Inventory

    Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airway resistance. Exposure to diesel exhaust particles (DEP) associated with the combustion of diesel fuel exacerbates allergic airways responses. We tested t...

  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. Combination therapy with relaxin and methylprednisolone augments the effects of either treatment alone in inhibiting subepithelial fibrosis in an experimental model of allergic airways disease.

    PubMed

    Royce, Simon G; Sedjahtera, Amelia; Samuel, Chrishan S; Tang, Mimi L K

    2013-01-01

    Although CSs (corticosteroids) demonstrate potent effects in the control of airway inflammation in asthma, many patients continue to experience symptoms and AHR (airway hyper-responsiveness) despite optimal treatment with these agents, probably due to progressive airway remodelling. Identifying novel therapies that can target airway remodelling and/or airway reactivity may improve symptom control in these patients. We have demonstrated previously that the anti-fibrotic hormone RLN (relaxin) can reverse airway remodelling (epithelial thickening and subepithelial fibrosis) and AHR in a murine model of AAD (allergic airways disease). In the present study, we compared the effects of RLN with a CS (methylprednisolone) on airway remodelling and AHR when administered independently or in combination in the mouse AAD model. Female mice at 6-8 weeks of age were sensitized and challenged to OVA (ovalbumin) over a 9-week period and treated with methylprednisolone, RLN, a combination of both treatments or vehicle controls. Methylprednisolone was administered intraperitoneally on the same day as nebulization for 6 weeks, whereas recombinant human RLN-2 was administered via subcutaneously implanted osmotic mini-pumps from weeks 9-11. RLN or methylprednisolone alone were both able to significantly decrease subepithelial thickness and total lung collagen deposition; whereas RLN but not methylprednisolone significantly decreased epithelial thickness and AHR. Additionally, combination therapy with CS and RLN more effectively reduced subepithelial collagen thickness than either therapy alone. These findings demonstrate that RLN can modulate a broader range of airway remodelling changes and AHR than methylprednisolone and the combination of both treatments offers enhanced control of subepithelial fibrosis. PMID:22817662

  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

    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

    2015-07-15

    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 the 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. 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

  17. 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...

  18. 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.

  19. Epigenomics and allergic disease

    PubMed Central

    Lockett, Gabrielle A; Patil, Veeresh K; Soto-Ramírez, Nelís; Ziyab, Ali H; Holloway, John W; Karmaus, Wilfried

    2014-01-01

    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. PMID:24283882

  20. Genetics of Allergic Diseases

    PubMed Central

    Ortiz, Romina A.; Barnes, Kathleen C.

    2015-01-01

    The allergic diseases are complex phenotypes for which a strong genetic basis has been firmly established. Genome-wide association studies (GWAS) has been widely employed in the field of allergic disease, and to date significant associations have been published for nearly 100 asthma genes/loci, in addition to multiple genes/loci for AD, AR and IgE levels, for which the overwhelming number of candidates are novel and have given a new appreciation for the role of innate as well as adaptive immune-response genes in allergic disease. A major outcome of GWAS in allergic disease has been the formation of national and international collaborations leading to consortia meta-analyses, and an appreciation for the specificity of genetic associations to sub-phenotypes of allergic disease. Molecular genetics has undergone a technological revolution, leading to next generation sequencing (NGS) strategies that are increasingly employed to hone in on the causal variants associated with allergic diseases. Unmet needs in the field include the inclusion of ethnically and racially diverse cohorts, and strategies for managing ‘big data’ that is an outcome of technological advances such as sequencing. PMID:25459575

  1. Airway Epithelial Regulation of Allergic Sensitization in Asthma

    PubMed Central

    Poynter, Matthew E.

    2012-01-01

    While many of the contributing cell types and mediators of allergic asthma are known, less well understood are the factors that influence the development of allergic responses that lead to the development of allergic asthma. As the first airway cell type to respond to inhaled factors, the epithelium orchestrates downstream interactions between dendritic cells (DCs) and CD4+ T cells that quantitatively and qualitatively dictate the degree and type of the allergic asthma phenotype, making the epithelium of critical importance for the genesis of allergies that later manifest in allergic asthma. Amongst the molecular processes of critical importance in airway epithelium is the transcription factor, nuclear factor-kappaB (NF-κB). This review will focus primarily on the genesis of pulmonary allergies and the participation of airway epithelial NF-κB activation therein, using examples from our own work on nitrogen dioxide (NO2) exposure and genetic modulation of airway epithelial NF-κB activation. In addition, the mechanisms through which Serum Amyloid A (SAA), an NF-κB-regulated, epithelial-derived mediator, influences allergic sensitization and asthma severity will be presented. Knowledge of the molecular and cellular processes regulating allergic sensitization in the airways has the potential to provide powerful insight into the pathogenesis of allergy, as well as targets for the prevention and treatment of asthma. PMID:22579987

  2. 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

  3. 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

  4. TLR2, TLR4 AND MyD88 Mediate Allergic Airway Disease (AAD) and Streptococcus pneumoniae-Induced Suppression of AAD

    PubMed Central

    Thorburn, Alison N.; Tseng, Hsin-Yi; Donovan, Chantal; Hansbro, Nicole G.; Jarnicki, Andrew G.; Foster, Paul S.; Gibson, Peter G.; Hansbro, Philip M.

    2016-01-01

    Background Exposure to non-pathogenic Streptococcus pneumoniae and vaccination are inversely associated with asthma. Studies in animal models demonstrate that airway administration of S. pneumoniae (live or killed), or its vaccines or components, suppresses the characteristic features of asthma in mouse models of allergic airway disease (AAD). These components could be developed into immunoregulatory therapies. S. pneumoniae components are recognized by Toll-like receptors (TLR) 2 and TLR4, and both induce inflammatory cell responses through the adaptor protein myeloid differentiation primary response gene 88 (MyD88). The involvement of TLR2, TLR4 and MyD88 in the pathogenesis of AAD and asthma is incompletely understood, and has not been studied in S. pneumoniae-mediated suppression of AAD. We investigated the role of TLR2, TLR4 and MyD88 in the development of AAD and S. pneumoniae-mediated suppression of AAD. Methods and Findings OVA-induced AAD and killed S. pneumoniae-mediated suppression of AAD were assessed in wild-type, TLR2-/-, TLR4-/-, TLR2/4-/- and MyD88-/- BALB/c mice. During OVA-induced AAD, TLR2, TLR4 and MyD88 were variously involved in promoting eosinophil accumulation in bronchoalveolar lavage fluid and blood, and T-helper type (Th)2 cytokine release from mediastinal lymph node T cells and splenocytes. However, all were required for the induction of airways hyperresponsiveness (AHR). In S. pneumoniae-mediated suppression of AAD, TLR2, TLR4 and MyD88 were variously involved in the suppression of eosinophilic and splenocyte Th2 responses but all were required for the reduction in AHR. Conclusions These results highlight important but complex roles for TLR2, TLR4 and MyD88 in promoting the development of OVA-induced AAD, but conversely in the S. pneumoniae-mediated suppression of AAD, with consistent and major contributions in both the induction and suppression of AHR. Thus, TLR signaling is likely required for both the development of asthma and the

  5. Dual oxidase regulates neutrophil recruitment in allergic airways.

    PubMed

    Chang, Sandra; Linderholm, Angela; Franzi, Lisa; Kenyon, Nicholas; Grasberger, Helmut; Harper, Richart

    2013-12-01

    Enhanced reactive oxygen species production in allergic airways is well described and correlates with increased airway contractions, inflammatory cell infiltration, goblet cell metaplasia, and mucus hypersecretion. There is also an abundance of interleukin-4/interleukin-13 (IL-4/IL-13)- or interleukin-5-secreting cells that are thought to be central to the pathogenesis of allergic asthma. We postulated that the dual oxidases (DUOX1 and DUOX2), members of the nicotinamide adenine dinucleotide phosphate oxidase family that release hydrogen peroxide (H2O2) in the respiratory tract, are critical proteins in the pathogenesis of allergic airways. DUOX activity is regulated by cytokines, including IL-4 and IL-13, and DUOX-mediated H2O2 influences several important features of allergic asthma: mucin production, IL-8 secretion, and wound healing. The objective of this study was to establish the contribution of DUOXs to the development of allergic asthma in a murine model. To accomplish this goal, we utilized a DUOXA-deficient mouse model (Duoxa(-/-)) that lacked maturation factors for both DUOX1 and DUOX2. Our results are the first to demonstrate evidence of DUOX protein and DUOX functional activity in murine airway epithelium. We also demonstrate that DUOXA maturation factors are required for airway-specific H2O2 production and localization of DUOX to cilia of fully differentiated airway epithelial cells. We compared wild-type and Duoxa(-/-) mice in an ovalbumin exposure model to determine the role of DUOX in allergic asthma. In comparison to DUOX-intact mice, Duoxa(-/-) mice had reduced mucous cell metaplasia and lower levels of TH2 cytokine levels in bronchoalveolar fluid. In addition, increased airway resistance in response to methacholine was observed in Duoxa(+/+) mice, as expected, but was absent in Duoxa(-/-) mice. Surprisingly, Duoxa(-/-) mice had decreased influx of neutrophils in bronchoalveolar fluid and lung tissue sections associated with a lower level of the

  6. 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

  7. Effects of local nasal immunotherapy in allergic airway inflammation: Using urea denatured Dermatophagoides pteronyssinus.

    PubMed

    Yu, Sheng-Jie; Liao, En-Chih; Tsai, Jaw-Ji

    2015-01-01

    Despite improvements in anti-allergy medication, the prevalence of allergic airway inflammation remains high, affecting up to 40% of the population worldwide. Allergen immunotherapy is effective for inducing tolerance but has the adverse effect of severe allergic reaction. This can be avoided by denaturing with urea. In this study, we demonstrated that the serum level of allergen-specific IgE in mice sensitized with native Dermatophagoides pteronyssinus (Der p) crude extract after receiving local nasal immunotherapy (LNIT) with urea-denatured Der p crude extract (DN-Dp) significantly decreased compared to that in the normal saline (NS) treatment group. Expressions of IL-4 were significantly reduced in lung tissues after treatment. Inflammation around the bronchial epithelium improved and airway hypersensitivity was down-regulated. LNIT with DN-Dp can down-regulate IL-1b, IL-6 and TNF-a expression and then decrease Der p-induced allergic airway inflammation. This therapeutic modality may be used as an alternative treatment for airway allergic diseases.

  8. 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

  9. 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.

  10. 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. PMID:26667977

  11. 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

  12. Airway Surface Mycosis in Chronic Th2-Associated Airway Disease

    PubMed Central

    Porter, Paul; Lim, Dae Jun; Maskatia, Zahida Khan; Mak, Garbo; Tsai, Chu-Lin; Citardi, Martin J; Fakhri, Samer; Shaw, Joanne L.; Fothergil, Annette; Kheradmand, Farrah; Corry, David B; Luong, Amber

    2014-01-01

    Background Environmental fungi have been linked to T helper type 2 (Th2) cell-related airway inflammation and the Th2-associated chronic airway diseases asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. Objective To determine the frequency of fungus isolation and fungus-specific immunity in Th2-associated and non-associated airway disease patients. Methods Sinus lavage fluid and blood were collected from sinus surgery patients (n=118) including CRS patients with and without nasal polyps and AFRS and non-CRS/non-asthmatic control patients. Asthma status was deteremined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. Peripheral blood mononuclear cells were restimulated with fungal antigens in an enzyme linked immunocell spot (ELISpot) assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared to fungus-specific IgE levels measured from plasma by ELISA. Results Filamentous fungi were significantly more commonly cultured from Th2-associated airway disease subjects (asthma, CRSwNP, or AFRS: n=68) compared to non-Th2-associated control patients (n=31); 74% vs 16% respectively, p<0.001. Both fungus-specific IL-4 ELISpot (n=48) and specific IgE (n=70) data correlated with Th2-associated diseases (sensitivity 73% and specificity 100% vs. 50% and 77%, respectively). Conclusions The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with Th2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients. Clinical Implications Airway fungi may contribute to the expression of sinusitis with nasal polyps and

  13. Volatile Organic Compounds Enhance Allergic Airway Inflammation in an Experimental Mouse Model

    PubMed Central

    Bönisch, Ulrike; Böhme, Alexander; Kohajda, Tibor; Mögel, Iljana; Schütze, Nicole; von Bergen, Martin; Simon, Jan C.; Lehmann, Irina; Polte, Tobias

    2012-01-01

    Background Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. Methods To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. Results Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. Conclusions Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases. PMID:22802943

  14. 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.

  15. 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...

  16. 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

  17. 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

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

    PubMed

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

    2006-06-01

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

  19. Inflammatory bowel disease and airway diseases

    PubMed Central

    Vutcovici, Maria; Brassard, Paul; Bitton, Alain

    2016-01-01

    Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact. PMID:27678355

  20. Inflammatory bowel disease and airway diseases

    PubMed Central

    Vutcovici, Maria; Brassard, Paul; Bitton, Alain

    2016-01-01

    Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.

  1. Climate change and allergic disease.

    PubMed

    Shea, Katherine M; Truckner, Robert T; Weber, Richard W; Peden, David B

    2008-09-01

    Climate change is potentially the largest global threat to human health ever encountered. The earth is warming, the warming is accelerating, and human actions are largely responsible. If current emissions and land use trends continue unchecked, the next generations will face more injury, disease, and death related to natural disasters and heat waves, higher rates of climate-related infections, and wide-spread malnutrition, as well as more allergic and air pollution-related morbidity and mortality. This review highlights links between global climate change and anticipated increases in prevalence and severity of asthma and related allergic disease mediated through worsening ambient air pollution and altered local and regional pollen production. The pattern of change will vary regionally depending on latitude, altitude, rainfall and storms, land-use patterns, urbanization, transportation, and energy production. The magnitude of climate change and related increases in allergic disease will be affected by how aggressively greenhouse gas mitigation strategies are pursued, but at best an average warming of 1 to 2 degrees C is certain this century. Thus, anticipation of a higher allergic disease burden will affect clinical practice as well as public health planning. A number of practical primary and secondary prevention strategies are suggested at the end of the review to assist in meeting this unprecedented public health challenge.

  2. ALLERGIC DISEASES AND ASTHMA IN ADOLESCENTS.

    PubMed

    Adamia, N; Jorjoliani, L; Khachapuridze, D; Katamadze, N; Chkuaseli, N

    2015-06-01

    common accompanying disease. Subjects with non-specific hyperresponsiveness of bronchi and asthma before age of 12, were classified only as being in remission and having accompanying allergic disease and subjects without obstruction and asthma were classified as absence of asthma and were designated as independent group. Population was divided into "active" (indicate presence of symptoms or are subjected to treatment) and "ever" (diagnosis was made before involvement into the study) groups. Main finding is identification of correlation between airways inflammation and phenotype accompanying asthma in children of age from 2 to 16. Research showed than of 860 children (398 males and 462 females) of age from 2 to 8, 62 children had asthma (17 females and 45 males) with at least accompanying disease. Of 590 children (311 males and 279 females) of age from 9 to 17, 81 children had asthma (26 females and 55 males) with at least accompanying allergic disease. The most common asthma phenotype was only asthma, in 32.8%, further asthma and allergic rhinitis (27.9%), asthma with allergic rhinitis and atopic dermatitis (13%), asthma with atopic dermatitis (4.9%). Asthma phenotypes did not differ significantly, with respect of asthma severity and need of anti-inflammation medication. Gender was notably correlated with only one phenotype of asthma; boys are more susceptible to asthma and allergic rhinitis, compared with the girls (9.5% boys and 4.9% girls) p=0.001. Lung function is significantly correlated with hyperresponsiveness of bronchi associated with asthma phenotype with the lowest FEV 2% data - in case of asthma, allergic rhinitis and atopic dermatitis. Our research showed than asthma in adults is accompanied with allergic rhinitis or atopic dermatitis (approximately 14.9%). In puberty, asthma phenotypes with allergic rhinitis was mostly associated with non-specific hyperresponsiveness of bronchi and airways inflammation (p>0.05). In the combinations of allergic diseases the

  3. 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. PMID:22952678

  4. 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

  5. Elimination of Aspergillus fumigatus conidia from the airways of mice with allergic airway inflammation

    PubMed Central

    2013-01-01

    Background Aspergillus fumigatus conidia can exacerbate asthma symptoms. Phagocytosis of conidia is a principal component of the host antifungal defense. We investigated whether allergic airway inflammation (AAI) affects the ability of phagocytic cells in the airways to internalize the resting fungal spores. Methods Using BALB/c mice with experimentally induced AAI, we tested the ability of neutrophils, macrophages, and dendritic cells to internalize A. fumigatus conidia at various anatomical locations. We used light microscopy and differential cell and conidium counts to determine the ingestion potential of neutrophils and macrophages present in bronchoalveolar lavage (BAL). To identify phagocyte-conidia interactions in conducting airways, conidia labeled with tetramethylrhodamine-(5-(and-6))-isothiocyanate were administered to the oropharyngeal cavity of mice. Confocal microscopy was used to quantify the ingestion potential of Ly-6G+ neutrophils and MHC II+ antigen-presenting cells located in the intraepithelial and subepithelial areas of conducting airways. Results Allergen challenge induced transient neutrophil recruitment to the airways. Application of A. fumigatus conidia at the acute phase of AAI provoked recurrent neutrophil infiltration, and consequently increased the number and the ingestion potential of the airway neutrophils. In the absence of recurrent allergen or conidia provocation, both the ingestion potential and the number of BAL neutrophils decreased. As a result, conidia were primarily internalized by alveolar macrophages in both AAI and control mice at 24 hours post-inhalation. Transient influx of neutrophils to conducting airways shortly after conidial application was observed in mice with AAI. In addition, the ingestion potential of conducting airway neutrophils in mice with induced asthma exceeded that of control mice. Although the number of neutrophils subsequently decreased, the ingestion capacity remained elevated in AAI mice, even at 24

  6. Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization.

    PubMed

    Smarr, Charles B; Yap, Woon Teck; Neef, Tobias P; Pearson, Ryan M; Hunter, Zoe N; Ifergan, Igal; Getts, Daniel R; Bryce, Paul J; Shea, Lonnie D; Miller, Stephen D

    2016-05-01

    Specific immunotherapy (SIT) is the most widely used treatment for allergic diseases that directly targets the T helper 2 (Th2) bias underlying allergy. However, the most widespread clinical applications of SIT require a long period of dose escalation with soluble antigen (Ag) and carry a significant risk of adverse reactions, particularly in highly sensitized patients who stand to benefit most from a curative treatment. Thus, the development of safer, more efficient methods to induce Ag-specific immune tolerance is critical to advancing allergy treatment. We hypothesized that antigen-associated nanoparticles (Ag-NPs), which we have used to prevent and treat Th1/Th17-mediated autoimmune disease, would also be effective for the induction of tolerance in a murine model of Th2-mediated ovalbumin/alum-induced allergic airway inflammation. We demonstrate here that antigen-conjugated polystyrene (Ag-PS) NPs, although effective for the prophylactic induction of tolerance, induce anaphylaxis in presensitized mice. Antigen-conjugated NPs made of biodegradable poly(lactide-co-glycolide) (Ag-PLG) are similarly effective prophylactically, are well tolerated by sensitized animals, but only partially inhibit Th2 responses when administered therapeutically. PLG NPs containing encapsulated antigen [PLG(Ag)], however, were well tolerated and effectively inhibited Th2 responses and airway inflammation both prophylactically and therapeutically. Thus, we illustrate progression toward PLG(Ag) as a biodegradable Ag carrier platform for the safe and effective inhibition of allergic airway inflammation without the need for nonspecific immunosuppression in animals with established Th2 sensitization. PMID:27091976

  7. 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.

  8. 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

  9. Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

    PubMed

    Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

    2015-12-07

    Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk.

  10. Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

    PubMed

    Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

    2016-02-01

    Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk. PMID:26644379

  11. Rapamycin attenuates airway hyperreactivity, goblet cells, and IgE in experimental allergic asthma.

    PubMed

    Mushaben, Elizabeth M; Kramer, Elizabeth L; Brandt, Eric B; Khurana Hershey, Gurjit K; Le Cras, Timothy D

    2011-12-01

    The mammalian target of rapamycin (mTOR) signaling pathway integrates environmental cues, promotes cell growth/differentiation, and regulates immune responses. Although inhibition of mTOR with rapamycin has potent immunosuppressive activity, mixed effects have been reported in OVA-induced models of allergic asthma. We investigated the impact of two rapamycin treatment protocols on the major characteristics of allergic asthma induced by the clinically relevant allergen, house dust mite (HDM). In protocol 1, BALB/c mice were exposed to 10 intranasal HDM doses over a period of 24 d and treated with rapamycin simultaneously during the sensitization/exposure period. In protocol 2, rapamycin was administered after the mice had been sensitized to HDM (i.p. injection) and prior to initiation of two intranasal HDM challenges over 4 d. Airway hyperreactivity (AHR), IgE, inflammatory cells, cytokines, leukotrienes, goblet cells, and activated T cells were assessed. In protocol 1, rapamycin blocked HDM-induced increases in AHR, inflammatory cell counts, and IgE, as well as attenuated goblet cell metaplasia. In protocol 2, rapamycin blocked increases in AHR, IgE, and T cell activation and reduced goblet cell metaplasia, but it had no effect on inflammatory cell counts. Increases in IL-13 and leukotrienes were also blocked by rapamycin, although increases in IL-4 were unaffected. These data demonstrated that rapamycin can inhibit cardinal features of allergic asthma, including increases in AHR, IgE, and goblet cells, most likely as a result of its ability to reduce the production of two key mediators of asthma: IL-13 and leukotrienes. These findings highlight the importance of the mTOR pathway in allergic airway disease. PMID:22021618

  12. Rapamycin attenuates airway hyperreactivity, goblet cells, and IgE in experimental allergic asthma.

    PubMed

    Mushaben, Elizabeth M; Kramer, Elizabeth L; Brandt, Eric B; Khurana Hershey, Gurjit K; Le Cras, Timothy D

    2011-12-01

    The mammalian target of rapamycin (mTOR) signaling pathway integrates environmental cues, promotes cell growth/differentiation, and regulates immune responses. Although inhibition of mTOR with rapamycin has potent immunosuppressive activity, mixed effects have been reported in OVA-induced models of allergic asthma. We investigated the impact of two rapamycin treatment protocols on the major characteristics of allergic asthma induced by the clinically relevant allergen, house dust mite (HDM). In protocol 1, BALB/c mice were exposed to 10 intranasal HDM doses over a period of 24 d and treated with rapamycin simultaneously during the sensitization/exposure period. In protocol 2, rapamycin was administered after the mice had been sensitized to HDM (i.p. injection) and prior to initiation of two intranasal HDM challenges over 4 d. Airway hyperreactivity (AHR), IgE, inflammatory cells, cytokines, leukotrienes, goblet cells, and activated T cells were assessed. In protocol 1, rapamycin blocked HDM-induced increases in AHR, inflammatory cell counts, and IgE, as well as attenuated goblet cell metaplasia. In protocol 2, rapamycin blocked increases in AHR, IgE, and T cell activation and reduced goblet cell metaplasia, but it had no effect on inflammatory cell counts. Increases in IL-13 and leukotrienes were also blocked by rapamycin, although increases in IL-4 were unaffected. These data demonstrated that rapamycin can inhibit cardinal features of allergic asthma, including increases in AHR, IgE, and goblet cells, most likely as a result of its ability to reduce the production of two key mediators of asthma: IL-13 and leukotrienes. These findings highlight the importance of the mTOR pathway in allergic airway disease.

  13. Nanoparticle uptake by airway phagocytes after fungal spore challenge in murine allergic asthma and chronic bronchitis

    PubMed Central

    2014-01-01

    Background In healthy lungs, deposited micrometer-sized particles are efficiently phagocytosed by macrophages present on airway surfaces; however, uptake of nanoparticles (NP) by macrophages appears less effective and is largely unstudied in lung disease. Using mouse models of allergic asthma and chronic obstructive pulmonary disease (COPD), we investigated NP uptake after challenge with common biogenic ambient air microparticles. Methods Bronchoalveolar lavage (BAL) cells from diseased mice (allergic asthma: ovalbumin [OVA] sensitized and COPD: Scnn1b-transgenic [Tg]) and their respective healthy controls were exposed ex vivo first to 3-μm fungal spores of Calvatia excipuliformis and then to 20-nm gold (Au) NP. Electron microscopic imaging was performed and NP uptake was assessed by quantitative morphometry. Results Macrophages from diseased mice were significantly larger compared to controls in OVA-allergic versus sham controls and in Scnn1b-Tg versus wild type (WT) mice. The percentage of macrophages containing AuNP tended to be lower in Scnn1b-Tg than in WT mice. In all animal groups, fungal spores were localized in macrophage phagosomes, the membrane tightly surrounding the spore, whilst AuNP were found in vesicles largely exceeding NP size, co-localized in spore phagosomes and occasionally, in the cytoplasm. AuNP in vesicles were located close to the membrane. In BAL from OVA-allergic mice, 13.9 ± 8.3% of all eosinophils contained AuNP in vesicles exceeding NP size and close to the membrane. Conclusions Overall, AuNP uptake by BAL macrophages occurred mainly by co-uptake together with other material, including micrometer-sized ambient air particles like fungal spores. The lower percentage of NP containing macrophages in BAL from Scnn1b-Tg mice points to a change in the macrophage population from a highly to a less phagocytic phenotype. This likely contributes to inefficient macrophage clearance of NP in lung disease. Finally, the AuNP containing

  14. 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. PMID:27027953

  15. Antileukotrienes in upper airway inflammatory diseases.

    PubMed

    Cingi, Cemal; Muluk, Nuray Bayar; Ipci, Kagan; Şahin, Ethem

    2015-11-01

    Leukotrienes (LTs) are a family of inflammatory mediators including LTA4, LTB4, LTC4, LTD4, and LTE4. By competitive binding to the cysteinyl LT1 (CysLT1) receptor, LT receptor antagonist drugs, such as montelukast, zafirlukast, and pranlukast, block the effects of CysLTs, improving the symptoms of some chronic respiratory diseases, particularly bronchial asthma and allergic rhinitis. We reviewed the efficacy of antileukotrienes in upper airway inflammatory diseases. An update on the use of antileukotrienes in upper airway diseases in children and adults is presented with a detailed literature survey. Data on LTs, antileukotrienes, and antileukotrienes in chronic rhinosinusitis and nasal polyps, asthma, and allergic rhinitis are presented. Antileukotriene drugs are classified into two groups: CysLT receptor antagonists (zafirlukast, pranlukast, and montelukast) and LT synthesis inhibitors (5-lipoxygenase inhibitors such as zileuton, ZD2138, Bay X 1005, and MK-0591). CysLTs have important proinflammatory and profibrotic effects that contribute to the extensive hyperplastic rhinosinusitis and nasal polyposis (NP) that characterise these disorders. Patients who receive zafirlukast or zileuton tend to show objective improvements in, or at least stabilisation of, NP. Montelukast treatment may lead to clinical subjective improvement in NP. Montelukast treatment after sinus surgery can lead to a significant reduction in eosinophilic cationic protein levels in serum, with a beneficial effect on nasal and pulmonary symptoms and less impact in NP. Combined inhaled corticosteroids and long-acting β-agonists treatments are most effective for preventing exacerbations among paediatric asthma patients. Treatments with medium- or high-dose inhaled corticosteroids, combined inhaled corticosteroids and LT receptor antagonists, and low-dose inhaled corticosteroids have been reported to be equally effective. Antileukotrienes have also been reported to be effective for allergic

  16. Immunoregulatory Role of HLA-G in Allergic Diseases

    PubMed Central

    Contini, Paola; Negrini, Simone; Ciprandi, Giorgio; Puppo, Francesco

    2016-01-01

    Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation. PMID:27413762

  17. Immunoregulatory Role of HLA-G in Allergic Diseases.

    PubMed

    Murdaca, Giuseppe; Contini, Paola; Negrini, Simone; Ciprandi, Giorgio; Puppo, Francesco

    2016-01-01

    Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation. PMID:27413762

  18. 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.

  19. Impact of Adiponectin Overexpression on Allergic Airways Responses in Mice

    PubMed Central

    Verbout, Norah G.; Williams, Alison S.; Kasahara, David I.; Wurmbrand, Allison P.; Halayko, Andrew J.; Shore, Stephanie A.

    2013-01-01

    Obesity is an important risk factor for asthma. Obese individuals have decreased circulating adiponectin, an adipose-derived hormone with anti-inflammatory properties. We hypothesized that transgenic overexpression of adiponectin would attenuate allergic airways inflammation and mucous hyperplasia in mice. To test this hypothesis, we used mice overexpressing adiponectin (Adipo Tg). Adipo Tg mice had marked increases in both serum adiponectin and bronchoalveolar lavage (BAL) fluid adiponectin. Both acute and chronic ovalbumin (OVA) sensitization and challenge protocols were used. In both protocols, OVA-induced increases in total BAL cells were attenuated in Adipo Tg versus WT mice. In the acute protocol, OVA-induced increases in several IL-13 dependent genes were attenuated in Adipo Tg versus WT mice, even though IL-13 per se was not affected. With chronic exposure, though OVA-induced increases in goblet cells numbers per millimeter of basement membrane were greater in Adipo Tg versus WT mice, mRNA abundance of mucous genes in lungs was not different. Also, adiponectin overexpression did not induce M2 polarization in alveolar macrophages. Our results indicate that adiponectin protects against allergen-induced inflammatory cell recruitment to the airspaces, but not development of goblet cell hyperplasia. PMID:23861690

  20. 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

  1. 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

  2. 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

  3. Role of sensitization to mammalian serum albumin in allergic disease.

    PubMed

    Liccardi, Gennaro; Asero, Riccardo; D'Amato, Maria; D'Amato, Gennaro

    2011-10-01

    Serum albumin (SA) constitutes an intriguing puzzle that is involved in allergic sensitizations from different sources and induces different clinical manifestations. In this article, we describe the role of sensitization to SAs in inducing allergic diseases and the complex interactions and cross-reactivity between SA resulting from its presence in various mammalian tissues and fluids. SAs alone are an uncommon cause of allergic sensitization in airways, but these allergenic proteins likely play a significant role as cross-reacting allergens in individuals sensitized to several types of animal dander. SAs are a minor allergen in milk but a major allergen in meats. Recently, bovine SA has been added to the culture medium of spermatozoids used for artificial insemination. As a consequence, some case reports have shown that bovine SA may be a causative agent in severe anaphylaxis after standard intrauterine insemination or in vitro fertilization. PMID:21809117

  4. Role of sensitization to mammalian serum albumin in allergic disease.

    PubMed

    Liccardi, Gennaro; Asero, Riccardo; D'Amato, Maria; D'Amato, Gennaro

    2011-10-01

    Serum albumin (SA) constitutes an intriguing puzzle that is involved in allergic sensitizations from different sources and induces different clinical manifestations. In this article, we describe the role of sensitization to SAs in inducing allergic diseases and the complex interactions and cross-reactivity between SA resulting from its presence in various mammalian tissues and fluids. SAs alone are an uncommon cause of allergic sensitization in airways, but these allergenic proteins likely play a significant role as cross-reacting allergens in individuals sensitized to several types of animal dander. SAs are a minor allergen in milk but a major allergen in meats. Recently, bovine SA has been added to the culture medium of spermatozoids used for artificial insemination. As a consequence, some case reports have shown that bovine SA may be a causative agent in severe anaphylaxis after standard intrauterine insemination or in vitro fertilization.

  5. Nerve growth factor and neurotrophin-3 mediate survival of pulmonary plasma cells during the allergic airway inflammation.

    PubMed

    Abram, Melanie; Wegmann, Michael; Fokuhl, Verena; Sonar, Sanchaita; Luger, Elke Olga; Kerzel, Sebastian; Radbruch, Andreas; Renz, Harald; Zemlin, Michael

    2009-04-15

    Allergen-specific Abs play a pivotal role in the induction and maintenance of allergic airway inflammation. During secondary immune responses, plasma cell survival and Ab production is mediated by extrinsic factors provided by the local environment (survival niches). It is unknown whether neurotrophins, a characteristic marker of allergic airway inflammation, influence plasma cell survival in the lung. Using a mouse model of allergic asthma, we found that plasma cells from the lung and spleen are distinct subpopulations exhibiting differential expression patterns of neurotrophins and their receptors (Trks). In vitro, the nerve growth factor (NGF) and neurotrophin-3 (NT3) led to a dose-dependent increase in viability of isolated pulmonary plasma cells due to up-regulation of the antiapoptotic Bcl2 pathway. In parallel, the expression of transcription factors that stimulate the production of immunoglobulins (X-box binding protein 1 and NF-kappaB subunit RelA) was enhanced in plasma cells treated with NGF and NT3. These findings were supported in vivo. When the NGF pathway was blocked by intranasal application of a selective TrkA inhibitor, sensitized mice showed reduced numbers of pulmonary plasma cells and developed lower levels of allergen-specific and total serum IgE in response to OVA inhalation. This suggests that in the allergic airway inflammation, NGF/TrkA-mediated pulmonary IgE production contributes significantly to serum-IgE levels. We conclude that the neurotrophins NGF and NT3 act as survival factors for pulmonary plasma cells and thus are important regulators of the local Ab production in the allergic airway disease.

  6. Environmental Changes, Microbiota, and Allergic Diseases

    PubMed Central

    Kim, Byoung-Ju; Lee, So-Yeon; Kim, Hyo-Bin; Lee, Eun

    2014-01-01

    During the last few decades, the prevalence of allergic disease has increased dramatically. The development of allergic diseases has been attributed to complex interactions between environmental factors and genetic factors. Of the many possible environmental factors, most research has focused on the most commonly encountered environmental factors, such as air pollution and environmental microbiota in combination with climate change. There is increasing evidence that such environmental factors play a critical role in the regulation of the immune response that is associated with allergic diseases, especially in genetically susceptible individuals. This review deals with not only these environmental factors and genetic factors but also their interactions in the development of allergic diseases. It will also emphasize the need for early interventions that can prevent the development of allergic diseases in susceptible populations and how these interventions can be identified. PMID:25228995

  7. Outdoor air pollution in urban areas and allergic respiratory diseases.

    PubMed

    D'Amato, G

    1999-12-01

    Respiratory allergic diseases (rhinitis, rhinosinusitis, bronchial asthma and its equivalents) appear to be increasing in most countries, and subjects living in urban and industrialized areas are more likely to experience respiratory allergic symptoms than those living in rural areas. This increase has been linked, among various factors, to air pollution, which is now an important public health hazard. Laboratory studies confirm the epidemiological evidence that inhalation of some pollutants, either individually or in combination, adversely affect lung function in asthmatics. The most abundant air pollutants in urban areas with high levels of vehicle traffic are respirable particulate matter, nitrogen dioxide and ozone. While nitrogen dioxide does not exert consistent effects on lung function, ozone, respirable particulate matter and allergens impair lung function and lead to increased airway responsiveness and bronchial obstruction in predisposed subjects. However, besides acting as irritants, airborne pollutants can modulate the allergenicity of antigens carried by airborne particles. By attaching to the surface of pollen grains and of plant-derived paucimicronic particles, pollutants can modify the morphology of these antigen-carrying agents and after their allergenic potential. In addition, by inducing airway inflammation, which increases airway epithelial permeability, pollutants overcome the mucosal barrier and so facilitate the allergen-induced inflammatory responses. Moreover, air pollutants such as diesel exhaust emissions are thought to modulate the immune response by increasing immunoglobulin E synthesis, thus facilitating allergic sensitization in atopic subjects and the subsequent development of clinical respiratory symptoms. PMID:10695313

  8. Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment.

    PubMed

    Hong, Gyong Hwa; Kwon, Hyouk-Soo; Moon, Keun-Ai; Park, So Young; Park, Sunjoo; Lee, Kyoung Young; Ha, Eun Hee; Kim, Tae-Bum; Moon, Hee-Bom; Lee, Heung Kyu; Cho, You Sook

    2016-03-01

    Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu(-/-)), clusterin heterogeneous (Clu(+/-)), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu(-/-) and Clu(+/-) mice. Of these immune cells, inflammatory DCs (CD11b(+)CD11c(+)) and Ly6C(high) monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway. PMID:26826245

  9. Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment.

    PubMed

    Hong, Gyong Hwa; Kwon, Hyouk-Soo; Moon, Keun-Ai; Park, So Young; Park, Sunjoo; Lee, Kyoung Young; Ha, Eun Hee; Kim, Tae-Bum; Moon, Hee-Bom; Lee, Heung Kyu; Cho, You Sook

    2016-03-01

    Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu(-/-)), clusterin heterogeneous (Clu(+/-)), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu(-/-) and Clu(+/-) mice. Of these immune cells, inflammatory DCs (CD11b(+)CD11c(+)) and Ly6C(high) monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway.

  10. Lung function and airway diseases.

    PubMed

    Weiss, Scott T

    2010-01-01

    Two studies report genome-wide association studies for lung function, using cross-sectional spirometric measurements in healthy individuals. They identify six genetic loci newly associated to natural variation in lung function, which may have implications for the related airway diseases of asthma and chronic obstructive pulmonary disease. PMID:20037613

  11. A common cold virus, rhinovirus 16, potentiates airway inflammation after segmental antigen bronchoprovocation in allergic subjects.

    PubMed Central

    Calhoun, W J; Dick, E C; Schwartz, L B; Busse, W W

    1994-01-01

    Many patients with asthma have increased wheezing with colds. We hypothesized that rhinovirus colds might increase asthma by augmenting airway allergic responses (histamine release and eosinophil influx) after antigen challenge. Seven allergic rhinitis patients and five normal volunteers were infected with rhinovirus type 16 (RV16) and evaluated by segmental bronchoprovocation and bronchoalveolar lavage. Segmental challenge with saline and antigen was performed 1 mo before infection, during the acute infection, and 1 mo after infection. Lavage was performed immediately and 48 h after antigen challenge. Data were analyzed by two-way analysis of variance, and a P value of < or = 0.05 was considered to be significant. All volunteers inoculated with RV16 developed an acute respiratory infection. BAL fluid obtained from allergic rhinitis subjects during the acute viral infection, and 1 mo after infection, showed the following significant RV16-associated changes after antigen challenge: (a) an enhanced release of histamine immediately after local antigen challenge; (b) persistent histamine leak 48 h afterwards; and (c) a greater recruitment of eosinophils to the airway 48 h after challenge. These changes were not seen in non-allergic volunteers infected with RV16 and challenged with antigen, nor in allergic volunteers repetitively challenged with antigen but not infected with RV16, nor in RV16 infected allergic volunteers sham challenged with saline. We conclude that rhinovirus upper respiratory infection significantly augments immediate and late allergic responses in the airways of allergic individuals after local antigen challenge. These data suggest that one mechanism of increased asthma during a cold is an accentuation of allergic responses in the airway which may then contribute to bronchial inflammation. PMID:7989575

  12. Allergic disease as an association of steroid sulphatase deficiency.

    PubMed

    Sakura, N; Nishimura, S; Matsumoto, T; Ohsaki, M; Ogata, T

    1997-11-01

    Ten of 31 patients with steroid sulphatase (STS) deficiency were found to have an allergic disease (bronchial asthma, allergic rhinitis, or atopic dermatitis). STS deficiency may predispose patients to allergic disease.

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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.

  19. 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

  20. [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. PMID:27055949

  1. [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.

  2. Role of selective blocking of bradykinin receptor subtypes in attenuating allergic airway inflammation in guinea pigs.

    PubMed

    El-Kady, Mohamed M; Girgis, Zarif I; Abd El-Rasheed, Eman A; Shaker, Olfat; Attallah, Magdy I; Soliman, Ahmed A

    2016-10-01

    The present study was designed to evaluate the potential role of bradykinin antagonists (R-715; bradykinin B1 receptor antagonist and icatibant; bradykinin B2 receptor antagonist) in treatment of allergic airway inflammation in comparison to dexamethasone and montelukast. R-715 as dexamethasone significantly decreased peribronchial leukocyte infiltration, bronchoalveolar lavage fluid (BALF) albumin and interleukin 1β as well as serum OVA-specific IgE level. Also, R-715 like montelukast significantly decreased BALF cell count (total and eosinophils). Icatibant showed negative results. The current findings suggest that selective bradykinin B1 receptor antagonists may have the therapeutic potential for the treatment of allergic airway inflammation. PMID:27321873

  3. Alterations of the Lung Methylome in Allergic Airway Hyper-Responsiveness

    PubMed Central

    Cheng, Robert YS; Shang, Yan; Limjunyawong, Nathachit; Dao, Tyna; Das, Sandhya; Rabold, Richard; Sham, James SK; Mitzner, Wayne; Tang, Wan-Yee

    2014-01-01

    Asthma is a chronic airway disorder characterized by recurrent attacks of breathlessness and wheezing, affecting 300 million people around the world (available at: www.who.int). To date, genetic factors associated with asthma susceptibility have been unable to explain the full etiology of asthma. Recent studies have demonstrated that the epigenetic disruption of gene expression plays an equally important role in the development of asthma through interaction with our environment. We sensitized 6-week-old C57BL/6J mice with house-dust-mite (HDM) extracts intraperitoneally followed by 5 weeks of exposure to HDM challenges (three times a week) intratracheally. HDM-exposed mice showed an increase in airway hyper-responsiveness (AHR) and inflammation together with structural remodeling of the airways. We applied methylated DNA immunoprecipitation-next generation sequencing (MeDIP-seq) for profiling of DNA methylation changes in the lungs in response to HDM. We observed about 20 million reads by a single-run of massive parallel sequencing. We performed bioinformatics and pathway analysis on the raw sequencing data to identify differentially methylated candidate genes in HDM-exposed mice. Specifically, we have revealed that the transforming growth factor beta signaling pathway is epigenetically modulated by chronic exposure to HDM. Here, we demonstrated that a specific allergen may play a role in AHR through an epigenetic mechanism by disrupting the expression of genes in lungs that might be involved in airway inflammation and remodeling. Our findings provide new insights into the potential mechanisms by which environmental allergens induce allergic asthma and such insights may assist in the development of novel preventive and therapeutic options for this debilitative disease. PMID:24446183

  4. Regulatory T cells in allergic diseases.

    PubMed

    Noval Rivas, Magali; Chatila, Talal A

    2016-09-01

    The pathogenesis of allergic diseases entails an ineffective tolerogenic immune response to allergens. Regulatory T (Treg) cells play a key role in sustaining immune tolerance to allergens, yet mechanisms by which Treg cells fail to maintain tolerance in patients with allergic diseases are not well understood. We review current concepts and established mechanisms regarding how Treg cells regulate different components of allergen-triggered immune responses to promote and maintain tolerance. We will also discuss more recent advances that emphasize the "dual" functionality of Treg cells in patients with allergic diseases: how Treg cells are essential in promoting tolerance to allergens but also how a proallergic inflammatory environment can skew Treg cells toward a pathogenic phenotype that aggravates and perpetuates disease. These advances highlight opportunities for novel therapeutic strategies that aim to re-establish tolerance in patients with chronic allergic diseases by promoting Treg cell stability and function. PMID:27596705

  5. Ambient air pollution and allergic diseases in children.

    PubMed

    Kim, Byoung-Ju; Hong, Soo-Jong

    2012-06-01

    The prevalence of allergic diseases has increased worldwide, a phenomenon that can be largely attributed to environmental effects. Among environmental factors, air pollution due to traffic is thought to be a major threat to childhood health. Residing near busy roadways is associated with increased asthma hospitalization, decreased lung function, and increased prevalence and severity of wheezing and allergic rhinitis. Recently, prospective cohort studies using more accurate measurements of individual exposure to air pollution have been conducted and have provided definitive evidence of the impact of air pollution on allergic diseases. Particulate matter and ground-level ozone are the most frequent air pollutants that cause harmful effects, and the mechanisms underlying these effects may be related to oxidative stress. The reactive oxidative species produced in response to air pollutants can overwhelm the redox system and damage the cell wall, lipids, proteins, and DNA, leading to airway inflammation and hyper-reactivity. Pollutants may also cause harmful effects via epigenetic mechanisms, which control the expression of genes without changing the DNA sequence itself. These mechanisms are likely to be a target for the prevention of allergies. Further studies are necessary to identify children at risk and understand how these mechanisms regulate gene-environment interactions. This review provides an update of the current understanding on the impact of air pollution on allergic diseases in children and facilitates the integration of issues regarding air pollution and allergies into pediatric practices, with the goal of improving pediatric health.

  6. Role of Eosinophil Granulocytes in Allergic Airway Inflammation Endotypes.

    PubMed

    Amin, K; Janson, C; Bystrom, J

    2016-08-01

    Eosinophil granulocytes are intriguing members of the innate immunity system that have been considered important defenders during parasitic diseases as well as culprits during allergy-associated inflammatory diseases. Novel studies have, however, found new homoeostasis-maintaining roles for the cell. Recent clinical trials blocking different Th2 cytokines have uncovered that asthma is heterogeneous entity and forms different characteristic endotypes. Although eosinophils are present in allergic asthma with early onset, the cells may not be essential for the pathology. The cells are, however, likely disease causing in asthma with a late onset, which is often associated with chronic rhinosinusitis. Assessment of eosinophilia, fraction exhaled nitric oxide (FeNO) and periostin are markers that have emerged useful in assessing and monitoring asthma severity and endotype. Current scientific knowledge suggests that eosinophils are recruited by the inflammatory environment, activated by the innate interleukin (IL)-33 and prevented from apoptosis by both lymphocytes and innate immune cells such as type two innate immune cells. Eosinophils contain four specific granule proteins that exhibit an array of toxic and immune-modulatory activates. The granule proteins can be released by different mechanisms. Additionally, eosinophils contain a number of inflammatory cytokines and lipid mediators as well as radical oxygen species that might contribute to the disease both by the recruitment of other cells and the direct damage to supporting cells, leading to exacerbations and tissue fibrosis. This review aimed to outline current knowledge how eosinophils are recruited, activated and mediate damage to tissues and therapies used to control the cells. PMID:27167590

  7. Targeted inhibition of KCa3.1 channel attenuates airway inflammation and remodeling in allergic asthma.

    PubMed

    Yu, Zhi-Hua; Xu, Jian-Rong; Wang, Yan-Xia; Xu, Guang-Ni; Xu, Zu-Peng; Yang, Kai; Wu, Da-Zheng; Cui, Yong-Yao; Chen, Hong-Zhuan

    2013-06-01

    KCa3.1 has been suggested to be involved in regulating cell activation, proliferation, and migration in multiple cell types, including airway inflammatory and structural cells. However, the contributions of KCa3.1 to airway inflammation and remodeling and subsequent airway hyperresponsiveness (AHR) in allergic asthma remain to be explored. The main purpose of this study was to elucidate the roles of KCa3.1 and the potential therapeutic value of KCa3.1 blockers in chronic allergic asthma. Using real-time PCR, Western blotting, or immunohistochemical analyses, we explored the precise role of KCa3.1 in the bronchi of allergic mice and asthmatic human bronchial smooth muscle cells (BSMCs). We found that KCa3.1 mRNA and protein expression were elevated in the bronchi of allergic mice, and double labeling revealed that up-regulation occurred primarily in airway smooth muscle cells. Triarylmethane (TRAM)-34, a KCa3.1 blocker, dose-dependently inhibited the generation and maintenance of the ovalbumin-induced airway inflammation associated with increased Th2-type cytokines and decreased Th1-type cytokine, as well as subepithelial extracellular matrix deposition, goblet-cell hyperplasia, and AHR in a murine model of asthma. Moreover, the pharmacological blockade and gene silencing of KCa3.1, which was evidently elevated after mitogen stimulation, suppressed asthmatic human BSMC proliferation and migration, and arrested the cell cycle at the G0/G1 phase. In addition, the KCa3.1 activator 1-ethylbenzimidazolinone-induced membrane hyperpolarization and intracellular calcium increase in asthmatic human BSMCs were attenuated by TRAM-34. We demonstrate for the first time an important role for KCa3.1 in the pathogenesis of airway inflammation and remodeling in allergic asthma, and we suggest that KCa3.1 blockers may represent a promising therapeutic strategy for asthma.

  8. 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

  9. HIF-1 expression is associated with CCL2 chemokine expression in airway inflammatory cells: implications in allergic airway inflammation

    PubMed Central

    2012-01-01

    Background The pathogenesis of allergic airway inflammation in asthmatic patients is complex and characterized by cellular infiltrates and activity of many cytokines and chemokines. Both the transcription factor hypoxia inducible factor-1 (HIF-1) and chemokine CCL2 have been shown to play pivotal roles in allergic airway inflammation. The interrelationship between these two factors is not known. We hypothesized that the expression of HIF-1 and CCL2 may be correlated and that the expression of CCL2 may be under the regulation of HIF-1. Several lines of evidence are presented to support this hypothesis. Methods The effects of treating wild-type OVA (ovalbumin)-sensitized/challenged mice with ethyl-3,4-dihydroxybenzoate (EDHB), which upregulate HIF, on CCL2 expression, were determined. Mice conditionally knocked out for HIF-1β was examined for their ability to mount an allergic inflammatory response and CCL2 expression in the lung after intratracheal exposure to ovalbumin. The association of HIF-1α and CCL2 levels was also measured in endobronchial biopsies and bronchial fluid of asthma patients after challenge. Results We show that both HIF-1α and CCL2 were upregulated during an OVA (ovalbumin)-induced allergic response in mice. The levels of HIF-1α and CCL2 were significantly increased following treatment with a pharmacological agent which upregulates HIF-1α, ethyl-3,4-dihydroxybenzoate (EDHB). In contrast, the expression levels of HIF-1α and CCL2 were decreased in the lungs of mice that have been conditionally knocked out for ARNT (HIF-1β) following sensitization with OVA when compared to levels in wild type mice. In asthma patients, the levels of HIF-1α and CCL2 increased after challenge with the allergen. Conclusions These data suggest that CCL2 expression is regulated, in part, by HIF-1 in the lung. These findings also demonstrate that both CCL2 and HIF-1 are implicated in the pathogenesis of allergic airway inflammation. PMID:22823210

  10. SYNTHETIC COPPER-CONTAINING PARTICLES ENHANCE ALLERGIC AIRWAY RESPONSES IN MICE

    EPA Science Inventory

    SYNTHETIC COPPER-CONTAINING PARTICLES ENHANCE ALLERGIC AIRWAY RESPONSES IN MICE. SH Gavett, MI Gilmour, and N Haykal-Coates. National Health and Environ Effects Research Lab, USEPA, Res Triangle Park, NC USA
    Respiratory morbidity and mortality associated with increases in ...

  11. Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma

    PubMed Central

    Folestad, Erika; Rowley, Jessica E.; Noll, Elisa M.; Walker, Simone A.; Lloyd, Clare M.; Rankin, Sara M.; Pietras, Kristian; Eriksson, Ulf; Fuxe, Jonas

    2015-01-01

    Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma. PMID:25637607

  12. Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma.

    PubMed

    Johnson, Jill R; Folestad, Erika; Rowley, Jessica E; Noll, Elisa M; Walker, Simone A; Lloyd, Clare M; Rankin, Sara M; Pietras, Kristian; Eriksson, Ulf; Fuxe, Jonas

    2015-04-01

    Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma. PMID:25637607

  13. 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

  14. 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.

  15. The inflammatory nature of allergic disease.

    PubMed

    Durham, S R

    1998-12-01

    The allergic inflammatory response in allergic rhinitis has been studied extensively owing to the high frequency of the condition, the significant morbidity it causes and the accessibility of the nasal tissue. The allergic inflammatory response is characterized by IgE synthesis, IgE-dependent mast cell activation and infiltration of the nasal mucosa by T lymphocytes and eosinophils. The immediate-phase response is mediated by a range of inflammatory mediators (such as histamine, leukotrienes and prostaglandins), resulting in vasodilatation, oedema, mucus secretion, itching and sneezing. Individuals who experience a late-phase response have further nasal symptoms 4-24 h after the initial challenge with allergen. Results of nasal biopsy studies indicate that the late-phase allergic response involves T-lymphocyte activation, production of TH2-type cytokines and tissue eosinophilia. Corticosteroids potently inhibit T-lymphocyte responses, and clinical studies in subjects with allergic rhinitis have demonstrated that they are extremely effective in blocking both early- and late-phase allergic reactions. Topical aqueous triamcinolone acetonide nasal spray represents a novel formulation of a topical corticosteroid for the treatment of allergic rhinitis. Data from controlled clinical studies indicate that it is effective in treating seasonal and perennial disease, is well tolerated, does not suppress adrenocortical function, is odourless, and can be administered as a once-daily dose. PMID:9988430

  16. Allergic Disease and Autoimmune Effectors Pathways

    PubMed Central

    Rottem, Menachem; Gershwin, M. Eric; Shoenfeld, Yehuda

    2002-01-01

    Allergy and autoimmunity result from dysregulation of the immune system. Until recently, it was generally accepted that the mechanisms that govern these disease processes are quite disparate; however, new discoveries suggest possible common pathogenetic effector pathways. This review illustrates the concomitant presentation of these conditions and the potential relationship or common mechanism in some cases, by looking at the key elements that regulate the immune response in both allergic and autoimmunite conditions: mast cells, antibodies, T cells, cytokines, and genetic determinants. The parallel appearance of allergic and autoimmune conditions in the some patients may reveal that such aberrations of the immune system have a common pathophysiologic mechanism. Mast cells, which play a key role in allergic reactions, and the wealth of inflammatory mediators they express, make it likely that they have profound effects on many autoimmune processes. Activation of protein kinases by inflammatory cytokines and environmental stresses may contribute to both allergic and autoimmune diseases. The presence of autoantibodies in some allergic conditions suggests an autoimmune basis for these conditions. Because of the central role T cells play in immune reactivity, the T-cell receptor (TCR) loci have long been considered important candidates for common disease susceptibility within the immune system such as asthma, atopy, and autoimmunity. Immunomodulation is the key to a successful treatment of allergic and autoimmune conditions. PMID:12885156

  17. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported.

  18. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported. PMID:27090934

  19. 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.

  20. 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. ...

  1. Hyaluronan fragments as mediators of inflammation in allergic pulmonary disease

    PubMed Central

    Ghosh, Sumit; Hoselton, Scott A.; Dorsam, Glenn P.; Schuh, Jane M.

    2015-01-01

    Asthma is frequently caused and/or exacerbated by sensitization to allergens, which are ubiquitous in many indoor and outdoor environments. Severe asthma is characterized by airway hyperresponsiveness and bronchial constriction in response to an inhaled allergen, leading to a disease course that is often very difficult to treat with standard asthma therapies. As a result of interactions among inflammatory cells, structural cells, and the intercellular matrix of the allergic lung, patients with sensitization to allergens may experience a greater degree of tissue injury followed by airway wall remodeling and progressive, accumulated pulmonary dysfunction as part of the disease sequela. In addition, turnover of extracellular matrix (ECM) components is a hallmark of tissue injury and repair. This review focuses on the role of the glycosaminoglycan hyaluronan (HA), a component of the ECM, in pulmonary injury and repair with an emphasis on allergic asthma. Both the synthesis and degradation of the ECM are critical contributors to tissue repair and remodeling. Fragmented HA accumulates during tissue injury and functions in ways distinct from the larger native polymer. There is gathering evidence that HA degradation products are active participants in stimulating the expression of inflammatory genes in a variety of immune cells at the injury site. In this review, we will consider recent advances in the understanding of the mechanisms that are associated with HA accumulation and inflammatory cell recruitment in the asthmatic lung. PMID:25582403

  2. 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

  3. 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

  4. Epigenetic regulation of asthma and allergic disease

    PubMed Central

    2014-01-01

    Epigenetics of asthma and allergic disease is a field that has expanded greatly in the last decade. Previously thought only in terms of cell differentiation, it is now evident the epigenetics regulate many processes. With T cell activation, commitment toward an allergic phenotype is tightly regulated by DNA methylation and histone modifications at the Th2 locus control region. When normal epigenetic control is disturbed, either experimentally or by environmental exposures, Th1/Th2 balance can be affected. Epigenetic marks are not only transferred to daughter cells with cell replication but they can also be inherited through generations. In animal models, with constant environmental pressure, epigenetically determined phenotypes are amplified through generations and can last up to 2 generations after the environment is back to normal. In this review on the epigenetic regulation of asthma and allergic diseases we review basic epigenetic mechanisms and discuss the epigenetic control of Th2 cells. We then cover the transgenerational inheritance model of epigenetic traits and discuss how this could relate the amplification of asthma and allergic disease prevalence and severity through the last decades. Finally, we discuss recent epigenetic association studies for allergic phenotypes and related environmental risk factors as well as potential underlying mechanisms for these associations. PMID:24932182

  5. Precision medicine in patients with allergic diseases: Airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology.

    PubMed

    Muraro, Antonella; Lemanske, Robert F; Hellings, Peter W; Akdis, Cezmi A; Bieber, Thomas; Casale, Thomas B; Jutel, Marek; Ong, Peck Y; Poulsen, Lars K; Schmid-Grendelmeier, Peter; Simon, Hans-Uwe; Seys, Sven F; Agache, Ioana

    2016-05-01

    In this consensus document we summarize the current knowledge on major asthma, rhinitis, and atopic dermatitis endotypes under the auspices of the PRACTALL collaboration platform. PRACTALL is an initiative of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology aiming to harmonize the European and American approaches to best allergy practice and science. Precision medicine is of broad relevance for the management of asthma, rhinitis, and atopic dermatitis in the context of a better selection of treatment responders, risk prediction, and design of disease-modifying strategies. Progress has been made in profiling the type 2 immune response-driven asthma. The endotype driven approach for non-type 2 immune response asthma, rhinitis, and atopic dermatitis is lagging behind. Validation and qualification of biomarkers are needed to facilitate their translation into pathway-specific diagnostic tests. Wide consensus between academia, governmental regulators, and industry for further development and application of precision medicine in management of allergic diseases is of utmost importance. Improved knowledge of disease pathogenesis together with defining validated and qualified biomarkers are key approaches to precision medicine. PMID:27155030

  6. Precision medicine in patients with allergic diseases: Airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology.

    PubMed

    Muraro, Antonella; Lemanske, Robert F; Hellings, Peter W; Akdis, Cezmi A; Bieber, Thomas; Casale, Thomas B; Jutel, Marek; Ong, Peck Y; Poulsen, Lars K; Schmid-Grendelmeier, Peter; Simon, Hans-Uwe; Seys, Sven F; Agache, Ioana

    2016-05-01

    In this consensus document we summarize the current knowledge on major asthma, rhinitis, and atopic dermatitis endotypes under the auspices of the PRACTALL collaboration platform. PRACTALL is an initiative of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology aiming to harmonize the European and American approaches to best allergy practice and science. Precision medicine is of broad relevance for the management of asthma, rhinitis, and atopic dermatitis in the context of a better selection of treatment responders, risk prediction, and design of disease-modifying strategies. Progress has been made in profiling the type 2 immune response-driven asthma. The endotype driven approach for non-type 2 immune response asthma, rhinitis, and atopic dermatitis is lagging behind. Validation and qualification of biomarkers are needed to facilitate their translation into pathway-specific diagnostic tests. Wide consensus between academia, governmental regulators, and industry for further development and application of precision medicine in management of allergic diseases is of utmost importance. Improved knowledge of disease pathogenesis together with defining validated and qualified biomarkers are key approaches to precision medicine.

  7. Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation.

    PubMed

    Polte, Tobias; Petzold, Susanne; Bertrand, Jessica; Schütze, Nicole; Hinz, Denise; Simon, Jan C; Lehmann, Irina; Echtermeyer, Frank; Pap, Thomas; Averbeck, Marco

    2015-07-13

    Syndecan-4 (SDC4), expressed on dendritic cells (DCs) and activated T cells, plays a crucial role in DC motility and has been shown as a potential target for activated T-cell-driven diseases. In the present study, we investigate the role of SDC4 in the development of T-helper 2 cell-mediated allergic asthma. Using SDC4-deficient mice or an anti-SDC4 antibody we show that the absence or blocking of SDC4 signalling in ovalbumin-sensitized mice results in a reduced asthma phenotype compared with control animals. Most importantly, even established asthma is significantly decreased using the anti-SDC4 antibody. The disturbed SDC4 signalling leads to an impaired motility and directional migration of antigen-presenting DCs and therefore, to a modified sensitization leading to diminished airway inflammation. Our results demonstrate that SDC4 plays an important role in asthma induction and indicate SDC4 as possible target for therapeutic intervention in this disease.

  8. Adam8 Limits the Development of Allergic Airway Inflammation in Mice

    PubMed Central

    Knolle, Martin D.; Nakajima, Takahiro; Hergrueter, Anja; Gupta, Kushagra; Polverino, Francesca; Craig, Vanessa J.; Fyfe, Susanne E.; Zahid, Muhammad; Permaul, Perdita; Cernadas, Manuela; Montano, Gilbert; Tesfaigzi, Yohannes; Sholl, Lynette; Kobzik, Lester; Israel, Elliot; Owen, Caroline A.

    2013-01-01

    To determine whether a disintegrin and a metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyper-responsiveness (AHR), we compared AAI and AHR in wild type (WT) versus Adam8−/− mice in different genetic backgrounds sensitized and challenged with ovalbumin (OVA) or house dust mite protein extract (HDM). OVA- and HDM-treated Adam8−/− mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some TH2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8’s anti-inflammatory activities in murine airways. Airway eosinophils and macrophages both expressed Adam8 in WT mice with AAI. Adam8 limited AAI and AHR in mice by reducing leukocyte survival because: 1) Adam8−/− mice with AAI had fewer apoptotic eosinophils and macrophages in their airways than WT mice with AAI; and 2) Adam8−/− macrophages and eosinophils had reduced rates of apoptosis compared with WT leukocytes when the intrinsic (but not the extrinsic) apoptosis pathway was triggered in the cells in vitro. ADAM8 was robustly expressed by airway granulocytes in lung sections from human asthma patients but, surprisingly, airway macrophages had less ADAM8 staining than airway eosinophils. Thus, ADAM8 has anti-inflammatory activities during AAI in mice by activating the intrinsic apoptosis pathway in myeloid leukocytes. Strategies that increase ADAM8 levels in myeloid leukocytes may have therapeutic efficacy in asthma. PMID:23670189

  9. Differences in airway reactivity in normal and allergic sheep after exposure to sulfur dioxide

    SciTech Connect

    Abraham, W.M.; Oliver, W. Jr.; Welker, M.J.; King, M.M.; Wanner, A.; Sackner, M.A.

    1981-12-01

    The effect of breathing 5 ppm sulfur dioxide (SO/sub 2/) on airway reactivity was studied in both normal and allergic conscious sheep. Allergic sheep were defined as animals in which inhalation of Axcaris suum extract resulted in bronchospasm as evidenced by an increase in mean pulmonary flow resistance (RL), hyperinflation, and a fall in dynamic compliance. Airway reactivity was assessed by measuring the increase of RL after 18 breaths of 0.25% carbachol (c), from an initial RL value obtained after 18 breaths of buffered saline (s) (RL(c-s)). RL and RL(c-s) were determined prior to, immediately after, and 24 h after exposure to 5 ppm SO/sub 2/ for 4 h. In both groups RL remained unchanged after SO/sub 2/ exposure. Prior to exposure, RL(c-s) was not significantly different in seven normal (0.3 +/- 0.1) and seven allergic sheep (0.4 +/- 0.2 (SD) cmH/sub 2/O.l/sup -1/.s), and there was no significant change in RL (c-s) immediately after SO/sub 2/ exposure in either group. Twenty-four h later, RL(c-s) RL(c-s) increased to 0.7 +/- 0.8 (P < 0.2) in normal and to 1.8 +/- 0.9 cmH/sub 2/O.l/sup -1/.s (P < 0.01) in allergic sheep. Because the increase in RL(c-s) after 24 h was greater (P < 0.01) in allergic than in normal sheep, we conclude that SO/sub 2/ exposure increased airway reactivity more in the former than in the latter.

  10. Intranasal sirna targeting c-kit reduces airway inflammation in experimental allergic asthma.

    PubMed

    Wu, Wei; Chen, Hui; Li, Ya-Ming; Wang, Sheng-Yu; Diao, Xin; Liu, Kai-Ge

    2014-01-01

    Allergic asthma is characterized by airway inflammation caused by infiltration and activation of inflammatory cells that produce cytokines. Many studies have revealed that c-kit, a proto-oncogene, and its ligand, stem cell factor (SCF), play an important role in the development of asthmatic inflammation. Intranasal small interference RNA (siRNA) nanoparticles targeting specific viral gene could inhibit airway inflammation. In this study, we assessed whether silencing of c-kit with intranasal small interference RNA could reduce inflammation in allergic asthma. A mouse model of experimental asthma was treated with intranasal administration of anti-c-kit siRNA to inhibit the expression of the c-kit gene. We assessed the inflammatory response in both anti-c-kit siRNA-treated and control mice. Local administration of siRNA effectively inhibited the expression of the c-kit gene and reduced airway mucus secretion and the infiltration of eosinophils in bronchoalveolar lavage fluid. Moreover, c-kit siRNA reduced the production of SCF, interleukin-4 (IL-4), and IL-5, but had no effect on interferon-γ (IFN-γ) generation. These results show that intranasal siRNA nanoparticles targeting c-kit can decrease the inflammatory response in experimental allergic asthma.

  11. CARMA3 Is Critical for the Initiation of Allergic Airway Inflammation.

    PubMed

    Causton, Benjamin; Ramadas, Ravisankar A; Cho, Josalyn L; Jones, Khristianna; Pardo-Saganta, Ana; Rajagopal, Jayaraj; Xavier, Ramnik J; Medoff, Benjamin D

    2015-07-15

    Innate immune responses to allergens by airway epithelial cells (AECs) help initiate and propagate the adaptive immune response associated with allergic airway inflammation in asthma. Activation of the transcription factor NF-κB in AECs by allergens or secondary mediators via G protein-coupled receptors (GPCRs) is an important component of this multifaceted inflammatory cascade. Members of the caspase recruitment domain family of proteins display tissue-specific expression and help mediate NF-κB activity in response to numerous stimuli. We have previously shown that caspase recruitment domain-containing membrane-associated guanylate kinase protein (CARMA)3 is specifically expressed in AECs and mediates NF-κB activation in these cells in response to stimulation with the GPCR agonist lysophosphatidic acid. In this study, we demonstrate that reduced levels of CARMA3 in normal human bronchial epithelial cells decreases the production of proasthmatic mediators in response to a panel of asthma-relevant GPCR ligands such as lysophosphatidic acid, adenosine triphosphate, and allergens that activate GPCRs such as Alternaria alternata and house dust mite. We then show that genetically modified mice with CARMA3-deficient AECs have reduced airway eosinophilia and proinflammatory cytokine production in a murine model of allergic airway inflammation. Additionally, we demonstrate that these mice have impaired dendritic cell maturation in the lung and that dendritic cells from mice with CARMA3-deficient AECs have impaired Ag processing. In conclusion, we show that AEC CARMA3 helps mediate allergic airway inflammation, and that CARMA3 is a critical signaling molecule bridging the innate and adaptive immune responses in the lung. PMID:26041536

  12. 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...

  13. Inhaled multiwalled carbon nanotubes potentiate airway fibrosis in murine allergic asthma.

    PubMed

    Ryman-Rasmussen, Jessica P; Tewksbury, Earl W; Moss, Owen R; Cesta, Mark F; Wong, Brian A; Bonner, James C

    2009-03-01

    Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m(3)) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-beta1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-beta1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-beta1, which stimulates collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT.

  14. Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma

    PubMed Central

    Ryman-Rasmussen, Jessica P.; Tewksbury, Earl W.; Moss, Owen R.; Cesta, Mark F.; Wong, Brian A.; Bonner, James C.

    2009-01-01

    Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m3) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-β1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-β1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-β1, which stimulates collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT. PMID:18787175

  15. Nrf2 reduces allergic asthma in mice through enhanced airway epithelial cytoprotective function.

    PubMed

    Sussan, Thomas E; Gajghate, Sachin; Chatterjee, Samit; Mandke, Pooja; McCormick, Sarah; Sudini, Kuladeep; Kumar, Sarvesh; Breysse, Patrick N; Diette, Gregory B; Sidhaye, Venkataramana K; Biswal, Shyam

    2015-07-01

    Asthma development and pathogenesis are influenced by the interactions of airway epithelial cells and innate and adaptive immune cells in response to allergens. Oxidative stress is an important mediator of asthmatic phenotypes in these cell types. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and environmental stress. We previously demonstrated that Nrf2-deficient mice have heightened susceptibility to asthma, including elevated oxidative stress, inflammation, mucus, and airway hyperresponsiveness (AHR) (Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas SN, Biswal S. J Exp Med 202: 47-59, 2005). Here we dissected the role of Nrf2 in lung epithelial cells and tested whether genetic or pharmacological activation of Nrf2 reduces allergic asthma in mice. Cell-specific activation of Nrf2 in club cells of the airway epithelium significantly reduced allergen-induced AHR, inflammation, mucus, Th2 cytokine secretion, oxidative stress, and airway leakiness and increased airway levels of tight junction proteins zonula occludens-1 and E-cadherin. In isolated airway epithelial cells, Nrf2 enhanced epithelial barrier function and increased localization of zonula occludens-1 to the cell surface. Pharmacological activation of Nrf2 by 2-trifluoromethyl-2'-methoxychalone during the allergen challenge was sufficient to reduce allergic inflammation and AHR. New therapeutic options are needed for asthma, and this study demonstrates that activation of Nrf2 in lung epithelial cells is a novel potential therapeutic target to reduce asthma susceptibility.

  16. Allergic rhinoconjunctivitis: burden of disease.

    PubMed

    Blaiss, Michael S

    2007-01-01

    Even though there is no mortality associated with allergic rhinoconjunctivitis (AR), there is significant morbidity in sufferers of this condition. The exact number of patients with AR is difficult to ascertain, with studies showing ranges from 9 to 42% of the population. Recently, the Allergies in America survey found that 14.2% of the adult U.S. population has been diagnosed with AR. It is well established that AR has a profound influence on the patient's quality of life. Not only do people with AR complain of rhinorrhea, nasal congestion, sneezing, itching, and associated eye problems disturbing, but they also have impaired emotional wellbeing and social functioning. Costs are a major burden in AR studies showing at least $6 billion/year. Although most attention related to costs in AR have been evaluating direct costs due to physician consultation and medical treatment, it is now clear that indirect costs are a major aspect of total costs in AR, especially for American businesses. Indirect costs include absenteeism from work or school because of illness and decreased productivity when at work or presenteeism. AR should be treated seriously by the medical community. Proper treatment of AR patients should not only greatly improve their quality of life, but also bring down health care costs, especially indirect ones, associated with this condition. PMID:17883905

  17. Abietic acid attenuates allergic airway inflammation in a mouse allergic asthma model.

    PubMed

    Gao, Yi; Zhaoyu, Liu; Xiangming, Fang; Chunyi, Lin; Jiayu, Pan; Lu, Shen; Jitao, Chen; Liangcai, Chen; Jifang, Liu

    2016-09-01

    Abietic acid (AA), one of the terpenoids isolated from Pimenta racemosa var. grissea, has been reported to have anti-inflammatory and immunomodulatory effects. However, the anti-allergic effects of AA remain unclear. The aim of this study was to investigate the anti-allergic effects of AA in an ovalbumin (OVA)-induced asthma murine model. The model of mouse asthma was established by induction of OVA. AA (10, 20, 40mg/kg) was administered by oral gavage 1h after the OVA treatment on days 21 to 23. At 24h after the last challenge, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to assess pathological changes, cytokines production, and NF-κB expression. The results showed that AA attenuated lung histopathologic changes, inflammatory cells infiltration, and bronchial hyper-responsiveness. AA also inhibited OVA-induced the nitric oxide (NO), IL-4, IL-5, IL-13, and OVA-specific IgE production, as well as NF-κB activation. In conclusion, the current study demonstrated that AA exhibited protective effects against OVA-induced allergic asthma in mice and the possible mechanism was involved in inhibiting NF-κB activation. PMID:27318791

  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. 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. PMID:24504215

  20. Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-κB.

    PubMed

    Goh, Fera Y; Upton, Nadine; Guan, Shouping; Cheng, Chang; Shanmugam, Muthu K; Sethi, Gautam; Leung, Bernard P; Wong, W S Fred

    2012-03-15

    Persistent activation of nuclear factor-κB (NF-κB) has been associated with the development of asthma. Fisetin (3,7,3',4'-tetrahydroxyflavone), a naturally occurring bioactive flavonol, has been shown to inhibit NF-κB activity. We hypothesized that fisetin may attenuate allergic asthma via negative regulation of the NF-κB activity. Female BALB/c mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Fisetin dose-dependently inhibited ovalbumin-induced increases in total cell count, eosinophil count, and IL-4, IL-5 and IL-13 levels recovered in bronchoalveolar lavage fluid. It attenuated ovalbumin-induced lung tissue eosinophilia and airway mucus production, mRNA expression of adhesion molecules, chitinase, IL-17, IL-33, Muc5ac and inducible nitric oxide synthase in lung tissues, and airway hyperresponsiveness to methacholine. Fisetin blocked NF-κB subunit p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of ovalbumin-challenged mice. In normal human bronchial epithelial cells, fisetin repressed TNF-α-induced NF-κB-dependent reporter gene expression. Our findings implicate a potential therapeutic value of fisetin in the treatment of asthma through negative regulation of NF-κB pathway.

  1. 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. PMID:19032550

  2. Invasive versus noninvasive measurement of allergic and cholinergic airway responsiveness in mice

    PubMed Central

    Glaab, Thomas; Ziegert, Michaela; Baelder, Ralf; Korolewitz, Regina; Braun, Armin; Hohlfeld, Jens M; Mitzner, Wayne; Krug, Norbert; Hoymann, Heinz G

    2005-01-01

    Background This study seeks to compare the ability of repeatable invasive and noninvasive lung function methods to assess allergen-specific and cholinergic airway responsiveness (AR) in intact, spontaneously breathing BALB/c mice. Methods Using noninvasive head-out body plethysmography and the decrease in tidal midexpiratory flow (EF50), we determined early AR (EAR) to inhaled Aspergillus fumigatus antigens in conscious mice. These measurements were paralleled by invasive determination of pulmonary conductance (GL), dynamic compliance (Cdyn) and EF50 in another group of anesthetized, orotracheally intubated mice. Results With both methods, allergic mice, sensitized and boosted with A. fumigatus, elicited allergen-specific EAR to A. fumigatus (p < 0.05 versus controls). Dose-response studies to aerosolized methacholine (MCh) were performed in the same animals 48 h later, showing that allergic mice relative to controls were distinctly more responsive (p < 0.05) and revealed acute airway inflammation as evidenced from increased eosinophils and lymphocytes in bronchoalveolar lavage. Conclusion We conclude that invasive and noninvasive pulmonary function tests are capable of detecting both allergen-specific and cholinergic AR in intact, allergic mice. The invasive determination of GL and Cdyn is superior in sensitivity, whereas the noninvasive EF50 method is particularly appropriate for quick and repeatable screening of respiratory function in large numbers of conscious mice. PMID:16309547

  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. 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

  5. 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). PMID:24925919

  6. 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).

  7. The Role of Ion Channels to Regulate Airway Ciliary Beat Frequency During Allergic Inflammation.

    PubMed

    Joskova, M; Sutovska, M; Durdik, P; Koniar, D; Hargas, L; Banovcin, P; Hrianka, M; Khazaei, V; Pappova, L; Franova, S

    2016-01-01

    Overproduction of mucus is a hallmark of asthma. The aim of this study was to identify potentially effective therapies for removing excess mucus. The role of voltage-gated (Kir 6.1, KCa 1.1) and store-operated ion channels (SOC, CRAC) in respiratory cilia, relating to the tracheal ciliary beat frequency (CBF), was compared under the physiological and allergic airway conditions. Ex vivo experiments were designed to test the local effects of Kir 6.1, KCa 1.1 and CRAC ion channel modulators in a concentration-dependent manner on the CBF. Cilia, obtained with the brushing method, were monitored by a high-speed video camera and analyzed with ciliary analysis software. In natural conditions, a Kir 6.1 opener accelerated CBF, while CRAC blocker slowed it in a concentration-dependent manner. In allergic inflammation, the effect of Kir 6.1 opener was insignificant, with a tendency to decrease CBF. A cilio-inhibitory effect of a CRAC blocker, while gently reduced by allergic inflammation, remained significant. A KCa 1.1 opener turned out to significantly enhance the CBF under the allergic OVA-sensitized conditions. We conclude that optimally attuned concentration of KCa 1.1 openers or special types of bimodal SOC channel blockers, potentially given by inhalation, might benefit asthma. PMID:27369295

  8. Effects of multi-walled carbon nanotubes on a murine allergic airway inflammation model

    SciTech Connect

    Inoue, Ken-ichiro Koike, Eiko; Yanagisawa, Rie; Hirano, Seishiro; Nishikawa, Masataka; Takano, Hirohisa

    2009-06-15

    The development of nanotechnology has increased the risk of exposure to types of particles other than combustion-derived particles in the environment, namely, industrial nanomaterials. On the other hand, patients with bronchial asthma are sensitive to inhaled substances including particulate matters. This study examined the effects of pulmonary exposure to a type of nano-sized carbon nanotube (multi-walled nanotubes: MWCNT) on allergic airway inflammation in vivo and their cellular mechanisms in vitro. In vivo, ICR mice were divided into 4 experimental groups. Vehicle, MWCNT (50 {mu}g/animal), ovalbumin (OVA), and OVA + MWCNT were repeatedly administered intratracheally. Bronchoalveolar lavage (BAL) cellularity, lung histology, levels of cytokines related to allergic inflammation in lung homogenates/BAL fluids (BALFs), and serum immunoglobulin levels were studied. Also, we evaluated the impact of MWCNT (0.1-1 {mu}g/ml) on the phenotype and function of bone marrow-derived dendritic cells (DC) in vitro. MWCNT aggravated allergen-induced airway inflammation characterized by the infiltration of eosinophils, neutrophils, and mononuclear cells in the lung, and an increase in the number of goblet cells in the bronchial epithelium. MWCNT with allergen amplified lung protein levels of Th cytokines and chemokines compared with allergen alone. MWCNT exhibited adjuvant activity for allergen-specific IgG{sub 1} and IgE. MWCNT significantly increased allergen (OVA)-specific syngeneic T-cell proliferation, particularly at a lower concentration in vitro. Taken together, MWCNT can exacerbate murine allergic airway inflammation, at least partly, via the promotion of a Th-dominant milieu. In addition, the exacerbation may be partly through the inappropriate activation of antigen-presenting cells including DC.

  9. The Therapeutic Potential of Targeting Cytokine Alarmins to Treat Allergic Airway Inflammation.

    PubMed

    Sy, Chandler B; Siracusa, Mark C

    2016-01-01

    Asthma is a heterogeneous disorder that results in recurrent attacks of breathlessness, coughing, and wheezing that affects millions of people worldwide. Although the precise causes of asthma are unclear, studies suggest that a combination of genetic predisposition and environmental exposure to various allergens and pathogens contribute to its development. Currently, the most common treatment to control asthma is a dual combination of β2-adrenergic receptor agonists and corticosteroids. However, studies have shown that some patients do not respond well to these medications, while others experience significant side effects. It is reported that the majority of asthmas are associated with T helper type 2 (TH2) responses. In these patients, allergen challenge initiates the influx of TH2 cells in the airways leading to an increased production of TH2-associated cytokines and the promotion of allergy-induced asthma. Therefore, biologics that target this pathway may provide an alternative method to treat the allergic airway inflammation associated with asthma. As of now, only two biologics (omalizumab and mepolizumab), which target immunoglobulin E and interleukin-5, respectively, are FDA-approved and being prescribed to asthmatics. However, recent studies have reported that targeting other components of the TH2 response also show great promise. In this review, we will briefly describe the immunologic mechanisms underlying allergic asthma. Furthermore, we will discuss the current therapeutic strategies used to treat asthma including their limitations. Finally, we will highlight the benefits of using biologics to treat asthma-associated allergic airway inflammation with an emphasis on the potential of targeting cytokine alarmins, especially thymic stromal lymphopoietin. PMID:27378934

  10. The Therapeutic Potential of Targeting Cytokine Alarmins to Treat Allergic Airway Inflammation

    PubMed Central

    Sy, Chandler B.; Siracusa, Mark C.

    2016-01-01

    Asthma is a heterogeneous disorder that results in recurrent attacks of breathlessness, coughing, and wheezing that affects millions of people worldwide. Although the precise causes of asthma are unclear, studies suggest that a combination of genetic predisposition and environmental exposure to various allergens and pathogens contribute to its development. Currently, the most common treatment to control asthma is a dual combination of β2-adrenergic receptor agonists and corticosteroids. However, studies have shown that some patients do not respond well to these medications, while others experience significant side effects. It is reported that the majority of asthmas are associated with T helper type 2 (TH2) responses. In these patients, allergen challenge initiates the influx of TH2 cells in the airways leading to an increased production of TH2-associated cytokines and the promotion of allergy-induced asthma. Therefore, biologics that target this pathway may provide an alternative method to treat the allergic airway inflammation associated with asthma. As of now, only two biologics (omalizumab and mepolizumab), which target immunoglobulin E and interleukin-5, respectively, are FDA-approved and being prescribed to asthmatics. However, recent studies have reported that targeting other components of the TH2 response also show great promise. In this review, we will briefly describe the immunologic mechanisms underlying allergic asthma. Furthermore, we will discuss the current therapeutic strategies used to treat asthma including their limitations. Finally, we will highlight the benefits of using biologics to treat asthma-associated allergic airway inflammation with an emphasis on the potential of targeting cytokine alarmins, especially thymic stromal lymphopoietin. PMID:27378934

  11. [Probiotics in allergic diseases of childhood].

    PubMed

    Hauer, A

    2006-08-31

    The increase in allergic diseases in children in the industrialized countries is attributed, among things, to the "exaggerated hygiene" in early childhood typical of western lifestyle, since insufficient microbial exposure in this phase would appear to promote the development of allergies ("hygiene hypothesis"). Experimental data and initial results of clinical studies show that the immune system of infants can be stimulated by the endogenous intestinal flora. Probiotics, (apathogenic organisms present in human intestinal flora) have a very similar effect: Infants at risk of developing atopy, who, in the first 6 months of life received a special probiotic, contracted atopic dermatitis after two years only half as frequently as a control group of infants. Therapeutic effects were also observed in this clinical condition. For no other allergic manifestations have reports so far been published on the successful use of probiotics for prevention or treatment.

  12. 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.

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

    PubMed

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

    2016-01-01

    The root of Polygonum multiflorum (also called He-Shou-Wu in Chinese) is a common herb and medicinal food in Asia used for its anti-aging properties. Our study investigated the therapeutic potential of an extract of the root of Polygonum multiflorum (PME) in allergic asthma by using a mouse model. Feeding of 0.5 and 1 mg/mouse PME inhibited ovalbumin (OVA)-induced allergic asthma symptoms, including airway inflammation, mucus production, and airway hyper-responsiveness (AHR), in a dose-dependent manner. To discern PME's mechanism of action, we examined the profile and cytokine production of inflammatory cells in bronchial alveolar lavage fluid (BALF). We found that eosinophils, the main inflammatory cell infiltrate in the lung of OVA-immunized mice, significantly decreased after PME treatment. Th2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13, eotaxin, and the proinflammatory cytokine tumor necrosis factor (TNF)-[Formula: see text], decreased in PME-treated mice. Elevated mRNA expression of Th2 transcription factor GATA-3 in the lung tissue was also inhibited after oral feeding of PME in OVA-immunized mice. Thus, we conclude that PME produces anti-asthma activity through the inhibition of Th2 cell activation. PMID:26916919

  14. Airborne lipid antigens mobilize resident intravascular NKT cells to induce allergic airway inflammation.

    PubMed

    Scanlon, Seth T; Thomas, Seddon Y; Ferreira, Caroline M; Bai, Li; Krausz, Thomas; Savage, Paul B; Bendelac, Albert

    2011-09-26

    Airborne exposure to microbial cell wall lipids such as lipopolysaccharide triggers innate immune responses that regulate susceptibility to allergic airway inflammation. α-Glycosylceramides represent another widespread class of microbial lipids that directly stimulate innate-like, IL-4- and IL-13-producing, CD1d-restricted NKT cells. In this study, we demonstrate that NKT cells constitutively accumulate and reside in the microvasculature of the mouse lung. After a single airborne exposure to lipid antigen, they promptly extravasate to orchestrate the formation of peribronchiolar and interstitial lymphohistiocytic granulomas containing numerous eosinophils. Concomitant airborne exposure to ovalbumin (OVA) induces the priming of OVA-specific Th2 cells and IgE antibodies by the same dendritic cell coexpressing CD1d and MHC class II. Although NKT cell activation remains confined to the lipid-exposed lung and draining lymph nodes, Th2 cells recirculate and seed the lung of a parabiotic partner, conferring susceptibility to OVA challenge months after the initial exposure, in a manner independent of NKT cells and CD1d. Thus, transient recruitment and activation of lung-resident intravascular NKT cells can trigger long-term susceptibility to allergic airway inflammation.

  15. Oscar Wilde's skin disease: allergic contact dermatitis?

    PubMed

    Nater, J P

    1992-07-01

    During the last years of his life, Oscar Wilde (1856-1900) suffered from a suppurating otitis media as well as from an unidentified skin disease. The eruption was localized to his face, arms, chest and back and itched severely. A new theory is suggested, based on the fact that Wilde almost certainly used a dye to conceal his rapidly graying hair. He sensitized himself to p-phenylenediamine and developed a stubborn allergic contact dermatitis. Patch testing, the only proof of such a diagnosis, had not yet been devised.

  16. Antigen-specific cytotoxic T lymphocytes target airway CD103+ and CD11b+ dendritic cells to suppress allergic inflammation.

    PubMed

    Daniels, N J; Hyde, E; Ghosh, S; Seo, K; Price, K M; Hoshino, K; Kaisho, T; Okada, T; Ronchese, F

    2016-01-01

    Allergic airway inflammation is driven by the recognition of inhaled allergen by T helper type 2 (Th2) cells in the airway and lung. Allergen-specific cytotoxic T lymphocytes (CTLs) can strongly reduce airway inflammation, however, the mechanism of their inhibitory activity is not fully defined. We used mouse models to show that allergen-specific CTLs reduced early cytokine production by Th2 cells in lung, and their subsequent accumulation and production of interleukin (IL)-4 and IL-13. In addition, treatment with specific CTLs also increased the proportion of caspase(+) dendritic cells (DCs) in mediastinal lymph node (MLN), and decreased the numbers of CD103(+) and CD11b(+) DCs in the lung. This decrease required expression of the cytotoxic mediator perforin in CTLs and of the appropriate MHC-antigen ligand on DCs, suggesting that direct CTL-DC contact was necessary. Lastly, lung imaging experiments revealed that in airway-challenged mice XCR1-GFP(+) DCs, corresponding to the CD103(+) DC subset, and XCR1-GFP(-) CD11c(+) cells, which include CD11b(+) DCs and alveolar macrophages, both clustered in the areas surrounding the small airways and were closely associated with allergen-specific CTLs. Thus, allergen-specific CTLs reduce allergic airway inflammation by depleting CD103(+) and CD11b(+) DC populations in the lung, and may constitute a mechanism through which allergic immune responses are regulated.

  17. Effects of airway exposure to di-(2-ethylhexyl) phthalate on allergic rhinitis.

    PubMed

    He, Miao; Inoue, Ken-Ichiro; Yoshida, Seiichi; Tanaka, Michitaka; Takano, Hirohisa; Sun, Guifan; Ichinose, Takamichi

    2013-06-01

    Recent epidemiological studies have suggested a positive link between atopy morbidity and exposure to phthalate esters, which are environmental chemicals mainly involved in house dust. Nevertheless, experimental studies applying several allergic in vivo models (in addition to epidemiological studies) are needed to prove the precise correlation between phthalates and facilitation of the allergic response/pathophysiology. Among the phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) has been widely used in flexible polyvinyl chloride products, including vinyl flooring and wall covering, and has been widely suggested to have immunomodulating potential. In the present study, we examined the effects of airway exposure to DEHP on allergen (ovalbumin: OVA)-induced rhinitis in mice. The repeated administration of OVA via an intranasal route induced nasal inflammation characterized by the infiltration of granulocytes (neutrophils and eosinophils) into the nasal cavity. In this experimental setting, DEHP did not exaggerate OVA-related inflammatory pathology. However, local (nasal) IL-13 levels were significantly higher in mice treated with allergen plus DEHP than with allergen alone. Taken together, phthalate esters including DEHP have the potential to exacerbate the allergic milieu in the nasal system, as well as dermal and respiratory systems. PMID:23672524

  18. 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.

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

    PubMed Central

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

    2016-01-01

    Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyper-reactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics. PMID:25904744

  20. Alveolar macrophages from allergic lungs are not committed to a pro-allergic response and can reduce airway hyperresponsiveness following ex vivo culture

    PubMed Central

    Pouliot, P.; Spahr, A.; Careau, É.; Turmel, V.; Bissonnette, E. Y.

    2016-01-01

    Summary Background We already demonstrated that adoptive transfer of alveolar macrophages (AMs) from non-allergic rats into AM-depleted allergic rats prevents airway hyperresponsiveness (AHR). We also showed that AMs from non-sensitized, but not from sensitized, allergy-prone rats can prevent AHR following allergen challenge in sensitized allergic animals, establishing the importance of rat immunological status on the modulation of AM functions and suggesting that an allergic lung environment alters AM functions. Objective We investigated how the activation of allergic AMs can be modulated to reinstitute them with their capacity to reduce AHR. Methods AMs from sensitized Brown Norway rats were cultured ex vivo for up to 18 h in culture media to deprogram them from the influence of the allergic lung before being reintroduced into the lung of AM-depleted sensitized recipient. AHR and cytokines in bronchoalveolar lavage (BAL) were measured following allergen challenge. AMs stimulated ex vivo with Bacillus Calmette-Guerin(BCG) were used as positive controls as BCG induces a T-helper type 1 activation in AMs. Results AMs ex vivo cultured for 4–18 h reduced AHR to normal level. Interestingly, pro-allergic functions of AMs were dampened by 18 h culture and they reduced AHR even after spending 48 h in an allergic lung microenvironment. Furthermore, transfer of cultured AMs caused an increase in the levels of IFN-γ and IL-12 in BAL when compared with their ovalbumin control. After 18 h of ex vivo culture, AMs expressed reduced levels of TNF, IL-1α, IL-6, and Arginase-2 mRNAs compared with freshly isolated AMs, suggesting that ex vivo culture exempted AMs from lung stimuli that affected their functions. Conclusions There is a significant crosstalk between lung microenvironment and AMs, affecting their functions. It is also the first report showing that sensitized AMs can be modulated ex vivo to reduce lung pro-allergic environment, opening the way to therapies targetting

  1. 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

  2. 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

  3. The impact of diet on asthma and allergic diseases.

    PubMed

    Julia, Valerie; Macia, Laurence; Dombrowicz, David

    2015-05-01

    The incidence of allergic diseases is increasing, both in developed and developing countries, concomitantly with the rise in living standards and the adoption of a 'western lifestyle'. For two decades, the hygiene hypothesis - which proposes that the lack of early childhood exposure to infectious agents increases susceptibility to allergic diseases in later life - provided the conceptual framework for unravelling the mechanisms that could account for the increased incidence of allergic diseases. In this Review, we discuss recent evidence that highlights the role of diet as a key factor influencing immune homeostasis and the development of allergic diseases through a complex interplay between nutrients, their metabolites and immune cell populations. Although further investigations are still required to understand these complex relationships, recent data have established a possible connection between metabolic homeostasis and allergic diseases.

  4. Rapamycin decreases airway remodeling and hyperreactivity in a transgenic model of noninflammatory lung disease.

    PubMed

    Kramer, Elizabeth L; Hardie, William D; Mushaben, Elizabeth M; Acciani, Thomas H; Pastura, Patricia A; Korfhagen, Thomas R; Hershey, Gurjit Khurana; Whitsett, Jeffrey A; Le Cras, Timothy D

    2011-12-01

    Airway hyperreactivity (AHR) and remodeling are cardinal features of asthma and chronic obstructive pulmonary disease. New therapeutic targets are needed as some patients are refractory to current therapies and develop progressive airway remodeling and worsening AHR. The mammalian target of rapamycin (mTOR) is a key regulator of cellular proliferation and survival. Treatment with the mTOR inhibitor rapamycin inhibits inflammation and AHR in allergic asthma models, but it is unclear if rapamycin can directly inhibit airway remodeling and AHR, or whether its therapeutic effects are entirely mediated through immunosuppression. To address this question, we utilized transforming growth factor-α (TGF-α) transgenic mice null for the transcription factor early growth response-1 (Egr-1) (TGF-α Tg/Egr-1(ko/ko) mice). These mice develop airway smooth muscle thickening and AHR in the absence of altered lung inflammation, as previously reported. In this study, TGF-α Tg/Egr-1(ko/ko) mice lost body weight and developed severe AHR after 3 wk of lung-specific TGF-α induction. Rapamycin treatment prevented body weight loss, airway wall thickening, abnormal lung mechanics, and increases in airway resistance to methacholine after 3 wk of TGF-α induction. Increases in tissue damping and airway elastance were also attenuated in transgenic mice treated with rapamycin. TGF-α/Egr-1(ko/ko) mice on doxycycline for 8 wk developed severe airway remodeling. Immunostaining for α-smooth muscle actin and morphometric analysis showed that rapamycin treatment prevented airway smooth muscle thickening around small airways. Pentachrome staining, assessments of lung collagen and fibronectin mRNA levels, indicated that rapamycin also attenuated fibrotic pathways induced by TGF-α expression for 8 wk. Thus rapamycin reduced airway remodeling and AHR, demonstrating an important role for mTOR signaling in TGF-α-induced/EGF receptor-mediated reactive airway disease. PMID:21903885

  5. Rapamycin decreases airway remodeling and hyperreactivity in a transgenic model of noninflammatory lung disease.

    PubMed

    Kramer, Elizabeth L; Hardie, William D; Mushaben, Elizabeth M; Acciani, Thomas H; Pastura, Patricia A; Korfhagen, Thomas R; Hershey, Gurjit Khurana; Whitsett, Jeffrey A; Le Cras, Timothy D

    2011-12-01

    Airway hyperreactivity (AHR) and remodeling are cardinal features of asthma and chronic obstructive pulmonary disease. New therapeutic targets are needed as some patients are refractory to current therapies and develop progressive airway remodeling and worsening AHR. The mammalian target of rapamycin (mTOR) is a key regulator of cellular proliferation and survival. Treatment with the mTOR inhibitor rapamycin inhibits inflammation and AHR in allergic asthma models, but it is unclear if rapamycin can directly inhibit airway remodeling and AHR, or whether its therapeutic effects are entirely mediated through immunosuppression. To address this question, we utilized transforming growth factor-α (TGF-α) transgenic mice null for the transcription factor early growth response-1 (Egr-1) (TGF-α Tg/Egr-1(ko/ko) mice). These mice develop airway smooth muscle thickening and AHR in the absence of altered lung inflammation, as previously reported. In this study, TGF-α Tg/Egr-1(ko/ko) mice lost body weight and developed severe AHR after 3 wk of lung-specific TGF-α induction. Rapamycin treatment prevented body weight loss, airway wall thickening, abnormal lung mechanics, and increases in airway resistance to methacholine after 3 wk of TGF-α induction. Increases in tissue damping and airway elastance were also attenuated in transgenic mice treated with rapamycin. TGF-α/Egr-1(ko/ko) mice on doxycycline for 8 wk developed severe airway remodeling. Immunostaining for α-smooth muscle actin and morphometric analysis showed that rapamycin treatment prevented airway smooth muscle thickening around small airways. Pentachrome staining, assessments of lung collagen and fibronectin mRNA levels, indicated that rapamycin also attenuated fibrotic pathways induced by TGF-α expression for 8 wk. Thus rapamycin reduced airway remodeling and AHR, demonstrating an important role for mTOR signaling in TGF-α-induced/EGF receptor-mediated reactive airway disease.

  6. 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.

  7. [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.

  8. Respiratory effects of air pollution on allergic disease

    SciTech Connect

    Pierson, W.E.; Koenig, J.Q. )

    1992-10-01

    Allergic patients have an increased susceptibility to the adverse effects of both natural and man-made air pollutants. This goes for both indoor and outdoor air pollutants and manifests itself with biochemical, cellular, and pathophysiologic expressions of adverse health effects in allergic individuals. Also occupationally induced allergic diseases will remain very important. This area has been reviewed recently by Cullen et al. Since allergic patients comprise somewhere between 15% and 20% of the population, this increased susceptibility is of crucial importance not only for medical care and research but for legislative and regulatory consideration to protect these vulnerable individuals.108 references.

  9. 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.

  10. 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...

  11. The relationship between autoimmunity and specific immunotherapy for allergic diseases

    PubMed Central

    Bozek, Andrzej; Kołodziejczyk, Krzysztof; Bednarski, Piotr

    2015-01-01

    The aim of this study was to perform a 20-year post-specific immunotherapy (SIT) observational evaluation for an assessment of any manifestations of autoimmune disease or the appearance of autoantibodies in serum. In total, 1,888 patients (902 women and 986 men) were observed. The mean age of the patients was 34.1±12.4 y at the start of the prospective observation after finishing SIT. New incidences of autoimmune disease and/or the presence of autoantibodies in serum were monitored. The SIT group was compared with control groups consisting of allergic patients who had very received SIT and with non-allergic subjects. There were no significant differences in the autoimmune disease prevalence between the allergic patients with or without SIT. However, significantly higher prevalence of 4 different autoimmune diseases (AID) were observed in the non-allergic patients during the same period. Additionally, the incidence of 8 different autoantibodies was significantly higher in non-allergic patients than in control subjects. Hashimoto disease was the most common autoimmune disease observed. The results of this long-term observational study indicated a lack of a significant prevalence of new instances of autoimmune disease during 20 y of observation post-SIT and at a rate lower than that of non-allergic control subjects, suggesting that SIT is safe in this regard in the long term. PMID:26431066

  12. Novel delivery systems for anti-allergic agents: allergic disease and innovative treatments.

    PubMed

    Lopes, Carla M; Coelho, Pedro B; Oliveira, Rita

    2015-01-01

    Anti-allergic agents are used to treat a great variety of diseases which usually involve an inflammation reaction. These compounds act by inhibiting the release and the effects of inflammatory mediators (e.g. histamine) in the target tissue. The purpose of anti-allergy therapy is to deliver the drug to its local of action in a therapeutic concentration, minimizing the undesired side effects. In order to solve some of the anti-allergic agents' physicochemical drawbacks and the limitations associated to conventional pharmaceutical formulations (e.g. poor solubility and absorption, skin permeation, stability), novel drug delivery systems, such as cyclodextrins, liposomes, micelles, microemulsions, nano and microparticles, have been developed. Depending on the allergic condition, several administration routes are used to deliver anti-allergic agents, each with its own disadvantages to overcome. In the literature, there are a vast number of papers concerning novel delivery systems for anti-allergic agents, making it difficult to evaluate the information and the promising outcomes. The aim of the present review article is to compile the recent (i.e. in the new millennium) improvements of novel drug delivery technology focusing on the achievement of anti-allergic therapeutic delivery. The potential intrinsic benefits of these systems will reflect an increased therapeutic adherence and better patients' life quality. A critical prospect of future clinical trial directions will also be discussed. PMID:25895551

  13. Tracking of Inhaled Near-Infrared Fluorescent Nanoparticles in Lungs of SKH-1 Mice with Allergic Airway Inflammation.

    PubMed

    Markus, M Andrea; Napp, Joanna; Behnke, Thomas; Mitkovski, Miso; Monecke, Sebastian; Dullin, Christian; Kilfeather, Stephen; Dressel, Ralf; Resch-Genger, Ute; Alves, Frauke

    2015-12-22

    Molecular imaging of inflammatory lung diseases, such as asthma, has been limited to date. The recruitment of innate immune cells to the airways is central to the inflammation process. This study exploits these cells for imaging purposes within the lung, using inhaled polystyrene nanoparticles loaded with the near-infrared fluorescence dye Itrybe (Itrybe-NPs). By means of in vivo and ex vivo fluorescence reflectance imaging of an ovalbumin-based allergic airway inflammation (AAI) model in hairless SKH-1 mice, we show that subsequent to intranasal application of Itrybe-NPs, AAI lungs display fluorescence intensities significantly higher than those in lungs of control mice for at least 24 h. Ex vivo immunofluorescence analysis of lung tissue demonstrates the uptake of Itrybe-NPs predominantly by CD68(+)CD11c(+)ECF-L(+)MHCII(low) cells, identifying them as alveolar M2 macrophages in the peribronchial and alveolar areas. The in vivo results were validated by confocal microscopy, overlapping tile analysis, and flow cytometry, showing an amount of Itrybe-NP-containing macrophages in lungs of AAI mice significantly larger than that in controls. A small percentage of NP-containing cells were identified as dendritic cells. Flow cytometry of tracheobronchial lymph nodes showed that Itrybe-NPs were negligible in lung draining lymph nodes 24 h after inhalation. This imaging approach may advance preclinical monitoring of AAI in vivo over time and aid the investigation of the role that macrophages play during lung inflammation. Furthermore, it allows for tracking of inhaled nanoparticles and can hence be utilized for studies of the fate of potential new nanotherapeutics.

  14. Weighted Road Density and Allergic Disease in Children at High Risk of Developing Asthma

    PubMed Central

    Hansell, Anna L.; Rose, Nectarios; Cowie, Christine T.; Belousova, Elena G.; Bakolis, Ioannis; Ng, Kitty; Toelle, Brett G.; Marks, Guy B.; Almqvist, plus Catarina; Ampon, Rosario D; Ayer, Julian; Bird, Tessa; Brew, Bronwyn K; Britton, Warwick J; Celermajer, David; Cowell, Christopher T; Crisafulli, Daniele; Criss, Sally; Davis, Stella; Nabil Ezz, Wafaa; Forbes, Samantha; Garden, Frances L; Kemp, Andrew S; Knezevic, Natalia; Krause, William; Leeder, Stephen R; Mellis, Craig M; Mihrshahi, Seema; Neumann, Mark; Peat, Jennifer K; Quinones-Lucio, Andres; Skilton, Michael; Tattam, Anne; Tovey, Euan R; Vanlaar, Carl H.; Vukasin, Nicola; Wainwright, Craig; Webb, Karen L; Weber-Chrysochoou, Christina; Woolcock, Ann J; Zhou, Jie

    2014-01-01

    Background Evidence for an association between traffic-related air pollution and allergic disease is inconsistent, possibly because the adverse effects may be limited to susceptible subgroups and these have not been identified. This study examined children in the Childhood Asthma Prevention Study (CAPS), potentially susceptible to air pollution effects because of a family history of asthma. Methods We examined cross-sectional associations at age eight years between road density within 75 m and 50 m of home address weighted by road type (traffic density), as a proxy for traffic-related air pollution, on the following allergic and respiratory outcomes: skin prick tests (SPTs), total and specific serum IgE, pre- and post-bronchodilator lung function, airway hyperresponsiveness, exhaled NO, and reported asthma and rhinitis. Results Weighted road density was positively associated with allergic sensitisation and allergic rhinitis. Adjusted relative risk (RR) for house dust mite (HDM) positive SPT was 1.25 (95% CI: 1.06–1.48), for detectable house dust mite-specific IgE was 1.19 (95% CI: 1.01–1.41) and for allergic rhinitis was 1.30 (95% CI: 1.03–1.63) per 100 m local road or 33.3 m motorway within 50 m of home. Associations were also seen with small decrements of peak and mid-expiratory flows and increased risk of asthma, current wheeze and rhinitis in atopic children. Conclusion Associations between road density and allergic disease were found in a potentially susceptible subgroup of children at high risk of developing atopy and asthma. PMID:24949625

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

    PubMed Central

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

    2016-01-01

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

  16. [Airway Management in a Patient with Forestier's Disease].

    PubMed

    Kondo, Yuriko; Echigo, Noriyuki; Akata, Mariko; Yokoyama, Kaori; Takasugi, Naoya; Goto, Takahisa

    2016-04-01

    Airway management in a patient with Forestier's disease can be challenging clinically because this disease may cause not only dysphagia but also airway obstruction due to the compression of the pharynx and esophagus caused by the ossification of anterior longitudinal ligament. We report our anesthetic management in a patient with Forestier's disease. Meanwhile, we studied the causes of difficult airway and the most suitable airway device for a patient with this disease from a standpoint of anatomy of upper airway. Our study indicated the possibility that the most suitable airway device differed depending on the actual location of the ossification of anterior longitudinal ligament in the cervical spine and that more prudent airway management would be required if its lesion location extended to upper cervical spine. PMID:27188118

  17. 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

  18. 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

  19. Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin-induced allergic airway inflammation

    PubMed Central

    Zhong, Wenwei; Su, Wen; Zhang, Yanjie; Liu, Qi; Wu, Jinhong; Di, Caixia; Zhang, Zili; Xia, Zhenwei

    2014-01-01

    Antigen-induced allergic airway inflammation is mediated by T helper type 2 (Th2) cells and their cytokines, but the mechanism that initiates the Th2 immunity is not fully understood. Recent studies show that basophils play important roles in initiating Th2 immunity in some inflammatory models. Here we explored the role of basophils in ovalbumin (OVA) -induced airway allergic inflammation in BALB/c mice. We found that OVA sensitization and challenge resulted in a significant increase in the amount of basophils in blood and lung, along with the up-regulation of activation marker of CD200R. However, depletion of basophils with MAR-1 or Ba103 antibody attenuated airway inflammation, represented by the significantly decreased amount of the Th2 subset in spleen and draining lymph nodes, interlukin-4 level in lung and OVA-special immunoglobulin E (sIgE) levels in serum. On the other hand, adoptive transfer of basophils from OVA-challenged lung tissue to naive BALB/c mice provoked the Th2 immune response. In addition, pulmonary basophils from OVA-challenged mice were able to uptake DQ-OVA and express MHC class II molecules and CD40 in vivo, as well as to release interleukin-4 following stimulation by IgE–antigen complexes and promote Th2 polarization in vitro. These findings demonstrate that basophils may participate in Th2 immune responses in antigen-induced allergic airway inflammation and that they do so through facilitating antigen presentation and providing interleukin-4. PMID:24383680

  20. Phenotyping airways disease: an A to E approach.

    PubMed

    Gonem, S; Raj, V; Wardlaw, A J; Pavord, I D; Green, R; Siddiqui, S

    2012-12-01

    The airway diseases asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous conditions with overlapping pathophysiological and clinical features. It has previously been proposed that this heterogeneity may be characterized in terms of five relatively independent domains labelled from A to E, namely airway hyperresponsiveness (AHR), bronchitis, cough reflex hypersensitivity, damage to the airways and surrounding lung parenchyma, and extrapulmonary factors. Airway hyperresponsiveness occurs in both asthma and COPD, accounting for variable day to day symptoms, although the mechanisms most likely differ between the two conditions. Bronchitis, or airway inflammation, may be predominantly eosinophilic or neutrophilic, with different treatments required for each. Cough reflex hypersensitivity is thought to underlie the chronic dry cough out of proportion to other symptoms that can occur in association with airways disease. Structural changes associated with airway disease (damage) include bronchial wall thickening, airway smooth muscle hypertrophy, bronchiectasis and emphysema. Finally, a variety of extrapulmonary factors may impact upon airway disease, including rhinosinusitis, gastroesophageal reflux disease, obesity and dysfunctional breathing. This article discusses the A to E concept in detail and describes how this framework may be used to assess and treat patients with airway diseases in the clinic. PMID:23181785

  1. Schistosoma mansoni Venom Allergen Like Proteins Present Differential Allergic Responses in a Murine Model of Airway Inflammation

    PubMed Central

    Farias, Leonardo Paiva; Rodrigues, Dunia; Cunna, Vinicius; Rofatto, Henrique Krambeck; Faquim-Mauro, Eliana L.; Leite, Luciana C. C.

    2012-01-01

    Background The Schistosoma mansoni Venom-Allergen-Like proteins (SmVALs) are members of the SCP/TAPS (Sperm-coating protein/Tpx-1/Ag5/PR-1/Sc7) protein superfamily, which may be important in the host-pathogen interaction. Some of these molecules were suggested by us and others as potential immunomodulators and vaccine candidates, due to their functional classification, expression profile and predicted localization. From a vaccine perspective, one of the concerns is the potential allergic effect of these molecules. Methodology/Principal Findings Herein, we characterized the putative secreted proteins SmVAL4 and SmVAL26 and explored the mouse model of airway inflammation to investigate their potential allergenic properties. The respective recombinant proteins were obtained in the Pichia pastoris system and the purified proteins used to produce specific antibodies. SmVAL4 protein was revealed to be present only in the cercarial stage, increasing from 0–6 h in the secretions of newly transformed schistosomulum. SmVAL26 was identified only in the egg stage, mainly in the hatched eggs' fluid and also in the secretions of cultured eggs. Concerning the investigation of the allergic properties of these proteins in the mouse model of airway inflammation, SmVAL4 induced a significant increase in total cells in the bronchoalveolar lavage fluid, mostly due to an increase in eosinophils and macrophages, which correlated with increases in IgG1, IgE and IL-5, characterizing a typical allergic airway inflammation response. High titers of anaphylactic IgG1 were revealed by the Passive Cutaneous Anaphylactic (PCA) hypersensitivity assay. Additionally, in a more conventional protocol of immunization for vaccine trials, rSmVAL4 still induced high levels of IgG1 and IgE. Conclusions Our results suggest that members of the SmVAL family do present allergic properties; however, this varies significantly and therefore should be considered in the design of a schistosomiasis vaccine

  2. [Anaesthesia for patients with obstructive airway diseases].

    PubMed

    Groeben, H; Keller, V; Silvanus, M T

    2014-01-01

    Obstructive lung diseases like asthma or chronic obstructive lung diseases have a high prevalence and are one of the four most frequent causes of death. Obstructive lung diseases can be significantly influenced by the choice of anesthetic techniques and anesthetic agents. Basically, the severity of the COPD and the degree of bronchial hyperreactivity will determine the perioperative anesthetic risk. This risk has to be assessed by a thorough preoperative evaluation and will give the rationale on which to decide for the adequate anaesthetic technique. In particular, airway instrumentation can cause severe reflex bronchoconstriction. The use of regional anaesthesia alone or in combination with general anaesthesia can help to avoid airway irritation and leads to reduced postoperative complications. Prophylactic antiobstructive treatment, volatile anesthetics, propofol, opioids, and an adequate choice of muscle relaxants minimize the anesthetic risk, when general anesthesia is required In case, despite all precautions intra-operative bronchospasm occurs, deepening of anaesthesia, repeated administration of beta2-adrenergic agents and parasympatholytics, and a single systemic dose of corticosteroids represent the main treatment options. PMID:24749300

  3. Effects of provinol and its combinations with clinically used antiasthmatics on airway defense mechanisms in experimental allergic asthma.

    PubMed

    Kazimierová, I; Jošková, M; Pecháňová, O; Šutovská, M; Fraňová, S

    2015-01-01

    Our previous studies show that provinol, a polyphenolic compound, has anti-inflammatory activity during allergic inflammation. In the present study we investigated the effects of provinol and its combinations with clinically used antiasthmatics: budesonide or theophylline on airway defense mechanisms during experimental allergic asthma. Separate groups of guinea pigs were treated during the course of 21-day ovalbumin sensitization with provinol (20 mg/kg/day, p.o.), or budesonide (1 mM by inhalation), or theophylline (10 mg/kg/day, i.p.), and with a half-dose combination of provinol+budesonide or provinol+theophylline. Airways defense mechanisms: cough reflex and specific airway resistance (sRaw) were evaluated in vivo. Tracheal smooth muscle reactivity and mucociliary clearance were examined in vitro. The findings were that provinol caused significant decreases in sRaw and in tracheal smooth muscle contractility, a suppression of cough reflex, and positively modulated ciliary beat frequency. The bronchodilatory and antitussive effects of provinol were comparable with those of budesonide and theophylline. Provinol given as add-on treatment significantly potentiated the effects of budesonide or theophylline, although the doses of each were halved. We conclude that provinol not only has bronchodilatory and antitussive effects, but also potentiates similar effects exerted by budesonide and theophylline.

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

    PubMed

    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; Mizrachi Nebenzahl, Yaffa; Porgador, Angel

    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

  5. 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

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

    PubMed Central

    Malmhäll, Carina; Rådinger, Madeleine; Ramos-Ramirez, Patricia; Lu, You; Deák, Tünde; Semitekolou, Maria; Gaga, Mina; Sjöstrand, Margareta; Lötvall, Jan; Bossios, Apostolos

    2016-01-01

    Background B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive. Methods A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF) and their receptors (CD127 and BAFFR, BCMA, TACI, respectively) were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein) and in vitro (colony forming cell assay). Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL) of asthmatic patients and healthy controls. Results Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4) and co-stimulation (CD40, CD86) and are resistant to apoptosis (Bax). Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics. Conclusion Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation. PMID:27513955

  7. Allergic and nonallergic interactions between house dust mite allergens and airway mucosa.

    PubMed

    Roche, N; Chinet, T C; Huchon, G J

    1997-03-01

    Asthma and allergy are extremely frequent diseases, affecting 5-10% and 30% of the population, respectively. The prevalence of asthma has increased in many developed countries, which may be due to several factors, including increased exposure to house dust mite (HDM) allergens. HDM to which humans are most frequently sensitized are Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Euroglyphus maynei. These mites multiply in carpets, bedding and upholstered furniture in a hot and humid atmosphere. The allergens are digestive enzymes of the mites. Several epidemiological studies have shown that an increase in exposure to HDMs is associated with an increase in the prevalence of sensitization and asthma, whereas mite avoidance leads to a decrease in respiratory symptoms of sensitized asthmatic subjects. Sensitized subjects have specific immunoglobulin G and E (IgG and IgE) humoral responses, as well as proliferative T-cell responses to HDM allergens. Experimental exposure to HDM allergens induces bronchoalveolar inflammatory responses, that are characterized by the recruitment and activation of eosinophils, mastocytes, neutrophils, monocytes and lymphocytes. The cysteine protease activity of Der p 1 (a major allergen of D. pteronyssinus) has been shown to increase airway mucosal permeability, and may thereby contribute to the pathogenesis of airway inflammation and hyperresponsiveness by nonimmunological mechanisms. These epidemiological and experimental data support the recommendations for mite avoidance, especially in persons at high risk of developing asthma.

  8. Phosphodiesterase 4B is essential for TH2-cell function and development of airway hyperresponsiveness in allergic asthma

    PubMed Central

    Catherine Jin, S.-L.; Goya, Sho; Nakae, Susumu; Wang, Dan; Bruss, Matthew; Hou, Chiaoyin; Umetsu, Dale; Conti, Marco

    2010-01-01

    Background Cyclic AMP (cAMP) signaling modulates functions of inflammatory cells involved in the pathogenesis of asthma, and type 4 cAMP-specific phosphodiesterases (PDE4s) are essential components of this pathway. Induction of the PDE4 isoform PDE4B is necessary for Toll-like receptor signaling in monocytes and macrophages and is associated with T cell receptor/CD3 in T cells; however, its exact physiological function in the development of allergic asthma remains undefined. Objectives We investigated the role of PDE4B in the development of allergen-induced airway hyperresponsiveness (AHR) and TH2-driven inflammatory responses. Methods Wild-type and PDE4B−/− mice were sensitized and challenged with ovalbumin and AHR measured in response to inhaled methacholine. Airway inflammation was characterized by analyzing leukocyte infiltration and cytokine accumulation in the airways. Ovalbumin-stimulated cell proliferation and TH2 cytokine production were determined in cultured bronchial lymph node cells. Results Mice deficient in PDE4B do not develop AHR. This protective effect was associated with a significant decrease in eosinophils recruitment to the lungs and decreased TH2 cytokine levels in the bronchoalveolar lavage fluid. Defects in T-cell replication, TH2 cytokine production, and dendritic cell migration were evident in cells from the airway-draining lymph nodes. Conversely, accumulation of the TH1 cytokine IFN-γ was not affected in PDE4B−/− mice. Ablation of the orthologous PDE4 gene PDE4A has no impact on airway inflammation. Conclusion By relieving a cAMP-negative constraint, PDE4B plays an essential role in TH2-cell activation and dendritic cell recruitment during airway inflammation. These findings provide proof of concept that PDE4 inhibitors with PDE4B selectivity may have efficacy in asthma treatment. PMID:21047676

  9. Carbon Nanofibers Have IgE Adjuvant Capacity but Are Less Potent Than Nanotubes in Promoting Allergic Airway Responses

    PubMed Central

    Samuelsen, Mari; Marioara, Calin Daniel; Løvik, Martinus

    2013-01-01

    There is a growing concern for the possible health impact of nanoparticles. The main objective of this study was to investigate the allergy-promoting capacity of four different carbon nanofiber (CNF) samples in an injection and an airway mouse model of allergy. Secondly, the potency of the CNF was compared to the previously reported allergy-promoting capacity of carbon nanotubes (CNT) in the airway model. Ultrafine carbon black particles (ufCBP) were used as a positive control. Particles were given together with the allergen ovalbumin (OVA) either by subcutaneous injection into the footpad or intranasally to BALB/cA mice. After allergen booster, OVA-specific IgE, IgG1, and IgG2a in serum were measured. In the airway model, inflammation was determined as influx of inflammatory cells (eosinophils, neutrophils, lymphocytes, and macrophages) and by mediators (MCP-1 and TNF-α present in bronchoalveolar fluid (BALF)). CNF and CNT both increased OVA-specific IgE levels in the two models, but in the airway model, the CNT gave a significantly stronger IgE response than the CNF. Furthermore, the CNT and not the CNF promoted eosinophil lung inflammation. Our data therefore suggest that nanotube-associated properties are particularly potent in promoting allergic responses. PMID:24024193

  10. Essential Role of Nuclear Factor κB in the Induction of Eosinophilia in Allergic Airway Inflammation

    PubMed Central

    Yang, Liyan; Cohn, Lauren; Zhang, Dong-Hong; Homer, Robert; Ray, Anuradha; Ray, Prabir

    1998-01-01

    The molecular mechanisms that contribute to an eosinophil-rich airway inflammation in asthma are unclear. A predominantly T helper 2 (Th2)-type cell response has been documented in allergic asthma. Here we show that mice deficient in the p50 subunit of nuclear factor (NF)- κB are incapable of mounting eosinophilic airway inflammation compared with wild-type mice. This deficiency was not due to a block in T cell priming or proliferation in the p50−/− mice, nor was it due to a defect in the expression of the cell adhesion molecules VCAM-1 and ICAM-1 that are required for the extravasation of eosinophils into the airways. The major defects in the p50−/− mice were the lack of production of the Th2 cytokine interleukin 5 and the chemokine eotaxin, which are crucial for proliferation and for differentiation and recruitment, respectively, of eosinophils into the asthmatic airway. Additionally, the p50−/− mice were deficient in the production of the chemokines macrophage inflammatory protein (MIP)-1α and MIP-1β that have been implicated in T cell recruitment to sites of inflammation. These results demonstrate a crucial role for NF-κB in vivo in the expression of important molecules that have been implicated in the pathogenesis of asthma. PMID:9802985

  11. Incense smoke: clinical, structural and molecular effects on airway disease

    PubMed Central

    Lin, Ta-Chang; Krishnaswamy, Guha; Chi, David S

    2008-01-01

    In Asian countries where the Buddhism and Taoism are mainstream religions, incense burning is a daily practice. A typical composition of stick incense consists of 21% (by weight) of herbal and wood powder, 35% of fragrance material, 11% of adhesive powder, and 33% of bamboo stick. Incense smoke (fumes) contains particulate matter (PM), gas products and many organic compounds. On average, incense burning produces particulates greater than 45 mg/g burned as compared to 10 mg/g burned for cigarettes. The gas products from burning incense include CO, CO2, NO2, SO2, and others. Incense burning also produces volatile organic compounds, such as benzene, toluene, and xylenes, as well as aldehydes and polycyclic aromatic hydrocarbons (PAHs). The air pollution in and around various temples has been documented to have harmful effects on health. When incense smoke pollutants are inhaled, they cause respiratory system dysfunction. Incense smoke is a risk factor for elevated cord blood IgE levels and has been indicated to cause allergic contact dermatitis. Incense smoke also has been associated with neoplasm and extracts of particulate matter from incense smoke are found to be mutagenic in the Ames Salmonella test with TA98 and activation. In order to prevent airway disease and other health problem, it is advisable that people should reduce the exposure time when they worship at the temple with heavy incense smokes, and ventilate their house when they burn incense at home. PMID:18439280

  12. Incense smoke: clinical, structural and molecular effects on airway disease.

    PubMed

    Lin, Ta-Chang; Krishnaswamy, Guha; Chi, David S

    2008-01-01

    In Asian countries where the Buddhism and Taoism are mainstream religions, incense burning is a daily practice. A typical composition of stick incense consists of 21% (by weight) of herbal and wood powder, 35% of fragrance material, 11% of adhesive powder, and 33% of bamboo stick. Incense smoke (fumes) contains particulate matter (PM), gas products and many organic compounds. On average, incense burning produces particulates greater than 45 mg/g burned as compared to 10 mg/g burned for cigarettes. The gas products from burning incense include CO, CO2, NO2, SO2, and others. Incense burning also produces volatile organic compounds, such as benzene, toluene, and xylenes, as well as aldehydes and polycyclic aromatic hydrocarbons (PAHs). The air pollution in and around various temples has been documented to have harmful effects on health. When incense smoke pollutants are inhaled, they cause respiratory system dysfunction. Incense smoke is a risk factor for elevated cord blood IgE levels and has been indicated to cause allergic contact dermatitis. Incense smoke also has been associated with neoplasm and extracts of particulate matter from incense smoke are found to be mutagenic in the Ames Salmonella test with TA98 and activation. In order to prevent airway disease and other health problem, it is advisable that people should reduce the exposure time when they worship at the temple with heavy incense smokes, and ventilate their house when they burn incense at home. PMID:18439280

  13. Incense smoke: clinical, structural and molecular effects on airway disease.

    PubMed

    Lin, Ta-Chang; Krishnaswamy, Guha; Chi, David S

    2008-04-25

    In Asian countries where the Buddhism and Taoism are mainstream religions, incense burning is a daily practice. A typical composition of stick incense consists of 21% (by weight) of herbal and wood powder, 35% of fragrance material, 11% of adhesive powder, and 33% of bamboo stick. Incense smoke (fumes) contains particulate matter (PM), gas products and many organic compounds. On average, incense burning produces particulates greater than 45 mg/g burned as compared to 10 mg/g burned for cigarettes. The gas products from burning incense include CO, CO2, NO2, SO2, and others. Incense burning also produces volatile organic compounds, such as benzene, toluene, and xylenes, as well as aldehydes and polycyclic aromatic hydrocarbons (PAHs). The air pollution in and around various temples has been documented to have harmful effects on health. When incense smoke pollutants are inhaled, they cause respiratory system dysfunction. Incense smoke is a risk factor for elevated cord blood IgE levels and has been indicated to cause allergic contact dermatitis. Incense smoke also has been associated with neoplasm and extracts of particulate matter from incense smoke are found to be mutagenic in the Ames Salmonella test with TA98 and activation. In order to prevent airway disease and other health problem, it is advisable that people should reduce the exposure time when they worship at the temple with heavy incense smokes, and ventilate their house when they burn incense at home.

  14. 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

  15. Epidemiology and current status of allergic rhinitis, asthma, and associated allergic diseases in Korea: ARIA Asia-Pacific workshop report.

    PubMed

    Park, Hae Sim; Choi, Gil Soon; Cho, Joong Sang; Kim, You-Young

    2009-01-01

    The prevalence of allergic rhinitis and asthma has recently increased in Korea, and both conditions are recognized as major chronic respiratory diseases requiring active intervention. The prevalence of rhinitis among asthmatic patients is high, ranging from 60 to 80%, and could seriously affect asthma severity and outcome. We suggest that allergic rhinitis should be properly evaluated in asthmatic patients to achieve better asthma control.

  16. Allergic diseases among children: nutritional prevention and intervention.

    PubMed

    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

  17. 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

  18. Allergic diseases among children: nutritional prevention and intervention.

    PubMed

    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

  19. [Preliminary results of prophylactic program of allergic diseases in children in Lodz district].

    PubMed

    Stelmach, Włodzimierz; Korzeniewska, Aleksandra; Piechota, Mariusz; Podsiadłowicz-Borzecka, Małgorzata; Majak, Paweł; Stelmach, Iwona

    2002-01-01

    Allergic diseases are one of the most important problems in medicine. As a consequence of increased frequency of allergic diseases, negative health, economical and social problems appear. To eliminate these consequences prophylactic programmes are created. In this paper preliminary results of Prophylactic Program of Allergic Diseases in Children in Łodz district in 2000-2001 years is presented. PMID:12884565

  20. 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.

  1. Therapeutic targets in allergic eye disease.

    PubMed

    Bielory, L

    2001-01-01

    The objective of this article is to provide an overview of the present state of treatment of ocular allergy. Immuno-ophthalmology arose in the portion of this past century when investigators uncovered the uniqueness of the lens proteins and that it could induce an immunological response otherwise know as phacoanaphylaxis. Further studies have shown many similarities between the eye and other organ systems, but one of the most profound problems was the spring "catarrh" that involved the eyes and nose, i.e., rhinoconjunctivitis. Treatment over the past 10 years has expanded with the better understanding of the allergic response at the conjunctival surface. Allergen immunotherapy remains a cornerstone of treatment. In fact, the very first report of the use of immunotherapy in 1911 "measured the patient's resistance during experiments ... of pollen extracts to excite a conjunctival reaction" (Noon L, and Cantar BO, Lancet 1572-1573, 1911).

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

    PubMed Central

    Hung, Chien-Ya; Shi, Li-Shian; Wang, Jing-Yao; Tsai, Yu-Cheng; 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. PMID:24386002

  3. The evaluation of allergens and allergic diseases in children.

    PubMed

    Lee, C S; Tang, R B; Chung, R L

    2000-12-01

    Knowing the incidence of allergic diseases and their relationship with allergens is a crucial requirement for therapeutic judgment. We present our experience on the incidence, clinical features and allergens of the allergic diseases detected by multiple allergosorbent chemiluminescent assay (MAST-CLA) in children from 1997 to 1999 at the Taipei Veterans General Hospital. The incidence of bronchial asthma, allergic rhinitis and atopic dermatitis are significantly different when stratified by age groups. Among the enrolled 2008 patients, 980 (48.8%) patients have positive MAST-CLA results. Of these, 562 (57.3%) are male and 418 (42.7%) are female. A significant increase among patients with positive allergens is also found when stratified by age group. Inhalant allergen is the major allergen detected in our patients. House dust mites Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df), cockroaches, feathers, and dog dander show the highest incidence in the 7- to 12-year-old group. In the fungal group, Aspergillus and Penicillium also show a significant difference in the incidence among different age groups. Pollen allergens, on a whole, show significant difference in incidence among different age groups. The food allergen group shows variable significant difference in incidence. Crab, milk, and egg white show the highest significant incidence in the 2- to 6-year-old group. These results suggest that the incidence of allergens detected in allergic diseases varies among different age groups. PMID:11269366

  4. Gender Associated High Body Mass Index in Allergic Diseases

    PubMed Central

    Lokaj-Berisha, Violeta; Gacaferri-Lumezi, Besa; Minci–Bejtullahu, Ganimete; Latifi-Pupovci, Hatixhe; Karahoda–Gjurgjeala, Natyra; Berisha, Naser; Morina, Teuta

    2014-01-01

    BACKGROUND: The increasing prevalence of allergic diseases and atopy is affected by sex, age and lifestyle factors. Obesity and excess weight are reported to be potential risk factors for atopy and specifically for asthma symptoms in children and adults. OBJECTIVE: To assess the relation between body mass index (BMI) and allergic diseases in patients of both genders, as well as association of BMI with atopy in healthy subjects. METHODS: BMI (kg/m2), skin-prick test and total serum immunoglobulin E levels were assessed in 139 subjects: 109 were patients with allergic diseases (M to F ratio was 51:58) and 30 were healthy controls (M to F ratio was 6:24). RESULTS: The study population was grouped into asthma, asthmarhinitis, rhinitis, Urticaria oreczema and controls by BMI and sex. Females with the highest BMI were in asthma and urticaria/eczema group. Males with the highest BMI were in asthmarhinitis and urticariaeczema group. High BMI was associated with atopy in both genders of healthy controls. High levels of total IgE were in male allergic patients. CONCLUSION: High BMI was associated with asthma in females, urticaria/eczema in both genders and atopy in both genders of healthy controls. Higher levels of total IgE were concluded in male patients. PMID:27275199

  5. Indoor air pollution and airway disease.

    PubMed

    Viegi, G; Simoni, M; Scognamiglio, A; Baldacci, S; Pistelli, F; Carrozzi, L; Annesi-Maesano, I

    2004-12-01

    Scientific interest in indoor pollution has been increasing since the second half of the 1980s. Growing scientific evidence has shown that because people generally spend the majority of their time indoors, indoor pollution plays a significant role in affecting health and is thus an important health issue. Indoor environments include dwellings, workplaces, schools and day care centres, bars, discotheques and vehicles. Common indoor pollutants are environmental tobacco smoke, particulate matter, nitrogen dioxide, carbon monoxide, volatile organic compounds and biological allergens. In developing countries, relevant sources of indoor pollution include biomass and coal burning for cooking and heating. Concentrations of these pollutants can be many times higher indoors than outdoors. Indoor air pollution may increase the risk of irritation phenomena, allergic sensitisation, acute and chronic respiratory disorders and lung function impairment. Recent conservative estimates have shown that 1.5-2 million deaths per year worldwide could be attributed to indoor air pollution. Approximately 1 million of these deaths occur in children aged under 5 years due to acute respiratory infections, and significant proportions of deaths occur due to chronic obstructive pulmonary disease and lung cancer in women. Today, indoor air pollution ranks tenth among preventable risk factors contributing to the global burden of disease. Further research is necessary to better evaluate the respiratory health effects of indoor pollution and to implement protective programmes for public health.

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

    PubMed Central

    2010-01-01

    Background Clinical and experimental data suggest that the inflammatory response is impaired in diabetics and can be modulated by insulin. The present study was undertaken to investigate the role of insulin on the early phase of allergic airway inflammation. Methods Diabetic male Wistar rats (alloxan, 42 mg/Kg, i.v., 10 days) and controls were sensitized by s.c. injection of ovalbumin (OA) in aluminium hydroxide 14 days before OA (1 mg/0.4 mL) or saline intratracheal challenge. The following analyses were performed 6 hours thereafter: a) quantification of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC)-1 in the bronchoalveolar lavage fluid (BALF) by Enzyme-Linked Immunosorbent Assay, b) expression of E- and P- selectins on lung vessels by immunohistochemistry, and c) inflammatory cell infiltration into the airways and lung parenchyma. NPH insulin (4 IU, s.c.) was given i.v. 2 hours before antigen challenge. Results Diabetic rats exhibited significant reduction in the BALF concentrations of IL-1β (30%) and TNF-α (45%), and in the lung expression of P-selectin (30%) compared to non-diabetic animals. This was accompanied by reduced number of neutrophils into the airways and around bronchi and blood vessels. There were no differences in the CINC-1 levels in BALF, and E-selectin expression. Treatment of diabetic rats with NPH insulin, 2 hours before antigen challenge, restored the reduced levels of IL-1β, TNF-α and P-selectin, and neutrophil migration. Conclusion Data presented suggest that insulin modulates the production/release of TNF-α and IL-1β, the expression of P- and E-selectin, and the associated neutrophil migration into the lungs during the early phase of the allergic inflammatory reaction. PMID:20667094

  7. 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.

  8. 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 ...

  9. 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

  10. Non-pulmonary allergic diseases and inflammatory bowel disease: A qualitative review

    PubMed Central

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

    2014-01-01

    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. PMID:25170192

  11. Necessary and sufficient role for T helper cells to prevent fungal dissemination in allergic lung disease.

    PubMed

    Porter, Paul C; Roberts, Luz; Fields, Anna; Knight, Morgan; Qian, Yuping; Delclos, George L; Han, Shuhua; Kheradmand, Farrah; Corry, David B

    2011-11-01

    Mucosal immune responses to fungal infection range from T helper type 2 (Th2) cell-directed allergic inflammation to Th1-predominant neutrophilic inflammation, but the mechanisms directing these divergent mucosal immune outcomes and the role of T cells in host defense against mucosal fungal infections are not known. Here we examined the mouse mucosal immune responses to 12 filamentous environmental fungal species over a broad range of exposure doses and determined the requirement of T cells for host defense. For all tested fungi, low-grade conidium exposures induced Th2- and eosinophil-predominant allergic lung disease, whereas higher exposures led to rapid conversion to neutrophil- and Th1 cell-predominant inflammation, a phenomenon we term immune phenotype switching. All fungal exposure doses were further linked to the secretion of interleukin-17A (IL-17A). Fungal infections with Curvularia lunata and Aspergillus fumigatus were typically confined to the airway during allergic inflammation but became locally invasive and disseminated to the brain at higher conidium challenge doses, in association with predominant Th1 responses. Fungal dissemination occurred at relatively low challenge doses with the conidia of Aspergillus fumigatus administered to recombinase activating gene 1 (Rag-1)-deficient mice, which lack B and T cells, but B cell-deficient μMT mice and T helper cell-reconstituted Rag-1-deficient mice were comparable to wild-type mice in preventing fungal dissemination. Our findings demonstrate that Th2 cell-predominant allergic responses followed by immune phenotype switching and fungal dissemination are highly predictable outcomes with progressive fungal infectious burdens and that T helper cell responses are protective against lethal fungal dissemination.

  12. 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.

  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. [The role of immunotherapy in the prevention of allergic diseases].

    PubMed

    Lugović-Mihić, Liborija; Duvancić, Tomislav

    2011-01-01

    Immunotherapy through repeated administration of allergens and augmentation of doses (hyposensibilization) with the purpose of decreasing the severity of type I allergic reactions or even its complete elimination is known already for a longer period of time. This type of therapy is especially beneficial in allergies to Hymenoptera venom, allergic rhinoconjunctivitis, allergic asthma and is implemented in patients with previously proven allergy to appropriate allergens (insects, pollen, house dust mite, pet dander and other). The most common form of therapy is subcutaneous immunotherapy which includes a series of injections containing specific allergens (allergy vaccines) with increasingly larger doses administered subcutaneously during a period of 3-5 years. There are also other forms of immunotherapy (for instance sublingual immunotherapy) although these are less effective. Repetition of the hyposensibilization procedure leads to further reduction in severity of allergy disease in the majority of patients. The efficacy of immunotherapy is also proven by a lower risk of allergic rhinitis patients developing asthma as well as by prevention of new sensibilizations.

  15. Modulation of immune responses by immunotherapy in allergic diseases.

    PubMed

    Cavkaytar, Ozlem; Akdis, Cezmi A; Akdis, Mübeccel

    2014-08-01

    Allergen immunotherapy (AIT) has been used for 100 years and until now different immunoregulatory pathways have been shown to take place in its mechanisms of action. It is characterized by administration of the causative allergen and is shown to be clinically efficient even after discontinuation of therapy particularly in allergic respiratory diseases, bee venom allergy, and food allergy. Generation of antigen/allergen-specific peripheral tolerance is the key mechanism during immunotherapy. It is mediated by development of T and B regulatory cells, IgG4 isotype allergen-specific antibodies and the involvement of multiple suppressor factors, which lead to decreased tissue inflammation, early and late phase responses. Describing novel regulatory mechanisms in the process of immune tolerance induction will help to identify treatment modalities not only for allergic disorders, but also for autoimmune diseases, organ transplantation, chronic infections, and cancer.

  16. Immune responses to airborne fungi and non-invasive airway diseases.

    PubMed

    Vacher, Gaëlle; Niculita-Hirzel, Hélène; Roger, Thierry

    2015-03-01

    Inhalation of fungal particles is a ubiquitous way of exposure to microorganisms during human life; however, this exposure may promote or exacerbate respiratory diseases only in particular exposure conditions and human genetic background. Depending on the fungal species and form, fungal particles can induce symptoms in the lung by acting as irritants, aeroallergens or pathogens causing infection. Some thermophilic species can even act in all these three ways (e.g. Aspergillus, Penicillium), mesophilic species being only involved in allergic and/or non-allergic airway diseases (e.g. Cladosporium, Alternaria, Fusarium). The goal of the present review is to present the current knowledge on the interaction between airborne fungal particles and the host immune system, to illustrate the differences of immune sensing of different fungal species and to emphasise the importance of conducting research on non-conventional mesophilic fungal species. Indeed, the diversity of fungal species we inhale and the complexity of their composition have a direct impact on fungal particle recognition and immune system decision to tolerate or respond to those particles, eventually leading to collateral damages promoting airway pathologies. PMID:25502371

  17. Intranasal Administration of Recombinant Mycobacterium smegmatis Inducing IL-17A Autoantibody Attenuates Airway Inflammation in a Murine Model of Allergic Asthma.

    PubMed

    Xu, Wanting; Chen, Ling; Guo, Sheng; Wu, Liangxia; Zhang, Jianhua

    2016-01-01

    Asthma is a chronic inflammatory disorder, previous studies have shown that IL-17A contributes to the development of asthma, and there is a positive correlation between the level of IL-17A and the severity of disease. Here, we constructed recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS-Ag85a-IL-17a) and evaluated whether it could attenuate allergic airway inflammation, and further investigated the underlying mechanism. In this work, the murine model of asthma was established with ovalbumin, and mice were intranasally vaccinated with rMS-Ag85a-IL-17a. Autoantibody of IL-17A in sera was detected, and the airway inflammatory cells infiltration, the local cytokines and chemokines production and the histopathological changes of lung tissue were investigated. We found that the administration of rMS-Ag85a-IL-17a induced the autoantibody of IL-17A in sera. The vaccination of rMS-Ag85a-IL-17a remarkably reduced the infiltration of inflammatory cells and the secretion of mucus in lung tissue and significantly decreased the numbers of the total cells, eosinophils and neutrophils in BALF. Th1 cells count in spleen, Th1 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and T-bet mRNA in lung tissue were significantly increased with rMS-Ag85a-IL-17a administration. Meanwhile, rMS-Ag85a-IL-17a vaccination markedly decreased Th2 cells count, Th2 cytokine and Th17 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and chemokines mRNA expression in lung tissue. These data confirmed that recombinant Mycobacterium smegmatis in vivo could induce autoantibody of IL-17A, which attenuated asthmatic airway inflammation.

  18. Intranasal Administration of Recombinant Mycobacterium smegmatis Inducing IL-17A Autoantibody Attenuates Airway Inflammation in a Murine Model of Allergic Asthma.

    PubMed

    Xu, Wanting; Chen, Ling; Guo, Sheng; Wu, Liangxia; Zhang, Jianhua

    2016-01-01

    Asthma is a chronic inflammatory disorder, previous studies have shown that IL-17A contributes to the development of asthma, and there is a positive correlation between the level of IL-17A and the severity of disease. Here, we constructed recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS-Ag85a-IL-17a) and evaluated whether it could attenuate allergic airway inflammation, and further investigated the underlying mechanism. In this work, the murine model of asthma was established with ovalbumin, and mice were intranasally vaccinated with rMS-Ag85a-IL-17a. Autoantibody of IL-17A in sera was detected, and the airway inflammatory cells infiltration, the local cytokines and chemokines production and the histopathological changes of lung tissue were investigated. We found that the administration of rMS-Ag85a-IL-17a induced the autoantibody of IL-17A in sera. The vaccination of rMS-Ag85a-IL-17a remarkably reduced the infiltration of inflammatory cells and the secretion of mucus in lung tissue and significantly decreased the numbers of the total cells, eosinophils and neutrophils in BALF. Th1 cells count in spleen, Th1 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and T-bet mRNA in lung tissue were significantly increased with rMS-Ag85a-IL-17a administration. Meanwhile, rMS-Ag85a-IL-17a vaccination markedly decreased Th2 cells count, Th2 cytokine and Th17 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and chemokines mRNA expression in lung tissue. These data confirmed that recombinant Mycobacterium smegmatis in vivo could induce autoantibody of IL-17A, which attenuated asthmatic airway inflammation. PMID:26974537

  19. 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

  20. 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.

  1. Identification of an interleukin 13-induced epigenetic signature in allergic airway inflammation

    PubMed Central

    Ooi, Aik T; Ram, Sonal; Kuo, Alan; Gilbert, Jennifer L; Yan, Weihong; Pellegrini, Matteo; Nickerson, Derek W; Chatila, Talal A; Gomperts, Brigitte N

    2012-01-01

    Epigenetic changes have been implicated in the pathogenesis of asthma. We sought to determine if IL13, a key cytokine in airway inflammation and remodeling, induced epigenetic DNA methylation and miRNAs expression changes in the airways in conjunction with its transcriptional gene regulation. Inducible expression of an IL13 transgene in the airways resulted in significant changes in DNA methylation in 177 genes, most of which were associated with the IL13 transcriptional signature in the airways. A large number of genes whose expression was induced by IL13 were found to have decreased methylation, including those involved in tissue remodeling (Olr1), leukocyte influx (Cxcl3, Cxcl5, CSFr2b), and the Th2 response (C3ar1, Chi3l4). Reciprocally, some genes whose expression was suppressed were found to have increased methylation (e.g. Itga8). In addition, miRNAs were identified with targets for lung development and Wnt signaling, amongst others. These results indicate that IL13 confers an epigenetic methylation and miRNA signature that accompanies its transcriptional program in the airways, which may play a critical role in airway inflammation and remodeling. PMID:22611474

  2. 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

  3. [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.

  4. 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.

  5. Investigating the Effects of Particulate Matter on House Dust Mite and Ovalbumin Allergic Airway Inflammation in Mice.

    PubMed

    Castañeda, Alejandro R; Pinkerton, Kent E

    2016-01-01

    Particulate matter (PM), a component of air pollution, has been shown to enhance allergen-mediated airway hypersensitivity and inflammation. Surprisingly, exposure to PM during the sensitization to allergen is sufficient to produce immunological changes that result in heightened inflammatory effects upon future allergen exposures (challenge) in the absence of PM. This suggests that PM has the ability to modulate the allergic immune response, thereby acting as an adjuvant by enhancing the immunological memory formed during the adaptive immune response; however, the mechanisms through which this occurs remain elusive. Establishing a reproducible animal model to study the PM-mediated immunotoxicological effects that enhance allergy, may provide insights to understand how air pollution activates the immune system and thereby modulates the pathophysiology of asthma. The basic protocol can be used to study various characteristics of air pollution, such as PM size, source, or chemical composition, to help elucidate how such features may affect the allergic response in a mouse model of asthma. Using a BALB/c model of acute exposure (14 days), mice are first sensitized with allergen and PM, and then subsequently challenged with allergen only. The endpoints of this basic protocol include the assessment of inflammation via cells recovered from broncho-alveolar lavage (BAL), histopathological analysis, gene expression profiles, and protein quantification of inflammatory markers. © 2016 by John Wiley & Sons, Inc. PMID:27145110

  6. Investigating the Effects of Particulate Matter on House Dust Mite and Ovalbumin Allergic Airway Inflammation in Mice.

    PubMed

    Castañeda, Alejandro R; Pinkerton, Kent E

    2016-05-04

    Particulate matter (PM), a component of air pollution, has been shown to enhance allergen-mediated airway hypersensitivity and inflammation. Surprisingly, exposure to PM during the sensitization to allergen is sufficient to produce immunological changes that result in heightened inflammatory effects upon future allergen exposures (challenge) in the absence of PM. This suggests that PM has the ability to modulate the allergic immune response, thereby acting as an adjuvant by enhancing the immunological memory formed during the adaptive immune response; however, the mechanisms through which this occurs remain elusive. Establishing a reproducible animal model to study the PM-mediated immunotoxicological effects that enhance allergy, may provide insights to understand how air pollution activates the immune system and thereby modulates the pathophysiology of asthma. The basic protocol can be used to study various characteristics of air pollution, such as PM size, source, or chemical composition, to help elucidate how such features may affect the allergic response in a mouse model of asthma. Using a BALB/c model of acute exposure (14 days), mice are first sensitized with allergen and PM, and then subsequently challenged with allergen only. The endpoints of this basic protocol include the assessment of inflammation via cells recovered from broncho-alveolar lavage (BAL), histopathological analysis, gene expression profiles, and protein quantification of inflammatory markers. © 2016 by John Wiley & Sons, Inc.

  7. [The role of immunoglobulin preparations in treatment of allergic diseases].

    PubMed

    Boznański, Andrzej; Widerska, Alicja

    2002-01-01

    Intravenous immunoglobulin (IVIG) has been used for many years to treat patients with primary immunodeficiencies. More recently, IVIG has been shown to have antiinflammatory activity when used at substantially higher concentrations. A number of studies have examined the efficacy of IVIG in allergic diseases. For patients with severe refractory asthma, sinusitis, atopic dermatitis, and urticaria, IVIG offers an alternative therapy with relatively few side effects. Although the mechanism by which IVIG may attenuate the allergic response is still undetermined, clinical studies have shown that immunoglobulin therapy can decrease serum IgE levels and increase glucocorticoid binding affinity, while in vitro studies have shown that IVIG can decrease T-cell secretion of TH2 cytokines.

  8. Airway Gene Expression in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Steiling, Katrina; Lenburg, Marc E.; Spira, Avrum

    2009-01-01

    Although cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD), only a subset of smokers develops this disease. There is significant clinical, radiographic, and pathologic heterogeneity within smokers who develop COPD that likely reflects multiple molecular mechanisms of disease. It is possible that variations in the individual response to cigarette smoking form the basis for the distinct clinical and molecular phenotypes and variable natural history associated with COPD. Using the biologic premise of a molecular field of airway injury created by cigarette smoking, this response to tobacco exposure can be measured by molecular profiling of the airway epithelium. Noninvasive study of this field effect by profiling airway gene expression in patients with COPD holds important implications for our understanding of disease heterogeneity, early disease detection, and identification of novel disease-modifying therapies. PMID:20008878

  9. 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.

  10. Epidermal RAF prevents allergic skin disease

    PubMed Central

    Raguz, Josipa; Jeric, Ines; Niault, Theodora; Nowacka, Joanna Daniela; Kuzet, Sanya Eduarda; Rupp, Christian; Fischer, Irmgard; Biggi, Silvia; Borsello, Tiziana; Baccarini, Manuela

    2016-01-01

    The RAS pathway is central to epidermal homeostasis, and its activation in tumors or in Rasopathies correlates with hyperproliferation. Downstream of RAS, RAF kinases are actionable targets regulating keratinocyte turnover; however, chemical RAF inhibitors paradoxically activate the pathway, promoting epidermal proliferation. We generated mice with compound epidermis-restricted BRAF/RAF1 ablation. In these animals, transient barrier defects and production of chemokines and Th2-type cytokines by keratinocytes cause a disease akin to human atopic dermatitis, characterized by IgE responses and local and systemic inflammation. Mechanistically, BRAF and RAF1 operate independently to balance MAPK signaling: BRAF promotes ERK activation, while RAF1 dims stress kinase activation. In vivo, JNK inhibition prevents disease onset, while MEK/ERK inhibition in mice lacking epidermal RAF1 phenocopies it. These results support a primary role of keratinocytes in the pathogenesis of atopic dermatitis, and the animals lacking BRAF and RAF1 in the epidermis represent a useful model for this disease. DOI: http://dx.doi.org/10.7554/eLife.14012.001 PMID:27431613

  11. 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.

  12. Epidemiology and disease burden from allergic disease in Scotland: analyses of national databases

    PubMed Central

    Anandan, C; Gupta, R; Simpson, CR; Fischbacher, C; Sheikh, A

    2009-01-01

    Summary Background There are ongoing concerns about the quality of care provided to patients with allergic disorders in Scotland, but there are relatively few reliable data on the overall disease burden. We sought to: (1) describe the incidence, prevalence and outcome of allergic disorders; (2) estimate healthcare burden and costs; and (3) investigate ethnic variations in the epidemiology and outcomes from allergic disorders in Scotland. Methods Data sources: national surveys; primary care data; prescribing and medication data; hospital admissions data and mortality data. Results Allergic disorders are extremely common in Scotland, affecting about one in three of the population at some time in their lives. Incidence was highest for eczema (10.2 per 1000 registered patients). Over 4% of all GP consultations and 1.5% of hospital admissions were for allergic disorders. There were 100 asthma deaths in 2005 (20 per million people). Direct healthcare costs for allergic disorders were an estimated £130 million per year, the majority of these being incurred in primary care and related to asthma. Conclusions Allergic disorders are common in Scotland and given the very high proportion of children now affected, the high disease burden associated with these conditions is likely to persist for many decades. PMID:19797601

  13. Is allergic rhinitis a trivial disease?

    PubMed Central

    Solé, Dirceu; Camelo-Nunes, Inês Cristina; Wandalsen, Gustavo F.; Rosário, Nelson A.; Sarinho, Emanuel C.; ISAAC Group, Brazilian

    2011-01-01

    BACKGROUND: Asthma and rhinitis often coexist, which potentially increases the disease severity and can negatively impact a patients' quality of life. However, there are few reports based on data obtained from the International Study of Asthma and Allergies in Childhood examining asthma severity in combination with rhinitis-related symptoms. OBJECTIVE: To demonstrate whether current rhinitis and current rhinoconjunctivitis are associated with the development of asthma or its increasing severity in Brazilian adolescents. METHODS: The prevalence of current asthma was correlated with the prevalence of current rhinitis and current rhinoconjunctivitis in adolescents (13 to 14 year olds) from 16 Brazilian centers (based on Spearman's rank correlation index). The influence of current rhinitis and current rhinoconjunctivitis on asthma presentation was also evaluated using the chi-squared test and was expressed as odds ratios with 95% confidence intervals (95%CI). RESULTS: A significant positive correlation was observed between the prevalence of current asthma and current rhinitis (rs = 0.82; 95%CI: 0.60–0.93, p<0.0001) and between the prevalence of current asthma and current rhinoconjunctivitis (rs = 0.75; 95%CI: 0.47–0.89, p<0.0001). Current rhinitis was associated with a significantly increased risk of current asthma and of more severe asthma. Similar results were observed for current rhinoconjunctivitis. CONCLUSION: In this epidemiologic study of Brazilian adolescents, the presence of current rhinitis and current rhinoconjunctivitis was associated with a high risk of developing asthma and increased asthma severity. The mutual evaluation of rhinitis and asthma is necessary to establish an adequate treatment plan. PMID:22179162

  14. 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

  15. 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.

  16. The use of antihistamines for the treatment of airway disease.

    PubMed

    Meltzer, E O

    1988-10-27

    This report reviews studies of the use of antihistamines for the treatment of allergic respiratory diseases. The cumulative results indicate that the nonsedative antihistamine terfenadine, given orally at a dosage of 60 mg twice daily, is effective in the treatment of seasonal allergic rhinitis in both adults and children. No major side effects have been reported, and sensitivity to this agent is not decreased after eight weeks of treatment. Preliminary data on the use of antihistamines for the treatment of asthma are also reviewed.

  17. TRP channels and temperature in airway disease-clinical significance.

    PubMed

    Millqvist, Eva

    2015-01-01

    Temperatures above and below what is generally regarded as "comfortable" for the human being have long been known to induce various airway symptoms, especially in combination with exercise in cold climate with temperatures below 0°C, which is naturally since exercise is followed by enhanced ventilation and thus greater amounts of inhaled cold air. The aim was to highlight the knowledge we have today on symptoms from the airways (here also including the eyes) arisen from various temperatures; the mechanisms, the pathophysiology and their clinical significance. The most common eye and airway conditions related to temperature changes are dry eye disease, rhinitis, laryngeal dysfunction, asthma, chronic obstructive pulmonary disease and chronic cough. Transient receptor potential (TRP) ion channels are probably involved in all temperature induced airway symptoms but via different pathways, which are now beginning to be mapped out. In asthma, the most persuasive hypothesis today is that cold-induced asthmatic bronchoconstriction is induced by dehydration of the airway mucosa, from which it follows that provocations with osmotic stimuli like hypertonic saline and mannitol can be used as a surrogate for exercise provocation as well as dry air inhalation. In chronic unexplained cough there seems to be a direct influence of cold air on the TRP ion channels followed by coughing and increased cough sensitivity to inhaled capsaicin. Revelations in the last decades of the ability of several airway TRP ion channels to sense and react to ambient air temperature have opened new windows for the understanding of the pathogenesis in a diversity of airway reactions appearing in many common respiratory diseases. PMID:27227021

  18. Anti-IgE monoclonal antibody (omalizumab) in the treatment of atopic asthma and allergic respiratory diseases.

    PubMed

    D'Amato, Gennaro; Liccardi, Gennaro; Noschese, Paolo; Salzillo, Antonello; D'Amato, Maria; Cazzola, Mario

    2004-09-01

    Since the discovery of immunoglobulin E (IgE) antibodies thirty-six years ago, our understanding of the mechanisms of allergy has improved to such an extent that we can now better differentiate allergy from non-allergic hypersensitivity, and allergic/atopic from intrinsic/non-atopic bronchial asthma. IgE antibodies are crucial immune mediators of airway inflammation in allergic atopic asthma and IgE-mediated hypersensitivity reactions are the likely mechanisms of allergen-induced airway obstruction. In addition, IgE may cause chronic airway inflammation in asthma through effector cells activated via high-affinity (Fcepsilon RI) or low-affinity (Fcepsilon RII) IgE receptors. Therapeutic anti-IgE antibodies able to reduce free IgE levels and to block the binding of IgE to Fcepsilon RI without cross-linking IgE and triggering degranulation of IgE-sensitised cells have been developed. This non-anaphylactogenic anti-IgE monoclonal antibody (rhuMAb-E25; omalizumab) binds IgE at the same site as these antibodies bind Fcepsilon RI and Fcepsilon RII. As a consequence, omalizumab inhibits IgE effector functions by blocking IgE binding to high-affinity receptors on IgE effector cells and does not cause mast cell or basophil activation because it cannot bind to IgE on cell surfaces where the Fcepsilon R1 receptor already masks the anti-IgE epitope. Studies in patients with atopic asthma demonstrated that omalizumab decreases serum IgE levels and allergen-induced bronchoconstriction during both the early and late-phase responses to inhaled allergen. In several clinical controlled trials omalizumab resulted to be able to reduce asthma-related symptoms, to decrease corticosteroid use and to improve quality of life of asthmatic patients. The anti-IgE approach to asthma treatment has several advantages, including concomitant treatment of other IgE-mediated diseases (allergic rhinitis, allergic conjunctivitis, atopic dermatitis and food allergies), a favourable side-effect profile

  19. Asthma and Allergic Diseases in Pregnancy: A Review

    PubMed Central

    2009-01-01

    Asthma and allergic disorders can affect the course and outcome of pregnancy. Pregnancy itself may also affect the course of asthma and related diseases. Optimal management of these disorders during pregnancy is vital to ensure the welfare of the mother and the baby. Specific pharmacological agents for treatment of asthma or allergic diseases must be cautiously selected and are discussed here with respect to safety considerations in pregnancy. Although most drugs do not harm the fetus, this knowledge is incomplete. Any drug may carry a small risk that must be balanced against the benefits of keeping the mother and baby healthy. The goals and principles of management for acute and chronic asthma, rhinitis, and dermatologic disorders are the same during pregnancy as those for asthma in the general population. Diagnosis of allergy during pregnancy should mainly consist of the patient's history and in vitro testing. The assured and well-evaluated risk factors revealed for sensitization in mother and child are very limited, to date, and include alcohol consumption, exposure to tobacco smoke, maternal diet and diet of the newborn, drug usage, and insufficient exposure to environmental bacteria. Consequently, the recommendations for primary and secondary preventive measures are also very limited in number and verification. PMID:21151812

  20. The microbiome in chronic inflammatory airway disease: A threatened species.

    PubMed

    Green, Robin John; Van Niekerk, Andre; Jeevarathnum, Ashley C; Feldman, Charles; Richards On Behalf Of The South African Allergic Rhinitis Working Group, Guy A

    2016-08-01

    The human body is exposed to a multitude of microbes and infectious organisms throughout life. Many of these organisms colonise the skin, gastrointestinal tract (GIT) and airway. We now recognise that this colonisation includes the lower airway, previously thought to be sterile. These colonising organisms play an important role in disease prevention, including an array of chronic inflammatory conditions that are unrelated to infectious diseases. However, new evidence of immune dysregulation suggests that early colonisation, especially of the GITand airway, by pathogenic micro-organisms, has deleterious effects that may contribute to the potential to induce chronic inflammation in young children, which may only express itself in adult life. PMID:27499401

  1. 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

    2016-01-01

    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

  2. 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

  3. 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

  4. Effect of diesel exhaust particles on allergic reactions and airway responsiveness in ovalbumin-sensitized brown Norway rats.

    PubMed

    Dong, Caroline C; Yin, Xuejun J; Ma, Jane Y C; Millecchia, Lyndell; Wu, Zhong-Xin; Barger, Mark W; Roberts, Jenny R; Antonini, James M; Dey, Richard D; Ma, Joseph K H

    2005-11-01

    We have previously demonstrated that exposure to diesel exhaust particles (DEP) prior to ovalbumin (OVA) sensitization in rats reduced OVA-induced airway inflammation. In the present study, Brown Norway rats were first sensitized to OVA (42.3 +/- 5.7 mg/m3) for 30 min on days 1, 8, and 15, then exposed to filtered air or DEP (22.7 +/- 2.5 mg/m3) for 4 h/day on days 24-28, and challenged with OVA on day 29. Airway responsiveness was examined on day 30, and animals were sacrificed on day 31. Ovalbumin sensitization and challenge resulted in a significant infiltration of neutrophils, lymphocytes, and eosinophils into the lung, elevated presence of CD4+ and CD8+ T lymphocytes in lung draining lymph nodes, and increased production of serum OVA-specific immunoglobulin (Ig)E and IgG. Diesel exhaust particles pre-exposure augmented OVA-induced production of allergen-specific IgE and IgG and pulmonary inflammation characterized by marked increases in T lymphocytes and infiltration of eosinophils after OVA challenge, whereas DEP alone did not have these effects. Although OVA-sensitized rats showed modest response to methacholine challenge, it was the combined DEP and OVA exposure that produced significant airway hyperresponsiveness in this animal model. The effect of DEP pre-exposure on OVA-induced immune responses correlated with an interactive effect of DEP with OVA on increased production of reactive oxygen species (ROS) and nitric oxide (NO) by alveolar macrophages (AM) and alveolar type II (ATII) cells, NO levels in bronchoalveolar lavage fluid, the induction of inducible NO synthase expression in AM and ATII cells, and a depletion of total intracellular glutathione (GSH) in AM and lymphocytes. These results show that DEP pre-exposure exacerbates the allergic responses to the subsequent challenge with OVA in OVA-sensitized rats. This DEP effect may be, at least partially, attributed to the elevated generation of ROS in AM and ATII cells, a depletion of GSH in AM and

  5. T cell derived IL-10 is dispensable for tolerance induction in a murine model of allergic airway inflammation.

    PubMed

    Kunz, Stefanie; Dolch, Anja; Surianarayanan, Sangeetha; Dorn, Britta; Bewersdorff, Mayte; Alessandrini, Francesca; Behrendt, Rayk; Karp, Christopher L; Muller, Werner; Martin, Stefan F; Roers, Axel; Jakob, Thilo

    2016-08-01

    Regulatory mechanisms initiated by allergen-specific immunotherapy are mainly attributed to T cell derived IL-10. However, it has not been shown that T cell derived IL-10 is required for successful tolerance induction (TI). Here, we analyze cellular sources and the functional relevance of cell type specific IL-10 during TI in a murine model of allergic airway inflammation. While TI was effective in IL-10 competent mice, neutralizing IL-10 prior to tolerogenic treatment completely abrogated the beneficial effects. Cellular sources of IL-10 during TI were identified by using transcriptional reporter mice as T cells, B cells, and to a lesser extent DCs. Interestingly, TI was still effective in mice with T cell, B cell, B and T cell, or DC-specific IL-10 deficiency. In contrast, TI was not possible in mice lacking IL-10 in all hematopoetic cells, while it was effective in bone marrow (BM) chimera that lacked IL-10 only in nonhematopoetic cells. Taken together, allergen-specific tolerance depends on IL-10 from hematopoetic sources. The beneficial effects of allergen-specific immunotherapy cannot solely be attributed to IL-10 from T cells, B cells, or even DCs, suggesting a high degree of cellular redundancy in IL-10-mediated tolerance. PMID:27287239

  6. Clinical significance of upper airway dysfunction in motor neurone disease.

    PubMed Central

    García-Pachón, E.; Martí, J.; Mayos, M.; Casan, P.; Sanchis, J.

    1994-01-01

    BACKGROUND--To assess the occurrence, functional characteristics and prognostic value of upper airway dysfunction in motor neurone disease, 27 patients unselected for respiratory symptoms were studied. METHODS--Upper airway function was evaluated by analysis of the maximal flow-volume loop. Neurological diagnosis was established from the clinical history and physical examination. The degree of impairment was quantified by the Appel score. RESULTS--Twelve patients (group A) showed abnormalities of the maximal flow-volume loop consistent with flow limitation (seven patients) or instability of upper airway function (gross oscillations of airflow, five patients). The remaining 15 patients (group B) exhibited a normal or generally reduced maximal flow-volume loop, suggestive of muscle weakness. No differences were observed between groups in general physical condition, rate of disease progression, or duration of disease. CONCLUSIONS--Upper airway dysfunction in patients with motor neurone disease was a frequent finding. It was present more often, but not exclusively, in patients with bulbar features and was unrelated to prognosis. PMID:7940430

  7. Pathogenesis of Viral Infection in Exacerbations of Airway Disease.

    PubMed

    Ritchie, Andrew I; Farne, Hugo A; Singanayagam, Aran; Jackson, David J; Mallia, Patrick; Johnston, Sebastian L

    2015-11-01

    Chronic airway diseases are a significant cause of morbidity and mortality worldwide, and their prevalence is predicted to increase in the future. Respiratory viruses are the most common cause of acute pulmonary infection, and there is clear evidence of their role in acute exacerbations of inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease. Studies have reported impaired host responses to virus infection in these diseases, and a better understanding of the mechanisms of these abnormal immune responses has the potential to lead to the development of novel therapeutic targets for virus-induced exacerbations. The aim of this article is to review the current knowledge regarding the role of viruses and immune modulation in acute exacerbations of chronic pulmonary diseases and to discuss exciting areas for future research and novel treatments.

  8. Effects of environmental pollutants on airways, allergic inflammation, and the immune response.

    PubMed

    Handzel, Z T

    2000-01-01

    Particulate and gaseous air pollutants are capable of damaging the airway epithelial lining and of shifting the local immune balance, thereby facilitating the induction of persistent inflammation. Epidemiological studies are inconclusive regarding whether air pollution increases the incidence of asthma and chronic bronchitis in the population. Clearly, environmental pollution can, however, precipitate attacks and emergency-room admissions in those already suffering from such conditions. The catastrophic potential of airborne pollution was demonstrated in the 1960s and 1970s, when inverted atmospheric pressure conditions trapped smog over cities on the Eastern coast of the United States and over Europe. This smog resulted in thousands of hospital admissions and dozens of deaths. With the general rise in the incidence of atopy and asthma in the Western population, it is of major public health interest to reduce, as much as possible, the exposure of such populations to anthropogenic and natural sources of pollution. PMID:11048334

  9. Transfer of allergic airway responses with antigen-primed CD4+ but not CD8+ T cells in brown Norway rats.

    PubMed Central

    Watanabe, A; Mishima, H; Renzi, P M; Xu, L J; Hamid, Q; Martin, J G

    1995-01-01

    Activated CD4+ helper T cells have been demonstrated in asthmatic airways and postulated to play a central role in eliciting allergic inflammation; direct evidence of their involvement seems to be lacking. We hypothesized that CD4+ T cells have the potential to induce allergic responses to antigen challenge, and tested this hypothesis in a model of allergic bronchoconstriction, the Brown Norway rat, using the approach of adoptive transfer. Animals were actively sensitized to either ovalbumin (OVA) or BSA and were used as donors of T cells. W3/25(CD4)+ or OX8(CD8)+ T cells were isolated from the cervical lymph nodes of sensitized donors and transferred to naive BN rats. 2 d after adoptive transfer recipient rats were challenged by OVA inhalation, and changes in lung resistance (RL), bronchoalveolar lavage (BAL) cells, and serum levels of antigen-specific IgE were studied. After OVA challenge recipients of OVA-primed W3/25+ T cells exhibited sustained increases in RL throughout the entire 8-h observation period and had significant bronchoalveolar lavage eosinophilia, which was detected by immunocytochemistry using an antimajor basic protein mAb. Recipients of BSA-primed W3/25+ T cells or OVA-primed OX8+ T cells failed to respond to inhaled OVA. OVA-specific immunoglobulin E was undetectable by ELISA or skin testing in any of the recipient rats after adoptive transfer. In conclusion, antigen-induced airway bronchoconstriction and eosinophilia were successfully transferred by antigen-specific W3/25+ T cells in Brown Norway rats. These responses were dependent on antigen-primed W3/25+ T cells and appeared to be independent of IgE-mediated mast cell activation. This study provides clear evidence for T cell mediated immune mechanisms in allergic airway responses in this experimental model. Images PMID:7657805

  10. [Sensitization to granary mites in patients with allergic diseases].

    PubMed

    Golysheva, M A

    1991-01-01

    As many as 71 patients selected from a group of 550 patients suffering from allergic diseases, sensitized to the house dust mites Dermatophagoides pteronyssinus were examined. A study was made of the presence of allergen-specific IgE antibodies against house dust mites, storage mites (7 species altogether) using allergenic discs and commercial kits RAST (Pharmacia, Sweden). The group under examination mostly manifested sensitization to the house dust mites: Dermatophagoides ferinae (80%), Euroglyphus maynei (55%); storage mites: Acarus siro (45%), Lepidoglyphus destructor (35%). The latter one possesses the most powerful allergenic properties as compared to the acaroid mites of other types. The elevated sensitivity to storage mites is encountered among adults and children living both in Moscow and other regions (urban and rural). The problem of sensitization to storage mites in the USSR mandates thorough studies, which will enable the treatment and diagnostic agents to be designed and introduced into practice.

  11. 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

  12. Dietary prevention of allergic diseases in infants and small children.

    PubMed

    Høst, Arne; Halken, Susanne; Muraro, Antonella; Dreborg, Sten; Niggemann, Bodo; Aalberse, Rob; Arshad, Syed H; von Berg, Andrea; Carlsen, Kai-Håkon; Duschén, Karel; Eigenmann, Philippe A; Hill, David; Jones, Catherine; Mellon, Michael; Oldeus, Göran; Oranje, Arnold; Pascual, Cristina; Prescott, Susan; Sampson, Hugh; Svartengren, Magnus; Wahn, Ulrich; Warner, Jill A; Warner, John O; Vandenplas, Yvan; Wickman, Magnus; Zeiger, Robert S

    2008-02-01

    Because of scientific fraud four trials have been excluded from the original Cochrane meta-analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP-EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi-randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high-quality systematic reviews of high-quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta-analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer-reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer-reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4-6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.

  13. 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

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

    PubMed

    Yang, Hyeon-Jong

    2016-08-01

    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

  15. 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.

  16. Therapy with resveratrol attenuates obesity-associated allergic airway inflammation in mice.

    PubMed

    André, Diana Majolli; Calixto, Marina Ciarallo; Sollon, Carolina; Alexandre, Eduardo Costa; Leiria, Luiz O; Tobar, Natalia; Anhê, Gabriel Forato; Antunes, Edson

    2016-09-01

    Obesity and insulin resistance have been associated with deterioration in asthma outcomes. High oxidative stress and deficient activation of AMP-activated protein kinase (AMPK) have emerged as important regulators linking insulin resistance and inflammation. This study aimed to evaluate the effects of resveratrol on obesity-associated allergic pulmonary inflammation. Male C57/Bl6 mice fed with high-fat diet to induce obesity (obese group) or standard-chow diet (lean group) were treated or not with resveratrol (100mg/kg/day, two weeks). Mice were sensitized and challenged with ovalbumin (OVA). At 48h thereafter, bronchoalveolar lavage fluid was performed, and lungs collected for morphological studies and Western blot analysis. Treatment of obese mice with resveratrol significantly reduced hyperglycemia and insulin resistance, as well as the body measures (body mass, fat mass, % fat, and body area). OVA-challenge promoted a higher increase in pulmonary eosinophil infiltration in obese compared with lean mice, which was nearly abrogated by resveratrol treatment. Resveratrol markedly increased the phosphorylated AMPK expression in lung tissues of obese compared with lean mice. Resveratrol reduced the p47phox expression and reactive-oxygen species (ROS) production, and elevated the superoxide dismutase (SOD) levels in lung tissues of obese mice. The increased pulmonary levels of TNF-α and inducible nitric oxide synthase (iNOS) in obese mice were also normalized after resveratrol treatment. In lean mice, resveratrol failed to affect the levels of fasting glucose, p47phox, ROS levels, TNF-α, iNOS and phosphorylated AMPK. Resveratrol exhibits protective effects in obesity-associated lung inflammation that is accompanied by local AMPK activation and antioxidant property. PMID:27344038

  17. 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.

  18. Characteristic of Inflammatory Airway Disease in Japanese Thoroughbred Racehorses

    PubMed Central

    KUSANO, Kanichi; ISHIKAWA, Yuhiro; SEKI, Kazuhiro; KUSUNOSE, Ryo

    2008-01-01

    Inflammatory airway disease (IAD) is a common cause of poor performance, interruption of training and premature retirement in racehorses. It is also reported that up to 80% of horses are affected at some point in the first years of training in UK and Australia. However, no studies with regard to the information on occurrence of IAD in Japanese Thoroughbred racehorses have been reported. To investigate the occurrence and the characteristics of IAD, epidemic research including endoscopic examination of the airway tract and trachea wash was conducted for Thoroughbred racehorses presenting coughs or poor performance which airway tract disease was suspected stalled in training facility managed by Japan Racing Association. Fifty-six out of 76 Thoroughbred racehorses (73.7%) presenting coughing or poor performance were diagnosed as IAD. Mean incidence rate of IAD was 0.3% and it has been confirmed that constant number of IAD exists in Japan. Up to 35.7% of IAD horses showed upper airway abnormalities in some extent. There was a trend for IAD horses to use wood shavings for bedding and fed hay from the ground compared with the control group. Therefore, improvement of stabling environment may aid in preventing IAD. This study demonstrated that Japanese Thoroughbred racehorses are affected by IAD likewise other countries as well as demonstrated the characteristics of IAD which may contribute to the clarification of the pathogenesis of IAD. PMID:24833952

  19. Effects of climate change on environmental factors in respiratory allergic diseases.

    PubMed

    D'Amato, G; Cecchi, L

    2008-08-01

    A body of evidence suggests that major changes involving the atmosphere and the climate, including global warming induced by human activity, have an impact on the biosphere and the human environment. Studies on the effects of climate change on respiratory allergy are still lacking and current knowledge is provided by epidemiological and experimental studies on the relationship between asthma and environmental factors, such as meteorological variables, airborne allergens and air pollution. However, there is also considerable evidence that subjects affected by asthma are at an increased risk of developing obstructive airway exacerbations with exposure to gaseous and particulate components of air pollution. It is not easy to evaluate the impact of climate change and air pollution on the prevalence of asthma in general and on the timing of asthma exacerbations. However, the global rise in asthma prevalence and severity suggests that air pollution and climate changes could be contributing. Pollen allergy is frequently used to study the interrelationship between air pollution, rhinitis and bronchial asthma. Epidemiological studies have demonstrated that urbanization, high levels of vehicle emissions and westernized lifestyle are correlated to an increase in the frequency of pollen-induced respiratory allergy, prevalent in people who live in urban areas compared with those who live in rural areas. Meteorological factors (temperature, wind speed, humidity, etc.) along with their climatological regimes (warm or cold anomalies and dry or wet periods, etc.), can affect both biological and chemical components of this interaction. In addition, by inducing airway inflammation, air pollution overcomes the mucosal barrier priming allergen-induced responses. In conclusion, climate change might induce negative effects on respiratory allergic diseases. In particular, the increased length and severity of the pollen season, the higher occurrence of heavy precipitation events and the

  20. Evidence for linkage of a new region (11p14) to eczema and allergic diseases

    PubMed Central

    Guilloud-Bataille, Michel; Bouzigon, Emmanuelle; Annesi-Maesano, Isabella; Bousquet, Jean; Charpin, Denis; Gormand, Frédéric; Hochez, Joëlle; Just, Jocelyne; Lemainque, Arnaud; Le Moual, Nicole; Matran, Régis; Neukirch, Françoise; Oryszczyn, Marie-Pierre; Paty, Evelyne; Pin, Isabelle; Vervloet, Daniel; Kauffmann, Francine; Lathrop, Mark; Demenais, Florence; Dizier, Marie-Hélène

    2008-01-01

    SUMMARY Asthma, allergic rhinitis (AR) and atopic dermatitis also called eczema are allergic co-morbidites which are likely to depend on pleiotropic genetic effects as well as on specific genetic factors. After a previous genome-wide linkage screen conducted for asthma and AR in a sample of 295 French EGEA families ascertained through asthmatic subjects, the aim here was to search for genetic factors involved in eczema and more particularly those ones shared by the three allergic diseases using the same EGEA data. In this sake, eczema and phenotypes of ‘allergic disease’ accounting for the joint information on the presence/absence of the three diseases were examined by linkage analyses using the Maximum Likelihood Binomial (MLB) method. A fine mapping was carried out in regions detected for potential linkage, followed by association studies using the Family Based Association Test (FBAT). Evidence for linkage to 11p14 region was shown for ‘allergic disease’ and eczema. Linkage was also indicated between eczema and 5q13 and between ‘allergic disease’ and both 5p15 and 17q21 regions. Fine mapping supported the evidence of linkage to 11p14 and FBAT analyses showed association between ‘allergic disease’ and a marker located at the linkage peak on 11p14. Further investigations in this region will allow identifying genetic factor(s) which could have pleiotropic effect in the three allergic diseases. PMID:17943316

  1. Patterns of airway involvement in inflammatory bowel diseases

    PubMed Central

    Papanikolaou, Ilias; Kagouridis, Konstantinos; Papiris, Spyros A

    2014-01-01

    Extraintestinal manifestations occur commonly in inflammatory bowel diseases (IBD). Pulmonary manifestations (PM) of IBD may be divided in airway disorders, interstitial lung disorders, serositis, pulmonary vasculitis, necrobiotic nodules, drug-induced lung disease, thromboembolic lung disease and enteropulmonary fistulas. Pulmonary involvement may often be asymptomatic and detected solely on the basis of abnormal screening tests. The common embryonic origin of the intestine and the lungs from the primitive foregut, the co-existence of mucosa associated lymphoid tissue in both organs, autoimmunity, smoking and bacterial translocation from the colon to the lungs may all be involved in the pathogenesis of PM in IBD. PM are mainly detected by pulmonary function tests and high-resolution computed tomography. This review will focus on the involvement of the airways in the context of IBD, especially stenoses of the large airways, tracheobronchitis, bronchiectasis, bronchitis, mucoid impaction, bronchial granulomas, bronchiolitis, bronchiolitis obliterans syndrome and the co-existence of IBD with asthma, chronic obstructive pulmonary disease, sarcoidosis and a1-antitrypsin deficiency. PMID:25400999

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

    PubMed Central

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

    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

  3. 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

  4. The effects of pregnancy on the exacerbation and development of maternal allergic respiratory disease.

    PubMed

    Pucheu-Haston, Cherie M; Copeland, Lisa B; Haykal-Coates, Najwa; Ward, Marsha D W

    2009-12-01

    The T-helper 2 (T(H)2) bias associated with pregnancy may predispose the pregnant mother to the development or exacerbation of allergic disease. To determine the effects of pregnancy on pre-existing maternal sensitization, we sensitized BALB/c mice before breeding by two intratracheal aspiration (IA) exposures to the fungal allergen, Metarhizium anisopliae crude antigen (MACA). Some mice also received three IA exposures to MACA on gestational days 11, 15, and 19. After weaning, all mice were challenged IA with MACA before killing. To determine the effects of pregnancy on susceptibility to future sensitization, naïve parous and nulliparous BALB/c mice were sensitized by three IA exposures to MACA or to Hank's buffered salt solution vehicle control. Pregnancy did not have a significant effect on individual inflammatory parameters (airway responsiveness to methacholine, total serum and bronchoalveolar lavage fluid (BALF) IgE, BALF total protein, lactate dehydrogenase activity, and total and differential cell counts) following allergen challenge in sensitized mice, regardless of post-breeding allergen exposure. In conclusion there was a weak inhibition of the overall response in mice exposed to allergen during pregnancy compared to identically treated nulliparous mice. In contrast, parous mice that did not encounter allergen post-breeding tended to have exacerbated responses. Parity had no significant impact on future susceptibility to sensitization. PMID:19845451

  5. Computed Tomographic Airway Morphology in Chronic Obstructive Pulmonary Disease. Remodeling or Innate Anatomy?

    PubMed

    Diaz, Alejandro A; Estépar, Raul San José; Washko, George R

    2016-01-01

    Computed tomographic measures of central airway morphology have been used in clinical, epidemiologic, and genetic investigation as an inference of the presence and severity of small-airway disease in smokers. Although several association studies have brought us to believe that these computed tomographic measures reflect airway remodeling, a careful review of such data and more recent evidence may reveal underappreciated complexity to these measures and limitations that prompt us to question that belief. This Perspective offers a review of seminal papers and alternative explanations of their data in the light of more recent evidence. The relationships between airway morphology and lung function are observed in subjects who never smoked, implying that native airway structure indeed contributes to lung function; computed tomographic measures of central airways such as wall area, lumen area, and total bronchial area are smaller in smokers with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease; and the airways are smaller as disease severity increases. The observations suggest that (1) native airway morphology likely contributes to the relationships between computed tomographic measures of airways and lung function; and (2) the presence of smaller airways in those with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease as well as their decrease with disease severity suggests that smokers with chronic obstructive pulmonary disease may simply have smaller airways to begin with, which put them at greater risk for the development of smoking-related disease.

  6. Obstructive airway disease associated with occupational sodium hydroxide inhalation.

    PubMed Central

    Rubin, A E; Bentur, L; Bentur, Y

    1992-01-01

    Sodium hydroxide (NaOH) is well known for its corrosive properties and its ability to generate heat on contact with water. The respiratory effects of industrial exposure to NaOH have, however, never been reported. A 63 year old man worked daily for 20 years cleaning large industrial jam containers by boiling lye (NaOH) solution without using respiratory protective equipment. Physical examination, chest x ray film, pulmonary function tests, and arterial blood gases were all compatible with severe obstructive airway disease with significant air trapping. It is probable that this massive and prolonged occupational exposure to the corrosive effect of NaOH mists induced irritation and burns to the respiratory system, eventually leading to severe obstructive airway disease. PMID:1554619

  7. 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.

  8. Systems Biology of Asthma and Allergic Diseases: A Multiscale Approach

    PubMed Central

    Bunyavanich, Supinda; Schadt, Eric E.

    2014-01-01

    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. PMID:25468194

  9. 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.

  10. 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. PMID:21459504

  11. Transient receptor potential (TRP) channels in the airway: role in airway disease

    PubMed Central

    Grace, M S; Baxter, M; Dubuis, E; Birrell, M A; Belvisi, M G

    2014-01-01

    Over the last few decades, there has been an explosion of scientific publications reporting the many and varied roles of transient receptor potential (TRP) ion channels in physiological and pathological systems throughout the body. The aim of this review is to summarize the existing literature on the role of TRP channels in the lungs and discuss what is known about their function under normal and diseased conditions. The review will focus mainly on the pathogenesis and symptoms of asthma and chronic obstructive pulmonary disease and the role of four members of the TRP family: TRPA1, TRPV1, TRPV4 and TRPM8. We hope that the article will help the reader understand the role of TRP channels in the normal airway and how their function may be changed in the context of respiratory disease. PMID:24286227

  12. 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.

  13. Lung clearance index in the assessment of airways disease.

    PubMed

    Horsley, Alex

    2009-06-01

    In the last few years there has been a growing interest in lung clearance index (LCI), a measure of lung physiology derived from multiple breath washout tests. This resurgence of interest was initially driven by the recognition that such assessments were capable of detecting early airways disease in children, and are more sensitive and easier to perform in this population than conventional lung function tests [Aurora P, Kozlowska W, Stocks J. Gas mixing efficiency from birth to adulthood measured by multiple-breath washout. Respir Physiol Neurobiol, 2005;148(1-2):125-39]. With an appreciation of the importance of earlier identification of airways dysfunction, and prevention of irreversible structural airway changes, methods of following airways disease in these "silent years" are especially important. LCI has now been reported in studies involving all age groups, from infants to adults [Lum S, Gustafsson P, Ljungberg H, Hulskamp G, Bush A, Carr SB, et al. Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests. Thorax, 2007;62(4):341-7; Horsley AR, Gustafsson PM, Macleod K, Saunders CJ, Greening AP, Porteous D, et al. Lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis. Thorax, 2008;63:135-40], and has a narrow range of normal over this wide age range, making it especially suitable for long-term follow-up studies. In cystic fibrosis (CF) particularly, there is a pressing need for sensitive and repeatable clinical endpoints for therapeutic interventions [Rosenfeld M. An overview of endpoints for cystic fibrosis clinical trials: one size does not fit all. Proc Am Thorac Soc, 2007;4(4):299-301], and LCI has been proposed as an outcome measure in future CF gene therapy studies [Davies JC, Cunningham S, Alton EW, Innes JA. Lung clearance index in CF: a sensitive marker of lung disease severity. Thorax, 2008;63(2):96-7]. This review will consider how LCI is

  14. Role of anti-IgE monoclonal antibody (omalizumab) in the treatment of bronchial asthma and allergic respiratory diseases.

    PubMed

    D'Amato, Gennaro

    2006-03-01

    IgE molecules play a crucial role in allergic respiratory diseases and may cause chronic airway inflammation in asthma through activation of effector cells via high-affinity (FcepsilonRI) or low-affinity (FcepsilonRII) IgE receptors. Since the discovery of IgE antibodies our understanding of the mechanisms of allergy has improved to such an extent that we can differentiate allergic/atopic from intrinsic respiratory diseases. Therapeutic anti-IgE antibodies, able to reduce free IgE levels and to block the binding of IgE to FcepsilonRI without crosslinking IgE and triggering degranulation of IgE-sensitized cells have been developed. This non-anaphylactogenic anti-IgE monoclonal antibody (omalizumab) binds IgE at the same site as these antibodies bind FcepsilonRI and FcepsilonRII. Consequently, omalizumab inhibits IgE effector functions by blocking IgE binding to high-affinity receptors on IgE effector cells and does not cause mast cell or basophil activation because it cannot bind to IgE on cell surfaces where the FcepsilonR1 receptor already masks the anti-IgE epitope. Studies in patients with atopic asthma showed that omalizumab decreases serum IgE levels and allergen-induced bronchoconstriction during both the early and late-phase responses to inhaled allergen. In several clinical controlled trials omalizumab resulted effective in reducing asthma-related symptoms, decreasing corticosteroid use and improving quality of life of asthmatic patients. Recent studies show the benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled by optimal pharmacological therapy. The anti-IgE approach to asthma treatment has several advantages, including concomitant treatment of other IgE-mediated diseases such as allergic rhinitis, a favorable safety profile and a convenient dosing frequency.

  15. Maternal PUFA status and offspring allergic diseases up to the age of 18 months.

    PubMed

    Yu, Ya-Mei; Chan, Yiong-Huak; Calder, Philip C; Hardjojo, Antony; Soh, Shu-E; Lim, Ai Lin; Fisk, Helena L; Teoh, Oon Hoe; Goh, Anne; Saw, Seang-Mei; Kwek, Kenneth; Gluckman, Peter D; Godfrey, Keith M; Chong, Yap-Seng; Shek, Lynette Pei-Chi; Pan, An; Chong, Mary Foong Fong; van Bever, Hugo P S

    2015-03-28

    Studies have suggested that maternal PUFA status during pregnancy may influence early childhood allergic diseases, although findings are inconsistent. We examined the relationship between maternal PUFA status and risk of allergic diseases in early childhood in an Asian cohort. Maternal plasma samples from the Growing Up in Singapore Towards Healthy Outcomes mother-offspring cohort were assayed at 26-28 weeks of gestation for relative abundance of PUFA. Offspring (n 960) were followed up from 3 weeks to 18 months of age, and clinical outcomes of potential allergic diseases (rhinitis, eczema and wheezing) were assessed by repeated questionnaires. Skin prick testing (SPT) was also performed at the age of 18 months. Any allergic disease with positive SPT was defined as having any one of the clinical outcomes plus a positive SPT. The prevalence of a positive SPT, rhinitis, eczema, wheezing and any allergic disease with positive SPT was 14·1 % (103/728), 26·5 % (214/808), 17·6 % (147/833), 10·9 % (94/859) and 9·4 % (62/657), respectively. After adjustment for confounders, maternal total n-3, n-6 PUFA status and the n-6:n-3 PUFA ratio were not significantly associated with offspring rhinitis, eczema, wheezing, a positive SPT and having any allergic disease with positive SPT in the offspring (P>0·01 for all). A weak trend of higher maternal n-3 PUFA being associated with higher risk of allergic diseases with positive SPT in offspring was observed. These findings do not support the hypothesis that the risk of early childhood allergic diseases is modified by variation in maternal n-3 and n-6 PUFA status during pregnancy in an Asian population.

  16. Use of inhaled anticholinergic agents in obstructive airway disease.

    PubMed

    Restrepo, Ruben D

    2007-07-01

    In the last 2 decades, anticholinergic agents have been generally regarded as the first-choice bronchodilator therapy in the routine management of stable chronic obstructive pulmonary disease (COPD) and, to a lesser extent, asthma. Anticholinergics are particularly important bronchodilators in COPD, because the vagal tone appears to be the only reversible component of airflow limitation in COPD. The inhaled anticholinergics approved for clinical use are synthetic quaternary ammonium congeners of atropine, and include ipratropium bromide, oxitropium bromide, and tiotropium bromide. This article reviews the most current evidence for inhaled anticholinergics in obstructive airway disease and summarizes outcomes reported in randomized controlled trials.

  17. Cigarette smoke causes acute airway disease and exacerbates chronic obstructive lung disease in neonatal mice.

    PubMed

    Jia, Jie; Conlon, Thomas M; Ballester Lopez, Carolina; Seimetz, Michael; Bednorz, Mariola; Zhou-Suckow, Zhe; Weissmann, Norbert; Eickelberg, Oliver; Mall, Marcus A; Yildirim, Ali Önder

    2016-09-01

    Epidemiological evidence demonstrates a strong link between postnatal cigarette smoke (CS) exposure and increased respiratory morbidity in young children. However, how CS induces early onset airway disease in young children, and how it interacts with endogenous risk factors, remains poorly understood. We, therefore, exposed 10-day-old neonatal wild-type and β-epithelial sodium ion channel (β-ENaC)-transgenic mice with cystic fibrosis-like lung disease to CS for 4 days. Neonatal wild-type mice exposed to CS demonstrated increased numbers of macrophages and neutrophils in the bronchoalveolar lavage fluid (BALF), which was accompanied by increased levels of Mmp12 and Cxcl1 BALF from β-ENaC-transgenic mice contained greater numbers of macrophages, which did not increase following acute CS exposure; however, there was significant increase in airway neutrophilia compared with filtered air transgenic and CS-exposed wild-type controls. Interestingly, wild-type and β-ENaC-transgenic mice demonstrated epithelial airway and vascular remodeling following CS exposure. Morphometric analysis of lung sections revealed that CS exposure caused increased mucus accumulation in the airway lumen of neonatal β-ENaC-transgenic mice compared with wild-type controls, which was accompanied by an increase in the number of goblet cells and Muc5ac upregulation. We conclude that short-term CS exposure 1) induces acute airway disease with airway epithelial and vascular remodeling in neonatal wild-type mice; and 2) exacerbates airway inflammation, mucus hypersecretion, and mucus plugging in neonatal β-ENaC-transgenic mice with chronic lung disease. Our results in neonatal mice suggest that young children may be highly susceptible to develop airway disease in response to tobacco smoke exposure, and that adverse effects may be aggravated in children with underlying chronic lung diseases. PMID:27448665

  18. [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. PMID:25996328

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

    PubMed Central

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

    2015-01-01

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

  20. 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

  1. Assessment of airway inflammation by exhaled breath condensate and impedance due to gastroesophageal reflux disease (GERD).

    PubMed

    Shimizu, Yasuo; Dobashi, Kunio; Nagoshi, Atsuto; Kawamura, Osamu; Mori, Masatomo

    2009-09-01

    Avoiding oxidative stress in the airways is important for the treatment of respiratory disease associated with gastroesophageal reflux disease (GERD). It is often difficult to decide whether GERD is causing airway inflammation or whether an airway disease is complicated by GERD. Measurement of exhaled breath condensate (EBC) is performed by cooling and collecting the airway lining fluid contained in exhaled air. A decrease of pH and an increase of the 8-isoprostane concentration in EBC have been observed in patients with mild to moderate asthma accompanied by GERD. There are still problems to be overcome before EBC can be used clinically, but pH and 8-isoprostane may be promising objective markers of airway inflammation due to GERD. The disease concept and diagnosis of GERD are constantly advancing, including the development of impedance methods. It is expected that treatment will be based on the latest diagnostic knowledge of GERD associated with respiratory disease and on monitoring of airway inflammation.

  2. Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice.

    PubMed

    Mall, Marcus; Grubb, Barbara R; Harkema, Jack R; O'Neal, Wanda K; Boucher, Richard C

    2004-05-01

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in defective epithelial cAMP-dependent Cl(-) secretion and increased airway Na(+) absorption. The mechanistic links between these altered ion transport processes and the pathogenesis of cystic fibrosis lung disease, however, are unclear. To test the hypothesis that accelerated Na(+) transport alone can produce cystic fibrosis-like lung disease, we generated mice with airway-specific overexpression of epithelial Na(+) channels (ENaC). Here we show that increased airway Na(+) absorption in vivo caused airway surface liquid (ASL) volume depletion, increased mucus concentration, delayed mucus transport and mucus adhesion to airway surfaces. Defective mucus transport caused a severe spontaneous lung disease sharing features with cystic fibrosis, including mucus obstruction, goblet cell metaplasia, neutrophilic inflammation and poor bacterial clearance. We conclude that increasing airway Na(+) absorption initiates cystic fibrosis-like lung disease and produces a model for the study of the pathogenesis and therapy of this disease. PMID:15077107

  3. T cell treatment with small interfering RNA for suppressor of cytokine signaling 3 modulates allergic airway responses in a murine model of asthma.

    PubMed

    Moriwaki, Atsushi; Inoue, Hiromasa; Nakano, Takako; Matsunaga, Yuko; Matsuno, Yukiko; Matsumoto, Takafumi; Fukuyama, Satoru; Kan-O, Keiko; Matsumoto, Koichiro; Tsuda-Eguchi, Miyuki; Nagakubo, Daisuke; Yoshie, Osamu; Yoshimura, Akihiko; Kubo, Masato; Nakanishi, Yoichi

    2011-04-01

    CD4(+) T cells, particularly T helper (Th) 2 cells, play a pivotal role in the pathophysiology of allergic asthma. Suppressor of cytokine signaling (SOCS) proteins control the balance of CD4(+) T cell differentiation. Mice that lack SOCS3 in T cells by crossing SOCS3-floxed mice with Lck-Cre-transgenic mice have reduced allergen-induced eosinophilia in the airways. Here, we studied the effects of SOCS3 silencing with small interfering (si) RNA in primary CD4(+) T cells on Th2 cell differentiation and on asthmatic responses in mice. Th2 cells were generated from ovalbumin (OVA)-specific T cell receptor-transgenic mice in vitro and transferred into recipient mice. Transfection of SOCS3-specific siRNA attenuated Th2 response in vitro. Adoptive transfer of SOCS3-siRNA T cells exhibited markedly suppressed airway hyperresponsiveness and eosinophilia after OVA challenge, with a concomitant decrease in OVA-specific CD4(+) T cell accumulation in the airways. To investigate the mechanism of this impaired CD4(+) T cell accumulation, we inactivated SOCS3 of T cells by crossing SOCS3-floxed (SOCS3(flox/flox)) mice with CD4-Cre transgenic mice. CD4-Cre × SOCS3(flox/flox) mice exhibited fewer IL-4-producing cells and more reduced eosinophil infiltration in bronchoalveolar lavage fluids than control mice in a model of OVA-induced asthma. Expression of CCR3 and CCR4 in CD4(+) T cells was decreased in CD4-Cre × SOCS3(flox/flox) mice. CCR4 expression was also decreased in CD4(+) T cells after transfer of SOCS3 siRNA-treated T cells. These findings suggest that the therapeutic modulation of SOCS3 expression in CD4(+) T cells might be effective in preventing the development of allergic asthma.

  4. [Clinical diagnosis and treatment of allergic pharyngitis].

    PubMed

    Liu, Jinfeng; Yan, Zhanfeng; Zhang, Mingxia

    2015-08-01

    Although the concept of united airway disease has been widely accepted, most scholars emphasize only the effect of rhino-sinusitis while ignoring the pharyngeal factors to the lower airway, especially to the allergic pharyngitis (AP), which still lacks enough awareness. First of all, absence of unified diagnostic standard leads to the lack of epidemiological data, which, results in doctors' personal experience but no guideline in treatments. In addition, it is still not clear that the role of AP in the allergic airway diseases and its relationship with asthma. However, the number of patients with AP has been increasing obviously in daily clinic practice. Combined with the previous observation, this paper does a systematic review about the clinical problems of AP, expecting to give a hand to the clinical diagnosis and treatment of AP. PMID:26685417

  5. Recent advances in understanding inflammation and remodeling in the airways in chronic obstructive pulmonary disease.

    PubMed

    Sohal, Sukhwinder Singh; Ward, Chris; Danial, Wan; Wood-Baker, Richard; Walters, Eugene Haydn

    2013-06-01

    The authors have reviewed the current literature on airway inflammation and remodeling in smoking-related chronic obstructive pulmonary disease (COPD). Detailed data on airway remodeling in COPD are especially sparse and how these changes lead to decline in lung function is not well understood. Small airway fibrosis and obliteration are likely to be the main contributors to physiological airway dysfunction and occur earlier than any subsequent development of emphysema. One potential mechanism contributing to small airway fibrosis/obliteration and change in extracellular matrix is epithelial-mesenchymal transition. When associated with angiogenesis (so-called epithelial-mesenchymal transition type 3) it may well also be the link with the development of cancer, which is closely associated with COPD, predominantly in large airways. The authors have focused on our recent publications in these areas. Further investigations teasing out these mechanisms will help improve our understanding of key airway disease processes in COPD, which may have major therapeutic implications.

  6. 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...

  7. Effect of Traffic-Related Air Pollution on Allergic Disease: Results of the Children's Health and Environmental Research

    PubMed Central

    Jung, Dal-Young; Kim, Hwan-Cheol; Kim, Jeong-Hee; Hwang, Seung-Sik; Lee, Ji-Young; Kim, Byoung-Ju; Hong, Yun-Chul; Hong, Soo-Jong; Kwon, Ho-Jang

    2015-01-01

    Purpose This study evaluated the relationship of living near to main roads to allergic diseases, airway hyperresponsiveness (AHR), allergic sensitization, and lung function in Korean children. Methods A total of 5,443 children aged 6-14 years from 33 elementary schools in 10 cities during 2005-2006 were included in a baseline survey of the Children's Health and Environmental Research. We assessed association of traffic-related air pollution (TAP) exposure with the distance to the nearest main road, total road length of main roads and the proportion of the main road area within the 200-m home area. Results Positive exposure-response relationships were found between the length of the main road within the 200-m home area and lifetime wheeze (adjusted prevalence ratio [PR] for comparison of the longest to the shortest length categories=1.24; 95% CIs, 1.04-1.47; P for trend=0.022) and diagnosed asthma (PR=1.42; 95% CIs, 1.08-1.86; P for trend=0.011). Living less than 75 m from the main road was significantly associated with lifetime allergic rhinitis (AR), past-year AR symptoms, diagnosed AR, and treated AR. The distance to the main road (P for trend=0.001), the length of the main road (P for trend=0.041), and the proportion of the main road area (P for trend=0.006) had an exposure-response relationship with allergic sensitization. A strong inverse association was observed between residential proximity to the main load and lung function, especially FEV1, FEV1/FVC, and FEF25-75. The length of the main road and the proportion of the main road area were associated with reduced FEV1 in schoolchildren. Conclusions The results of this study suggest that exposure to traffic-related air pollution may be associated with increased risk of asthma, AR, and allergic sensitization, and with reduced lung function in schoolchildren. PMID:25936911

  8. 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

  9. Oxidative airway inflammation leads to systemic and vascular oxidative stress in a murine model of allergic asthma.

    PubMed

    Al-Harbi, Naif O; Nadeem, A; Al-Harbi, Mohamed M; Imam, F; Al-Shabanah, Othman A; Ahmad, Sheikh F; Sayed-Ahmed, Mohamed M; Bahashwan, Saleh A

    2015-05-01

    Oxidant-antioxidant imbalance plays an important role in repeated cycles of airway inflammation observed in asthma. It is when reactive oxygen species (ROS) overwhelm antioxidant defenses that a severe inflammatory state becomes apparent and may impact vasculature. Several studies have shown an association between airway inflammation and cardiovascular complications; however so far none has investigated the link between airway oxidative stress and systemic/vascular oxidative stress in a murine model of asthma. Therefore, this study investigated the contribution of oxidative stress encountered in asthmatic airways in modulation of vascular/systemic oxidant-antioxidant balance. Rats were sensitized intraperitoneally with ovalbumin (OVA) in the presence of aluminum hydroxide followed by several intranasal (i.n.) challenges with OVA. Rats were then assessed for airway and vascular inflammation, oxidative stress (ROS, lipid peroxides) and antioxidants measured as total antioxidant capacity (TAC) and thiol content. Challenge with OVA led to increased airway inflammation and oxidative stress with a concomitant increase in vascular inflammation and oxidative stress. Oxidative stress in the vasculature was significantly inhibited by antioxidant treatment, N-acetyl cysteine; whereas hydrogen peroxide (H2O2) inhalation worsened it. Therefore, our study shows that oxidative airway inflammation is associated with vascular/systemic oxidative stress which might predispose these patients to increased cardiovascular risk.

  10. 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.

  11. 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. PMID:24509255

  12. The S1P/S1PR2 axis regulates early airway T cell infiltration in murine mast cell-dependent acute allergic responses

    PubMed Central

    Oskeritzian, Carole A.; Hait, Nitai C.; Wedman, Piper; Chumanevich, Alena; Kolawole, Elizabeth M.; Price, Megan M.; Falanga, Yves T.; Harikumar, Kuzhuvelil B.; Ryan, John J.; Milstien, Sheldon; Sabbadini, Roger; Spiegel, Sarah

    2014-01-01

    Background Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid produced by mast cells (MC) upon cross-linking of their high affinity receptors for IgE by antigen (Ag) that can amplify MC responses by binding to its S1P receptors. Acute MC-dependent allergic reaction can lead to systemic shock but the early events of its development in lung tissues have not been investigated, and S1P functions in the onset of allergic processes remain to be examined. Objective We used a highly specific neutralizing anti-S1P antibody (mAb) and an S1P receptor 2 (S1PR2) antagonist, JTE-013, to study S1P and S1PR2 signaling contributions to MC- and IgE-dependent airway allergic responses in mice within minutes after Ag challenge. Methods Allergic reaction was triggered by a single intraperitoneal (i.p.) dose of Ag in sensitized mice pre-treated i.p. with anti-S1P or isotype control mAb, or JTE-013 or vehicle prior to Ag challenge. Results Kinetics experiments revealed early pulmonary infiltration of mostly T cells around blood vessels of sensitized mice 20 minutes post-Ag exposure. Pre-treatment with anti-S1P mAb inhibited in vitro MC activation, as well as in vivo development of airway infiltration and MC activation, reducing serum levels of histamine, cytokines and the chemokines MCP-1/CCL2, MIP-1α/CCL3 and RANTES/CCL5. S1PR2 antagonism or deficiency, or MC deficiency recapitulated these results. Both in vitro and in vivo experiments demonstrated MC S1PR2 dependency for chemokine release and the necessity for signal transducer and activator of transcription 3 (Stat3) activation. Conclusion Activation of S1PR2 by S1P and downstream Stat3 signaling in MC regulate early T cell recruitment to antigen-challenged lungs by chemokine production. PMID:25512083

  13. 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.

  14. [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.

  15. 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.

  16. Methaemoglobinaemia produced by phenazopyridine (Pyridium) in a man with chronic obstructive airways disease.

    PubMed

    Chakraborty, T K; Filshie, R J; Lee, M R

    1987-12-01

    Life threatening methaemoglobinaemia developed after prolonged therapeutic use of phenazopyridine (Pyridium) in a patient with chronic obstructive airways disease. The combination of chronic obstructive airways disease and oxidant drugs (methaemoglobinaemia) may be lethal. The use of phenazopyridine should be abandoned. Certainly there is no indication to use it for more than a few days in any patient.

  17. Intra-airway administration of small interfering RNA targeting plasminogen activator inhibitor-1 attenuates allergic asthma in mice.

    PubMed

    Miyamoto, Shintaro; Hattori, Noboru; Senoo, Tadashi; Onari, Yojiro; Iwamoto, Hiroshi; Kanehara, Masashi; Ishikawa, Nobuhisa; Fujitaka, Kazunori; Haruta, Yoshinori; Murai, Hiroshi; Yokoyama, Akihito; Kohno, Nobuoki

    2011-12-01

    Recent studies suggest that plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system, may promote the development of asthma. To further investigate the significance of PAI-1 in the pathogenesis of asthma and determine the possibility that PAI-1 could be a therapeutic target for asthma, this study was conducted. First, PAI-1 levels in induced sputum (IS) from asthmatic subjects and healthy controls were measured. In asthmatic subjects, IS PAI-1 levels were elevated, compared with that of healthy controls, and were significantly higher in patients with long-duration asthma compared with short-duration asthma. PAI-1 levels were also found to correlate with IS transforming growth factor-β levels. Then, acute and chronic asthma models induced by ovalbumin were established in PAI-1-deficient mice and wild-type mice that received intra-airway administrations of small interfering RNA against PAI-1 (PAI-1-siRNA). We could demonstrate that eosinophilic airway inflammation and airway hyperresponsiveness were reduced in an acute asthma model, and airway remodeling was suppressed in a chronic asthma model in both PAI-1-deficient mice and wild-type mice that received intra-airway administration of PAI-1-siRNA. These results indicate that PAI-1 is strongly involved in the pathogenesis of asthma, and intra-airway administration of PAI-1-siRNA may be able to become a new therapeutic approach for asthma.

  18. Fexofenadine hydrochloride in the treatment of allergic disease: a review

    PubMed Central

    Axelrod, David; Bielory, Leonard

    2008-01-01

    Fexofenadine is a selective, non-sedating H1 receptor antagonist, marketed in the United States since 2000. The FDA approved an oral suspension in 2006, for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria in children. The tablet, capsule, and oral suspension are bioequivalent. Although fexofenadine does not use P450 CYP 3A4 it does interact with a number of drugs at P-glycoprotein and organic anion transporter polypeptides. The risk of toxicity from other drugs may increase with the administration of fexofenadine. Orange and grapefruit juices reduce the bioavailability of fexofenadine. Fexofenadine has been shown to have an impact on inflammatory mediators, other than histamine, such as decreasing the production of LTC4, LTD4, LTE4, PGE2, and PGF2α; inhibiting cyclo-oxygenase 2, thromboxane; limiting iNOS generation of NO; decreasing cytokine levels (ICAM-1, ELAM-1, VCAM-1, RANTES, I-TAC, MDC, TARC, MMP-2, MMP-9, tryptase); and diminishing eosinophil adherence, chemotaxis, and opsonization of particles. These effects may provide benefit to some of the inflammatory responses of an acute allergic reaction and provide a basis for future development of H1 antagonists with stronger anti-inflammatory effects. These studies also support the contention that fexofenadine is effective for the treatment of allergic rhinits and chronic idiopathic urticaria. PMID:21436982

  19. 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.

  20. 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.

  1. 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.

  2. The relationships among birth season, sunlight exposure during infancy, and allergic disease

    PubMed Central

    Hwang, Jung Min; Oh, Se Hyun

    2016-01-01

    Purpose The recent increase in the prevalence of allergic diseases is hypothetically attributed to immune dysregulation in turn caused by a reduction in exposure to sunlight. We explored relationships between birth season, sunlight exposure, exercise duration, and an allergic disease. Methods We performed a questionnaire-based survey on allergic diseases among elementary school students. Birth time was categorized according to the season (summer and winter). Results The prevalence of atopic dermatitis (AD) "symptoms ever" was higher in the children born in winter than in those born in summer (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.03-1.49; P=0.024). Birth in winter was associated with an increase in the "symptoms in the past 12 months" prevalence of food allergy (FA) (aOR, 1.56; 95% CI, 1.09-2.24; P=0.015). The lifetime prevalence of allergic diseases except FA was higher in the children whose parents considered their sunlight exposure prior to 24 months of ageas inadequate than those who considered their exposure as adequate ("diagnosis ever" asthma: aOR, 1.4; 95% CI, 1.17-1.67; P<0.001; allergic rhinitis [AR]: aOR, 1.4; 95% CI, 1.17-1.67; P<0.001; AD: aOR, 1.26; 95% CI, 1.06-1.51; P=0.01). Neither recent sunlight exposure nor exercise duration was associated with the prevalence of an allergic disease. Conclusion Birth in winter may be associated with development of AD and FA. Inadequate sunlight exposure before the age of 24 months might possibly increase the risks of development of asthma, AR, and AD. PMID:27279886

  3. 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...

  4. Advances in Surgical Treatment of Congenital Airway Disease.

    PubMed

    Ragalie, William S; Mitchell, Michael E

    2016-01-01

    Tracheobronchomalacia (TBM) is frequently present in infants and children with congenital heart disease (CHD). Infants with CHD and TBM appear to do worse than those without TBM. The principle of operative intervention for TBM is to improve function of the airway and clinical status. When indicated, conventional surgical options include tracheostomy, aortopexy, tracheoplasty, and anterior tracheal suspension. There is no consensus on the optimal treatment of severe tracheobonchomalacia, which can be associated with a mortality rate as high as 80%. Congenital tracheal stenosis is also frequently associated with CHD (vascular rings, atrioventricular canal defects, and septal defects) and may require concomitant repair. Repair of tracheal stenosis is often associated with distal TBM. This article addresses new techniques that can be performed in corrective surgery for both TBM and congenital tracheal stenosis. PMID:27568138

  5. Effects of cessation of terbutaline treatment on airway obstruction and responsiveness in patients with chronic obstructive pulmonary disease.

    PubMed Central

    de Jong, J. W.; Koëter, G. H.; van der Mark, T. W.; Postma, D. S.

    1996-01-01

    BACKGROUND: Cessation of regular therapy with inhaled beta 2 agonists in patients with asthma may lead to a temporary deterioration of lung function and airway responsiveness. Few such studies have been reported in patients with chronic obstructive pulmonary disease (COPD), so an investigation was carried out to determine whether rebound airway responsiveness and rebound bronchoconstriction also occurs in COPD and if there is any relationship with the dose of beta 2 agonist being used. METHODS: Lung function (forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF)), airway responsiveness (PC20 methacholine (PC20)) and symptoms were assessed in a double blind, placebo controlled crossover study during and after cessation of two weeks regular treatment with placebo, and low dose (250 micrograms) and high dose (1000 micrograms) inhaled terbutaline via a dry powder inhaler (Turbohaler) all given three times a day. Sixteen non-allergic patients with COPD of mean (SD) age 58.7 (6.5) years, FEV1 57.1 (12.8)% of predicted, and reversibility on 1000 micrograms terbutaline of 4.5 (3.5)% predicted were studied. PC20 and FEV1 were measured 10, 14, 34 and 82 hours after the last inhalation of terbutaline or placebo. Measurements performed at 10, 14, and 34 hours were expressed relative to 82 hour values in each period, transformed into an area under the curve (AUC) value and analysed by ANOVA. RESULTS: Mean morning and evening PEF increased during terbutaline treatment. PC20 and FEV1 did not change after cessation of terbutaline treatment. CONCLUSIONS: Cessation of regular treatment with both low and high dose inhaled terbutaline does not result in a rebound bronchoconstriction and rebound airway responsiveness in patients with COPD. PMID:8882073

  6. Vitamin D and the development of allergic disease: how important is it?

    PubMed Central

    Mirzakhani, Hooman; Al-Garawi, Amal; Weiss, Scott T.; Litonjua, Augusto A.

    2015-01-01

    Summary Vitamin D has known effects on lung development and the immune system that may be important in the development, severity and course of allergic diseases (asthma, eczema and food allergy). Vitamin D deficiency is prevalent worldwide and may partly explain the increases in asthma and allergic diseases that have occurred over the last 50–60 years. In this review we explore past and current knowledge on the effect of vitamin D on lung development and immunomodulation and present the evidence of its role in allergic conditions. While there is growing observational and experimental evidence for the role of vitamin D, well-designed and well-powered clinical trials are needed to determine whether supplementation of vitamin D should be recommended in these disorders. PMID:25307157

  7. Resolvin D1 and Resolvin E1 Promote the Resolution of Allergic Airway Inflammation via Shared and Distinct Molecular Counter-Regulatory Pathways

    PubMed Central

    Levy, Bruce D.

    2012-01-01

    Resolvins are generated from omega-3 fatty acids during inflammatory responses in the lung. These natural mediators interact with specific receptors to decrease lung inflammation and promote its resolution in healthy tissues. There are several lung diseases of chronic inflammation that fail to resolve, most notable asthma. This common disorder has a lifetime prevalence of nearly 10% and is characterized, in part, by chronic, non-resolving inflammation of the airway. Pro-resolving mediators are generated during asthma; however, their biosynthesis is decreased in severe and uncontrolled asthma, suggesting that the chronic, adaptive inflammation in asthmatic airways may result from a resolution defect. This article focuses on recent insights into the cellular and molecular mechanisms for resolvins that limit adaptive immune responses in healthy airways. PMID:23293638

  8. Use of antihistamines after serious allergic reaction to methimazole in pediatric Graves' disease.

    PubMed

    Toderian, Amy B; Lawson, Margaret L

    2014-05-01

    Antithyroid drugs are usually considered first-line therapy for management of pediatric Graves' disease because they avoid permanent hypothyroidism, provide a chance for remission, and are less invasive than the alternatives of thyroidectomy or radioactive iodine. Methimazole (MMI) is the only antithyroid drug recommended in pediatrics due to the risk of propylthiouracil-induced liver toxicity. Allergic reactions with MMI occur in up to 10% of patients and, when mild, can be managed with concurrent antihistamine therapy. Guidelines recommend discontinuation of MMI with serious allergic reactions. We present the case of an adolescent girl with Graves' disease and a serious allergic reaction after starting MMI whose family refused radioactive iodine and was reluctant to proceed to surgery. Antihistamine therapy was successfully used to allow continued treatment with MMI. This case demonstrates extension of management guidelines for minor cutaneous allergic reactions to MMI, through the use of antihistamines for a serious allergic reaction, allowing us to continue MMI and provide treatment consistent with the family's preferences and values.

  9. Allergic proctocolitis: the clinical evolution of a transitory disease with a familial trend. Case reports.

    PubMed

    Fagundes-Neto, Ulysses; Ganc, Arnaldo José

    2013-01-01

    Allergic colitis is a clinical manifestation of food allergy during the first months of life. It is estimated that genetic factors play a role in the expression of this allergic disease. This case report described the clinical progress of infants who were cousins from two distinct family groups with allergic colitis. Five infants under six months of age and of both sexes were studied, with a diagnosis of allergic colitis characterized clinically and histologically by (1) rectal bleeding; (2) exclusion of infectious causes of colitis; (3) disappearance of symptoms after elimination of cow's milk and dairy products from the child's and/or the mother's diet. Patients were submitted to the following diagnostic investigation: complete blood count; stool culture; parasitologic examination of stools; rectoscopy or colonoscopy; and rectal biopsy. Patient age varied from 40 days to six months; three were males. All patients presented with complaints of intense colic and rectal bleeding. The colonoscopy showed presence of hyperemia of the mucosa with microerosions and spontaneous bleeding upon the procedure. Microscopy revealed the existence of colitis with eosinophilia > 20 e/HPF. Patients were treated with a hypoallergenic formula and showed remission of symptoms. After one year of age, all were submitted to an oral challenge with a milk formula and presented food tolerance. Allergic colitis is a disease with evident genetic inheritance and a temporary character. PMID:23843067

  10. Chemokine receptors in airway disease: which receptors to target?

    PubMed

    Owen, C

    2001-01-01

    Many disease states within the airway result in the co-ordinated infiltration of key inflammatory cells. The cellular influx is choreographed through the temporal and spatially-regulated expression of chemokines, which potentiate the migration of cells along gradients of chemotactic ligands. Chemokines act as ligands for the chemokine receptors; a distinct class of G-protein-coupled receptor. Over 40 chemokine ligands and 18 chemokine receptors have been identified on human cells. Chemokine receptors are divided into several classes; the two most prominent of which are the CC- and CXC-chemokine receptors, classified through the spatial arrangement of two conserved cysteine residues. The role of chemokine receptors such as CCR2, CCR3, CCR4, CCR8 and the CXC chemokine receptors; CXCR1 and CXCR2 on cell types of relevance to respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) and chronic bronchitis will be explored in this review. Chemokines have proven to be amenable drug targets for the development of low molecular weight antagonists by the pharmaceutical industry. So far, no chemokine receptor antagonist has entered the clinic in trials for respiratory disease, but over the next few years it is expected that many will do so, at which time the potential of these exciting new targets will be fully realised.

  11. Vascular endothelial growth factor as a key inducer of angiogenesis in the asthmatic airways.

    PubMed

    Meyer, Norbert; Akdis, Cezmi A

    2013-02-01

    Asthma is a chronic inflammatory disease of the airways characterized by structural airway changes, which are known as airway remodeling, including smooth muscle hypertrophy, goblet cell hyperplasia, subepithelial fibrosis, and angiogenesis. Vascular remodeling in asthmatic lungs results from increased angiogenesis, which is mainly mediated by vascular endothelial growth factor (VEGF). VEGF is a key regulator of blood vessel growth in the airways of asthma patients by promoting proliferation and differentiation of endothelial cells and inducing vascular leakage and permeability. In addition, VEGF induces allergic inflammation, enhances allergic sensitization, and has a role in Th2 type inflammatory responses. Specific inhibitors of VEGF and blockers of its receptors might be useful to control chronic airway inflammation and vascular remodeling, and might be a new therapeutic approach for chronic inflammatory airway disease like asthma.

  12. Mechanisms of allergic disease - environmental and genetic determinants for the development of allergy.

    PubMed

    Campbell, D E; Boyle, R J; Thornton, C A; Prescott, S L

    2015-05-01

    Allergic disease can be viewed as an early manifestation of immune dysregulation. Environmental exposures including maternal inflammation, diet, nutrient balance, microbial colonization and toxin exposures can directly and indirectly influence immune programming in both pregnancy and the postnatal period. The intrauterine microclimate is critical for maternal and fetal immunological tolerance to sustain viable pregnancy, but appears susceptible to environmental conditions. Targeting aspects of the modern environment that promote aberrant patterns of immune response is logical for interventions aimed at primary prevention of allergic disease. Defining the mechanisms that underpin both natural and therapeutic acquisition of immunological tolerance in childhood will provide insights into the drivers of persistent immune dysregulation. In this review, we summarize evidence that allergy is a consequence of intrauterine and early life immune dysregulation, with specific focus on contributing environmental risk factors occurring preconception, in utero and in the early postnatal period. We explore the immunological mechanisms which underpin tolerance and persistence of allergic disease during childhood. It is likely that future investigations within these two domains will ultimately provide a road map for the primary prevention of allergic disease.

  13. Sinobronchial allergic aspergillosis with allergic bronchopulmonary aspergillosis: a less common co-existence

    PubMed Central

    Upadhyay, Rashmi; Kant, Surya; Prakash, Ved; Saheer, S

    2014-01-01

    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. PMID:25371437

  14. Th2 responses without atopy: immunoregulation in chronic helminth infections and reduced allergic disease.

    PubMed

    Yazdanbakhsh, M; van den Biggelaar, A; Maizels, R M

    2001-07-01

    The immune response to helminth infections has long been known to share key features with the allergic response. In particular, both are typified by enhanced T helper 2 (Th2) responses with high levels of interleukin-4 (IL-4), IL-5 and IL-13, accompanied by eosinophilia and abundant IgE production. Paradoxically, the geographical distribution of helminth parasitism and allergic disease is complementary rather than coincident. Thus, the question arises does the Th2 response to parasites protect or pre-empt the host from developing Th2-linked allergic manifestations? It is suggested that downregulatory immune mechanisms, which dampen the anti-parasite response, might benefit the host by blocking progression to atopic reactions. This is of relevance in explaining how the "hygiene hypothesis" might operate immunologically and in the design of therapeutics. PMID:11429321

  15. 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.

  16. 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

  17. 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.

  18. [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. PMID:12658963

  19. [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.

  20. Composition of nasal airway surface liquid in cystic fibrosis and other airway diseases determined by X-ray microanalysis.

    PubMed

    Vanthanouvong, V; Kozlova, I; Johannesson, M; Nääs, E; Nordvall, S L; Dragomir, A; Roomans, G M

    2006-04-01

    The ionic composition of the airway surface liquid (ASL) in healthy individuals and in patients with cystic fibrosis (CF) has been debated. Ion transport properties of the upper airway epithelium are similar to those of the lower airways and it is easier to collect nasal ASL from the nose. ASL was collected with ion exchange beads, and the elemental composition of nasal fluid was determined by X-ray microanalysis in healthy subjects, CF patients, CF heterozygotes, patients with rhinitis, and with primary ciliary dyskinesia (PCD). In healthy subjects, the ionic concentrations were approximately isotonic. In CF patients, CF heterozygotes, rhinitis, and PCD patients, [Na] and [Cl] were significantly higher compared when compared with those in controls. [K] was significantly higher in CF and PCD patients compared with that in controls. Severely affected CF patients had higher ionic concentrations in their nasal ASL than in patients with mild or moderate symptoms. Female CF patients had higher levels of Na, Cl, and K than male patients. As higher salt concentrations in the ASL are also found in other patients with airway diseases involving chronic inflammation, it appears likely that inflammation-induced epithelial damage is important in determining the ionic composition of the ASL. PMID:16586482

  1. 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

  2. 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

  3. 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

  4. The impact of pharmacogenetics in the treatment of allergic disease and asthma.

    PubMed

    Jones, Bridgette L

    2011-01-01

    Personalized medicine includes the application of genomic information in predicting disease and therapeutic response to ultimately individualize patient care. Pharmacogenetics is key in achieving true personalized care. However, the clinical applicability of genetic testing to "everyday medicine" is yet to be realized. This paper will discuss areas in allergic/inflammatory disease that have been impacted by pharmacogenetic research and how this application may be brought from the "bench to the bedside." PMID:22073496

  5. Home dampness, current allergic diseases, and respiratory infections among young adults

    PubMed Central

    Kilpelainen, M; Terho, E; Helenius, H; Koskenvuo, M

    2001-01-01

    BACKGROUND—The relation between home dampness and respiratory symptoms among adults is well confirmed, but data on specific allergic diseases and respiratory infections is more limited. Individual factors that may enhance susceptibility to the effects of home dampness are mainly unknown.
METHODS—The association between home dampness and current physician diagnosed asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, common colds, and bacterial respiratory infections was studied in a questionnaire survey of 10 667 Finnish first year university students aged 18-25 years. The dampness categories analysed were visible mould and visible mould or damp stains or water damage during the last year. In multivariate analyses adjustment was made for parental education, active and passive smoking, type and place of residence, pets, and wall to wall carpets. The interaction effect of atopic heredity and dampness was investigated.
RESULTS—Visible mould or damp stains or water damage was reported by 15.0% of the respondents. In multivariate models there was a positive association between home dampness and current asthma, allergic rhinitis, and atopic dermatitis, as well as common colds ⩾4 times per year and other respiratory infections, but not between home dampness and allergic conjunctivitis. The strongest association was found between exposure to visible mould and asthma (OR 2.21,95% CI 1.48 to 3.28) and common colds (OR 1.49, 95% CI 1.18 to 1.87). The risk of current asthma in damp homes was highest among subjects with atopic heredity.
CONCLUSIONS—The risk of current asthma, allergic rhinitis, and atopic dermatitis was higher in damp homes. Of the respiratory infections, the risk of common colds was most clearly increased.

 PMID:11359962

  6. Novel Roles for Chloride Channels, Exchangers, and Regulators in Chronic Inflammatory Airway Diseases

    PubMed Central

    Sala-Rabanal, Monica; Yurtsever, Zeynep; Berry, Kayla N.; Brett, Tom J.

    2015-01-01

    Chloride transport proteins play critical roles in inflammatory airway diseases, contributing to the detrimental aspects of mucus overproduction, mucus secretion, and airway constriction. However, they also play crucial roles in contributing to the innate immune properties of mucus and mucociliary clearance. In this review, we focus on the emerging novel roles for a chloride channel regulator (CLCA1), a calcium-activated chloride channel (TMEM16A), and two chloride exchangers (SLC26A4/pendrin and SLC26A9) in chronic inflammatory airway diseases. PMID:26612971

  7. Questionnaire assessment of airway disease symptoms in equine barn personnel

    PubMed Central

    Svatek, Jessica; Maranda, Louise; Christiani, David; Ghio, Andrew; Nadeau, Jenifer; Hoffman, Andrew M.

    2009-01-01

    Background People working in cattle, swine and poultry barns have a higher prevalence of respiratory symptoms and decreased lung function. There is scant evidence regarding the respiratory health of humans working in horse barns, although it is well documented that stabled horses have a high prevalence of airway disease. Aims To determine whether people spending time in horse barns have a higher prevalence of self-reported respiratory symptoms than non-exposed controls. Methods A cross-sectional questionnaire study was conducted from May 2005 to January 2006 to investigate the prevalence of self-reported respiratory symptoms in 82 barn-exposed subjects and 74 control subjects. Logistic regression and the chi-square test were used to analyse the data. Results There was a significantly higher prevalence of self-reported respiratory symptoms in the barn-exposed group (50%) versus the control group (15%). Exposure to horse barns, smoking and family history of asthma or allergies was independent risk factors for respiratory symptoms. High exposure to the horse barn yielded a higher odds ratio for self-reported respiratory symptoms (8.9). Conclusions Exposure to the equine barn is a risk factor for respiratory symptoms. Investigation of organic dust exposures, lung function and horse dander allergies in the barn-exposed group will be necessary to determine how best to protect the health of this group. PMID:19223434

  8. New developments providing mechanistic insight into the impact of the microbiota on allergic disease.

    PubMed

    McCoy, Kathy D; Köller, Yasmin

    2015-08-01

    The increase in allergic diseases over the past several decades is correlated with changes in the composition and diversity of the intestinal microbiota. Microbial-derived signals are critical for instructing the developing immune system and conversely, immune regulation can impact the microbiota. Perturbations in the microbiota composition may be especially important during early-life when the immune system is still developing, resulting in a critical window of opportunity for instructing the immune system. This review highlights recent studies investigating the role of the microbiome in susceptibility or development of allergic diseases with a focus on animal models that provide insight into the mechanisms and pathways involved. Identification of a causal link between reduced microbial diversity or altered microbial composition and increased susceptibility to immune-mediated diseases will hopefully pave the way for better preventive therapies.

  9. [A birth cohort study on allergic diseases among toddlers in Northwest Germany].

    PubMed

    Pohlabeln, H; Jacobs, S; Böhmann, J

    2012-06-01

    In the late 1990s, a birth cohort study was conducted in the cities of Delmenhorst, Wilhelmshaven and Leer, where more than 3,000 newborn children were recruited in five hospitals. The baseline survey in the clinics was followed by three follow-up surveys 6, 12 and 24 months later. The prime concern of the study was to estimate prevalences and to conduct analyses concerning the association between breastfeeding as well as exposure to pets and the occurrence of allergy symptoms. Children living together with a dog in the same household were at higher risk of disease only if a familial predisposition of allergic diseases was present - without such a familial predisposition a dog in the same household seems to reduce the risk for atopic diseases during the first 2 years of life. A protective effect due to long breastfeeding could be observed in our study in particular in case of a paternal history of allergic diseases, whereas an exclusive maternal history of allergic diseases seems to increase the risk. The concept of the study has proved itself. Contacting mothers in obstetrical departments in hospitals as well as in medical offices of self-employed pediatricians has proven to be very practicable. With comparatively little effort a relatively large cohort was recruited, which allowed us to analyze longitudinal data, adequately taking into account several confounders as well as effect-modifying factors. PMID:22736168

  10. 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

  11. IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle

    PubMed Central

    Robinson, Mac B.; Deshpande, Deepak A.; Chou, Jeffery; Cui, Wei; Smith, Shelly; Langefeld, Carl; Hastie, Annette T.; Bleecker, Eugene R.

    2015-01-01

    Genetic data suggest that IL-6 trans-signaling may have a pathogenic role in the lung; however, the effects of IL-6 trans-signaling on lung effector cells have not been investigated. In this study, human airway smooth muscle (HASM) cells were treated with IL-6 (classical) or IL-6+sIL6R (trans-signaling) for 24 h and gene expression was measured by RNAseq. Intracellular signaling and transcription factor activation were assessed by Western blotting and luciferase assay, respectively. The functional effect of IL-6 trans-signaling was determined by proliferation assay. IL-6 trans-signaling had no effect on phosphoinositide-3 kinase and Erk MAP kinase pathways in HASM cells. Both classical and IL-6 trans-signaling in HASM involves activation of Stat3. However, the kinetics of Stat3 phosphorylation by IL-6 trans-signaling was different than classical IL-6 signaling. This was further reflected in the differential gene expression profile by IL-6 trans-signaling in HASM cells. Under IL-6 trans-signaling conditions 36 genes were upregulated, including PLA2G2A, IL13RA1, MUC1, and SOD2. Four genes, including CCL11, were downregulated at least twofold. The expression of 112 genes was divergent between IL-6 classical and trans-signaling, including the genes HILPDA, NNMT, DAB2, MUC1, WWC1, and VEGFA. Pathway analysis revealed that IL-6 trans-signaling induced expression of genes involved in regulation of airway remodeling, immune response, hypoxia, and glucose metabolism. Treatment of HASM cells with IL-6+sIL6R induced proliferation in a dose-dependent fashion, suggesting a role for IL-6 trans-signaling in asthma pathogenesis. These novel findings demonstrate differential effect of IL-6 trans-signaling on airway cells and identify IL-6 trans-signaling as a potential modifier of airway inflammation and remodeling. PMID:26001777

  12. Italian Multicenter Cross-Sectional Study (AISAG) on light smoking and allergic diseases in adults.

    PubMed

    Lombardi, C; Passalacqua, G

    2016-03-01

    Allergic rhinitis, allergic dermatitis, and food allergy are extremely common diseases and are frequently associated to each other and to asthma. Smoking is a potential risk factor for these conditions, but so far, results from individual studies have been conflicting. On the basis of these contradictory data in the literature we have carried out a multicenter cross-sectional study to evaluate the relationship between some allergic conditions and exposure or not to active light smoking. The study was carried out between May 2013 and November 2013 in 22 different Italian hospitals. Patients with respiratory and/or food allergy, and aged 18 years and over, visited at Allergy Outpatient Clinics, were invited to participate. A total of 1586 allergic patients (21.6% smokers) with a mean age of 39.2 years (standard deviation, SD = 15.1) were included. We demonstrated that the prevalence of tobacco smoking was higher in patients with food allergy and in asthmatic patients in stage III-IV. But no other statistical differences were found at univariate analysis. The sensitization patterns of non-smokers and smokers were similar. Furthermore, tobacco smoking was associated with higher risk of food allergy and lower risk of asthma. Moreover, tobacco smoking was an independent risk factor for persistent respect to intermittent rhinitis, and for asthma GINA stage III-IV with respect to stage I-II.

  13. Effects of corticosteroid treatment on airway inflammation, mechanics, and hyperpolarized ³He magnetic resonance imaging in an allergic mouse model.

    PubMed

    Thomas, Abraham C; Kaushik, S Sivaram; Nouls, John; Potts, Erin N; Slipetz, Deborah M; Foster, W Michael; Driehuys, Bastiaan

    2012-05-01

    The purpose of this study was to assess the effects of corticosteroid therapy on a murine model of allergic asthma using hyperpolarized (3)He magnetic resonance imaging (MRI) and respiratory mechanics measurements before, during, and after methacholine (MCh) challenge. Three groups of mice were prepared, consisting of ovalbumin sensitized/ovalbumin challenged (Ova/Ova, n = 5), Ova/Ova challenged but treated with the corticosteroid dexamethasone (Ova/Ova+Dex, n = 3), and ovalbumin-sensitized/saline-challenged (Ova/PBS, n = 4) control animals. All mice underwent baseline 3D (3)He MRI, then received a MCh challenge while 10 2D (3)He MR images were acquired for 2 min, followed by post-MCh 3D (3)He MRI. Identically treated groups underwent respiratory mechanics evaluation (n = 4/group) and inflammatory cell counts (n = 4/group). Ova/Ova animals exhibited predominantly large whole lobar defects at baseline, with significantly higher ventilation defect percentage (VDP = 19 ± 4%) than Ova/PBS (+2 ± 1%, P = 0.01) animals. Such baseline defects were suppressed by dexamethasone (0%, P = 0.009). In the Ova/Ova group, MCh challenge increased VDP on both 2D (+30 ± 8%) and 3D MRI scans (+14 ± 2%). MCh-induced VDP changes were diminished in Ova/Ova+Dex animals on both 2D (+21 ± 9%, P = 0.63) and 3D scans (+7 ± 2%, P = 0.11) and also in Ova/PBS animals on 2D (+6 ± 3%, P = 0.07) and 3D (+4 ± 1%, P = 0.01) scans. Because MCh challenge caused near complete cessation of ventilation in four of five Ova/Ova animals, even as large airways remained patent, this implies that small airway (<188 μm) obstruction predominates in this model. This corresponds with respiratory mechanics observations that MCh challenge significantly increases elastance and tissue damping but only modestly affects Newtonian airway resistance. PMID:22241062

  14. Time trends of the prevalence of asthma and allergic disease in Austrian children.

    PubMed

    Schernhammer, E S; Vutuc, C; Waldhör, T; Haidinger, G

    2008-03-01

    After a substantial increase in the prevalence of atopic disease in Europe, recent studies indicate that a plateau has been reached. However, variation across countries and age groups exists. We studied the prevalence and time trends of asthma and allergic disease among schoolchildren in Austria, a country with traditionally low rates of asthma, hay fever, and eczema. As part of the International Study of Asthma and Allergies in Childhood (ISAAC), symptoms and physician diagnoses of asthma and allergic disease of 13,399 Austrian children aged 6-7 yr and 1516 children aged 12-14 yr were surveyed between 1995 and 1997. A similar survey was conducted between 2001 and 2003. Among children aged 6-7 yr, significant increases were seen in the prevalence of physician-diagnosed asthma (+16%; p = 0.013), hay fever (+22%; p < 0.001), and eczema (+37%; p < 0.001) between 1995 and 2003. These changes were paralleled by an increase in the prevalence of symptoms typical for hay fever (itchy eyes and runny nose), but not by an increase in wheeze. Among children aged 12-14 yr, the lifetime prevalence of diagnosed asthma increased by 32%, of hay fever by 19%, and of eczema by 28% (all, p < 0.001). These changes were paralleled by increases in the prevalence of wheezing as documented by both questions before and after a video showing wheezing children but not by symptoms typical for hay fever such as itchy eyes and runny nose. In conclusion, in Austria, contrary to other European countries, the prevalence of asthma and allergic disease increased among schoolchildren. Additional studies are needed to continue monitoring the dynamics of the prevalence of asthma and allergic disease in Austria and to explore trends in their risk factors. PMID:18086231

  15. The role of the small airways in the pathophysiology of asthma and chronic obstructive pulmonary disease.

    PubMed

    Bonini, Matteo; Usmani, Omar S

    2015-12-01

    Chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), represent a major social and economic burden for worldwide health systems. During recent years, increasing attention has been directed to the role of small airways in respiratory diseases, and their exact contribution to the pathophysiology of asthma and COPD continues to be clarified. Indeed, it has been suggested that small airways play a distinct role in specific disease phenotypes. Besides providing information on small airways structure and diagnostic procedures, this review therefore aims to present updated and evidence-based findings on the role of small airways in the pathophysiology of asthma and COPD. Most of the available information derives from either pathological studies or review articles and there are few data on the natural history of small airways disease in the onset or progression of asthma and COPD. Comparisons between studies on the role of small airways are hard to draw because both asthma and COPD are highly heterogeneous conditions. Most studies have been performed in small population samples, and different techniques to characterize aspects of small airways function have been employed in order to assess inflammation and remodelling. Most methods of assessing small airways dysfunction have been largely confined to research purposes, but some data are encouraging, supporting the utilization of certain techniques into daily clinical practice, particularly for early-stage diseases, when subjects are often asymptomatic and routine pulmonary function tests may be within normal ranges. In this context further clinical trials and real-life feedback on large populations are desirable.

  16. 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

  17. Role in Allergic Diseases of Immunological Cross-Reactivity between Allergens and Homologues of Parasite Proteins.

    PubMed

    Santiago, Helton da Costa; Nutman, Thomas B

    2016-01-01

    Implied under the rubric of the hygiene hypothesis is that helminth infection can protect against allergic disease. It is well known that helminths induce processes associated with type 2 immune responses, but they also induce important regulatory responses that can modulate these type 2-associated responses-modulation that influences responses to bystander antigens including allergens. Indeed, most epidemiological studies demonstrate a beneficial effect of helminth infection on atopy, but there are also convincing data to demonstrate that helminth infection can precipitate or worsen allergic inflammation/disease. Reasons for these disparate findings are much debated, but there is a school of thought that suggests that helminth-triggered type 2-associated responses, including IgE to cross-reactive aeroallergens, can offset the regulatory effects imposed by the same organisms. The cross-reactivity among helminths and allergenic tropomyosins dominated the antigen/allergen cross-reactivity field, but recent data suggest that cross-reactivity is much more common than previously appreciated. It has been demonstrated that a high degree of molecular similarity exists between allergens and helminth proteins. Thus, an understanding of the mechanisms underlying the response induced by helminth infection and their impact on the induction of allergic disease in the host are critical for designing therapies using iatrogenic infections or parasite products to treat inflammatory diseases and for developing vaccines against helminth parasites. PMID:27480900

  18. CD11b+ and Sca-1+ Cells Exert the Main Beneficial Effects of Systemically Administered Bone Marrow-Derived Mononuclear Cells in a Murine Model of Mixed Th2/Th17 Allergic Airway Inflammation

    PubMed Central

    Cruz, Fernanda F.; Borg, Zachary D.; Goodwin, Meagan; Coffey, Amy L.; Wagner, Darcy E.; Rocco, Patricia R.M.

    2016-01-01

    Systemic administration of bone marrow-derived mononuclear cells (BMDMCs) or bone marrow-derived mesenchymal stromal cells (MSCs) reduces inflammation and airway hyperresponsiveness (AHR) in a murine model of Th2-mediated eosinophilic allergic airway inflammation. However, since BMDMCs are a heterogeneous population that includes MSCs, it is unclear whether the MSCs alone are responsible for the BMDMC effects. To determine which BMDMC population(s) is responsible for ameliorating AHR and lung inflammation in a model of mixed Th2-eosinophilic and Th17-neutrophilic allergic airway inflammation, reminiscent of severe clinical asthma, BMDMCs obtained from normal C57Bl/6 mice were serially depleted of CD45, CD34, CD11b, CD3, CD19, CD31, or Sca-1 positive cells. The different resulting cell populations were then assessed for ability to reduce lung inflammation and AHR in mixed Th2/Th17 allergic airway inflammation induced by mucosal sensitization to and challenge with Aspergillus hyphal extract (AHE) in syngeneic C56Bl/6 mice. BMDMCs depleted of either CD11b-positive (CD11b+) or Sca-1-positive (Sca-1+) cells were unable to ameliorate AHR or lung inflammation in this model. Depletion of the other cell types did not diminish the ameliorating effects of BMDMC administration. In conclusion, in the current model of allergic inflammation, CD11b+ cells (monocytes, macrophages, dendritic cells) and Sca-1+ cells (MSCs) are responsible for the beneficial effects of BMDMCs. Significance This study shows that bone marrow-derived mononuclear cells (BMDMCs) are as effective as bone marrow-derived mesenchymal stromal cells (MSCs) in ameliorating experimental asthma. It also demonstrates that not only MSCs present in the pool of BMDMCs are responsible for BMDMCs’ beneficial effects but also monocytes, which are the most important cell population to trigger these effects. All of this is in the setting of a clinically relevant model of severe allergic airways inflammation and thus

  19. 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

  20. Neurology of allergic inflammation and rhinitis.

    PubMed

    Canning, Brendan J

    2002-05-01

    Afferent nerves, derived from the trigeminal ganglion, and postganglionic autonomic nerves, derived from sympathetic and parasympathetic ganglia expressing many different neurotransmitters, innervate the nose. Reflexes that serve to optimize the air-conditioning function of the nose by altering sinus blood flow, or serve to protect the nasal mucosal surface by mucus secretion, vasodilatation, and sneezing, can be initiated by a variety of stimuli, including allergen, cold air, and chemical irritation. Activation of nasal afferent nerves can also have profound effects on respiration, heart rate, blood pressure, and airway caliber (the diving response). Dysregulation of the nerves in the nose plays an integral role in the pathogenesis of allergic rhinitis. Axon reflexes can precipitate inflammatory responses in the nose, resulting in plasma extravasation and inflammatory cell recruitment, while allergic inflammation can produce neuronal hyper-responsiveness. Targeting the neuronal dysregulation in the nose may be beneficial in treating upper airway disease. PMID:11918862

  1. 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.

  2. CLCA1 and TMEM16A: the link towards a potential cure for airway diseases.

    PubMed

    Brett, Tom J

    2015-10-01

    The hallmark traits of chronic obstructive airway diseases are inflammation, airway constriction due to hyperreactivity and mucus overproduction. The current common treatments for asthma and chronic obstructive pulmonary disease target the first two traits with none currently targeting mucus overproduction. The main source of obstructive mucus production is mucus cell metaplasia (MCM), the transdifferentiation of airway epithelial cells into mucus-producing goblet cells, in the small airways. Our current understanding of MCM is profusely incomplete. Few of the molecular players involved in driving MCM in humans have been identified and for many of those that have, their functions and mechanisms are unknown. This fact has limited the development of therapeutics that target mucus overproduction by inhibiting MCM. Current work in the field is aiming to change that. PMID:26296094

  3. 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

  4. 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

  5. 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.

  6. Overview on the pathomechanisms of allergic rhinitis

    PubMed Central

    Mori, Sachiko; Ozu, Chika; Kimura, Satoko

    2011-01-01

    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. PMID:22053313

  7. 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

  8. Allergic rhinitis and asthma: epidemiology and common pathophysiology.

    PubMed

    Khan, David A

    2014-01-01

    Allergic rhinitis and asthma are common diseases that frequently occur together. This concept has been referred to in the literature as united airway disease. Epidemiological studies have shown that the majority of patients with asthma have concomitant rhinitis and the presence of rhinitis is an increased risk factor for development of asthma. Patients with asthma and rhinitis share common physiology including heightened bronchial hyperresponsiveness and heightened reactivity to a variety of stimuli. Immunopathology of allergic rhinitis is also similar with the predominance of T-helper type 2 inflammation and tissue eosinophilia. Although several mechanisms have been proposed to explain the united airway theory, some of the best lines of evidence suggest that local airway inflammation can result in a systemic inflammatory response. Pharmacotherapeutic studies have shown that the treatment of rhinitis can improve asthma and vice versa. Nevertheless, systemic approaches such as immunotherapy lead to better outcomes for treating both disease states simultaneously. This article will focus on the data supporting the common epidemiology, shared pathophysiology, and therapeutic interventions aimed at allergic rhinitis and asthma as united airway diseases.

  9. Allergic- and immune-associated diseases of the urinary tract.

    PubMed

    Nichols, R

    1994-07-01

    Glomerular injury has a decided immunologic basis. Any infectious, inflammatory, neoplastic, or degenerative processes capable of sustained antigenic stimulation can induce immune-mediated glomerular injury. A variety of conditions and antigens, both endogenous and exogenous, are known to initiate immunologic glomerular damage. In many clinical situations, however, the precise antigenic source is occult and unrecognizable, and the glomerular disease is referred to as idiopathic. PMID:7975046

  10. The effect of hypoallergenic formula on the occurrence of allergic diseases in high risk infants.

    PubMed

    Tsai, Y T; Chou, C C; Hsieh, K H

    1991-01-01

    To study the influence of hypoallergenic milk on the occurrence of allergic diseases, thirty-three high risk, normal full-term newborns were divided into two groups with comparable family allergy score (FAS) and cord serum IgE. Group A consisted of 18 babies fed since birth with regular formula, while group B included 15 babies fed breast milk and/or NAN H.A. (Hypoallergenic infant formula) for the first 6 months of life. Close clinical observations for the appearance of atopic dermatitis, allergic rhinitis and wheezing as well as serial examination of total serum IgE and milk-specific IgE antibodies were done during the first year of life. The results showed: 1) Infants fed regular formula had a higher incidence of moderate to severe atopic dermatitis (AD) and allergic rhinitis (AR) than those fed NAN H.A. (39% vs 13% for AD; and 33% vs 13% for AR), but the difference was not significant. There was no difference in the incidence of wheezing between these two groups; 2) There was no relationship between cord blood IgE and FAS; 3) Neither the cord blood IgE nor FAS influenced the occurrence of allergic diseases and total serum IgE at one year of age; 4) Hypoallergenic milk (NAN H.A.) could support normal growth and development. In conclusion, a higher incidence of moderate to severe AD and AR was found in high risk infants fed regular formula than in those fed hypoallergenic milk. However, a study with a larger number of babies and a longer period of follow-up is needed to obtain a solid conclusion.

  11. Exposure to ambient bioaerosols is associated with allergic skin diseases in Greater Taipei residents.

    PubMed

    Kallawicha, Kraiwuth; Chuang, Ying-Chih; Lung, Shih-Chun Candice; Han, Bor-Cheng; Ting, Yi-Fang; Chao, Hsing Jasmine

    2016-09-01

    Allergic skin diseases may result from various types of chemical and biological allergens. This study investigated the association between ambient bioaerosol exposure and allergic skin diseases by using the exposure data obtained from land use regression models and interpolated data. Data on daily average outpatient visits for atopic dermatitis (ICD-9-CM 691.8) and contact dermatitis and other eczema (ICD-9-CM 692.9) between November 2011 and August 2012 were obtained from the National Health Insurance Research Database. A generalized estimating equation was used to analyze the associations between the skin diseases and ambient bioaerosol levels. The results indicated that during the study period, contact dermatitis and other eczema were more prevalent than atopic dermatitis in the study area. Most cases were observed in districts of Taipei City and 3 major districts of New Taipei City, namely Xinzhuang, Banqiao, and Xindian. In univariate analysis, most bioaerosols were positively associated with both skin diseases. After adjustment for air pollution and sociodemographic factors, exposure to total fungal spores was significantly associated with atopic dermatitis in males (relative risk [RR] = 1.12; 95% confidence interval [CI] = 1.05-1.19). Contact dermatitis and other eczema had significant relationships with Cladosporium in males (RR = 1.07; 95% CI = 1.02-1.14) and with Aspergillus/Penicillium in females (RR = 1.04; 95% CI = 1.02-1.07). Meteorological parameters, namely wind speed, temperature, and rainfall, were also significantly associated with skin diseases. Our findings reveal that exposure to ambient bioaerosols is a significant and independent risk factor for allergic skin diseases. PMID:27389548

  12. The effect of parental allergy on childhood allergic diseases depends on the sex of the child

    PubMed Central

    Arshad, S. Hasan; Karmaus, Wilfried; Raza, Abid; Kurukulaaratchy, Ramesh J.; Matthews, Sharon M.; Holloway, John W; Sadeghnejad, Alireza; Zhang, Hongmei; Roberts, Graham; Ewart, Susan L.

    2012-01-01

    Background Parent of origin effect is important in understanding the genetic basis of childhood allergic diseases and to improve our ability to identify high risk children. Objective To investigate parent of origin effect in childhood allergic diseases. Methods The Isle of Wight Birth Cohort (n=1,456) has been examined at 1, 2, 4, 10 and 18-years. Information on prevalence of asthma, eczema, rhinitis and environmental factors was obtained using validated questionnaires. Skin prick tests were carried out at ages 4, 10 and 18 year, and total IgE at 10 and 18 years. Parental history of allergic disease was assessed soon after the birth of the child when maternal IgE was also measured. Prevalence ratios (PR) and their 95% confidence intervals (CI) were estimated, applying log-linear models, adjusted for confounding variables. Results When stratified for sex of the child, maternal asthma was associated with asthma in girls [PR:1.91 (CI:1.34–2.72), p=0.0003], but not in boys [PR:1.29 (CI:0.85–1.96), p=0.23), while paternal asthma was associated with asthma in boys [PR:1.99 (CI:1.42–2.79), p<0.0001], but not in girls [PR: 1.03 (0.59–1.80) p=0.92). Maternal eczema increased the risk of eczema in girls [PR: 1.92 (CI: 1.37–2.68); p=0.0001] only, while paternal eczema did the same for boys (PR: 2.07 (CI:1.32–3.25); P=0.002). Similar trends were observed when the effect of maternal and paternal allergic disease was assessed for childhood atopy and when maternal total IgE was related to total IgE in children at age 10 and 18 years. Conclusions The current study indicates a sex dependent association of parental allergic conditions with childhood allergies; maternal allergy increasing the risk in girls and paternal allergy in boys. This has implications for childhood allergy prediction and prevention. PMID:22607991

  13. Etiology and pathogenesis of airway disease in children and adults from rural communities.

    PubMed Central

    Schwartz, D A

    1999-01-01

    Asthma is the most common chronic disease of childhood and affects nearly 5 million children. The prevalence and severity of childhood asthma have continued to increase over the past decade despite major advances in the recognition and treatment of this condition. A comparison of urban and rural children suggests that the etiology of airway disease is multifactorial and that unique exposures and genetic factors contribute to the development of asthma in both settings. The most important environmental exposure that distinguishes the rural environment and is known to cause asthma is the organic dusts. However, animal-derived proteins, common allergens, and low concentrations of irritants also contribute to the development of airway disease in children and adults living in rural communities. A fundamental unanswered question regarding asthma is why only a minority of children who wheeze at an early age develop persistent airway disease that continues throughout their life. Although genetic factors are important in the development of asthma, recurrent airway inflammation, presumably mediated by environmental exposures, may result in persistent airway hyperresponsiveness and the development of chronic airway disease. Increasing evidence indicates that control of the acute inflammatory response substantially improves airflow and reduces chronic airway remodeling. Reducing exposure to agricultural dusts and treatment with anti-inflammatory medication is indicated in most cases of childhood asthma. In addition, children with asthma from rural (in comparison to urban) America face multiple barriers that adversely affect their health e.g., more poverty, geographic barriers to health care, less health insurance, and poorer access to health care providers. These unique problems must be considered in developing interventions that effectively reduce the morbidity and mortality of asthma in children from rural communities. Images Figure 1 Figure 2 Figure 3 PMID:10346988

  14. 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. PMID:27155026

  15. Airway basal cells. The "smoking gun" of chronic obstructive pulmonary disease.

    PubMed

    Crystal, Ronald G

    2014-12-15

    The earliest abnormality in the lung associated with smoking is hyperplasia of airway basal cells, the stem/progenitor cells of the ciliated and secretory cells that are central to pulmonary host defense. Using cell biology and 'omics technologies to assess basal cells isolated from bronchoscopic brushings of nonsmokers, smokers, and smokers with chronic obstructive pulmonary disease (COPD), compelling evidence has been provided in support of the concept that airway basal cells are central to the pathogenesis of smoking-associated lung diseases. When confronted by the chronic stress of smoking, airway basal cells become disorderly, regress to a more primitive state, behave as dictated by their inheritance, are susceptible to acquired changes in their genome, lose the capacity to regenerate the epithelium, are responsible for the major changes in the airway that characterize COPD, and, with persistent stress, can undergo malignant transformation. Together, these observations led to the conclusion that accelerated loss of lung function in susceptible individuals begins with disordered airway basal cell biology (i.e., that airway basal cells are the "smoking gun" of COPD, a potential target for the development of therapies to prevent smoking-related lung disorders).

  16. Airway smooth muscle in asthma: linking contraction and mechanotransduction to disease pathogenesis and remodelling.

    PubMed

    Noble, Peter B; Pascoe, Chris D; Lan, Bo; Ito, Satoru; Kistemaker, Loes E M; Tatler, Amanda L; Pera, Tonio; Brook, Bindi S; Gosens, Reinoud; West, Adrian R

    2014-12-01

    Asthma is an obstructive airway disease, with a heterogeneous and multifactorial pathogenesis. Although generally considered to be a disease principally driven by chronic inflammation, it is becoming increasingly recognised that the immune component of the pathology poorly correlates with the clinical symptoms of asthma, thus highlighting a potentially central role for non-immune cells. In this context airway smooth muscle (ASM) may be a key player, as it comprises a significant proportion of the airway wall and is the ultimate effector of acute airway narrowing. Historically, the contribution of ASM to asthma pathogenesis has been contentious, yet emerging evidence suggests that ASM contractile activation imparts chronic effects that extend well beyond the temporary effects of bronchoconstriction. In this review article we describe the effects that ASM contraction, in combination with cellular mechanotransduction and novel contraction-inflammation synergies, contribute to asthma pathogenesis. Specific emphasis will be placed on the effects that ASM contraction exerts on the mechanical properties of the airway wall, as well as novel mechanisms by which ASM contraction may contribute to more established features of asthma such as airway wall remodelling.

  17. 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

  18. [The application of "preventive treatment theory" in chronic airway inflammatory disease].

    PubMed

    Dong, Jing-Cheng; Liu, Bao-Jun; Zhang, Hong-Ying

    2013-07-01

    Bronchial asthma and chronic obstructive pulmonary disease (COPD), as chronic airway inflammatory diseases, seriously threaten the health of human beings. Chinese medicine has obvious advantages in prevention and treatment of them. "Preventive treatment theory" is a sort summarization of preventive medicine in Chinese medicine. The theory is not only reflected at the disease prevention levels, also embodied in the active treatment and the rehabilitation process. It was especially deep and colorfully embodied in the prevention and treatment of chronic airway inflammatory diseases such as asthma and COPD. In this paper,clarified were the prevention and treatment targets, ways of thinking and methods in different stages of asthma and COPD from various viewpoints including prevention before disease occurrence, treating disease at disease onset, preventing the aggravation once disease occurs, and consolidation after disease occurs. We hope to improve ways of thinking and prevention and treatment levels of bronchial asthma and COPD by Chinese medicine. PMID:24063226

  19. 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.

  20. 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. PMID:25736171

  1. Potential of Immunoglobulin A to Prevent Allergic Asthma

    PubMed Central

    Gloudemans, Anouk K.; Lambrecht, Bart N.; Smits, Hermelijn H.

    2013-01-01

    Allergic asthma is characterized by bronchial hyperresponsiveness, a defective barrier function, and eosinophilic lower airway inflammation in response to allergens. The inflammation is dominated by Th2 cells and IgE molecules and supplemented with Th17 cells in severe asthma. In contrast, in healthy individuals, allergen-specific IgA and IgG4 molecules are found but no IgE, and their T cells fail to proliferate in response to allergens, probably because of the development of regulatory processes that actively suppress responses to allergens. The presence of allergen-specific secretory IgA has drawn little attention so far, although a few epidemiological studies point at a reverse association between IgA levels and the incidence of allergic airway disease. This review highlights the latest literature on the role of mucosal IgA in protection against allergic airway disease, the mechanisms described to induce secretory IgA, and the role of (mucosal) dendritic cells in this process. Finally, we discuss how this information can be used to translate into the development of new therapies for allergic diseases based on, or supplemented with, IgA boosting strategies. PMID:23690823

  2. Allergic dermatoses and respiratory diseases from reactive dyes.

    PubMed

    Estlander, T

    1988-05-01

    5 cases of occupational eczema, urticaria and respiratory disease from reactive dyes, occurring during 1977-1987, are reported. The patients, 4 men and 1 woman, were 24-52 years old when examined. They had been working in dye houses or textile plants, and had been exposed to reactive dyes for 8 months to 4 years before symptoms developed. Only 1 of the patients has been able to continue in the same occupation. On patch testing, the 4 patients with eczema reacted positively to 9 commercial dye powders. 2 patients reacted to the same dye, Remazol Schwarz B. On scratch and/or prick testing, the 2 patients who also had respiratory symptoms and/or urticaria reacted positively to the same dyes as on patch testing. The 5th patient, who had urticaria and respiratory symptoms, reacted positively to a dye, Remazol Gold Gelb RNL, but the patch test with that dye was negative. None of the patients was patch-test-positive to para-phenylenediamine (PPD) or to textile dye allergens in a series of organic dyes. Thus, the series of organic dyes has little value in the screening of allergy to reactive dyes. A 1% pet. dilution of commercial dye powder for patch testing and the same concentration in distilled water for prick testing seem to be suitable for the screening of allergy to reactive dyes.

  3. 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.

  4. 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

  5. Allergen-specific immunotherapy: towards combination vaccines for allergic and infectious diseases.

    PubMed

    Edlmayr, Johanna; Niespodziana, Katarzyna; Focke-Tejkl, Margarete; Linhart, Birgit; Valenta, Rudolf

    2011-01-01

    IgE-mediated allergies affect more than 25% of the population. Allergen-specific immunotherapy (SIT) is an antigen-specific and disease-modifying form of treatment. It is based on the therapeutic administration of the disease-causing allergens to allergic patients. However, the fact that only allergen extracts of insufficient quality are currently available and the possible occurrence of side effects during treatment limit the broad use of SIT and prophylactic vaccination is has not yet been performed. In the last 20 years the DNA sequences of the most common allergens have been isolated and the corresponding allergens have been produced as recombinant allergens. Based on the progress made in the field of allergen characterization it is possible to improve the quality and safety of allergy vaccines and to develop new, more effective strategies for a broad application of SIT and even for prophylactic treatment. Here we discuss the development of combination vaccines for allergy and infectious diseases. This approach is based on the selection of allergen-derived peptides with reduced IgE- and T cell reactivity in order to minimize IgE- and T cell-mediated side effects as well as the potential of the vaccine to induce allergic sensitization. These peptides are fused by recombinant technology onto a viral carrier protein to obtain a combination vaccine which induces protective immunity against allergy and viral infections. The application of such combination vaccines for therapy and prophylaxis of allergy and infectious diseases is discussed.

  6. Is Folate Status a Risk Factor for Asthma or Other Allergic Diseases?

    PubMed Central

    Wang, Ting; Zhang, Hong-Ping; Zhang, Xin; Liang, Zong-An; Ji, Yu-Lin

    2015-01-01

    Purpose It is controversial whether folate status is a risk factor for the development of asthma or other allergic diseases. This study was conducted to investigate whether indirect or direct exposure to folate and impaired folate metabolism, reflected as methylene-tetrahydrofolate reductase (MTHFR) C677T polymorphism, would contribute to the development of asthma and other allergic diseases. Methods Electronic databases were searched to identify all studies assessing the association between folate status and asthma or other allergic diseases. Two reviewers independently assessed the eligibility of studies and extracted data. The relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CI) was calculated and pooled. Results Twenty-six studies (16 cohort, 7 case-control, and 3 cross-sectional studies) were identified. Maternal folic acid supplementation was not associated with the development of asthma, atopic dermatitis (AD), eczema, and sensitization in the offspring, whereas exposure during early pregnancy was related to wheeze occurrence in the offspring (RR=1.06, 95% CI=[1.02-1.09]). The TT genotype of MTHFR C677T polymorphism was at high risk of asthma (OR=1.41, 95% CI=[1.07-1.86]). Conclusions It is indicated that maternal folic acid supplementation during early pregnancy may increase the risk of wheeze in early childhood and that the TT genotype of MTHFR C677T polymorphism impairing folic acid metabolism would be at high risk of asthma development. These results might provide additional information for recommendations regarding forced folate consumption or folic acid supplements during pregnancy based on its well-established benefits for the prevention of congenital malformations. However, currently available evidence is of low quality which is needed to further elucidate. PMID:26333700

  7. Mucosal-associated invariant T cells in autoimmunity, immune-mediated diseases and airways disease.

    PubMed

    Hinks, Timothy S C

    2016-05-01

    Mucosal-associated invariant T (MAIT) cells are a novel class of innate-like T cells, expressing a semi-invariant T-cell receptor (TCR) and able to recognize small molecules presented on the non-polymorphic MHC-related protein 1. Their intrinsic effector-memory phenotype, enabling secretion of pro-inflammatory cytokines, and their relative abundance in humans imply a significant potential to contribute to autoimmune processes. However, as MAIT cells were unknown until recently and specific immunological tools were unavailable, little is known of their roles in disease. Here I review observations from clinical studies and animal models of autoimmune and immune-mediated diseases including the roles of MAIT cells in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and airways diseases. MAIT cell deficiencies are frequently observed in peripheral blood, and at sites of disease such as the airways in asthma. However, MAIT cells have a specific sensitivity to suppression by therapeutic corticosteroids that may confound many of these observations, as may the tendency of the surface marker CD161 to activation-induced down-regulation. Nonetheless, the dependence on bacteria for the development of MAIT cells suggests a potentially important protective role linking the influences of early life microbial exposures and subsequent development of autoimmunity. Conversely, MAIT cells could contribute to chronic inflammation either through TCR-independent activation, or potentially by TCR recognition of as yet undiscovered ligands. Future research will be greatly facilitated by the immunological tools that are now available, including murine genetic models and human and murine specific tetramers.

  8. Mucosal-associated invariant T cells in autoimmunity, immune-mediated diseases and airways disease.

    PubMed

    Hinks, Timothy S C

    2016-05-01

    Mucosal-associated invariant T (MAIT) cells are a novel class of innate-like T cells, expressing a semi-invariant T-cell receptor (TCR) and able to recognize small molecules presented on the non-polymorphic MHC-related protein 1. Their intrinsic effector-memory phenotype, enabling secretion of pro-inflammatory cytokines, and their relative abundance in humans imply a significant potential to contribute to autoimmune processes. However, as MAIT cells were unknown until recently and specific immunological tools were unavailable, little is known of their roles in disease. Here I review observations from clinical studies and animal models of autoimmune and immune-mediated diseases including the roles of MAIT cells in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and airways diseases. MAIT cell deficiencies are frequently observed in peripheral blood, and at sites of disease such as the airways in asthma. However, MAIT cells have a specific sensitivity to suppression by therapeutic corticosteroids that may confound many of these observations, as may the tendency of the surface marker CD161 to activation-induced down-regulation. Nonetheless, the dependence on bacteria for the development of MAIT cells suggests a potentially important protective role linking the influences of early life microbial exposures and subsequent development of autoimmunity. Conversely, MAIT cells could contribute to chronic inflammation either through TCR-independent activation, or potentially by TCR recognition of as yet undiscovered ligands. Future research will be greatly facilitated by the immunological tools that are now available, including murine genetic models and human and murine specific tetramers. PMID:26778581

  9. 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.

  10. Brain-Derived Neurotrophic Factor in the Airways

    PubMed Central

    Prakash, Y.S.; Martin, Richard J.

    2014-01-01

    In addition to their well-known roles in the nervous system, there is increasing recognition that neurotrophins such as brain derived neurotrophic factor (BDNF) as well as their receptors are expressed in peripheral tissues including the lung, and can thus potentially contribute to both normal physiology and pathophysiology of several diseases. The relevance of this family of growth factors lies in emerging clinical data indicating altered neurotrophin levels and function in a range of diseases including neonatal and adult asthma, sinusitis, influenza, and lung cancer. The current review focuses on 1) the importance of BDNF expression and signaling mechanisms in early airway and lung development, critical to both normal neonatal lung function and also its disruption in prematurity and insults such as inflammation and infection; 2) how BDNF, potentially derived from airway nerves modulate neurogenic control of airway tone, a key aspect of airway reflexes as well as dysfunctional responses to allergic inflammation; 3) the emerging idea that local BDNF production by resident airway cells such as epithelium and airway smooth muscle can contribute to normal airway structure and function, and to airway hyperreactivity and remodeling in diseases such as asthma. Furthermore, given its pleiotropic effects in the airway, BDNF may be a novel and appealing therapeutic target. PMID:24560686

  11. Adaptation to Impacts of Climate Change on Aeroallergens and Allergic Respiratory Diseases

    PubMed Central

    Beggs, Paul J.

    2010-01-01

    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. PMID:20948943

  12. 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. PMID:20948943

  13. [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.

  14. 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.

  15. Inhaled birch pollen extract induces airway hyperresponsiveness via oxidative stress but independently of pollen-intrinsic NADPH oxidase activity, or the TLR4-TRIF pathway.

    PubMed

    Shalaby, Karim H; Allard-Coutu, Alexandra; O'Sullivan, Michael J; Nakada, Emily; Qureshi, Salman T; Day, Brian J; Martin, James G

    2013-07-15

    Oxidative stress in allergic asthma may result from oxidase activity or proinflammatory molecules in pollens. Signaling via TLR4 and its adaptor Toll-IL-1R domain-containing adapter inducing IFN-β (TRIF) has been implicated in reactive oxygen species-mediated acute lung injury and in Th2 immune responses. We investigated the contributions of oxidative stress and TLR4/TRIF signaling to experimental asthma induced by birch pollen exposure exclusively via the airways. Mice were exposed to native or heat-inactivated white birch pollen extract (BPEx) intratracheally and injected with the antioxidants, N-acetyl-L-cysteine or dimethylthiourea, prior to sensitization, challenge, or all allergen exposures, to assess the role of oxidative stress and pollen-intrinsic NADPH oxidase activity in allergic sensitization, inflammation, and airway hyperresponsiveness (AHR). Additionally, TLR4 signaling was antagonized concomitantly with allergen exposure, or the development of allergic airway disease was evaluated in TLR4 or TRIF knockout mice. N-acetyl-L-cysteine inhibited BPEx-induced eosinophilic airway inflammation and AHR except when given exclusively during sensitization, whereas dimethylthiourea was inhibitory even when administered with the sensitization alone. Heat inactivation of BPEx had no effect on the development of allergic airway disease. Oxidative stress-mediated AHR was also TLR4 and TRIF independent; however, TLR4 deficiency decreased, whereas TRIF deficiency increased BPEx-induced airway inflammation. In conclusion, oxidative stress plays a significant role in allergic sensitization to pollen via the airway mucosa, but the pollen-intrinsic NADPH oxidase activity and TLR4 or TRIF signaling are unnecessary for the induction of allergic airway disease and AHR. Pollen extract does, however, activate TLR4, thereby enhancing airway inflammation, which is restrained by the TRIF-dependent pathway.

  16. 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...

  17. 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...

  18. 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

  19. 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

  20. [Real effect of specific hyposensitisation in therapy of allergic respiratory diseases].

    PubMed

    Plavsić, Z; Petrović, M; Popovac, D

    1994-01-01

    There are different opinions on the positive effect of hyposensitisation in the treatment of allergic respiratory diseases. In this paper we wish to point out our experience, without intention to clear up these "contrary opinions". Sixty patients of both sexes, aged from 10-55 years, were on specific hyposensitisation over a period from three to five years. Two thirds (63%) were with bronchial asthma and 37% with allergic rhinitis. Most of them (80%) were on specific hyposensitisation to one allergen (Dermatophagoides pteronyssinus, grass or reguid polen), and to two allergens 20% patients. During this therapy 63% of patients had no additional medicamentae therapy. Most of them stopped additional medication during the first year of immunotherapy. Ten percent of patients took medicaments when they needed them, and 28% took them continually. Clinical symptoms characteristic of these diseases were also rare. The average value of IgE was 636 UI/ml before and 341 UI/ml after the immunotherapy. The efficacy of immunotherapy depended on the correct selection of patients, good standardisation of antigen extract, and a right dose of allergen in the prolonged immunotherapy. PMID:17974388

  1. 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.

  2. The genetics of asthma and allergic disease: a 21st century perspective.

    PubMed

    Ober, Carole; Yao, Tsung-Chieh

    2011-07-01

    Asthma and allergy are common conditions with complex etiologies involving both genetic and environmental contributions. Recent genome-wide association studies (GWAS) and meta-analyses of GWAS have begun to shed light on both common and distinct pathways that contribute to asthma and allergic diseases. Associations with variation in genes encoding the epithelial cell-derived cytokines, interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), and the IL1RL1 gene encoding the IL-33 receptor, ST2, highlight the central roles for innate immune response pathways that promote the activation and differentiation of T-helper 2 cells in the pathogenesis of both asthma and allergic diseases. In contrast, variation at the 17q21 asthma locus, encoding the ORMDL3 and GSDML genes, is specifically associated with risk for childhood onset asthma. These and other genetic findings are providing a list of well-validated asthma and allergy susceptibility genes that are expanding our understanding of the common and unique biological pathways that are dysregulated in these related conditions. Ongoing studies will continue to broaden our understanding of asthma and allergy and unravel the mechanisms for the development of these complex traits. PMID:21682736

  3. 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

  4. Allergic inflammation: where epithelial function interacts with immune response in atopic diseases.

    PubMed

    Godoy, Laura

    2009-05-01

    Current hot topics in allergy and asthma were presented this year at the annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) in Washington, D.C. Understanding the natural history of allergic diseases is an area of interest because it could help to identify relevant biomarkers to predict allergy early in infancy. An abnormal epithelial barrier allows easy access to allergens/ pathogens and such a dysfunction could also be involved in the initiation of the natural course of allergic diseases. In addition, newly identified cytokines produced by epithelial cells such as thymic stromal lymphopoietin, interleukin-33 (IL-33) and IL-25 are involved in the generation of T helper type 2 (Th2) cell response. Genetic studies are also providing relevant information on biomarkers and new targets for allergy and asthma. Different genetic studies to identify single nucleotide polymorphisms of relevant mediators of allergy in patients, application of gene array analysis to identify biomarkers during asthma exacerbation, and IL-13-induced inflammatory events, are some examples of the interesting information presented at the AAAAI this year.

  5. Comparison of breast, cow, and soy feedings in the prevention of onset of allergic disease: a 15-year prospective study.

    PubMed

    Gruskay, F L

    1982-08-01

    It has been reported that the feeding of cow's milk may enhance the development of atopy in predisposed infants. A prospective study following children from birth through 15 years of age in a private pediatric practice was designed to determine if the food ingested during the first months of life is related to the development of atopy in the offspring of allergic families. Each of 328 children with a positive family history of allergy was assigned to one of three groups according to the feeding preference of the parents: 48 were fed breast milk; 79 soy-based formula; and 201, cow's milk formula. All groups had egg, citrus, tomato, and wheat restrictions as well as inhalant allergen avoidance. These were compared to a control group of 580 children with no family history of allergy. Breast fed infants were found to have approximately one-half the incidence of atopy of cow's milk or soy formula fed infants from atopic families when followed for up to 15 years. Soy feeding produced no advantage over cow's milk in the prophylaxis of allergic disease. There was a three-fold increase in clinically apparent atopic disease in offspring of allergic families when compared to controls but only a two-fold increase if the infant was breast fed. These results support the hypothesis that breast feeding and delay of exposure to known allergens may reduce the frequency of clinical allergic disease in the offspring of allergic families.

  6. Effects of allergic diseases and age on the composition of serum IgG glycome in children.

    PubMed

    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

  7. 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

  8. [Value of the study of the functional potential of neutrophils in suppurative, septic and allergic diseases in children].

    PubMed

    Nesterova, I V; Svetlichnaia, M A

    1989-01-01

    A method for measuring the content of cationic proteins in neutrophil granulocytes of the peripheral blood was employed in patients with pyoseptic (n = 12) and allergic (n = 28) diseases during the exposure to composite infections in vitro. The method enables one to assess the functional potentialities of the cells in mobilizing the internal reserves and the readiness for the trigger of the cellular granular apparatus, for instance during real or predicted exposure of the child to bacterial infections. The determination of the functional potentialities of neutrophil phagocytes can be used as a test for the appraisal of the gravity of allergic and pyoseptic processes as well as for predicting outcomes of pyoseptic diseases.

  9. [Relationship of the ambient air concentrations of chemical substances to the spread of allergic diseases in children].

    PubMed

    Galeev, K A; Khakimova, R F

    2002-01-01

    The role of some ingredients that contaminate the ambient air in the occurrence and development of allergic diseases was studied. The closest relationships were found between the concentrations of hydrogen sulfide and the prevalence of eczema (rxy +/- m = 0.48 +/- 0.15). There was a direct correlation between the concentrations of each ingredient and the incidence of neurodermitis among children. The correlation between the summarized concentrations of ingredients and the incidence of bronchial asthma among children was rxy +/- m = 0.71 +/- 0.19. The findings serves as the basis for elaborating measures to reduce ecological tension and the incidence of allergic diseases in children. PMID:12380496

  10. Albuterol HFA for the management of obstructive airway disease.

    PubMed

    Colice, Gene L

    2008-04-01

    Albuterol (salbutamol outside the USA) is used to acutely relieve symptoms related to airway obstruction and prevent exercise-induced bronchospasm. Albuterol is most commonly administered by metered-dose inhaler (MDI). MDIs had used chlorofluorocarbon (CFC) propellants, but CFCs accumulate in the stratosphere and contribute to ozone catabolism. Loss of the 'ozone layer', which filters UVB rays, has public health concerns. Albuterol has been reformulated in MDIs using hydrofluoroalkane (HFA) propellants, which do not affect the ozone layer. Albuterol HFA MDIs deliver the same amount of drug per puff with similar particle size distributions as albuterol CFC MDIs, resulting in comparable bronchodilator efficacy of the two products. The highly favorable safety profile of albuterol has not been altered with reformulation. The propellant HFA-134a appears to be devoid of safety concerns.

  11. Zinc oxide nanoparticles, a novel candidate for the treatment of allergic inflammatory diseases.

    PubMed

    Kim, Min-Ho; Seo, Jun-Ho; Kim, Hyung-Min; Jeong, Hyun-Ja

    2014-09-01

    Zinc (Zn) is an essential trace metal for eukaryotes. The roles of Zn in the numerous physiological functions have been elucidated. Bamboo salt contains Zn that was shown to have anti-inflammatory effect and other health benefits. Nanoparticles of various types have found application in the biology, medicine, and physics. Here we synthesized tetrapod-like, zinc oxide nanoparticles (ZO-NP; diameter 200 nm, source of Zn) using a radio frequency thermal plasma system and investigated its effects on mast cell-mediated allergic inflammatory reactions. ZO-NP was found to inhibit the productions and mRNA expressions of inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α on the phorbol 12-myristate 13-acetate plus A23187 (PMACI)-stimulated human mast cell line, HMC-1 cells. In these stimulated cells, caspase-1 and nuclear factor-κB activations were abolished by ZO-NP, and the expressions of receptor interacting protein2 (RIP2) and IκB kinaseβ (IKKβ) induced by PAMCI were reduced. On the other hand, ZO-NP alone increased the expressions of RIP2 and IKKβ in normal condition. ZO-NP inhibited the phosphorylation of extracellular signal-regulated protein kinase in the PMACI-stimulated HMC-1 cells. Furthermore, ZO-NP significantly inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl IgE. These findings indicate that ZO-NP effectively ameliorates mast cell-mediated allergic inflammatory reaction, and suggest that ZO-NP be considered a potential therapeutic for the treatment of mast cell-mediated allergic diseases.

  12. What's in a name? Inflammatory airway disease in racehorses in training.

    PubMed

    Cardwell, J M; Christley, R M; Gerber, V; Malikides, N; Wood, J L N; Newton, J R; Hodgson, J L

    2011-11-01

    The term 'inflammatory airway disease' (IAD) is often used to describe the syndrome of lower airway inflammation that frequently affects young racehorses in training around the world. In practice, this inflammation is generally diagnosed using a combination of endoscopic tracheal examination, including grading of amounts of mucus present and tracheal wash sampling. However, a recent consensus statement from the American College of Veterinary Internal Medicine concluded that bronchoalveolar lavage (BAL) sampling, rather than tracheal wash (TW) sampling, is required for cytological diagnosis of IAD and that tracheal mucus is not an essential criterion. However, as BAL is a relatively invasive procedure that is not commonly used on racing yards, this definition can only be applied routinely to a biased referral population. In contrast, many practitioners continue to diagnose IAD using endoscopic tracheal examination and sampling. We argue that, rather than restricting the use of the term IAD to phenotypes diagnosed by BAL, it is important to distinguish in the literature between airway inflammation diagnosed by BAL and that identified in the field using TW sampling. We suggest the use of the term brIAD for the former and trIAD for the latter. It is essential that we continue to endeavour to improve our understanding of the aetiology, pathogenesis and clinical relevance of airway inflammation identified in racehorses in training using tracheal examination and sampling. Future studies should focus on investigations of the component signs of airway inflammation.

  13. Pluripotent Allospecific CD8+ Effector T Cells Traffic to Lung in Murine Obliterative Airway Disease

    PubMed Central

    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-γ+ T cells were detected in airway allografts, with significant coexpression of TNF-α and granzyme B. Therefore, using IFN-γ as a surrogate marker, we assessed the distribution and kinetics of extragraft allo-specific T cells during OAD. Robust allospecific IFN-γ 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. PMID:16195540

  14. Climate change, air pollution and extreme events leading to increasing prevalence of allergic respiratory diseases.

    PubMed

    D'Amato, Gennaro; Baena-Cagnani, Carlos E; Cecchi, Lorenzo; Annesi-Maesano, Isabella; Nunes, Carlos; Ansotegui, Ignacio; D'Amato, Maria; Liccardi, Gennaro; Sofia, Matteo; Canonica, Walter G

    2013-01-01

    The prevalence of asthma and allergic diseases has increased dramatically during the past few decades not only in industrialized countries. Urban air pollution from motor vehicles has been indicated as one of the major risk factors responsible for this increase.Although genetic factors are important in the development of asthma and allergic diseases, the rising trend can be explained only in changes occurred in the environment. 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 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. Associations between thunderstorms and asthma morbidity in pollinosis subjects have been also identified in multiple locations around the world.Allergens patterns are also changing in response to climate change and air pollution can modify the allergenic potential of pollens especially in presence of specific weather conditions.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.Factor clouding the issue is that laboratory evaluations do not reflect what happens during natural exposition, when atmospheric pollution mixtures in polluted cities are inhaled. 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

  15. Climate change, air pollution and extreme events leading to increasing prevalence of allergic respiratory diseases

    PubMed Central

    2013-01-01

    The prevalence of asthma and allergic diseases has increased dramatically during the past few decades not only in industrialized countries. Urban air pollution from motor vehicles has been indicated as one of the major risk factors responsible for this increase. Although genetic factors are important in the development of asthma and allergic diseases, the rising trend can be explained only in changes occurred in the environment. 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 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. Associations between thunderstorms and asthma morbidity in pollinosis subjects have been also identified in multiple locations around the world. Allergens patterns are also changing in response to climate change and air pollution can modify the allergenic potential of pollens especially in presence of specific weather conditions. 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. Factor clouding the issue is that laboratory evaluations do not reflect what happens during natural exposition, when atmospheric pollution mixtures in polluted cities are inhaled. 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

  16. Climate change, air pollution and extreme events leading to increasing prevalence of allergic respiratory diseases.

    PubMed

    D'Amato, Gennaro; Baena-Cagnani, Carlos E; Cecchi, Lorenzo; Annesi-Maesano, Isabella; Nunes, Carlos; Ansotegui, Ignacio; D'Amato, Maria; Liccardi, Gennaro; Sofia, Matteo; Canonica, Walter G

    2013-02-11

    The prevalence of asthma and allergic diseases has increased dramatically during the past few decades not only in industrialized countries. Urban air pollution from motor vehicles has been indicated as one of the major risk factors responsible for this increase.Although genetic factors are important in the development of asthma and allergic diseases, the rising trend can be explained only in changes occurred in the environment. 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 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. Associations between thunderstorms and asthma morbidity in pollinosis subjects have been also identified in multiple locations around the world.Allergens patterns are also changing in response to climate change and air pollution can modify the allergenic potential of pollens especially in presence of specific weather conditions.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.Factor clouding the issue is that laboratory evaluations do not reflect what happens during natural exposition, when atmospheric pollution mixtures in polluted cities are inhaled. 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

  17. 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

  18. 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

  19. Subcutaneous allergen immunotherapy for allergic disease: examining efficacy, safety and cost-effectiveness of current and novel formulations.

    PubMed

    Cox, Linda; Calderón, Moisés; Pfaar, Oliver

    2012-06-01

    Subcutaneous immunotherapy (SCIT) is a unique therapy for allergic disease because it provides symptomatic relief while modifying the allergic disease by targeting the underlying immunological mechanism. Its efficacy and safety have been established in the treatment of asthma, allergic rhinitis/rhinoconjunctivitis and stinging insect hypersensitivity in numerous controlled clinical trials. This review evaluates a spectrum of clinical factors, ranging from efficacy to cost-effectiveness, which should be considered in evaluating SCIT. The evidence for SCIT safety and efficacy for these conditions is reviewed in an evaluation of the systematic reviews and meta-analyses. The evidence for the persistent and preventive effects of SCIT is also examined. An overview of the SCIT outcomes measures utilized in clinical trials is presented. The cost-effectiveness of SCIT compared with conventional medication treatment, novel indications and formulations for SCIT are also explored in this review. PMID:22788128

  20. Dietary prevention of allergic diseases in infants and small children. Part I: immunologic background and criteria for hypoallergenicity.

    PubMed

    Muraro, Antonella; Dreborg, Sten; Halken, Susanne; Høst, Arne; Niggemann, Bodo; Aalberse, Rob; Arshad, Syed H; Berg Av, Andrea von; Carlsen, Kai- Hå kon; Duschén, Karel; Eigenmann, Philippe; Hill, David; Jones, Catherine; Mellon, Michael; Oldeus, Göran; Oranje, Arnold; Pascual, Cristina; Prescott, Susan; Sampson, Hugh; Svartengren, Magnus; Vandenplas, Yvan; Wahn, Ulrich; Warner, Jill A; Warner, John O; Wickman, Magnus; Zeiger, Robert S

    2004-04-01

    The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light into this issue, a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. In this paper, the immunology of the fetus and newborn is reviewed as well as the post-natal development of the immune system. The influence of post-natal environment and breastfeeding on tolerance induction and sensitization are examined. Allergic diseases result from a strong relationship between genetic and environmental factors. Sensitization to food allergens occurs in the first year of life and cow's milk allergy is the first food allergy to appear in the susceptible infants. Hypoallergenicity of food formulas to be used is a critical issue both for treatment of cow's milk-allergic children and for prevention. Methods to document hypoallergenicity are discussed and evaluated in the preclinical and clinical steps.

  1. Reversal of established CD4+ type 2 T helper-mediated allergic airway inflammation and eosinophilia by therapeutic treatment with DNA vaccines limits progression towards chronic inflammation and remodelling

    PubMed Central

    Jarman, Elizabeth R; Lamb, Jonathan R

    2004-01-01

    Immunostimulatory DNA-based vaccines can prevent the induction of CD4+ type 2 T helper (Th2) cell-mediated airway inflammation in experimental models, when administered before or at the time of allergen exposure. Here we demonstrate their efficacy in limiting the progression of an established response to chronic pulmonary inflammation and airway remodelling on subsequent allergen challenge. Mice exhibiting Th2-mediated airway inflammation induced following sensitization and challenge with group 1 allergen derived from Dermatophagoides pteronyssinus group species (Der p 1), a major allergen of house dust mite, were treated with pDNA vaccines. Their airways were rechallenged and the extent of inflammation assessed. In plasma DNA (pDNA)-vaccinated mice, infiltration of inflammatory cells, goblet cell hyperplasia and mucus production were reduced and subepithelial fibrosis attenuated. The reduction in eosinophil numbers correlated with a fall in levels of the profibrotic mediator transforming growth factor (TGF)-β1 in bronchoalveolar lavage (BAL) and lung tissue. In addition to lung epithelial cells and resident alveolar macrophages, infiltrating eosinophils, the principle inflammatory cells recruited following allergen exposure, were a major source of TGF-β1. Protection, conferred irrespective of the specificity of the pDNA construct, did not correlate with a sustained increase in systemic interferon (IFN)-γ production but in a reduction in levels of the Th2 pro-inflammatory cytokines. Notably, there was a reduction in levels of interleukin (IL)-5 and IL-13 produced by systemic Der p 1 reactive CD4+ Th2 cells on in vitro stimulation as well as in IL-4 and IL-5 levels in BAL fluid. These data suggest that suppression of CD4+ Th2-mediated inflammation and eosinophilia were sufficient to attenuate progression towards airway remodelling. Immunostimulatory DNA may therefore have a therapeutic application in treatment of established allergic asthma in patients. PMID

  2. Early-Life Intranasal Colonization with Nontypeable Haemophilus influenzae Exacerbates Juvenile Airway Disease in Mice.

    PubMed

    McCann, Jessica R; Mason, Stanley N; Auten, Richard L; St Geme, Joseph W; Seed, Patrick C

    2016-07-01

    Accumulating evidence suggests a connection between asthma development and colonization with nontypeable Haemophilus influenzae (NTHi). Specifically, nasopharyngeal colonization of human infants with NTHi within 4 weeks of birth is associated with an increased risk of asthma development later in childhood. Monocytes derived from these infants have aberrant inflammatory responses to common upper respiratory bacterial antigens compared to those of cells derived from infants who were not colonized and do not go on to develop asthma symptoms in childhood. In this study, we hypothesized that early-life colonization with NTHi promotes immune system reprogramming and the development of atypical inflammatory responses. To address this hypothesis in a highly controlled model, we tested whether colonization of mice with NTHi on day of life 3 induced or exacerbated juvenile airway disease using an ovalbumin (OVA) allergy model of asthma. We found that animals that were colonized on day of life 3 and subjected to induction of allergy had exacerbated airway disease as juveniles, in which exacerbated airway disease was defined as increased cellular infiltration into the lung, increased amounts of inflammatory cytokines interleukin-5 (IL-5) and IL-13 in lung lavage fluid, decreased regulatory T cell-associated FOXP3 gene expression, and increased mucus production. We also found that colonization with NTHi amplified airway resistance in response to increasing doses of a bronchoconstrictor following OVA immunization and challenge. Together, the murine model provides evidence for early-life immune programming that precedes the development of juvenile airway disease and corroborates observations that have been made in human children.

  3. Bee venom phospholipase A2 suppresses allergic airway inflammation in an ovalbumin-induced asthma model through the induction of regulatory T cells.

    PubMed

    Park, Soojin; Baek, Hyunjung; Jung, Kyung-Hwa; Lee, Gihyun; Lee, Hyeonhoon; Kang, Geun-Hyung; Lee, Gyeseok; Bae, Hyunsu

    2015-12-01

    Bee venom (BV) is one of the alternative medicines that have been widely used in the treatment of chronic inflammatory diseases. We previously demonstrated that BV induces immune tolerance by increasing the population of regulatory T cells (Tregs) in immune disorders. However, the major component and how it regulates the immune response have not been elucidated. We investigated whether bee venom phospholipase A2 (bvPLA2) exerts protective effects that are mediated via Tregs in OVA-induced asthma model. bvPLA2 was administered by intraperitoneal injection into control and OVA-challenged mice. The Treg population, total and differential bronchoalveolar lavage fluid (BALF) cell count, Th2 cytokines, and lung histological features were assessed. Treg depletion was used to determine the involvement of Treg migration and the reduction of asthmatic symptoms. The CD206-dependence of bvPLA2-treated suppression of airway inflammation was evaluated in OVA-challenged CD206(-/-) mice. The bvPLA2 treatment induced the Tregs and reduced the infiltration of inflammatory cells into the lung in the OVA-challenged mice. Th2 cytokines in the bronchoalveolar lavage fluid (BALF) were reduced in bvPLA2-treated mice. Although bvPLA2 suppressed the number of inflammatory cells after OVA challenge, these effects were not observed in Treg-depleted mice. In addition, we investigated the involvement of CD206 in bvPLA2-mediated immune tolerance in OVA-induced asthma model. We observed a significant reduction in the levels of Th2 cytokines and inflammatory cells in the BALF of bvPLA2-treated OVA-induced mice but not in bvPLA2-treated OVA-induced CD206(-/-) mice. These results demonstrated that bvPLA2 can mitigate airway inflammation by the induction of Tregs in an OVA-induced asthma model. PMID:26734460

  4. 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. PMID:27150641

  5. Oral immunotherapy for allergic diseases using transgenic rice seeds: current state and future prospects.

    PubMed

    Saeki, Mayumi; Nishimura, Tomoe; Kaminuma, Osamu; Mori, Akio; Hiroi, Takachika

    2013-01-01

    Allergen-specific immunotherapy (IT) has been shown to provide clinical benefit for patients with allergic diseases. At present, subcutaneous and sublingual ITs are mainly authorized for clinical treatment. Oral administration of allergens seems to be the easiest way to achieve IT, though it has yet to be translated to the clinical setting, mainly due to the requirement of a large amount of allergens. Plants, especially rice seeds, have recently been recognized as superior allergen carriers for oral administration, because of their high productivity, stability and safety. Therefore, in order to establish clinically applicable oral IT, we have been developing transgenic rice seeds (Tg rice), in which major epitopes of cedar pollen allergens or house-dust mites (HDM) are expressed. The efficacy of this orally administered Tg rice was confirmed in murine models of allergic rhinitis and bronchial asthma. In the safety study of the Tg rice, no adverse effects on cynomolgus macaques were observed. In this review, we summarized the current state and future prospects of allergen-specific IT, focusing particularly on oral IT with allergen-expressing Tg rice.

  6. Nedocromil sodium in obstructive airways disease: effect on symptoms and plasma protein leakage in sputum.

    PubMed

    Schoonbrood, D F; Out, T A; Hart, A A; Habets, F J; Roos, C M; Jansen, H M

    1997-07-01

    In patients with asthma or chronic obstructive pulmonary disease, there is chronic airway inflammation with increased leakage of plasma proteins into the airway lumen, which can be reduced by inhaled glucocorticosteroids. Nedocromil sodium is an anti-inflammatory drug, and we questioned whether it also affects the leakage of plasma proteins. In a double-blind placebo-controlled study we investigated the effect of 12 weeks of treatment with nedocromil on forced expiratory volume in one second (FEV1), provocative concentration of histamine causing a 20% fall in FEV1 (PC20), peak flow, symptom scores, and plasma protein leakage in sputum, in 31 patients with obstructive airways disease and sputum production (mean (range) FEV1 61% of predicted (42-87%); geometric mean (range) PC20 0.39 (0.04-2.9) mg x mL(-1)). As a measure for plasma protein leakage we calculated the relative coefficients of excretion (RCE) of proteins from serum to the soluble phase of sputum. There was a small increase in morning and evening peak flow (p<0.05) and a decrease in night-time bronchodilator use (p<0.02) in favour of nedocromil. The RCE of alpha2-macroglobulin to albumin significantly decreased after treatment with nedocromil (p=0.03). The results show limited clinical efficacy of nedocromil in our study group. They further suggest that the anti-inflammatory properties of nedocromil extend to inhibition of plasma protein leakage into the airways.

  7. Smokers with emphysema and small airway disease on computed tomography have lower bone density

    PubMed Central

    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. PMID:27354779

  8. 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.

  9. 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. PMID:27354779

  10. Airway epithelial NF-κB activation promotes the ability to overcome inhalational antigen tolerance

    PubMed Central

    Ather, Jennifer L.; Foley, Kathryn L.; Suratt, Benjamin T.; Boyson, Jonathan E.; Poynter, Matthew E.

    2015-01-01

    Background Inhalational antigen tolerance typically protects against the development of allergic airway disease but may be overcome to induce allergic sensitization preceding the development of asthma. Objectives We examined in vivo whether pre-existing inhalational antigen tolerance could be overcome by activation of the transcription factor NF-κB in conducting airway epithelial cells, and used a combination of in vivo and in vitro approaches to examine the mechanisms involved. Methods Wildtype and transgenic mice capable of expressing constitutively active IκB kinase β (CAIKKβ) in airway epithelium were tolerized to inhaled ovalbumin. Twenty-eight days later, the transgene was transiently expressed and mice were exposed to inhaled OVA on day 30 in an attempt to overcome inhalational tolerance. Results Following ovalbumin challenge on days 40-42, CAIKKβ mice in which the transgene had been activated exhibited characteristic features of allergic airway disease, including airway eosinophilia and methacholine hyperresponsiveness. Increases in the CD103+ and CD11bHI lung dendritic cell populations were present in CAIKKβ mice on day 31. Bronchoalveolar lavage from mice expressing CAIKKβ mice induced CD4+ T cells to secrete TH2 and TH17 cytokines, an effect that required IL-4 and IL-1 signaling, respectively. CAIKKβ mice on Dox demonstrated increased numbers of innate lymphoid type 2 cells (ILC2) in the lung, which also exhibited elevated mRNA expression of the TH2-polarizing cytokine IL-4. Finally, airway epithelial NF-kB activation induced allergic sensitization in CAIKKβ mice on Dox that required IL-4 and IL-1-signaling in vivo. Conclusions Our studies demonstrate that soluble mediators generated in response to airway epithelial NF-κB activation orchestrate the breaking of inhalational tolerance and allergic antigen sensitization through the effects of soluble mediators, including IL-1 and IL-4, on pulmonary dendritic cells as well as innate lymphoid and CD

  11. Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity.

    PubMed

    Clayton, Gina M; Wang, Yang; Crawford, Frances; Novikov, Andrey; Wimberly, Brian T; Kieft, Jeffrey S; Falta, Michael T; Bowerman, Natalie A; Marrack, Philippa; Fontenot, Andrew P; Dai, Shaodong; Kappler, John W

    2014-07-01

    T-cell-mediated hypersensitivity to metal cations is common in humans. How the T cell antigen receptor (TCR) recognizes these cations bound to a major histocompatibility complex (MHC) protein and self-peptide is unknown. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. Here, we show that the T cell ligand is created when a Be(2+) cation becomes buried in an HLA-DP2/peptide complex, where it is coordinated by both MHC and peptide acidic amino acids. Surprisingly, the TCR does not interact with the Be(2+) itself, but rather with surface changes induced by the firmly bound Be(2+) and an accompanying Na(+) cation. Thus, CBD, by creating a new antigen by indirectly modifying the structure of preexisting self MHC-peptide complex, lies on the border between allergic hypersensitivity and autoimmunity.

  12. [Choice of an antihistamine administration route in the treatment of allergic diseases].

    PubMed

    Luss, L V

    2016-01-01

    Allergic diseases (AD) are an interdisciplinary problem in practical health care and characterized by high prevalence, severity, and huge financial costs of their treatment, prevention, and rehabilitation in patients. In this connection, control of allergy symptoms attracts the meticulous attention of physicians of all specialties. The efficiency of pharmacotherapy in clinical practice frequently depends not only on what medication, but also what mode of its delivery (administration) is used. Clinicians are well aware of the fact that oral administration of some drugs, antihistamines in particular, may be lowly effective or ineffective and their parenteral route gives rise to their sufficient clinical effect. This communication presents for general practitioners a pathogenetic rationale for prescribing histamines and indications for their parenteral administration in AD. PMID:27030338

  13. 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

  14. Therapeutic effect of 0.1% Tacrolimus Eye Ointment in Allergic Ocular Diseases

    PubMed Central

    Shitole, Satish C; Bhagat, Nupur; Patil, Deepak; Sawant, Pawan; Patil, Kalpita

    2016-01-01

    Introduction Allergic Ocular Diseases (AODs) like Atopic Keratoconjunctivitis (AKC) and Vernal Keratoconjunctivitis (VKC) are chronic forms of ocular allergy that can cause severe visual complications. Pathogenesis of AODs is uncertain and treatment has been a challenge for ophthalmologists. Tacrolimus, a 23-member cyclic macrolide lactone derived from [streptomyces tsukubaensis] now in ointment form has been successfully used in AODs. Aim To study the therapeutic effect of 0.1% Tacrolimus eye ointment in patients with Allergic Ocular Diseases (AODs). Materials and Methods This prospective observational study was conducted on 36 patients with severe AOD and moderate cases not responding to conventional treatment. They were treated with 0.1% tacrolimus eye ointment twice daily for minimum three months in addition to conventional treatment and observed for a period of 6 months. Symptoms and signs after treatment were evaluated. Grades of clinical signs were assessed based on slit lamp clinical photographs; development of possible complications was assessed and analysed by Wilcoxon signed rank test. Results Mean age of patients was 9.3±4.3 years and mean duration of AODs was 3.1±1.8 years. The scores on both the four point scales for signs and symptoms decreased significantly (p<0.0001) after 1 month of 0.1% Tacrolimus eye ointment treatment. Itching was the first symptom to show dramatic relief and conjunctival hyperaemia was the first sign to show improvement. 88.88% of patients were successfully weaned off topical steroids in 6 months into Tacrolimus treatment. Even in patients unresponsive to 0.1% topical Cyclosporine, symptoms and signs scores decreased significantly (p<0.0001). The most common adverse reaction was a transient burning sensation (36.11%). Conclusion Topical 0.1% Tacrolimus eye ointment was found to be a safe and effective treatment in cases of AODs and also worked as steroid sparing and replacing agent. It was also found effective in patient

  15. The gut microbiota and its role in the development of allergic disease: a wider perspective.

    PubMed

    West, C E; Jenmalm, M C; Prescott, S L

    2015-01-01

    The gut microbiota are critical in the homoeostasis of multiple interconnected host metabolic and immune networks. If early microbial colonization is delayed, the gut-associated lymphoid tissues (GALT) fail to develop, leading to persistent immune dysregulation in mice. Microbial colonization has also been proposed as a major driver for the normal age-related maturation of both Th1 and T regulatory (Treg) pathways that appear important in suppressing early propensity for Th2 allergic responses. There is emerging evidence that resident symbionts induce tolerogenic gut-associated Treg cells and dendritic cells that ensure the preferential growth of symbionts; keeping pathogenic strains in check and constraining proinflammatory Th1, Th2, and Th17 clones. Some effects of symbionts are mediated by short-chain fatty acids, which play a critical role in mucosal integrity and local and systemic metabolic function and stimulate the regulatory immune responses. The homoeostatic IL-10/TGF-β dominated tolerogenic response within the GALT also signals the production of secretory IgA, which have a regulating role in mucosal integrity. Contrary to the 'sterile womb' paradigm, recent studies suggest that maternal microbial transfer to the offspring begins during pregnancy, providing a pioneer microbiome. It is likely that appropriate microbial stimulation both pre- and postnatally is required for optimal Th1 and Treg development to avoid the pathophysiological processes leading to allergy. Disturbed gut colonization patterns have been associated with allergic disease, but whether microbial variation is the cause or effect of these diseases is still under investigation. We are far from understanding what constitutes a 'healthy gut microbiome' that promotes tolerance. This remains a major limitation and might explain some of the inconsistency in human intervention studies with prebiotics and probiotics. Multidisciplinary integrative approaches with researchers working in networks

  16. Interleukin-8 in airway inflammation in patients with asthma and chronic obstructive pulmonary disease.

    PubMed

    Nocker, R E; Schoonbrood, D F; van de Graaf, E A; Hack, C E; Lutter, R; Jansen, H M; Out, T A

    1996-02-01

    We have investigated whether IL-8 is present in airway secretions from patients with asthma and chronic obstructive pulmonary disease (COPD) to obtain information on its possible role in airway inflammation in obstructive airways disease. In the bronchoalveolar lavage fluid (BALF) from 11 clinically stable patients with asthma the levels of IL-8 were increased compared to 10 healthy subjects (median: controls 21.5 pg/ml, asthma 244 pg/ml: p < 0.005). In the patients with asthma the levels of IL-8 correlated with the percentage neutrophils in the BALF (r = 0.81; p < 0.001) and with a parameter of the permeability of the respiratory membrane, the quotient (alpha 2-macroglobulin in BALF)/(alpha 2-macroglobulin in serum) (r = 0.66; p < 0.025). In the sputum sol phase of 9 patients with symptomatic asthma the levels of IL-8 were lower than in 9 patients with COPD (asthma: 6.4 ng/ml; COPD: 16.3 ng/ml; p < 0.02) and significantly correlated with those of neutrophilic myeloperoxidase (MPO; r = 0.85; p < 0.005). The increased levels of IL-8 in the airway secretions from both patients with asthma and COPD may be markers of an ongoing inflammatory process, which is more pronounced in patients with COPD. In patients with asthma the strong correlation between the levels of IL-8 and the percentage neutrophils and/or the levels of MPO points to a role of IL-8 in the recruitment and activation of neutrophils in the airway lumen.

  17. 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

  18. Allergic rhinitis

    MedlinePlus

    ... allergic to, such as dust, animal dander, or pollen. Symptoms can also occur when you eat a ... article focuses on allergic rhinitis due to plant pollens. This type of allergic rhinitis is commonly called ...

  19. The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus.

    PubMed

    Morris, Abigail; Wang, Bo; Waern, Ida; Venkatasamy, Radhakrishnan; Page, Clive; Schmidt, Eric P; Wernersson, Sara; Li, Jin-Ping; Spina, Domenico

    2015-01-01

    Heparanase is an endo-β-glucuronidase that specifically cleaves heparan sulfate proteoglycans in the extracellular matrix. Expression of this enzyme is increased in several pathological conditions including inflammation. We have investigated the role of heparanase in pulmonary inflammation in the context of allergic and non-allergic pulmonary cell recruitment using heparanase knockout (Hpa-/-) mice as a model. Following local delivery of LPS or zymosan, no significant difference was found in the recruitment of neutrophils to the lung between Hpa-/- and wild type (WT) control. Similarly neutrophil recruitment was not inhibited in WT mice treated with a heparanase inhibitor. However, in allergic inflammatory models, Hpa-/- mice displayed a significantly reduced eosinophil (but not neutrophil) recruitment to the airways and this was also associated with a reduction in allergen-induced bronchial hyperresponsiveness, indicating that heparanase expression is associated with allergic reactions. This was further demonstrated by pharmacological treatment with a heparanase inhibitor in the WT allergic mice. Examination of lung specimens from patients with different severity of chronic obstructive pulmonary disease (COPD) found increased heparanase expression. Thus, it is established that heparanase contributes to allergen-induced eosinophil recruitment to the lung and could provide a novel therapeutic target for the development of anti-inflammatory drugs for the treatment of asthma and other allergic diseases.

  20. [Anti-nicotine education applied in relation of parents of the diseased children on chronic allergic diseases of respiratory system].

    PubMed

    Przybylski, Grzegorz; Gołda, Ryszard; Pyskir, Jerzy; Pasińska, Magdalena; Ludwikowski, Grzegorz; Kuziemski, Arkadiusz; Kopiński, Piotr

    2006-01-01

    The allergies of respiratory system are at children the frequent illnesses. Among favorable them factors, risk on passive smoking tobacco can be also. Passive smoking is defined as risk non-smoking on tobacco smoke in environment. Recent reports represent that smoking in home environment tobacco increase on passive smokers' asthma morbidity, especially children in school age. It in it was report the necessity of leadership of anti-nicotine education was underlined in the face of smoking parents. It bets that she should motivate she better parents to cessation smoking, using authority of doctor and love parental. Acting we decided with these principles to analyze effectiveness two year anti-nicotine education which be applied in the face of all treated smoking parents of children with reason of chronic allergic diseases of respiratory system in out-patients. The study comprised parents of 146 children at the Allergy out-Patients clinic, who were diagnosed and cured in years 2003-2005. Generally were 292 persons. The children be treated with reason of bronchial asthma and allergic rhinitis. It the data on subject of smoking of tobacco were collected was on basis of interview got from parents during visits at information bureau on beginning the treatment the children, in his track as well as after two years of education. The anti-nicotine education was applied by whole period of observation during routine medical visits. In moment beginning of treatment in studied group the parents' and education children (n = 292) it 79 the parents' couple did not smoke. Smoking parents among remaining 67 steams were. From among them parents 13 children smoked both, only father in 36 cases smoked and mother in remaining 18 parents' couple smoked. 80 parents smoked with generally. 63 persons after two years of anti-nicotine education the nonsmoking committed one from group smoking. 22 persons among them were from among 24 fathers and 17 mothers' peer in which smoked both parents

  1. Efficacy and tolerability of nedocromil sodium versus placebo in chronic reversible obstructive airways disease.

    PubMed

    Del Bufalo, C; Fasano, L; Fabbri, M; Quarta, C C; Gunella, G

    1993-01-01

    In this 8-week, double-blind, comparative trial of nedocromil sodium (4 mg q.i.d.) versus placebo in 42 patients with chronic reversible obstructive airways disease, there was a trend in favor of nedocromil sodium compared to placebo in parameters assessed by patients (nocturnal symptom scores, evening PEFR values) and those assessed by clinicians (asthma severity scores) compared with baseline values. There was a statistically significant difference (p < 0.05) in favor of nedocromil sodium in the inhaled bronchodilator requirements in the last 2 weeks of treatment. Both patients' and clinicians' evaluation of the overall efficacy of treatment was significant in favor of nedocromil sodium (p < 0.01 and p < 0.05, respectively). The treatments were well tolerated by the majority of patients. From these data, it can be concluded that nedocromil sodium (4 mg q.i.d.) is of value in the preventive treatment of chronic reversible obstructive airways disease.

  2. Oral tolerance in neonates: from basics to potential prevention of allergic disease.

    PubMed

    Verhasselt, V

    2010-07-01

    Oral tolerance refers to the observation that prior feeding of an antigen induces local and systemic immune tolerance to that antigen. Physiologically, this process is probably of central importance for preventing inflammatory responses to the numerous dietary and microbial antigens present in the gut. Defective oral tolerance can lead to gut inflammatory disease, food allergies, and celiac disease. In the last two cases, the diseases develop early in life, stressing the necessity of understanding how oral tolerance is set up in neonates. This article reviews the parameters that have been outlined in adult animal models as necessary for tolerance induction and assesses whether these factors operate in neonates. In addition, we highlight the factors that are specific for this period of life and discuss how they could have an impact on oral tolerance. We pay particular attention to maternal influence on early oral tolerance induction through breast-feeding and outline the major parameters that could be modified to optimize tolerance induction in early life and possibly prevent allergic diseases. PMID:20485330

  3. Staphylococcus δ-toxin promotes mouse allergic skin disease by inducing mast cell degranulation

    PubMed Central

    Nakamura, Yuumi; Oscherwitz, Jon; Cease, Kemp B.; Chan, Susana M.; Muñoz-Planillo, Raul; Hasegawa, Mizuho; Villaruz, Amer E.; Cheung, Gordon Y. C.; McGavin, Martin J.; Travers, Jeffrey B.; Otto, Michael; Inohara, Naohiro; Núñez, Gabriel

    2013-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15 to 30% of children and ~5% of adults in industrialized countries1. Although the pathogenesis of AD is not fully understood, the disease is mediated by an abnormal immunoglobulin E (IgE) immune response in the setting of skin barrier dysfunction2. Mast cells (MCs) contribute to IgE-mediated allergic disorders including AD3. Upon activation, MCs release their membrane-bound cytosolic granules leading to the release of multiple molecules that are important in the pathogenesis of AD and host defense4. More than 90% of AD patients are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbor the pathogen5. Several Staphylococcal exotoxins (SEs) can act as superantigens and/or antigens in models of AD6. However, the role of these SEs in disease pathogenesis remains unclear. Here, we report that culture supernatants of S. aureus contain potent MC degranulation activity. Biochemical analysis identified δ-toxin as the MC degranulation-inducing factor produced by S. aureus. MC degranulation induced by δ-toxin depended on phosphoinositide 3-kinase (PI3K) and calcium (Ca2+) influx, but unlike that mediated by IgE crosslinking, it did not require the spleen tyrosine kinase (Syk). In addition, IgE enhanced δ-toxin-induced MC degranulation in the absence of antigen. Furthermore, S. aureus isolates recovered from AD patients produced high levels of δ-toxin. Importantly, skin colonization with S. aureus, but not a mutant deficient in δ-toxin, promoted IgE and IL-4 production, as well as inflammatory skin disease. Furthermore, enhancement of IgE production and dermatitis by δ-toxin was abrogated in KitW-sh/W-sh MC-deficient mice and restored by MC reconstitution. These studies identify δ-toxin as a potent inducer of MC degranulation and suggest a mechanistic link between S. aureus colonization and allergic skin disease. PMID:24172897

  4. Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine.

    PubMed

    Agache, Ioana; Akdis, Cezmi A

    2016-07-01

    Discoveries from basic science research in the last decade have brought significant progress in knowledge of pathophysiologic processes of allergic diseases, with a compelling impact on understanding of the natural history, risk prediction, treatment selection or mechanism-specific prevention strategies. The view of the pathophysiology of allergic diseases developed from a mechanistic approach, with a focus on symptoms and organ function, to the recognition of a complex network of immunological pathways. Several subtypes of inflammation and complex immune-regulatory networks and the reasons for their failure are now described, that open the way for the development of new diagnostic tools and innovative targeted-treatments. An endotype is a subtype of a disease condition, which is defined by a distinct pathophysiological mechanism, whereas a disease phenotype defines any observable characteristic of a disease without any implication of a mechanism. Another key word linked to disease endotyping is biomarker that is measured and evaluated to examine any biological or pathogenic processes, including response to a therapeutic intervention. These three keywords will be discussed more and more in the future with the upcoming efforts to revolutionize patient care in the direction of precision medicine and precision health. The understanding of disease endotypes based on pathophysiological principles and their validation across clinically meaningful outcomes in asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis and food allergy will be crucial for the success of precision medicine as a new approach to patient management.

  5. Severe upper airway obstruction during sleep.

    PubMed

    Bonekat, H William; Hardin, Kimberly A

    2003-10-01

    Few disorders may manifest with predominantly sleep-related obstructive breathing. Obstructive sleep apnea (OSA) is a common disorder, varies in severity and is associated with significant cardiovascular and neurocognitive morbidity. It is estimated that between 8 and 18 million people in the United States have at least mild OSA. Although the exact mechanism of OSA is not well-delineated, multiple factors contribute to the development of upper airway obstruction and include anatomic, mechanical, neurologic, and inflammatory changes in the pharynx. OSA may occur concomitantly with asthma. Approximately 74% of asthmatics experience nocturnal symptoms of airflow obstruction secondary to reactive airways disease. Similar cytokine, chemokine, and histologic changes are seen in both disorders. Sleep deprivation, chronic upper airway edema, and inflammation associated with OSA may further exacerbate nocturnal asthma symptoms. Allergic rhinitis may contribute to both OSA and asthma. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA. Treatment with CPAP therapy has also been shown to improve both daytime and nighttime peak expiratory flow rates in patients with concomitant OSA and asthma. It is important for allergists to be aware of how OSA may complicate diagnosis and treatment of asthma and allergic rhinitis. A thorough sleep history and high clinical suspicion for OSA is indicated, particularly in asthma patients who are refractory to standard medication treatments.

  6. Clara cells drive eosinophil accumulation in allergic asthma.

    PubMed

    Sonar, S S; Ehmke, M; Marsh, L M; Dietze, J; Dudda, J C; Conrad, M L; Renz, H; Nockher, W A

    2012-02-01

    Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the "immunomodulatory barrier" of the airway epithelium. To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 μg endotoxin-free ovalbumin in conjunction with naphthalene-induced Clara cell depletion. Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung. These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma.

  7. General anesthesia exposure in early life reduces the risk of allergic diseases: A nationwide population-based cohort study.

    PubMed

    Kuo, Ho-Chang; Yang, Ya-Ling; Ho, Shu-Chen; Guo, Mindy Ming-Huey; Jiang, Jyun-Hong; Huang, Ying-Hsien

    2016-07-01

    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

  8. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

    PubMed Central

    George, Leena; Brightling, Christopher E.

    2016-01-01

    The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10–40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments. PMID:26770668

  9. Allergic rhinoconjunctivitis in the Australian population: Burden of disease and attitudes to intranasal corticosteroid treatment

    PubMed Central

    Sacks, Raymond; Theron, Paul N.

    2013-01-01

    Background: Allergic rhinoconjunctivitis (AR/C) is a global health problem causing significant morbidity and has a major impact on quality of life (QOL) and health expenditure. Despite the widespread prevalence, the overall health impact of AR/C may be underappreciated. The results of a survey designed to capture the burden of allergic rhinitis within the Asia-Pacific region have been published recently. Of particular note when evaluating treatment in this region was the fact that despite the value of intranasal corticosteroid (INCS) use, only a small percentage of patients used them. Whether this same trend is present within the population of Australian sufferers is unknown. This study examines the burden of AR/C and explores use of, and attitudes, to INCS sprays in the Australian population. Methods: Three hundred three completed interviews from adults and children who had physician-diagnosed AR/C and who were symptomatic or had received treatment in the previous 12 months were analyzed for QOL measures and attitudes to INCS use. Results: Most patients surveyed had received their diagnosis from a general practitioner (GP), and in most cases, a GP provided the majority of ongoing medical care. Only 8% of respondents had consulted a relevant specialist. Diagnostic tests had not been performed in 55% of respondents. The major symptoms causing most distress were nasal congestion and ocular symptoms. The burden of AR/C was considerable; 42% described significant work or school interference because of symptoms, one-third reporting moderate-to-extreme interference with sleep. Despite the significant impact on QOL reported by this sample, 17% had never used INCS and 27% had not used them in the previous 12 months. Respondents' knowledge about INCSs was poor. Conclusion: AR/C is a common disease associated with significant morbidity and impairment of QOL. Improvement in diagnosis, management, and patient education is needed. PMID:24274227

  10. Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease.

    PubMed

    Flynn, Jeffrey M; Niccum, David; Dunitz, Jordan M; Hunter, Ryan C

    2016-08-01

    Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung. PMID:27548479

  11. Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease

    PubMed Central

    Flynn, Jeffrey M.; Niccum, David; Dunitz, Jordan M.

    2016-01-01

    Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung. PMID:27548479

  12. Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation.

    PubMed

    Tran, Hai B; Lewis, Martin D; Tan, Lor Wai; Lester, Susan E; Baker, Leonie M; Ng, Jia; Hamilton-Bruce, Monica A; Hill, Catherine L; Koblar, Simon A; Rischmueller, Maureen; Ruffin, Richard E; Wormald, Peter J; Zalewski, Peter D; Lang, Carol J

    2012-01-01

    Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1β and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1β and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1β and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1β and TNFα. In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis. PMID:22523501

  13. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2012.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2013-01-01

    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 2012. Studies support an increase in peanut allergy prevalence in children and exposure to the antibacterial agent triclosan and having filaggrin (FLG) loss-of-function mutations as risk factors for food sensitization. The role of specific foods in causing eosinophilic esophagitis is elucidated by several studies, and microRNA analysis is identified as a possible noninvasive disease biomarker. Studies on food allergy diagnosis emphasize the utility of component testing and the possibility of improved diagnosis through stepped approaches, epitope-binding analysis, and bioinformatics. Treatment studies of food allergy show promise for oral immunotherapy, but tolerance induction remains elusive, and additional therapies are under study. Studies on anaphylaxis suggest an important role for platelet-activating factor and its relationship to the need for prompt treatment with epinephrine. Insights on the pathophysiology and diagnosis of non-IgE-mediated drug allergy are offered, with novel data regarding the interaction of drugs with HLA molecules. Numerous studies support influenza vaccination of persons with egg allergy using modest precautions. Evidence continues to mount that there is cross-talk between skin barrier defects and immune responses in patients with atopic dermatitis. Augmentation of the skin barrier with reduction in skin inflammatory responses will likely lead to the most effective intervention in patients with this common skin disease.

  14. Occupational allergic respiratory diseases in garbage workers: relevance of molds and actinomycetes.

    PubMed

    Hagemeyer, O; Bünger, J; van Kampen, V; Raulf-Heimsoth, M; Drath, C; Merget, R; Brüning, Th; Broding, H C

    2013-01-01

    Exposures to molds and bacteria (especially actinomycetes) at workplaces are common in garbage workers, but allergic respiratory diseases due to these microorganisms have been described rarely. The aim of our study was a detailed analysis of mold or bacteria-associated occupational respiratory diseases in garbage workers. From 2002 to 2011 four cases of occupational respiratory diseases related to garbage handling were identified in our institute (IPA). Hypersensitivity pneumonitis (HP) was diagnosed in three subjects (cases 1-3, one smoker, two non-smokers), occupational asthma (OA) was diagnosed in one subject (case 4, smoker), but could not be excluded completely in case 2. Cases 1 and 2 worked in composting sites, while cases 3 and 4 worked in packaging recycling plants. Exposure periods were 2-4 years. Molds and actinomycetes were identified as allergens in all cases. Specific IgE antibodies to Aspergillus fumigatus were detected exclusively in case 4. Diagnoses of HP were essentially based on symptoms and the detection of specific IgG serum antibodies to molds and actinomycetes. OA was confirmed by bronchial provocation test with Aspergillus fumigatus in case 4. In conclusion, occupational HP and OA due to molds occur rarely in garbage workers. Technical prevention measures are insufficient and the diagnosis of HP is often inconclusive. Therefore, it is recommended to implement the full repertoire of diagnostic tools including bronchoalveolar lavage and high resolution computed tomography in the baseline examination.

  15. Occupational allergic respiratory diseases in garbage workers: relevance of molds and actinomycetes.

    PubMed

    Hagemeyer, O; Bünger, J; van Kampen, V; Raulf-Heimsoth, M; Drath, C; Merget, R; Brüning, Th; Broding, H C

    2013-01-01

    Exposures to molds and bacteria (especially actinomycetes) at workplaces are common in garbage workers, but allergic respiratory diseases due to these microorganisms have been described rarely. The aim of our study was a detailed analysis of mold or bacteria-associated occupational respiratory diseases in garbage workers. From 2002 to 2011 four cases of occupational respiratory diseases related to garbage handling were identified in our institute (IPA). Hypersensitivity pneumonitis (HP) was diagnosed in three subjects (cases 1-3, one smoker, two non-smokers), occupational asthma (OA) was diagnosed in one subject (case 4, smoker), but could not be excluded completely in case 2. Cases 1 and 2 worked in composting sites, while cases 3 and 4 worked in packaging recycling plants. Exposure periods were 2-4 years. Molds and actinomycetes were identified as allergens in all cases. Specific IgE antibodies to Aspergillus fumigatus were detected exclusively in case 4. Diagnoses of HP were essentially based on symptoms and the detection of specific IgG serum antibodies to molds and actinomycetes. OA was confirmed by bronchial provocation test with Aspergillus fumigatus in case 4. In conclusion, occupational HP and OA due to molds occur rarely in garbage workers. Technical prevention measures are insufficient and the diagnosis of HP is often inconclusive. Therefore, it is recommended to implement the full repertoire of diagnostic tools including bronchoalveolar lavage and high resolution computed tomography in the baseline examination. PMID:23835992

  16. Nasal disease and asthma.

    PubMed

    Marseglia, G L; Merli, P; Caimmi, D; Licari, A; Labó, E; Marseglia, A; Ciprandi, G; La Rosa, M

    2011-10-01

    The nose plays a primary role within the airways, working as a filter and air-conditioner, together with other important functions. Thus, it is not surprising that nasal diseases are associated with several other comorbidities, including both upper and lower airways, such as bronchial hyperresponsiveness (BHR) and asthma. Several studies have investigated the relationship existing between the upper and the lower airways and new insights are rising. Nevertheless, some uncertainties still remain, mainly because nasal disorders are quite heterogeneous, overlapping (i.e. rhinitis-rhinosinusitis-sinusitis, acute or chronic, allergic or non-allergic) and difficult to diagnose, so that, frequently, many studies don’t differentiate between the various conditions. For this reason, the purpose of this review is to systematically analyze present epidemiological, pathophysiological and clinical data on the relationship between nasal diseases and asthma, splitting up three main conditions: allergic rhinitis, chronic rhinosinusitis and nasal polyposis. PMID:22032779

  17. Interference of a short-term exposure to nitrogen dioxide with allergic airways responses to allergenic challenges in BALB/c mice.

    PubMed Central

    Proust, Barbara; Lacroix, Ghislaine; Robidel, Franck; Marliere, Maryse; Lecomte, Anthony; Vargaftig, B Boris

    2002-01-01

    Nitrogen dioxide (NO(2)) is a common indoor and outdoor air pollutant whose role in the induction of asthma is unclear. We investigated the effects of NO(2) on the development of asthma-like responses to allergenic challenge in BALB/c mice. Ovalbumin (OVA)-immunized mice were intranasally challenged with OVA or saline solution just before starting a 3 h exposure to 5 or 20 ppm NO(2) or air. Twenty parts per million of NO(2) induced a significant increase of bronchopulmonary hyperreactivity in OVA-challenged mice and of permeability according to the fibronectin content of the bronchoalveolar lavage fluid (BALF) 24 h after exposure, as compared with air or 5 ppm NO(2). Eosinophilia (cell counts in the BALF and eosinophil peroxidase of lung tissue) was detected at 24 and 72 h with similar levels for air and 20 ppm NO(2), whereas a marked reduction was unexpectedly observed for 5 ppm NO(2). At 24 h, interleukin-5 in the BALF was markedly reduced at 5 ppm compared with 20 ppm NO(2) and was also more intense for 20 ppm NO(2) than for the air group. In contrast to specific IgG1 titers, anti-OVA IgE titers and interleukin-4 in the BALF were not affected by NO(2) exposure. Irrespective of the concentration of NO(2), OVA-challenged mice did not develop late mucosal metaplasia compared with those exposed to OVA-air. These results indicate that a short exposure to NO(2) can exacerbate or inhibit some features of the development of allergic disease in mice and may depend on the concentration of pollutant. PMID:12396477

  18. Physiological phenotyping of pediatric chronic obstructive airway diseases.

    PubMed

    Nyilas, Sylvia; Singer, Florian; Kumar, Nitin; Yammine, Sophie; Meier-Girard, Delphine; Koerner-Rettberg, Cordula; Casaulta, Carmen; Frey, Urs; Latzin, Philipp

    2016-07-01

    Inert tracer gas washout (IGW) measurements detect increased ventilation inhomogeneity (VI) in chronic lung diseases. Their suitability for different diseases, such as cystic fibrosis (CF) and primary ciliary dyskinesia (PCD), has already been shown. However, it is still unclear if physiological phenotypes based on different IGW variables can be defined independently of underlying disease. Eighty school-age children, 20 with CF, 20 with PCD, 20 former preterm children, and 20 healthy children, performed nitrogen multiple-breath washout, double-tracer gas (DTG) single-breath washout, and spirometry. Our primary outcome was the definition of physiological phenotypes based on IGW variables. We applied principal component analysis, hierarchical Ward's clustering, and enrichment analysis to compare clinical characteristics between the clusters. IGW variables used for clustering were lung clearance index (LCI) and convection-dependent [conductive ventilation heterogeneity index (Scond)] and diffusion-convection-dependent variables [acinar ventilation heterogeneity index (Sacin) and carbon dioxide and DTG phase III slopes]. Three main phenotypes were identified. Phenotype I (n = 38) showed normal values in all IGW outcome variables. Phenotype II (n = 21) was characterized by pronounced global and convection-dependent VI while diffusion-dependent VI was normal. Phenotype III (n = 21) was characterized by increased global and diffusion- and convection-dependent VI. Enrichment analysis revealed an overrepresentation of healthy children and former preterm children in phenotype I and of CF and PCD in phenotypes II and III. Patients in phenotype III showed the highest proportion and frequency of exacerbations and hospitalization in the year prior to the measurement. IGW techniques allow identification of clinically meaningful, disease-independent physiological clusters. Their predictive value of future disease outcomes remains to be determined.

  19. Early life exposure to antibiotics and the risk of childhood allergic diseases: an update from the perspective of the hygiene hypothesis.

    PubMed

    Kuo, Chang-Hung; Kuo, Hsuan-Fu; Huang, Ching-Hua; Yang, San-Nan; Lee, Min-Sheng; Hung, Chih-Hsing

    2013-10-01

    The prevalence of allergic diseases has been growing rapidly in industrial countries during recent decades. It is postulated that growing up with less microbial exposure may render the immune system susceptible to a T helper type 2 (Th2)-predominant allergic response-also known as the hygiene hypothesis. This review delineates recent epidemiological and experimental evidence for the hygiene hypothesis, and integrates this hypothesis into the association between early life exposure to antibiotics and the development of allergic diseases and asthma. Several retrospective or prospective epidemiological studies reveal that early exposure to antibiotics may be positively associated with the development of allergic diseases and asthma. However, the conclusion is inconsistent. Experimental studies show that antibiotics may induce the Th2-skewed response by suppressing the T helper type 1 (Th1) response through inhibition of Th1 cytokines and disruption of the natural course of infection, or by disturbing the microflora of the gastrointestinal (GI) tract and therefore jeopardizing the establishment of oral tolerance and regulatory T cell immune responses. The hygiene hypothesis may not be the only explanation for the rapid increase in the prevalence of allergic diseases and asthma. Further epidemiological and experimental studies addressing the issue of the impact of environmental factors on the development of allergic diseases and the underlying mechanisms may unveil novel strategies for the prevention and treatment of allergic diseases in the future.

  20. Biology of diesel exhaust effects on allergic pulmonary inflammation.

    PubMed

    Inoue, Ken-ichiro; Takano, Hirohisa

    2011-03-01

    Although the adverse health effects of diesel exhaust particles (DEP) have been proposed and are being clarified, their facilitating effects on preexisting pathological conditions (pathological conditions) have not been fully identified. On the other hand, there exist hypersensitive subjects against particulate matters. In this review, we provide insights into the immunotoxicity of DEP as an aggravating factor in hypersusceptible subjects, especially those with allergic pulmonary diseases using our in vivo experimental model. In brief, we examined the effects of DEP on allergic asthma in vivo, and showed that repetitive pulmonary exposure to DEP has promoting effects on allergic airway inflammation, including adjuvanticity on Th2-milieu. Further, we propose a causal machinery regarding the adverse impacts, i.e., via inappropriate activation of antigen-presenting cells such as dendritic cells.

  1. Treatment of allergic rhinitis during pregnancy.

    PubMed

    Demoly, Pascal; Piette, Vincent; Daures, Jean-Pierre

    2003-01-01

    Allergic rhinitis is a frequent problem during pregnancy. In addition, physiological changes associated with pregnancy can affect the upper airways. Evidence-based guidelines on the management of allergic rhinitis have recently been published, the most recent being the Allergic Rhinitis and its Impact on Asthma (ARIA)--World Health Organization consensus. Many pregnant women experience allergic rhinitis and particular attention is required when prescribing drugs to these patients. Medication can be prescribed during pregnancy when the apparent benefit of the drug is greater than the apparent risk. Usually, there is at least one drug from each major class that can be safely utilised to control symptoms. All glucocorticosteroids are teratogenic in animals but, when the indication is clear (for diseases possibly associated, such as severe asthma exacerbation), the benefit of the drug is far greater than the risk. Inhaled glucocorticosteroids (e.g. beclomethasone or budesonide) have not been incriminated as teratogens in humans and are used by pregnant women who have asthma. A few histamine H(1)-receptor antagonists (H(1)-antihistamines) can safely be used as well. Most oral decongestants (except pseudoephedrine) are teratogenic in animals. There are no such data available for intra-nasal decongestants. Finally, pregnancy is not considered as a contraindication for the continuation of allergen specific immunotherapy.

  2. Respiratory and allergic diseases: from upper respiratory tract infections to asthma.

    PubMed

    Jaber, Raja

    2002-06-01

    Andrographis shortens the duration of the common cold. The one study on Elderberry's use for the flu was encouraging, and the data on the homeopathic remedy Oscillococcinum interesting, but more studies should be performed. Saline washes may be helpful to patients with allergic rhinitis and chronic sinusitis. Patients also may try the German combination (available in the United States) of elderberry, vervain, gentian, primrose, and sorrel that has been tested in randomized clinical trials. Bromelain is safe to try; the trials of bromelain supplementation were promising but were never repeated. The preceding suggestions need to be grounded in a program based on optimal medical management. Patients need to be well educated in the proper medical management of their disease and skilled at monitoring disease stability and progress. Asthmatic patients need to monitor their bronchodilator usage and peak flow meter measurements to step up their medical treatment in a timely manner, if needed. Patients welcome physician guidance when exploring the breadth of treatments available today. A true patient-physician partnership is always empowering to patients who are serious about regaining their function and health.

  3. Fabry disease, respiratory symptoms, and airway limitation – a systematic review

    PubMed Central

    Svensson, Camilla Kara; Feldt-Rasmussen, Ulla; Backer, Vibeke

    2015-01-01

    Background Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A, resulting in accumulation of glycosphingolipids in multiple organs, primarily heart, kidneys, skin, CNS, and lungs. Materials and method A systematic literature search was performed using the PubMed database, leading to a total number of 154 hits. Due to language restriction, this number was reduced to 135; 53 papers did not concern Fabry disease, 19 were either animal studies or gene therapy studies, and 36 papers did not have lung involvement in Fabry disease as a topic. The remaining 27 articles were relevant for this review. Results The current literature concerning lung manifestations describes various respiratory symptoms such as dyspnoea or shortness of breath, wheezing, and dry cough. These symptoms are often related to cardiac involvement in Fabry disease as respiratory examinations are seldom performed. Pulmonary function tests primarily show obstructive airway limitation, but a few articles also report of patients with restrictive limitation and a mixture of both. No significant association has been found between smoking and the development of symptoms or spirometry abnormalities in patients with Fabry disease. Electron microscopy of lung biopsy and induced sputum show lamellar inclusion bodies (Zebra bodies) in the cytoplasm of cells in the airway wall. X-ray and CT scan have shown patchy ground-glass pulmonary infiltrations, fibrosis, and air trapping. Fibrosis diagnosed by high-resolution CT has not been significantly correlated with lung spirometry. Conclusion Consistent findings have not been shown in the current literature. Pulmonary function tests and registration of symptoms showed various results; however, there is a trend towards obstructive airway limitation in patients with Fabry disease. Further studies are needed to evaluate pathogenesis, progression, and the effects of treatment. PMID:26557248

  4. TGF-β: An Important Mediator of Allergic Disease and a Molecule with Dual Activity in Cancer Development

    PubMed Central

    Tirado-Rodriguez, Belen; Segura-Medina, Patricia; Huerta-Yepez, Sara

    2014-01-01

    The transforming growth factor-β (TGF-β) superfamily is a family of structurally related proteins that includes TGF-β, activins/inhibins, and bone morphogenic proteins (BMPs). Members of the TGF-β superfamily regulate cellular functions such as proliferation, apoptosis, differentiation, and migration and thus play key roles in organismal development. TGF-β is involved in several human diseases, including autoimmune disorders and vascular diseases. Activation of the TGF-β receptor induces phosphorylation of serine/threonine residues and triggers phosphorylation of intracellular effectors (Smads). Once activated, Smad proteins translocate to the nucleus and induce transcription of their target genes, regulating various processes and cellular functions. Recently, there has been an attempt to correlate the effect of TGF-β with various pathological entities such as allergic diseases and cancer, yielding a new area of research known as “allergooncology," which investigates the mechanisms by which allergic diseases may influence the progression of certain cancers. This knowledge could generate new therapeutic strategies aimed at correcting the pathologies in which TGF-β is involved. Here, we review recent studies that suggest an important role for TGF-β in both allergic disease and cancer progression. PMID:25110717

  5. The innate immune function of airway epithelial cells in inflammatory lung disease

    PubMed Central

    Hiemstra, Pieter S.; McCray, Paul B.; Bals, Robert

    2016-01-01

    The airway epithelium is now considered central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as a first barrier in the defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. In the review, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, COPD and cystic fibrosis, are discussed. PMID:25700381

  6. Protein microarrays for the diagnosis of allergic diseases: state-of-the-art and future development.

    PubMed

    Harwanegg, Christian; Hiller, Reinhard

    2005-01-01

    In the emerging field of Functional Proteomics, protein microarrays are considered to be one of the most promising tools for the simultaneous analysis of the a) abundance, b) function, and c) interaction of proteins on a system-wide scale. Resting on the technological grounds of widely used DNA biochips, the great power of microarray-based miniature solid-phase immunoassays lies in their potential to investigate in parallel large numbers of analyte pairs in a variety of biological samples. Consequently, this has fueled aspirations that protein microarrays may serve as tools for the high-throughput functional investigation of complete proteomes and, moreover, that they will develop into promising candidates for innovative in-vitro diagnostic (IVD) applications. To date, published examples of protein microarrays for IVD purposes have included tests for allergy, autoimmune and infectious diseases. Here, we discuss recent advancements in the development of protein microarrays for the profiling of IgE antibodies in the diagnosis of Type 1-related allergic diseases.

  7. Smoking-induced CXCL14 expression in the human airway epithelium links chronic obstructive pulmonary disease to lung cancer.

    PubMed

    Shaykhiev, Renat; Sackrowitz, Rachel; Fukui, Tomoya; Zuo, Wu-Lin; Chao, Ion Wa; Strulovici-Barel, Yael; Downey, Robert J; Crystal, Ronald G

    2013-09-01

    CXCL14, a recently described epithelial cytokine, plays putative multiple roles in inflammation and carcinogenesis. In the context that chronic obstructive pulmonary disease (COPD) and lung cancer are both smoking-related disorders associated with airway epithelial disorder and inflammation, we hypothesized that the airway epithelium responds to cigarette smoking with altered CXCL14 gene expression, contributing to the disease-relevant phenotype. Using genome-wide microarrays with subsequent immunohistochemical analysis, the data demonstrate that the expression of CXCL14 is up-regulated in the airway epithelium of healthy smokers and further increased in COPD smokers, especially within hyperplastic/metaplastic lesions, in association with multiple genes relevant to epithelial structural integrity and cancer. In vitro experiments revealed that the expression of CXCL14 is induced in the differentiated airway epithelium by cigarette smoke extract, and that epidermal growth factor mediates CXCL14 up-regulation in the airway epithelium through its effects on the basal stem/progenitor cell population. Analyses of two independent lung cancer cohorts revealed a dramatic up-regulation of CXCL14 expression in adenocarcinoma and squamous-cell carcinoma. High expression of the COPD-associated CXCL14-correlating cluster of genes was linked in lung adenocarcinoma with poor survival. These data suggest that the smoking-induced expression of CXCL14 in the airway epithelium represents a novel potential molecular link between smoking-associated airway epithelial injury, COPD, and lung cancer.

  8. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma.

    PubMed

    Caceres, Ana I; Brackmann, Marian; Elia, Maxwell D; Bessac, Bret F; del Camino, Donato; D'Amours, Marc; Witek, JoAnn S; Fanger, Chistopher M; Chong, Jayhong A; Hayward, Neil J; Homer, Robert J; Cohn, Lauren; Huang, Xiaozhu; Moran, Magdalene M; Jordt, Sven-Eric

    2009-06-01

    Asthma is an inflammatory disorder caused by airway exposures to allergens and chemical irritants. Studies focusing on immune, smooth muscle, and airway epithelial function revealed many aspects of the disease mechanism of asthma. However, the limited efficacies of immune-directed therapies suggest the involvement of additional mechanisms in asthmatic airway inflammation. TRPA1 is an irritant-sensing ion channel expressed in airway chemosensory nerves. TRPA1-activating stimuli such as cigarette smoke, chlorine, aldehydes, and scents are among the most prevalent triggers of asthma. Endogenous TRPA1 agonists, including reactive oxygen species and lipid peroxidation products, are potent drivers of allergen-induced airway inflammation in asthma. Here, we examined the role of TRPA1 in allergic asthma in the murine ovalbumin model. Strikingly, genetic ablation of TRPA1 inhibited allergen-induced leukocyte infiltration in the airways, reduced cytokine and mucus production, and almost completely abolished airway hyperreactivity to contractile stimuli. This phenotype is recapitulated by treatment of wild-type mice with HC-030031, a TRPA1 antagonist. HC-030031, when administered during airway allergen challenge, inhibited eosinophil infiltration and prevented the development of airway hyperreactivity. Trpa1(-/-) mice displayed deficiencies in chemically and allergen-induced neuropeptide release in the airways, providing a potential explanation for the impaired inflammatory response. Our data suggest that TRPA1 is a key integrator of interactions between the immune and nervous systems in the airways, driving asthmatic airway inflammation following inhaled allergen challenge. TRPA1 may represent a promising pharmacological target for the treatment of asthma and other allergic inflammatory conditions. PMID:19458046

  9. Epigenetic changes associated with disease progression in a mouse model of childhood allergic asthma.

    PubMed

    Collison, Adam; Siegle, Jessica S; Hansbro, Nicole G; Kwok, Chau-To; Herbert, Cristan; Mattes, Joerg; Hitchins, Megan; Foster, Paul S; Kumar, Rakesh K

    2013-07-01

    Development of asthma in childhood is linked to viral infections of the lower respiratory tract in early life, with subsequent chronic exposure to allergens. Progression to persistent asthma is associated with a Th2-biased immunological response and structural remodelling of the airways. The underlying mechanisms are unclear, but could involve epigenetic changes. To investigate this, we employed a recently