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Sample records for allergen-induced airway eosinophilia

  1. Temporal role of chemokines in a murine model of cockroach allergen-induced airway hyperreactivity and eosinophilia.

    PubMed

    Campbell, E M; Kunkel, S L; Strieter, R M; Lukacs, N W

    1998-12-15

    The increase in inner-city asthma among children appears to be due to allergic responses to several allergens. Recent studies have demonstrated that Ags derived from cockroaches are especially prominent in these settings and a significant health concern for the induction of asthma in children. In the present study, we have outlined the development of a murine model of cockroach allergen-induced airway disease and assessed specific mechanisms of the response, which resembles atopic human asthma. The allergic responses in this model include allergen-specific airway eosinophilia and significantly altered airway physiology, which directly correlates with inflammation. We have further utilized this allergen to establish primary and secondary rechallenge stages of late phase hyperreactivity exacerbation. This latter stage is characterized by greater changes in airway physiology than the primary stage, and it is likely due to the preexisting peribronchial inflammation present at the time of the second allergen rechallenge. We have identified specific roles for CC chemokines during these stages, with MIP-1alpha being an important eosinophil attractant during the primary stage and eotaxin during the secondary rechallenge stage. The development of these models allows the evaluation of mediators involved in both stages of cockroach allergen challenge, as well as the testing of specific therapeutic modalities.

  2. Vagotomy Reverses Established Allergen-Induced Airway Hyperreactivity to Methacholine in the Mouse

    EPA Science Inventory

    We evaluated the role of vagal reflexes in a mouse model of allergen-induced airway hyperreactivity. Mice were actively sensitized to ovalbumin then exposed to the allergen via inhalation. Prior to ovalbumin inhalation, mice also received intratracheally-instilled particulate ma...

  3. Oral administration of allergen extracts from Dermatophagoides farinae desensitizes specific allergen-induced inflammation and airway hyperresponsiveness in rats.

    PubMed

    Xie, Qiang-min; Wu, Ximei; Wu, Hui-min; Deng, Yang-mei; Zhang, Shui-juan; Zhu, Jian-ping; Dong, Xin-wei

    2008-12-10

    Clinically sublingual immunotherapy (SLIT) by using allergen extracts effectively alleviates the symptoms of allergic rhinitis and asthma. Supposed that oral administration of high-dose of allergen extracts imitates SLIT and may prevent IgE-related responses in allergic diseases, we investigated the effects of oral administration of allergen extracts from Dermatophagoides farinae (Derf) on allergen-induced inflammation and airway hyperresponsiveness (AHR) in a model of asthmatic rat. After administration to the specific Derf-sensitized rats with Derfdrop solution containing Derf1 and Derf2 extracts derived from Derf, the effects of Derfdrop on AHR, inflammatory cell accumulation, cytokine production in the bronchoalveolar lavage fluid and lung tissue, as well as serum IgE and IgG levels were investigated. Results indicated that Derfdrop not only dose-dependently prevented the AHR in response to methacholine, but also significantly reduced the serum total and allergen-specific IgE levels, all the maximal effects were achieved at dose of 5 mg/kg/d, and were as comparable as those of dexamethasone at dose of 1.0 mg/kg/d. Furthermore, oral administration of Derfdrop not only dose-dependently elevated allergen-specific serum IgG levels and reduced total and allergen-specific IgE levels, but also normalized the imbalance between the Th1 cytokine, IFN-gamma and Th2 cytokine, IL-4. Finally, oral administration of Derfdrop significantly reduced Goblet cell hyperplasia and eosinophilia in the Derf-sensitized allergic rat model. These data suggest that Derfdrop effectively improves specific allergen-induced inflammation and AHR in Derf-sensitized and -challenged rats and provide with the rationale for clinical SLIT by using Derfdrop in a specific allergen-induced asthma.

  4. Single-dose desloratadine and montelukast and allergen-induced late airway responses.

    PubMed

    Davis, B E; Illamperuma, C; Gauvreau, G M; Watson, R M; O'Byrne, P M; Deschesnes, F; Boulet, L P; Cockcroft, D W

    2009-06-01

    Montelukast and desloratadine synergistically inhibit the allergen-induced early asthmatic response. Montelukast also suppresses the allergen-induced late asthmatic response, but there are no reports on the effect of desloratadine or the combination on the allergen-induced late asthmatic response. Atopic asthmatics (n = 10) completed a multicentric randomised double-blind crossover study comparing single-dose placebo, 5 mg desloratadine, 10 mg montelukast and the combination administered 2 h prior to allergen inhalation challenge. Methacholine challenges were performed 24 h before and after allergen challenge. Exhaled nitric oxide measurements and sputum inflammatory cell counts were also carried out. All active treatments significantly decreased the late asthmatic response area under the curve. Combination therapy provided the greatest inhibition compared to desloratadine and montelukast. Montelukast was nonsignificantly better than desloratadine but not as effective as the combination. There was a trend towards a decrease in airway responsiveness following montelukast and combination. Montelukast, but not desloratadine or the combination, decreased exhaled NO levels 24 h after allergen. The allergen-induced increase in sputum eosinophil numbers was significantly suppressed at 7 h with desloratadine and combination therapy, and at 24 h with montelukast and combination therapy. Single-dose co-administration of desloratadine and montelukast 2 h prior to allergen inhalation clinically abolished the late asthmatic response and eosinophil recruitment.

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

    PubMed

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

    2011-10-01

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

  6. Protease inhibitor reduces airway response and underlying inflammation in cockroach allergen-induced murine model.

    PubMed

    Saw, Sanjay; Arora, Naveen

    2015-04-01

    Protease(s) enhances airway inflammation and allergic cascade. In the present study, effect of a serine protease inhibitor was evaluated in mouse model of airway disease. Mice were sensitized with cockroach extract (CE) or Per a 10 and treated with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) 1 h before or after challenge to measure airway response. Mice were euthanized to collect bronchoalveolar lavage fluid (BALF), blood, and lung to evaluate inflammation. AEBSF treatment significantly reduced the AHR in allergen-challenged mice in dose-dependent manner (p≤ 0.01). IgE (p≤0.05) and Th2 cytokines (p≤0.05) were significantly reduced in treated mice. AEBSF treatment lowered total cell (p≤0.05), eosinophil (p≤0.05), and neutrophil (p≤0.05) in BALF and lung tissue. Oxidative stress parameters were impaired on treatment in allergen-challenged mice (p≤0.05). AEBSF had therapeutic effect in allergen-induced airway resistance and underling inflammation and had potential for combination or as add-on therapy for respiratory diseases.

  7. High-fat diet promotes lung fibrosis and attenuates airway eosinophilia after exposure to cockroach allergen in mice.

    PubMed

    Ge, Xiao Na; Greenberg, Yana; Hosseinkhani, M Reza; Long, Eric K; Bahaie, Nooshin S; Rao, Amrita; Ha, Sung Gil; Rao, Savita P; Bernlohr, David A; Sriramarao, P

    2013-11-01

    Obesity is an important risk factor for asthma but the mechanistic basis for this association is not well understood. In the current study, the impact of obesity on lung inflammatory responses after allergen exposure was investigated. C57BL/6 mice maintained on a high-fat diet (HFD) or a normal diet (ND) after weaning were sensitized and challenged with cockroach allergen (CRA). Airway inflammation was assessed based on inflammatory cell recruitment, measurement of lung Th1-Th2 cytokines, chemokines, eicosanoids, and other proinflammatory mediators as well as airway hyperresponsiveness (AHR). CRA-challenged mice fed a HFD exhibited significantly decreased allergen-induced airway eosinophilia along with reduced lung IL-5, IL-13, LTC4, CCL11, and CCL2 levels as well as reduced mucus secretion and smooth muscle mass compared to ND fed mice. However, allergen-challenged HFD fed mice demonstrated significantly increased PAI-1 and reduced PGE2 levels in the lung relative to corresponding ND fed mice. Interestingly, saline-exposed HFD fed mice demonstrated elevated baseline levels of TGF-β1, arginase-1, hypoxia-inducible factor-1α, and lung collagen expression associated with decreased lung function compared to corresponding ND fed mice. These studies indicate that a HFD inhibits airway eosinophilia while altering levels of PAI-1 and PGE2 in response to CRA in mice. Further, a HFD can lead to the development of lung fibrosis even in the absence of allergen exposure which could be due to innate elevated levels of specific profibrotic factors, potentially affecting lung function during asthma.

  8. Eosinophilia

    MedlinePlus

    ... uh) is a higher than normal level of eosinophils. Eosinophils are a type of disease-fighting white blood ... or cancer. You can have high levels of eosinophils in your blood (blood eosinophilia) or in tissues ...

  9. Allergen-induced airway remodeling is impaired in galectin-3 deficient mice1

    PubMed Central

    Ge, Xiao Na; Bahaie, Nooshin S.; Kang, Bit Na; Hosseinkhani, Reza M.; Ha, Sung Gil; Frenzel, Elizabeth M.; Liu, Fu-Tong; Rao, Savita P.; Sriramarao, P.

    2010-01-01

    The role played by the β-galactoside-binding lectin galectin-3 (Gal-3) in airway remodeling, a characteristic feature of asthma that leads to airway dysfunction and poor clinical outcome in humans, was investigated in a murine model of chronic allergic airway inflammation. Wild-type (WT) and Gal-3 knock-out (KO) mice were subjected to repetitive allergen challenge with ovalbumin (OVA) up to 12 weeks and bronchoalveolar lavage fluid (BALF) and lung tissue collected after the last challenge were evaluated for cellular features associated with airway remodeling. Compared to WT mice, chronic OVA challenge in Gal-3 KO mice resulted in diminished remodeling of the airways with significantly reduced mucus secretion, sub-epithelial fibrosis, smooth muscle thickness, and peribronchial angiogenesis. The higher degree of airway remodeling in WT mice was associated with higher Gal-3 expression in the BALF as well as lung tissue. Cell counts in BALF and lung immunohistology demonstrated that eosinophil infiltration in OVA-challenged Gal-3 KO mice was significantly reduced compared to WT mice. Evaluation of cellular mediators associated with eosinophil recruitment and airway remodeling revealed that levels of eotaxin-1, IL-5, IL-13, FIZZ1 and TGF-β were substantially lower in Gal-3 KO mice. Finally, leukocytes from Gal-3 KO mice demonstrated decreased trafficking (rolling) on vascular endothelial adhesion molecules compared to WT cells. Overall, these studies demonstrate that Gal-3 is an important lectin that promotes airway remodeling via airway recruitment of inflammatory cells, specifically eosinophils, and the development of a Th2 phenotype as well as increased expression of eosinophil-specific chemokines, pro-fibrogenic and angiogenic mediators. PMID:20543100

  10. Strain-Dependent Genomic Factors Affect Allergen-Induced Airway Hyperresponsiveness in Mice

    PubMed Central

    Kelada, Samir N. P.; Wilson, Mark S.; Tavarez, Urraca; Kubalanza, Kari; Borate, Bhavesh; Whitehead, Greg S.; Maruoka, Shuichiro; Roy, Michelle G.; Olive, Michelle; Carpenter, Danielle E.; Brass, David M.; Wynn, Thomas A.; Cook, Donald N.; Evans, Christopher M.; Schwartz, David A.

    2011-01-01

    Asthma is etiologically and clinically heterogeneous, making the genomic basis of asthma difficult to identify. We exploited the strain-dependence of a murine model of allergic airway disease to identify different genomic responses in the lung. BALB/cJ and C57BL/6J mice were sensitized with the immunodominant allergen from the Dermatophagoides pteronyssinus species of house dust mite (Der p 1), without exogenous adjuvant, and the mice then underwent a single challenge with Der p 1. Allergic inflammation, serum antibody titers, mucous metaplasia, and airway hyperresponsiveness were evaluated 72 hours after airway challenge. Whole-lung gene expression analyses were conducted to identify genomic responses to allergen challenge. Der p 1–challenged BALB/cJ mice produced all the key features of allergic airway disease. In comparison, C57BL/6J mice produced exaggerated Th2-biased responses and inflammation, but exhibited an unexpected decrease in airway hyperresponsiveness compared with control mice. Lung gene expression analysis revealed genes that were shared by both strains and a set of down-regulated genes unique to C57BL/6J mice, including several G-protein–coupled receptors involved in airway smooth muscle contraction, most notably the M2 muscarinic receptor, which we show is expressed in airway smooth muscle and was decreased at the protein level after challenge with Der p 1. Murine strain–dependent genomic responses in the lung offer insights into the different biological pathways that develop after allergen challenge. This study of two different murine strains demonstrates that inflammation and airway hyperresponsiveness can be decoupled, and suggests that the down-modulation of expression of G-protein–coupled receptors involved in regulating airway smooth muscle contraction may contribute to this dissociation. PMID:21378263

  11. Effect of choline chloride in allergen-induced mouse model of airway inflammation.

    PubMed

    Mehta, A K; Gaur, S N; Arora, N; Singh, B P

    2007-10-01

    The incidence of asthma has increased the world over, and current therapies for the disease suffer from potential side-effects. This has created an opportunity to develop novel therapeutic approaches. Here, the anti-inflammatory activity of choline was investigated in a mouse model of allergic airway inflammation. Choline (1 mg.kg(-1)) was administered via oral gavage or intranasally before and after ovalbumin (OVA) challenge in sensitised mice. Airway hyperresponsiveness (AHR) to methacholine was measured in the mice by whole-body plethysmography. Type-2 T-helper cell cytokine and leukotriene levels were estimated in bronchoalveolar lavage fluid (BALF) and spleen culture supernatant by ELISA. Eosinophil peroxidase activity was also determined in the BALF supernatant. Choline treatment in sensitised mice before OVA challenge via oral/intranasal routes significantly inhibited eosinophilic airway inflammation and eosinophil peroxidase activity. It also reduced immunoglobulin E and G1 production and inhibited the release of type-2 T-helper cell cytokines and leukotrienes. However, the development of AHR was prevented effectively by intranasal choline treatment. Most importantly, choline treatment after OVA challenge by both routes could reverse established asthmatic conditions in mice by inhibiting AHR, eosinophilic airway inflammation and other inflammatory parameters. This study provides a new therapeutic approach for controlling as well as preventing asthma exacerbations.

  12. Allergen-induced airway remodeling in brown norway rats: structural and metabolic changes in glycosaminoglycans.

    PubMed

    Venkatesan, Narayanan; Siddiqui, Sana; Jo, Taisuke; Martin, James G; Ludwig, Mara S

    2012-01-01

    Increased proteoglycan (PG) deposition is a feature of airway remodeling in asthma. Glycosaminoglycans (GAGs) mediate many of the biological and mechanical properties of PGs by providing docking sites through their carbohydrate chains to bioactive ligands; therefore, it is imperative to define structural and metabolic changes of GAGs in asthma. Using a Brown Norway (BN) ovalbumin (OVA)-sensitized and -challenged rat model to induce airway remodeling, we found excessive deposition of chondroitin/dermatan (CS/DS)-, heparan (HS), and keratan (KS) sulfate GAGs in the airways and bronchoalveolar lavage cells of OVA-challenged rats. Disaccharide composition of CS/DS of OVA-challenged rats was significantly different compared with saline-treated (SAL) control rats, with increased levels of 0-, 6-, and 4-sulfated disaccharides. Increases in the amount and a change in the proportion of CS/DS versus HS GAGs were noted in OVA-challenged rats. The higher content and sulfation of CS/DS disaccharides was reflected by the increased expression of xylosyltransferase-I, β1,3-glucuronosyltransferase-I, chondroitin-4, and chondroitin-6 sulfotransferase genes and protein expression of xylosyltransferase-I and β1,3-glucuronosyltransferase-I in OVA-challenged rats. Genes encoding the core proteins of the CS/DS and KS-containing PGs, such as versican, biglycan, decorin, and lumican, were overexpressed in OVA-challenged rats. Our results suggest that GAG biosynthetic enzymes may be involved in the altered expression of GAGs in the airways and are potential targets for inhibiting excess PG-GAG deposition and the airway remodeling process in asthma.

  13. Allergen-induced asthma

    PubMed Central

    Cockcroft, Donald W

    2014-01-01

    It was only in the late 19th century that specific allergens, pollen, animal antigens and, later, house dust mite, were identified to cause upper and lower airway disease. Early allergen challenge studies, crudely monitored before measurement of forced expiratory volume in 1 s became widespread in the 1950s, focused on the immediate effects but noted in passing prolonged and/or recurrent asthma symptoms. The late asthmatic response, recurrent bronchoconstriction after spontaneous resolution of the early responses occurring 3 h to 8 h or more postchallenge, has been identified and well characterized over the past 50 years. The associated allergen-induced airway hyper-responsiveness (1977) and allergen-induced airway inflammation (1985) indicate that these late sequelae are important in the mechanism of allergen-induced asthma. Allergens are now recognized to be the most important cause of asthma. A standardized allergen inhalation challenge model has been developed and is proving to be a valuable research tool in the investigation of asthma pathophysiology and of potential new pharmacological agents for the treatment of asthma. PMID:24791256

  14. Hydrogen sulfide inhalation ameliorates allergen induced airway hypereactivity by modulating mast cell activation.

    PubMed

    Roviezzo, Fiorentina; Bertolino, Antonio; Sorrentino, Rosalinda; Terlizzi, Michela; Matteis, Maria; Calderone, Vincenzo; Mattera, Valentina; Martelli, Alma; Spaziano, Giuseppe; Pinto, Aldo; D'Agostino, Bruno; Cirino, Giuseppe

    2015-10-01

    Compelling evidence suggests that hydrogen sulfide represents an important gaseous transmitter in the mammalian respiratory system. In the present study, we have evaluated the role of mast cells in hydrogen sulfide-induced effects on airways in a mouse model of asthma. Mice were sensitized to ovalbumin and received aerosol of a hydrogen sulfide donor (NaHS; 100 ppm) starting at day 7 after ovalbumin challenge. Exposure to hydrogen sulfide abrogated ovalbumin-induced bronchial hypereactivity as well as the increase in lung resistance. Concomitantly, hydrogen sulfide prevented mast cell activity as well as FGF-2 and IL-13 upregulation. Conversely, pulmonary inflammation and the increase in plasmatic IgE levels were not affected by hydrogen sulfide. A lack of hydrogen sulfide effects in mast cell deficient mice occurred. Primary fibroblasts harvested from ovalbumin-sensitized mice showed an increased proliferation rate that was inhibited by hydrogen sulfide aerosol. Furthermore, ovalbumin-induced transdifferentiation of pulmonary fibroblasts into myofibroblasts was reversed. Finally, hydrogen sulfide did abrogate in vitro the degranulation of the mast cell-like RBL-2H3 cell line. Similarly to the in vivo experiments the inhibitory effect was present only when the cells were activated by antigen exposure. In conclusion, inhaled hydrogen sulfide improves lung function and inhibits bronchial hyper-reactivity by modulating mast cells and in turn fibroblast activation.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2013-05-01

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

  17. Circulating, but not local lung, IL-5 is required for the development of antigen-induced airways eosinophilia.

    PubMed Central

    Wang, J; Palmer, K; Lŏtvall, J; Milan, S; Lei, X F; Matthaei, K I; Gauldie, J; Inman, M D; Jordana, M; Xing, Z

    1998-01-01

    IL-5 is induced locally in the lung and systemically in the circulation during allergic airways eosinophilic inflammation both in humans and experimental animals. However, the precise role of local and systemic IL-5 in the development of allergic airways eosinophilia remains to be elucidated. In our current study, we demonstrate that compared with their IL-5(+/+) counterparts, IL-5(-/-) mice lacked an IL-5 response both in the lung and peripheral blood, yet they released similar amounts of IL-4, eotaxin, and MIP-1alpha in the lung after ovalbumin (OVA) sensitization and challenge. At cellular levels, these mice failed to develop peripheral blood and airways eosinophilia while the responses of lymphocytes, neutrophils, and macrophages remained similar to those in IL-5(+/+) mice. To dissect the relative role of local and systemic IL-5 in this model, we constructed a gene transfer vector expressing murine IL-5. Intramuscular IL-5 gene transfer to OVA-sensitized IL-5(-/-) mice led to raised levels of IL-5 compartmentalized to the circulation and completely reconstituted airways eosinophilia upon OVA challenge, which was associated with reconstitution of eosinophilia in the bone marrow and peripheral blood. Significant airways eosinophilia was observed for at least 7 d in these mice. In contrast, intranasal IL-5 gene transfer, when rendered to give rise to a significant but compartmentalized level of transgene protein IL-5 in the lung, was unable to reconstitute airways eosinophilia in OVA-sensitized IL-5(-/-) mice upon OVA-challenge, which was associated with a lack of eosinophilic responses in bone marrow and peripheral blood. Our findings thus provide unequivocal evidence that circulating but not local lung IL-5 is critically required for the development of allergic airways eosinophilia. These findings also provide the rationale for developing strategies to target circulating IL-5 and/or its receptors in bone marrow to effectively control asthmatic airways

  18. α-Galactosylceramide-induced airway eosinophilia is mediated through the activation of NKT cells.

    PubMed

    Chuang, Ya-Hui; Wang, Tzu-Chun; Jen, Hsiao-Yu; Yu, Alice L; Chiang, Bor-Luen

    2011-04-15

    Invariant NKT (iNKT) cells bridge innate and adaptive immune responses, resulting in the expansion of Ag-specific B and T cell responses. α-Galactosylceramide (α-GalCer), the most studied glycolipid that activates iNKT cells, has been proposed to be an effective adjuvant against infections and tumors. We found that the activation of iNKT cells by intranasal injection of α-GalCer induced airway eosinophilia in naive mice. Eosinophils, which mediate tissue damage and dysfunction by secreting mediators, play important roles in the pathogenesis of allergic diseases. In this study, we investigated the mechanism of how eosinophils are recruited to the lung by α-GalCer. Our results demonstrated that α-GalCer-induced eosinophil inflammation was mediated through iNKT cells. These cells secreted IL-5 to recruit eosinophils directly to the lung and/or secreted IL-4 and IL-13 to recruit eosinophils indirectly by inducing lung epithelial cells, endothelial cells, and fibroblast to secrete the eosinophil chemoattractant eotaxin. In addition, in the OVA-alum murine model of allergic asthma, α-GalCer administration in OVA-immunized mice also increased airway eosinophilia after challenge. Given our findings, intranasal administration of α-GalCer induced airway eosinophilic inflammation in both naive and allergic mice. Hence, it remains to be determined whether the activation of iNKT cells would be applicable in therapeutics for human diseases.

  19. Nonhematopoietic NADPH oxidase regulation of lung eosinophilia and airway hyperresponsiveness in experimentally induced asthma

    PubMed Central

    Abdala-Valencia, Hiam; Earwood, Julie; Bansal, Shelly; Jansen, Michael; Babcock, George; Garvy, Beth; Wills-Karp, Marsha; Cook-Mills, Joan M.

    2009-01-01

    Pulmonary eosinophilia is one of the most consistent hallmarks of asthma. Infiltration of eosinophils into the lung in experimental asthma is dependent on the adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. Ligation of VCAM-1 activates endothelial cell NADPH oxidase, which is required for VCAM-1-dependent leukocyte migration in vitro. To examine whether endothelial-derived NADPH oxidase modulates eosinophil recruitment in vivo, mice deficient in NADPH oxidase (CYBB mice) were irradiated and received wild-type hematopoietic cells to generate chimeric CYBB mice. In response to ovalbumin (OVA) challenge, the chimeric CYBB mice had increased numbers of eosinophils bound to the endothelium as well as reduced eosinophilia in the lung tissue and bronchoalveolar lavage. This occurred independent of changes in VCAM-1 expression, cytokine/chemokine levels (IL-5, IL-10, IL-13, IFNγ, or eotaxin), or numbers of T cells, neutrophils, or mononuclear cells in the lavage fluids or lung tissue of OVA-challenged mice. Importantly, the OVA-challenged chimeric CYBB mice had reduced airway hyperresponsiveness (AHR). The AHR in OVA-challenged chimeric CYBB mice was restored by bypassing the endothelium with intratracheal administration of eosinophils. These data suggest that VCAM-1 induction of NADPH oxidase in the endothelium is necessary for the eosinophil recruitment during allergic inflammation. Moreover, these studies provide a basis for targeting VCAM-1-dependent signaling pathways in asthma therapies. PMID:17293377

  20. Protective effects of the polyphenol sesamin on allergen-induced T(H)2 responses and airway inflammation in mice.

    PubMed

    Lin, Ching-Huei; Shen, Mei-Lin; Zhou, Ning; Lee, Chen-Chen; Kao, Shung-Te; Wu, Dong Chuan

    2014-01-01

    Allergic asthma is a lifelong airway condition that affects people of all ages. In recent decades, asthma prevalence continues to increase globally, with an estimated number of 250,000 annual deaths attributed to the disease. Although inhaled corticosteroids and β-adrenergic receptor agonists are the primary therapeutic avenues that effectively reduce asthma symptoms, profound side effects may occur in patients with long-term treatments. Therefore, development of new therapeutic strategies is needed as alternative or supplement to current asthma treatments. Sesamin is a natural polyphenolic compound with strong anti-oxidative effects. Several studies have reported that sesamin is effective in preventing hypertension, thrombotic tendency, and neuroinflammation. However, it is still unknown whether sesamin can reduce asthma-induced allergic inflammation and airway hyperresponsiveness (AHR). Our study has revealed that sesamin exhibited significant anti-inflammatory effects in ovalbumin (OVA)-induced murine asthma model. We found that treatments with sesamin after OVA sensitization and challenge significantly decreased expression levels of interleukin-4 (IL-4), IL-5, IL-13, and serum IgE. The numbers of total inflammatory cells and eosinophils in BALF were also reduced in the sesamin-treated animals. Histological results demonstrated that sesamin attenuated OVA-induced eosinophil infiltration, airway goblet cell hyperplasia, mucus occlusion, and MUC5AC expression in the lung tissue. Mice administered with sesamin showed limited increases in AHR compared with mice receiving vehicle after OVA challenge. OVA increased phosphorylation levels of IκB-α and nuclear expression levels of NF-κB, both of which were reversed by sesamin treatments. These data indicate that sesamin is effective in treating allergic asthma responses induced by OVA in mice.

  1. Inhalation of inactivated‑Mycobacterium phlei prevents asthma‑mediated airway hyperresponsiveness and airway eosinophilia in mice by reducing IL‑5 and IL‑13 levels.

    PubMed

    Ming, Moyu; Luo, Zhixi; Lv, Shengqiu; Li, Chaoqian

    2016-12-01

    The present study aimed to investigate whether inhalation of inactivated‑Mycobacterium phlei could prevent airway hyperresponsiveness and airway eosinophilia. A total of 24 male Balb/c mice were randomly divided into three groups: Normal control group (group A), asthma model group (group B) and the intervention group (group C), (8 mice/group). Group A mice were sensitized and with challenged saline and group B with ovalbumin (OVA). Group C mice were administered with aerosol Mycobacterium phlei once daily prior to the allergen challenge. Airway responsiveness in each group was assessed. All the animals were sacrificed and lung tissues, blood samples and bronchoalveolar lavage fluid (BALF) were harvested. Cell fractionation and differential cells were counted in serum and BALF. HE staining and alcian blue/periodic acid Schiff staining were used to measure airway eosinophilic inflammation and mucus production. The levels of the cytokines IL‑5, IL‑13 and IgE were measured in lung and BALF as determined by ELISA and reverse transcription‑quantitative polymerase chain reaction assays. The results indicated that inactivated‑Mycobacterium phlei suppressed the airway hyperresponsiveness and mitigated airway eosinophilia induced by a methacholine challenge, and significantly reduced the levels of cytokines IL‑5 and IL‑13 in lung tissue and IgE level in BALF when compared with the OVA‑sensitized mice. In conclusion, inhalation of inactivated‑Mycobacterium phlei could reduce OVA‑induced airway hyperresponsiveness and may be a potential alternative therapy for allergic airway diseases.

  2. Peripheral blood eosinophils: a surrogate marker for airway eosinophilia in stable COPD

    PubMed Central

    Negewo, Netsanet A; McDonald, Vanessa M; Baines, Katherine J; Wark, Peter AB; Simpson, Jodie L; Jones, Paul W; Gibson, Peter G

    2016-01-01

    Introduction Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments. Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results. Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management. This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils. It also examined the repeatability of blood eosinophil counts. Methods Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (≥3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts. Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia. Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts. Results Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×109/L vs 0.15×109/L; P<0.0001). Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001). Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67–0.84; P<0.0001). At a threshold of ≥0.3×109/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases. A threshold of ≥0.4×109/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7). In contrast, ≥0.2×109/L

  3. Tbet Deficiency Causes T Helper Cell Dependent Airways Eosinophilia and Mucus Hypersecretion in Response to Rhinovirus Infection

    PubMed Central

    Glanville, Nicholas; Schröder, Armin; Walton, Ross P.; Johnston, Sebastian L.

    2016-01-01

    Current understanding of adaptive immune, particularly T cell, responses to human rhinoviruses (RV) is limited. Memory T cells are thought to be of a primarily T helper 1 type, but both T helper 1 and T helper 2 memory cells have been described, and heightened T helper 2/ lessened T helper 1 responses have been associated with increased RV-induced asthma exacerbation severity. We examined the contribution of T helper 1 cells to RV-induced airways inflammation using mice deficient in the transcription factor T-Box Expressed In T Cells (Tbet), a critical controller of T helper 1 cell differentiation. Using flow cytometry we showed that Tbet deficient mice lacked the T helper 1 response of wild type mice and instead developed mixed T helper 2/T helper 17 responses to RV infection, evidenced by increased numbers of GATA binding protein 3 (GATA-3) and RAR-related orphan receptor gamma t (RORγt), and interleukin-13 and interleukin-17A expressing CD4+ T cells in the lung. Forkhead box P3 (FOXP3) and interleukin-10 expressing T cell numbers were unaffected. Tbet deficient mice also displayed deficiencies in lung Natural Killer, Natural Killer T cell and γδT cell responses, and serum neutralising antibody responses. Tbet deficient mice exhibited pronounced airways eosinophilia and mucus production in response to RV infection that, by utilising a CD4+ cell depleting antibody, were found to be T helper cell dependent. RV induction of T helper 2 and T helper 17 responses may therefore have an important role in directly driving features of allergic airways disease such as eosinophilia and mucus hypersecretion during asthma exacerbations. PMID:27683080

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

    PubMed

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

    2016-08-16

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

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

    PubMed Central

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

    2016-01-01

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

  6. C5 Modulates Airway Hyperreactivity and Pulmonary Eosinophilia during Enhanced Respiratory Syncytial Virus Disease by Decreasing C3a Receptor Expression▿

    PubMed Central

    Melendi, Guillermina A.; Hoffman, Scott J.; Karron, Ruth A.; Irusta, Pablo M.; Laham, Federico R.; Humbles, Alison; Schofield, Brian; Pan, Chien-Hsiung; Rabold, Richard; Thumar, Bhagvanji; Thumar, Adeep; Gerard, Norma P.; Mitzner, Wayne; Barnum, Scott R.; Gerard, Craig; Kleeberger, Steven R.; Polack, Fernando P.

    2007-01-01

    Enhanced respiratory syncytial virus disease, a serious pulmonary disorder that affected recipients of an inactivated vaccine against respiratory syncytial virus in the 1960s, has delayed the development of vaccines against the virus. The enhanced disease was characterized by immune complex-mediated airway hyperreactivity and a severe pneumonia associated with pulmonary eosinophilia. In this paper, we show that complement factors contribute to enhanced-disease phenotypes. Mice with a targeted disruption of complement component C5 affected by the enhanced disease displayed enhanced airway reactivity, lung eosinophilia, and mucus production compared to wild-type mice and C5-deficient mice reconstituted with C5. C3aR expression in bronchial epithelial and smooth muscle cells in the lungs of C5-deficient mice was enhanced compared to that in wild-type and reconstituted rodents. Treatment of C5-deficient mice with a C3aR antagonist significantly attenuated airway reactivity, eosinophilia, and mucus production. These results indicate that C5 plays a crucial role in modulating the enhanced-disease phenotype, by affecting expression of C3aR in the lungs. These findings reveal a novel autoregulatory mechanism for the complement cascade that affects the innate and adaptive immune responses. PMID:17079327

  7. The allergen-induced airway hyperresponsiveness in a human-mouse chimera model of asthma is T cell and IL-4 and IL-5 dependent.

    PubMed

    Tournoy, K G; Kips, J C; Pauwels, R A

    2001-06-01

    The cellular and molecular mechanisms involved in the airway hyperresponsiveness (AHR) of patients with allergic asthma remain unclear. A role for Th2 inflammatory cells was suggested based on murine asthma models. No direct evidence exists on the role of these cells in human asthma. The development of a mouse-human chimera might be useful, allowing the in vivo study of the components of the human immune system relevant to asthma. We investigated the role of allergen-reactive T lymphocytes in a human-mouse SCID model. SCID mice were reconstituted intratracheally with human PBMC from healthy, nonallergic, nonasthmatic donors and exposed to an aerosol of house dust mite allergen after i.p. injection with Dermatophagoides pteronyssinus I Ag and alum. The donor T lymphocytes had a Th1 cytokine phenotype. The reconstituted and allergen-challenged mice developed AHR to carbachol. The mouse airways and lungs were infiltrated with human T lymphocytes. No eosinophils or increases in human IgE were observed. The intrapulmonary human T lymphocytes demonstrated an increase in intracytoplasmic IL-4 and IL-5 and a decrease in IFN-gamma after exposure to allergen adjuvant. Antagonizing human IL-4/IL-13 or IL-5 resulted in a normalization of the airway responsiveness, despite a sustained intracellular Th2 cytokine production. These results provide evidence that the activated human allergen-reactive Th2 cells producing IL-4 or IL-5 are pivotal in the induction of AHR, whereas no critical role for eosinophils or IgE could be demonstrated. They also demonstrate that human allergen-specific Th1 lymphocytes can be driven to a Th2 phenotype.

  8. Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: role of CB1/CB2 receptors.

    PubMed

    Braun, Andrea; Engel, Tabea; Aguilar-Pimentel, Juan Antonio; Zimmer, Andreas; Jakob, Thilo; Behrendt, Heidrun; Mempel, Martin

    2011-04-01

    The endocannabinoid system (ECS) consists of two cannabinoid (CB) receptors, namely CB(1) and CB(2) receptor, and their endogenous (endocannabinoids) and exogenous (cannabinoids, e.g. delta-9-tetrahydrocannabinol (THC)) ligands which bind to these receptors. Based on studies suggesting a role of THC and the ECS in inflammation, the objective of this study was to examine their involvement in type I hypersensitivity using a murine model of allergic airway inflammation. THC treatment of C57BL/6 wildtype mice dramatically reduced airway inflammation as determined by significantly reduced total cell counts in bronchoalveolar lavage (BAL). These effects were greatest when mice were treated during both, the sensitization and the challenge phase. Furthermore, systemic immune responses were significantly suppressed in mice which received THC during sensitization phase. To investigate a role of CB(1/2) receptors in this setting, we used pharmacological blockade of CB(1) and/or CB(2) receptors by the selective antagonists and moreover CB(1)/CB(2) receptor double-knockout mice (CB(1)(-/-)/CB(2)(-/-)) and found neither significant changes in the cell patterns in BAL nor in immunoglobulin levels as compared to wildtype mice. Our results indicate that the activation of the ECS by applying the agonist THC is involved in the development of type I allergies. However, CB(1)/CB(2) receptor-independent signalling seems likely in the observed results.

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

    PubMed

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

    2014-08-01

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

  10. Potential of Inducible Nitric Oxide Synthase as a Therapeutic Target for Allergen-Induced Airway Hyperresponsiveness: A Critical Connection to Nitric Oxide Levels and PARP Activity

    PubMed Central

    Ghonim, Mohamed A.; Pyakurel, Kusma; Mishra, Anil

    2016-01-01

    Although expression of inducible NO synthase (iNOS) in the lungs of asthmatics and associated nitrosative damage are established, iNOS failed as a therapeutic target for blocking airway hyperresponsiveness (AHR) and inflammation in asthmatics. This dichotomy calls for better strategies with which the enzyme is adequately targeted. Here, we confirm iNOS expression in the asthmatic lung with concomitant protein nitration and poly(ADP-ribose) polymerase (PARP) activation. We show, for the first time, that iNOS is highly expressed in peripheral blood mononuclear cells (PBMCs) of asthmatics with uncontrolled disease, which did not correspond to protein nitration. Selective iNOS inhibition with L-NIL protected against AHR upon acute, but not chronic, exposure to ovalbumin or house dust mite (HDM) in mice. Supplementation of NO by nitrite administration significantly blocked AHR in chronically HDM-exposed mice that were treated with L-NIL. Protection against chronic HDM exposure-induced AHR by olaparib-mediated PARP inhibition may be associated with the partial but not the complete blockade of iNOS expression. Indeed, L-NIL administration prevented olaparib-mediated protection against AHR in chronically HDM-exposed mice. Our study suggests that the amount of iNOS and NO are critical determinants in the modulation of AHR by selective iNOS inhibitors and renews the potential of iNOS as a therapeutic target for asthma. PMID:27524861

  11. Beneficial cross-protection of allergen-specific immunotherapy on airway eosinophilia using unrelated or a partial repertoire of allergen(s) implicated in experimental feline asthma.

    PubMed

    Reinero, Carol; Lee-Fowler, Tekla; Chang, Chee-Hoon; Cohn, Leah; Declue, Amy

    2012-06-01

    The study hypothesis was that in experimentally asthmatic cats rush immunotherapy (RIT) using allergens not completely matched with sensitizing allergen(s) would at least partially attenuate the asthmatic phenotype and modulate the aberrant immune response. In phase I, cats sensitized to Bermuda grass allergen (BGA), house dust mite allergen (HDMA) or placebo received BGA RIT. In phase II, cats dually sensitized to BGA and HDMA received RIT using BGA, HDMA or placebo. Efficacy of RIT was assessed using percentage bronchoalveolar lavage fluid (BALF) eosinophils. Additionally, a variety of immunologic assays were performed. Eosinophilic airway inflammation significantly decreased over time in asthmatic cats given RIT using sensitizing allergen or unrelated allergen (P<0.001). In dually sensitized cats, single allergen RIT but not placebo reduced airway eosinophilia (P=0.038). Differences in allergen-specific lymphocyte proliferation, in the number of IL-10 producing cells and in the percentage T regulatory cells were detected between asthmatic cats getting RIT and controls. Cross-protection manifested by reduced airway eosinophilia was noted in cats treated with RIT allergens which did not completely match allergen used in asthma induction. However, the mechanism of immunologic tolerance may differ when improperly matched allergens to the sensitizing allergens are used in RIT.

  12. Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung

    PubMed Central

    1995-01-01

    Eotaxin is a member of the C-C family of chemokines and is related during antigen challenge in a guinea pig model of allergic airway inflammation (asthma). Consistent with its putative role in eosinophilic inflammation, eotaxin induces the selective infiltration of eosinophils when injected into the lung and skin. Using a guinea pig lung cDNA library, we have cloned full-length eotaxin cDNA. The cDNA encodes a protein of 96 amino acids, including a putative 23-amino acid hydrophobic leader sequence, followed by 73 amino acids composing the mature active eotaxin protein. The protein-coding region of this cDNA is 73, 71, 50, and 48% identical in nucleic acid sequence to those of human macrophage chemoattractant protein (MCP) 3, MCP-1, macrophage inflammatory protein (MIP) 1 alpha, and RANTES, respectively. Analysis of genomic DNA suggested that there is a single eotaxin gene in guinea pig which is apparently conserved in mice. High constitutive levels of eotaxin mRNA expression were observed in the lung, while the intestines, stomach, spleen, liver, heart, thymus, testes, and kidney expressed lower levels. To determine if eotaxin mRNA levels are elevated during allergen-induced eosinophilic airway inflammation, ovalbumin (OVA)-sensitized guinea pigs were challenged with aerosolized antigen. Compared with the lungs from saline-challenged animals, eotaxin mRNA levels increased sixfold within 3 h and returned to baseline by 6 h. Thus, eotaxin mRNA levels are increased in response to allergen challenge during the late phase response. The identification of constitutive eotaxin mRNA expression in multiple tissues suggests that in addition to regulating airway eosinophilia, eotaxin is likely to be involved in eosinophil recruitment into other tissues as well as in baseline tissue homing. PMID:7869037

  13. Nebulized anti-IL-13 monoclonal antibody Fab' fragment reduces allergen-induced asthma.

    PubMed

    Hacha, Jonathan; Tomlinson, Kate; Maertens, Ludovic; Paulissen, Geneviève; Rocks, Natacha; Foidart, Jean-Michel; Noel, Agnès; Palframan, Roger; Gueders, Maud; Cataldo, Didier D

    2012-11-01

    IL-13 is a prototypic T helper type 2 cytokine and a central mediator of the complex cascade of events leading to asthmatic phenotype. Indeed, IL-13 plays key roles in IgE synthesis, bronchial hyperresponsiveness, mucus hypersecretion, subepithelial fibrosis, and eosinophil infiltration. We assessed the potential efficacy of inhaled anti-IL-13 monoclonal antibody Fab' fragment on allergen-induced airway inflammation, hyperresponsiveness, and remodeling in an experimental model of allergic asthma. Anti-IL-13 Fab' was administered to mice as a liquid aerosol generated by inExpose inhalation system in a tower allowing a nose-only exposure. BALB/c mice were treated by PBS, anti-IL-13 Fab', or A33 Fab' fragment and subjected to ovalbumin exposure for 1 and 5 weeks (short-term and long-term protocols). Our data demonstrate a significant antiasthma effect after nebulization of anti-IL-13 Fab' in a model of asthma driven by allergen exposure as compared with saline and nonimmune Fab fragments. In short- and long-term protocols, administration of the anti-IL-13 Fab' by inhalation significantly decreased bronchial responsiveness to methacholine, bronchoalveolar lavage fluid eosinophilia, inflammatory cell infiltration in lung tissue, and many features of airway remodeling. Levels of proinflammatory mediators and matrix metalloprotease were significantly lower in lung parenchyma of mice treated with anti-IL-13 Fab'. These data demonstrate that an inhaled anti-IL-13 Fab' significantly reduces airway inflammation, hyperresponsiveness, and remodeling. Specific neutralization of IL-13 in the lungs using an inhaled anti-IL-13 Fab' could represent a novel and effective therapy for the treatment of asthma.

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

    PubMed

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

    1998-02-01

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

  15. Ca(2+)-activated K(+) channel-3.1 blocker TRAM-34 attenuates airway remodeling and eosinophilia in a murine asthma model.

    PubMed

    Girodet, Pierre-Olivier; Ozier, Annaig; Carvalho, Gabrielle; Ilina, Olga; Ousova, Olga; Gadeau, Alain-Pierre; Begueret, Hugues; Wulff, Heike; Marthan, Roger; Bradding, Peter; Berger, Patrick

    2013-02-01

    Key features of asthma include bronchial hyperresponsiveness (BHR), eosinophilic airway inflammation, and bronchial remodeling, characterized by subepithelial collagen deposition, airway fibrosis, and increased bronchial smooth muscle (BSM) mass. The calcium-activated K(+) channel K(Ca)3.1 is expressed by many cells implicated in the pathogenesis of asthma, and is involved in both inflammatory and remodeling responses in a number of tissues. The specific K(Ca)3.1 blocker 5-[(2-chlorophenyl)(diphenyl)methyl]-1H-pyrazole (TRAM-34) attenuates BSM cell proliferation, and both mast cell and fibrocyte recruitment in vitro. We aimed to examine the effects of K(Ca)3.1 blockade on BSM remodeling, airway inflammation, and BHR in a murine model of chronic asthma. BALB/c mice were sensitized with intraperitoneal ovalbumin (OVA) on Days 0 and 14, and then challenged with intranasal OVA during Days 14-75. OVA-sensitized/challenged mice received TRAM-34 (120 mg/kg/day, subcutaneous) from Days -7 to 75 (combined treatment), Days -7 to 20 (preventive treatment), or Days 21 to 75 (curative treatment). Untreated mice received daily injections of vehicle (n = 8 per group). Bronchial remodeling was assessed by histological and immunohistochemical analyses. Inflammation was evaluated using bronchoalveolar lavage and flow cytometry. We also determined BHR in both conscious and anesthetized mice via plethysmography. We demonstrated that curative treatment with TRAM-34 abolishes BSM remodeling and subbasement collagen deposition, and attenuates airway eosinophilia. Although curative treatment alone did not significantly reduce BHR, the combined treatment attenuated nonspecific BHR to methacholine. This study indicates that K(Ca)3.1 blockade could provide a new therapeutic strategy in asthma.

  16. Intelectin contributes to allergen-induced IL-25, IL-33, and TSLP expression and type 2 response in asthma and atopic dermatitis.

    PubMed

    Yi, L; Cheng, D; Zhang, K; Huo, X; Mo, Y; Shi, H; Di, H; Zou, Y; Zhang, H; Zhao, J; Xu, Y; Erle, D J; Zhen, G

    2017-02-22

    The epithelial and epidermal innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) have pivotal roles in the initiation of allergic inflammation in asthma and atopic dermatitis (AD). However, the mechanism by which the expression of these innate cytokines is regulated remains unclear. Intelectin (ITLN) is expressed in airway epithelial cells and promotes allergic airway inflammation. We hypothesized that ITLN is required for allergen-induced IL-25, IL-33, and TSLP expression. In two asthma models, Itln knockdown reduced allergen-induced increases in Il-25, Il-33, and Tslp and development of type 2 response, eosinophilic inflammation, mucus overproduction, and airway hyperresponsiveness. Itln knockdown also inhibited house dust mite (HDM)-induced early upregulation of Il-25, Il-33, and Tslp in a model solely inducing airway sensitization. Using human airway epithelial cells, we demonstrated that HDM-induced increases in ITLN led to phosphorylation of epidermal growth factor receptor and extracellular-signal regulated kinase, which were required for induction of IL-25, IL-33, and TSLP expression. In two AD models, Itln knockdown suppressed expression of Il-33, Tslp, and Th2 cytokines and eosinophilic inflammation. In humans, ITLN1 expression was significantly increased in asthmatic airways and in lesional skin of AD. We conclude that ITLN contributes to allergen-induced Il-25, Il-33, and Tslp expression in asthma and AD.Mucosal Immunology advance online publication 22 February 2017. doi:10.1038/mi.2017.10.

  17. Control of allergen-induced inflammation and hyperresponsiveness by the metalloproteinase ADAMTS-12.

    PubMed

    Paulissen, Geneviève; El Hour, Mehdi; Rocks, Natacha; Guéders, Maud M; Bureau, Fabrice; Foidart, Jean-Michel; Lopez-Otin, Carlos; Noel, Agnès; Cataldo, Didier D

    2012-10-15

    A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) constitute a family of endopeptidases related to matrix metalloproteinases. These proteinases have been largely implicated in tissue remodeling associated with pathological processes. Among them, ADAMTS12 was identified as an asthma-associated gene in a human genome screening program. However, its functional implication in asthma is not yet documented. The present study aims at investigating potential ADAMTS-12 functions in experimental models of allergic airways disease. Two different in vivo protocols of allergen-induced airways disease were applied to the recently generated Adamts12-deficient mice and corresponding wild-type mice. In this study, we provide evidence for a protective effect of ADAMTS-12 against bronchial inflammation and hyperresponsiveness. In the absence of Adamts12, challenge with different allergens (OVA and house dust mite) led to exacerbated eosinophilic inflammation in the bronchoalveolar lavage fluid and in lung tissue, along with airway dysfunction assessed by increased airway responsiveness following methacholine exposure. Furthermore, mast cell counts and ST2 receptor and IL-33 levels were higher in the lungs of allergen-challenged Adamts12-deficient mice. The present study provides, to our knowledge, the first experimental evidence for a contribution of ADAMTS-12 as a key mediator in airways disease, interfering with immunological processes leading to inflammation and airway hyperresponsiveness.

  18. Eosinophilia in Infectious Diseases

    PubMed Central

    O'Connell, Elise M.; Nutman, Thomas B.

    2015-01-01

    In determining the etiology of eosinophilia, it is necessary to consider the type of patient, including previous travel and exposure history, comorbidities, and symptoms. In this review, we discuss the approach to the patient with eosinophilia from an infectious diseases perspective based on symptom complexes. PMID:26209897

  19. Allergen-induced Interleukin-18 promotes experimental eosinophilic esophagitis in mice

    PubMed Central

    Dutt, Parmesh; Shukla, Jai Shankar; Ventateshaiah, Sathisha Upparahalli; Mariswamy, Siddesha Jalahalli.; Mattner, Jochen; Shukla, Anshi; Mishra, Anil

    2015-01-01

    Elevated levels of IL-18 have been reported in a number of allergic diseases. We recently reported that IL-18 in the blood and IL-18Rα mRNA in the oesophagus are induced during human eosinophilic oesophagitis (EoE). Additionally, we earlier showed that iNKT cells are critical to EoE pathogenesis; however, the mechanism of iNKT cell activation in EoE is not well understood. Therefore, the current study focused on the hypothesis that allergen-induced IL-18 may have an important role in iNKT cell-mediated EoE pathogenesis. We first validated the human EoE findings of IL-18 in experimental EoE by examining blood levels of IL-18 and oesophageal IL-18Rα mRNA levels in aeroallergen- and food allergen-induced experimental mouse models of EoE. We demonstrate that blood IL-18 protein and oesophageal IL-18Rα mRNA are induced in the mouse model of EoE and that IL-18Rα is expressed by iNKT cells in the oesophagus. Intranasal delivery of rIL-18 induced both mast cells and eosinophilic inflammation in the oesophagus in a time- and dose-dependent manner. To establish the significance of IL-18 in EoE pathogenesis, we examined DOX-inducible rtTA-CC10-IL-18 bitransgenic mice that induce IL-18 protein expression in the oesophagus. Our analysis indicated that induction of IL-18 in these mice resulted in the development of many of the characteristics of EoE, including oesophageal intraepithelial eosinophilia, increased mast cells, oesophageal remodelling and fibrosis. The current study provides evidence that IL-18 may induce iNKT cell activation to release the eosinophil activating cytokine IL-5, as IL-5-deficient mice and iNKT cell-deficient (CD1d null) mice do not induce EoE in response to intranasal IL-18 challenge. Taken together, these findings provide evidence that allergen-induced IL-18 has a significant role in promoting IL-5- and iNKT-dependent EoE pathogenesis. PMID:25801352

  20. AGR2 is induced in asthma and promotes allergen-induced mucin overproduction.

    PubMed

    Schroeder, Bradley W; Verhaeghe, Catherine; Park, Sung-Woo; Nguyenvu, Louis T; Huang, Xiaozhu; Zhen, Guohua; Erle, David J

    2012-08-01

    Mucins are gel-forming proteins that are responsible for the characteristic viscoelastic properties of mucus. Mucin overproduction is a hallmark of asthma, but the cellular requirements for airway mucin production are poorly understood. The endoplasmic reticulum (ER) protein anterior gradient homolog 2 (AGR2) is required for production of the intestinal mucin MUC2, but its role in the production of the airway mucins MUC5AC and MUC5B is not established. Microarray data were analyzed to examine the relationship between AGR2 and MUC5AC expression in asthma. Immunofluorescence was used to localize AGR2 in airway cells. Coimmunoprecipitation was used to identify AGR2-immature MUC5AC complexes. Agr2(-/-) mice were used to determine the role of AGR2 in allergic airway disease. AGR2 localized to the ER of MUC5AC- and MUC5B-producing airway cells and formed a complex with immature MUC5AC. AGR2 expression increased together with MUC5AC expression in airway epithelium from "Th2-high" asthmatics. Allergen-challenged Agr2(-/-) mice had greater than 50% reductions in MUC5AC and MUC5B proteins compared with allergen-challenged wild-type mice. Impaired mucin production in Agr2(-/-) mice was accompanied by an increase in the proportion of mucins contained within the ER and by evidence of ER stress in airway epithelium. This study shows that AGR2 increases with mucin overproduction in individuals with asthma and in mouse models of allergic airway disease. AGR2 interacts with immature mucin in the ER and loss of AGR2 impairs allergen-induced MUC5AC and MUC5B overproduction.

  1. Involvement of fibrocytes in allergen-induced T cell responses and rhinovirus infections in asthma.

    PubMed

    Isgrò, Mirko; Bianchetti, Lorenza; Marini, Maurizio A; Mattoli, Sabrina

    2013-08-02

    Allergen exposure and rhinovirus infections that propagate from the upper to the lower airways are the most frequent causes of asthma exacerbation. In patients at increased risk of disease exacerbations, chronic airway inflammation is associated with the airway recruitment of circulating fibrocytes, bone marrow-derived CD34(+)CD45RO(+)CD11b(+)CD13(+)HLA-DR(+) progenitors that have antigen-presenting function and fibroblast-like properties. This study demonstrates that allergen-pulsed circulating fibrocytes from patients with allergic asthma are potent inducer of the predominant release of the T helper type (Th)2 cytokines IL-4 and IL-5 from autologous naïve and memory CD4(+) T cells. This study also provides evidence that circulating fibrocytes from allergic asthmatics are susceptible to rhinovirus infection. Infected cells release high amounts of pro-inflammatory cytokines with minimal production of IFN-α/β. Moreover, allergen-pulsed fibrocytes support prolonged rhinovirus replication and release larger quantities of pro-inflammatory cytokines upon rhinovirus infection than unpulsed fibrocytes. Thus, fibrocytes may amplify allergen-induced, Th2 cell-driven inflammatory responses and promote further inflammation by functioning as a reservoir for rhinovirus replication in asthmatic airways. Through these mechanisms, fibrocytes may play an important role in the provocation of disease exacerbations.

  2. p110γ/δ Double-Deficiency Induces Eosinophilia and IgE Production but Protects from OVA-Induced Airway Inflammation

    PubMed Central

    Ammon-Treiber, Susanne; Schwab, Matthias; Piekorz, Roland P.; Hirsch, Emilio; Nürnberg, Bernd; Beer-Hammer, Sandra

    2016-01-01

    The catalytical isoforms p110γ and p110δ of phosphatidylinositide 3-kinase γ (PI3Kγ) and PI3Kδ play an important role in the pathogenesis of asthma. Two key elements in allergic asthma are increased levels of eosinophils and IgE. Dual pharmacological inhibition of p110γ and p110δ reduces asthma-associated eosinophilic lung infiltration and ameliorates disease symptoms, whereas the absence of enzymatic activity in p110γKOδD910A mice increases IgE and basal eosinophil counts. This suggests that long-term inhibition of p110γ and p110δ might exacerbate asthma. Here, we analysed mice genetically deficient for both catalytical subunits (p110γ/δ-/-) and determined basal IgE and eosinophil levels and the immune response to ovalbumin-induced asthma. Serum concentrations of IgE, IL-5 and eosinophil numbers were significantly increased in p110γ/δ-/- mice compared to single knock-out and wildtype mice. However, p110γ/δ-/- mice were protected against OVA-induced infiltration of eosinophils, neutrophils, T and B cells into lung tissue and bronchoalveolar space. Moreover, p110γ/δ-/- mice, but not single knock-out mice, showed a reduced bronchial hyperresponsiveness. We conclude that increased levels of eosinophils and IgE in p110γ/δ-/- mice do not abolish the protective effect of p110γ/δ-deficiency against OVA-induced allergic airway inflammation. PMID:27442134

  3. Allergens induce enhanced bronchoconstriction and leukotriene production in C5 deficient mice

    PubMed Central

    McKinley, Laura; Kim, Jiyoun; Bolgos, Gerald L; Siddiqui, Javed; Remick, Daniel G

    2006-01-01

    Background Previous genetic analysis has shown that a deletion in the complement component 5 gene-coding region renders mice more susceptible to allergen-induced airway hyperresponsiveness (AHR) due to reduced IL-12 production. We investigated the role of complement in a murine model of asthma-like pulmonary inflammation. Methods In order to evaluate the role of complement B10 mice either sufficient or deficient in C5 were studied. Both groups of mice immunized and challenged with a house dust extract (HDE) containing high levels of cockroach allergens. Airways hyper-reactivity was determined with whole-body plesthysmography. Bronchoalveolar lavage (BAL) was performed to determine pulmonary cellular recruitment and measure inflammatory mediators. Lung homogenates were assayed for mediators and plasma levels of IgE determined. Pulmonary histology was also evaluated. Results C5-deficient mice showed enhanced AHR to methylcholine challenge, 474% and 91% increase above baseline Penh in C5-deficient and C5-sufficient mice respectively, p < 0.001. IL-12 levels in the lung homogenate (LH) were only slightly reduced and BAL IL-12 was comparable in C5-sufficient and C5-deficient mice. However, C5-deficient mice had significantly higher cysteinyl-leukotriene levels in the BAL fluid, 1913 +/- 246 pg/ml in C5d and 756 +/- 232 pg/ml in C5-sufficient, p = 0.003. Conclusion These data demonstrate that C5-deficient mice show enhanced AHR due to increased production of cysteinyl-leukotrienes. PMID:17044927

  4. Inhibition of SCF attenuates peribronchial remodeling in chronic cockroach allergen-induced asthma.

    PubMed

    Berlin, Aaron A; Hogaboam, Cory M; Lukacs, Nicholas W

    2006-06-01

    The progression and severity of chronic asthma likely depends upon the intensity of the damage and remodeling of the tissue. We have developed a chronic model of allergic asthma using multiple cockroach allergen challenges. Using this clinically relevant allergen we have established significant peribronchial fibrosis and mucus overproduction. These remodeling events are accompanied by intense peribronchial inflammation, including lymphocytes and eosinophils. A cytokine that has been identified as having a prominent role in short-term allergic events, stem cell factor (SCF), appears to have a significant role in this late-stage process. Using our polyclonal antibody specific for SCF administered into the airways of mice during the final allergen challenges, we find a significant effect on the chronic peribronchial allergen-induced fibrotic remodeling. This was characterized by reduced inflammation, especially eosinophils, as well as reduced hydroxyproline levels in anti-SCF compared to control antibody-treated animals. In addition, when we examined chemokines associated with the chronic disease and neutralized SCF in vivo we observed a corresponding decrease in CCL6 and CCL17. Using an inhibitor, imatinib mesylate, that blocks SCF/c-kit-associated RTK, we find similar results as with anti-SCF for attenuating AHR and fibrotic changes, suggesting that a potential clinical treatment for chronic asthma already exists related to this pathway. These results further support the potential use of SCF/c-kit inhibition for targeting chronic severe asthmatic responses.

  5. Tumour-associated eosinophilia in the bladder.

    PubMed Central

    Lowe, D; Fletcher, C D; Gower, R L

    1984-01-01

    Tumour eosinophilia is an uncommon but striking phenomenon which has been found in many tumours, mostly of large cell type or squamous differentiation. The incidence, appearance and importance of tumour eosinophilia in the bladder are described. Eosinophilia is commoner in deeply invasive tumours and in tumours showing squamous metaplasia. Transitional cell carcinomas with eosinophilia have a better prognosis than those without, but this improvement is not seen in squamous cell carcinomas of the bladder. When eosinophilia is found on superficial biopsies of a bladder tumour, the possibility of muscle invasion should be considered. PMID:6725595

  6. Allergen-induced generation of mediators in the mucosa.

    PubMed Central

    Mattoli, S

    2001-01-01

    The inhalation of antigens does not normally lead to allergic inflammation, but airway resident cells and their products may affect the outcome of antigen exposure. It is therefore important to elucidate how potential allergens interact with airway epithelial cells and other cells located within and below the epithelium. Some studies have indicated that certain antigens, particularly the major house dust mite antigen Der p1, penetrate the airway epithelium by intracellular transportation or paracellular passage, depending on their concentrations, time of exposure, and ability of the cells to inactivate them. If an antigen possesses proteolytic activity, such as Der p1, and it reaches high concentrations or the exposure is prolonged, the disruption of the tight junction can also favor the transepithelial passage of other antigens. In this way, the antigens can easily encounter the effector cells located between epithelial cells and below the basement membrane. The magnitude of this phenomenon may be more prominent in the airways of asthmatic patients, as their epithelium is more permeable to Der p1 than the epithelium of nonasthmatic patients and releases cytokines after exposure to very low concentrations of this antigen for brief periods. Epithelial cell activation may facilitate the development of allergic mucosal sensitization to Der p1 and contribute to the antigen-induced inflammatory response by affecting the migration and function of dendritic cells, mast cells, and eosinophils. Also, there might be a secondary release of interleukin-6 and endothelin-1, which can have a detrimental effect on the cardiovascular function. PMID:11544162

  7. [Secretory eosinophilia and obstructive rhinitis].

    PubMed

    Rouvier, P; Mondain, M; Elkhoury, J

    1992-01-01

    Detecting eosinophilia in the nasal secretions of patients complaining of nasal obstruction makes it possible to identify a group of high risk patients. Hosty use of surgery in these patients carries a high risk of iatrogenic complications and little potential for improvement. The 2 most frequently used methods of obtaining cytologic specimens (swabbing versus washing) were compared in 37 patients with obstructive rhinitis (early stage polyposis and nonallergic rhinitis with eosinophilia syndrome, NARES). Swabbing gave reliable results. Eosinophilia was negligible in a group of 25 control subjects. The mean eosinophil count was 2.5% and only 1 patient had a positive cystogram. The 220 patients which nasal obstruction were classed in 5 groups according to the severity of clinical signs and symptoms. The mean eosinophil count and the percentage of patients with positive cystogram increased with increased severity of the clinical syndrome. 28 patients had uncomplicated obstructive rhinitis, 10 had NARES, 43 had allergic rhinitis, 52 had chronic obstructive rhinitis, and 87 had nasosinal polyposis. The respective mean eosinophil counts were 6.42%, 10.3%, 13.8% 16.8% and 31.4%. The percentage of patients with positive cytograms was respectively, 10.8%, 20%, 23.3%, 28.8% and 54%.

  8. Effects of age and allergen-induced airway inflammation in cats: radiographic and cytologic correlation.

    PubMed

    Kirschvink, Nathalie; Kersnak, Emilie; Leemans, Jérôme; Delvaux, François; Clercx, Cécile; Snaps, Frédéric; Gustin, Pascal

    2007-11-01

    Thoracic radiography is an important diagnostic tool for feline respiratory medicine. The aim of this study was (1) to assess age-related changes of thoracic radiographic views in healthy young cats and (2) to test if experimentally-induced bronchial inflammation by inhaling Ascaris suum (AS) allergens leads to radiographic changes after single or repeated exposures. Healthy cats (n=15-30) aged between 6 and 30 months were evaluated. Eight healthy cats and eight AS-sensitised cats, respectively, inhaled sterile saline or allergen. Radiographs were taken 24h before, and 6, 24 and 48 h after the challenge. Bronchoalveolar lavage (BAL) was performed after the last radiographic examination. AS-sensitised cats underwent three further allergen challenges at 3-month intervals. The radiographic evaluation was based on a scoring system considering bronchial, interstitial and alveolar patterns. A significant age-related increase in interstitial and total radiographic score was detected in healthy cats older than 18 months and in healthy cats older than 24 months. Whilst saline inhalation did not affect radiographic scores, a single AS challenge induced significant changes of all scores within 6-24h. A significant positive correlation between radiographic scores and BAL neutrophils and eosinophils was found. Repeated AS challenges did not induce irreversible changes in radiographic scores.

  9. Eosinophilia in Rheumatologic/Vascular Disorders.

    PubMed

    Tamaki, Hiromichi; Chatterjee, Soumya; Langford, Carol A

    2015-08-01

    Peripheral and tissue eosinophilia can be a prominent feature of several unique rheumatologic and vascular diseases. These diseases span a wide range of clinical features, histologic findings, therapeutic approaches, and outcomes. Despite the rare nature of these entities--which makes large-scale studies challenging--knowledge has continued to grow regarding their epidemiology, pathophysiology, and management. This review compares and contrasts 5 rheumatologic and vascular conditions in which eosinophilia can be seen: eosinophilic granulomatosis with polyangiitis (Churg-Strauss), immunoglobulin G4-related disease, diffuse fasciitis with eosinophilia, eosinophilia-myalgia syndrome, and eosinophilic myositis.

  10. Aryl Hydrocarbon Receptor Protects Lungs from Cockroach Allergen Induced Inflammation by Modulating Mesenchymal Stem Cells

    PubMed Central

    Xu, Ting; Zhou, Yufeng; Qiu, Lipeng; Do, Danh C; Zhao, Yilin; Cui, Zhuang; Wang, Heng; Liu, Xiaopeng; Saradna, Arjun; Cao, Xu; Wan, Mei; Gao, Peisong

    2015-01-01

    Exposure to cockroach allergen leads to allergic sensitization and increased risk of developing asthma. Aryl hydrocarbon receptor (AhR), a receptor for many common environmental contaminants, can sense not only environmental pollutants but also microbial insults. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to modulate immune responses. In this study, we investigated whether AhR can sense cockroach allergens and modulate allergen-induced lung inflammation through MSCs. We found that cockroach allergen treated AhR-deficient (AhR−/−) mice showed exacerbation of lung inflammation when compared to wild-type (WT) mice. In contrast, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an AhR agonist, significantly suppressed allergen-induced mouse lung inflammation. MSCs were significantly reduced in cockroach allergen challenged AhR−/− mice as compared to WT mice, but increased in cockroach allergen-challenged WT mice when treated with TCDD. Moreover, MSCs express AhR and AhR signaling can be activated by cockroach allergen with increased expression of its downstream genes, cyp1a1 and cyp1b1. Furthermore, we tracked the migration of intravenously injected GFP+ MSCs and found that cockroach allergen-challenged AhR−/− mice displayed less migration of MSCs to the lungs compared to WT. The AhR mediated MSC migration was further verified by an in vitro Transwell migration assay. Epithelial conditioned medium (ECM) prepared from CRE-challenged epithelial cells significantly induced MSC migrations, which was further enhanced by TCDD. The administration of MSCs significantly attenuated cockroach allergen-induced inflammation, which was abolished by TGFβ1 neutralizing antibody. These results suggest that AhR plays an important role in protecting lungs from allergen-induced inflammation by modulating MSC recruitment and their immune-suppressive activity. PMID:26561548

  11. Aryl Hydrocarbon Receptor Protects Lungs from Cockroach Allergen-Induced Inflammation by Modulating Mesenchymal Stem Cells.

    PubMed

    Xu, Ting; Zhou, Yufeng; Qiu, Lipeng; Do, Danh C; Zhao, Yilin; Cui, Zhuang; Wang, Heng; Liu, Xiaopeng; Saradna, Arjun; Cao, Xu; Wan, Mei; Gao, Peisong

    2015-12-15

    Exposure to cockroach allergen leads to allergic sensitization and increased risk of developing asthma. Aryl hydrocarbon receptor (AhR), a receptor for many common environmental contaminants, can sense not only environmental pollutants but also microbial insults. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to modulate immune responses. In this study, we investigated whether AhR can sense cockroach allergens and modulate allergen-induced lung inflammation through MSCs. We found that cockroach allergen-treated AhR-deficient (AhR(-/-)) mice showed exacerbation of lung inflammation when compared with wild-type (WT) mice. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AhR agonist, significantly suppressed allergen-induced mouse lung inflammation. MSCs were significantly reduced in cockroach allergen-challenged AhR(-/-) mice as compared with WT mice, but increased in cockroach allergen-challenged WT mice when treated with TCDD. Moreover, MSCs express AhR, and AhR signaling can be activated by cockroach allergen with increased expression of its downstream genes cyp1a1 and cyp1b1. Furthermore, we tracked the migration of i.v.-injected GFP(+) MSCs and found that cockroach allergen-challenged AhR(-/-) mice displayed less migration of MSCs to the lungs compared with WT. The AhR-mediated MSC migration was further verified by an in vitro Transwell migration assay. Epithelial conditioned medium prepared from cockroach extract-challenged epithelial cells significantly induced MSC migration, which was further enhanced by TCDD. The administration of MSCs significantly attenuated cockroach allergen-induced inflammation, which was abolished by TGF-β1-neutralizing Ab. These results suggest that AhR plays an important role in protecting lungs from allergen-induced inflammation by modulating MSC recruitment and their immune-suppressive activity.

  12. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

    SciTech Connect

    Jeong, Young-Il; Kim, Seung Hyun; Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja; Park, Jin Wook; Park, Yeong-Min; Lee, Sang Eun

    2011-04-22

    Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical

  13. Angiolymphoid Hyperplasia with Eosinophilia: A Case Report

    PubMed Central

    Esteves, Paola; Barbalho, Marcella; Lima, Tiago; Quintella, Leonardo; Niemeyer-Corbellini, João Paulo; Ramos-e-Silva, Marcia

    2015-01-01

    Angiolymphoid hyperplasia with eosinophilia is a rare disease considered as being a vascular malformation resulting from a subjacent arteriovenous shunt. It affects mostly the head of women between 20 and 40 years old and may present spontaneous involution. PMID:26120306

  14. Eosinophilia in a cat with acute leukemia.

    PubMed

    Gilroy, Cornelia; Forzán, María; Drew, Anne; Vernau, William

    2011-09-01

    A 4-year-old castrated male domestic shorthaired cat with a history of vomiting and anorexia was diagnosed with leukemia with marked hepatic and splenic infiltration and concurrent eosinophilia with marked tissue infiltration. Despite thorough immunocytochemical and immunohistochemical immunophenotyping, the cell lineage of the leukemia was not identified.

  15. Eosinophilia in a cat with acute leukemia

    PubMed Central

    Gilroy, Cornelia; Forzán, María; Drew, Anne; Vernau, William

    2011-01-01

    A 4-year-old castrated male domestic shorthaired cat with a history of vomiting and anorexia was diagnosed with leukemia with marked hepatic and splenic infiltration and concurrent eosinophilia with marked tissue infiltration. Despite thorough immunocytochemical and immunohistochemical immunophenotyping, the cell lineage of the leukemia was not identified. PMID:22379202

  16. Second-Hand Smoke Increases Bronchial Hyperreactivity and Eosinophilia in a Murine Model of Allergic Aspergillosis

    PubMed Central

    Seymour, Brian W. P.; Schelegle, Edward S.; Pinkerton, Kent E.; Friebertshauser, Kathleen E.; Peake, Janice L.; Kurup, Viswanath P.; Coffman, Robert L.; Gershwin, Laurel J.

    2003-01-01

    Involuntary inhalation of tobacco smoke has been shown to aggravate the allergic response. Antibodies to fungal antigens such as Aspergillus fumigatus (Af) cause an allergic lung disease in humans. This study was carried out to determine the effect of environmental tobacco smoke (ETS) on a murine model of allergic bronchopulmonary aspergillosis (ABPA). BALB/c mice were exposed to aged and diluted sidestream cigarette smoke to simulate 'second-hand smoke'. The concentration was consistent with that achieved in enclosed public areas or households where multiple people smoke. During exposure, mice were sensitized to Af antigen intranasally. Mice that were sensitized to Af antigen and exposed to ETS developed significantly greater airway hyperreactivity than did mice similarly sensitized to Af but housed in ambient air. The effective concentration of aerosolized acetylcholine needed to double pulmonary flow resistance was significantly lower in Af + ETS mice compared to the Af + AIR mice. Immunological data that supports this exacerbation of airway hyperresponsiveness being mediated by an enhanced type 1 hypersensitivity response include: eosinophilia in peripheral blood and lung sections. All Af sensitized mice produced elevated levels of IL4, IL5 and IL10 but no IFN-γ indicating a polarized Th2 response. Thus, ETS can cause exacerbation of asthma in ABPA as demonstrated by functional airway hyperresponsiveness and elevated levels of blood eosinophilia. PMID:14575156

  17. Second-hand smoke increases bronchial hyperreactivity and eosinophilia in a murine model of allergic aspergillosis.

    PubMed

    Seymour, Brian W P; Schelegle, Edward S; Pinkerton, Kent E; Friebertshauser, Kathleen E; Peake, Janice L; Kurup, Viswanath P; Coffman, Robert L; Gershwin, Laurel J

    2003-03-01

    Involuntary inhalation of tobacco smoke has been shown to aggravate the allergic response. Antibodies to fungal antigens such as Aspergillus fumigatus (Af) cause an allergic lung disease in humans. This study was carried out to determine the effect of environmental tobacco smoke (ETS) on a murine model of allergic bronchopulmonary aspergillosis (ABPA). BALB/c mice were exposed to aged and diluted sidestream cigarette smoke to simulate 'second-hand smoke'. The concentration was consistent with that achieved in enclosed public areas or households where multiple people smoke. During exposure, mice were sensitized to Af antigen intranasally. Mice that were sensitized to Af antigen and exposed to ETS developed significantly greater airway hyperreactivity than did mice similarly sensitized to Af but housed in ambient air. The effective concentration of aerosolized acetylcholine needed to double pulmonary flow resistance was significantly lower in Af + ETS mice compared to the Af + AIR mice. Immunological data that supports this exacerbation of airway hyperresponsiveness being mediated by an enhanced type 1 hypersensitivity response include: eosinophilia in peripheral blood and lung sections. All Af sensitized mice produced elevated levels of IL4, IL5 and IL10 but no IFN-gamma indicating a polarized Th2 response. Thus, ETS can cause exacerbation of asthma in ABPA as demonstrated by functional airway hyperresponsiveness and elevated levels of blood eosinophilia.

  18. Treatment of cockroach allergen asthma model with imatinib attenuates airway responses.

    PubMed

    Berlin, Aaron A; Lukacs, Nicholas W

    2005-01-01

    In the present study it was determined whether a pharmacologic approach to blocking receptor tyrosine kinase-mediated activation during allergic airway responses could be beneficial. To examine these responses, allergic mice were given a single oral dose of imatinib at clinically relevant concentrations, ranging from 0.05 to 50 mg/kg, by oral gavages just before allergen challenge. The reduction in the allergen-induced responses was significant and centered on reducing overall inflammation as well as pulmonary cytokine levels. In particular, the treatment of the mice with imatinib significantly attenuated airway hyperreactivity and peribronchial eosinophil accumulation, and significantly reduced Th2 cytokines, interleukin-4 and interleukin-13. In addition, chemokines previously associated with allergen-induced pulmonary disease, CCL2, CCL5, and CCL6, were significantly reduced in the lungs of the imatinib-treated animals. Together these data demonstrate that the pharmacologic inhibitor imatinib may provide a clinically attractive therapy for allergic, asthmatic responses.

  19. Tryptophan-induced eosinophilia-myalgia syndrome.

    PubMed Central

    Criswell, L. A.; Sack, K. E.

    1990-01-01

    Eight patients who became ill while taking tryptophan had myalgia, fatigue, rash, fever, edema, alopecia, arthralgias, diminished joint motion, skin tightening, muscle cramping, and distal paresthesias. Three had shortness of breath, and one had pulmonary hypertension. Laboratory abnormalities included peripheral eosinophilia, leukocytosis, thrombocytosis, raised erythrocyte sedimentation rate, and elevated serum levels of aldolase, lactate dehydrogenase, and liver enzymes. Of 4 chest radiographs, 3 were abnormal. Of 5 skin and muscle biopsies, 4 showed sclerosis or mixed inflammatory cell infiltration of the dermis, subcutis, and fascia. Eosinophils were often present, but vasculitis was absent. Muscle inflammation was minimal. We conclude that the "eosinophilia-myalgia syndrome" is related to the ingestion of tryptophan and that abnormalities in the secretion of lymphokines may be important in its pathogenesis. PMID:2219890

  20. Pulmonary eosinophilia associated to treatment with natalizumab

    PubMed Central

    Curto, Elena; Munteis-Olivas, Elvira; Balcells, Eva; Domínguez-Álvarez, M. Marisol

    2016-01-01

    Natalizumab (Tysabri®) is a leukocytes chemotaxis inhibitor that decreases the leukocytes passage through the hematoencephalic barrier and it is currently used in relapsing-remitting forms of multiple sclerosis (MS). We present a patient with allergic rhinoconjunctivitis diagnosed with MS who started treatment with natalizumab. She began to show mild asthmatic symptoms until she needed admission to the hospital due to respiratory insufficiency. Blood tests showed peripheral eosinophilia and the thoracic computed tomography scan demonstrated pulmonary infiltrates. The bronchoscopy with the bronchoalveolar lavage resulted in eosinophilic alveolitis. No evidence of bacterial, fungal and parasitic infection, connective tissue disease, or vasculitis were observed. After discontinuation of natalizumab, the patient improved without other treatments. As MS is a prevalent disease and the use of natalizumab is increasing, we consider important to point out that this drug can be associated with pulmonary eosinophilia, especially in patients with allergic rhinoconjunctivitis or asthma. PMID:27512514

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

    PubMed

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

    2001-07-15

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

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

    PubMed Central

    2013-01-01

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

  3. Evaluation and differential diagnosis of marked, persistent eosinophilia

    PubMed Central

    Mejia, Rojelio; Nutman, Thomas B.

    2012-01-01

    High grade eosinophilia in patients can be a diagnostic dilemma, as the etiologies are extensive and varied. Hypereosinophilic syndromes (HES) are a group of heterogeneous disorders, many of which remain ill-defined. By definition, HES must be distinguished from other disorders with persistently elevated eosinophilia with a defined cause. Although marked eosinophilia worldwide is most commonly caused by helminth (worm) infections, non-infectious causes must be sought including drug reactions, malignancies, and immunologic, inflammatory and allergic diseases. PMID:22449625

  4. Evaluation and differential diagnosis of marked, persistent eosinophilia

    PubMed Central

    Nutman, Thomas B.

    2007-01-01

    Synopsis: Hyperosinophilic syndromes (HES) are a group of heterogeneous disorders many of which remain ill-defined. By definition, the HES must be distinguished from other disorders with persistently elevated eosinophilia with a defined cause. Although marked eosinophilia worldwide is most commonly caused by helminth (worm) infections, the diagnostic approach must include non-infectious (non-parasitic) causes of marked eosinophilia as well. PMID:17868863

  5. Administration of polysaccharides from Antrodia camphorata modulates dendritic cell function and alleviates allergen-induced T helper type 2 responses in a mouse model of asthma.

    PubMed

    Liu, Ko-Jiunn; Leu, Sy-Jye; Su, Ching-Hua; Chiang, Bor-Luen; Chen, Yi-Lien; Lee, Yueh-Lun

    2010-03-01

    Asthma is a chronic disease characterized by airway inflammation caused by the dysregulated production of cytokines secreted by allergen-specific type 2 T helper (Th2) cells. Antrodia camphorata is a commonly used fungus in Asian folk medicine, and A. camphorata polysaccharides are reported to possess anti-cancer activities. In this study, the immunomodulatory effects of purified fractionated polysaccharides (GF2) from A. camphorata on dendritic cells (DCs) and their potential preventive effects against ovalbumin (OVA) -induced asthma were investigated. In the presence of GF2, lipopolysaccharide (LPS) -activated DCs exhibited up-regulated expression of major histocompatibility complex (MHC) class II and co-stimulatory molecules, as well as enhanced interleukin-10 (IL-10) and IL-12 production. GF2 treatment on LPS-activated DCs suppressed naïve CD4(+) T-cell proliferation and Th2 cell polarization with IL-10 production in an allogeneic mixed lymphocyte reaction. In animal experiments, a high dose of GF2 efficiently reduced expression levels of OVA-specific immunoglobulin G1 (IgG1) and IgE. However, lower doses of GF2 significantly enhanced OVA-specific IgG2a production. Our data also showed that administration of GF2 dose-dependently inhibited the development of airway hyperresponsiveness, airway eosinophilia and Th2 responses. OVA-specific CD4(+) T cells from higher doses of GF2-treated mice had significantly lower proliferative capacities compared with control mice. Moreover, treatment with GF2 significantly increased the high levels of IL-10 and low levels of interferon-gamma produced by T cells. Taken together, these data indicate that administration of A. camphorata polysaccharides (GF2) may have therapeutic potential when used as an adjuvant for the immunomodulatory treatment of allergic asthma.

  6. Case report of eosinophilia induced by quetiapine

    PubMed Central

    CHEN, Liming; TAN, Pei; TAN, Xiaolin

    2015-01-01

    Summary An increase in the concentration of eosinophils in blood may lead to endocarditis, myocarditis, and pericarditis. When the absolute eosinophil count increases beyond 1.5 x 109/L, myocardial damage and even death can occur. This case report describes a 47-year-old male with an alcohol-induced psychotic disorder who developed eosinophilia 4 weeks after starting treatment with quetiapine 50-200 mg/d. His maximum recorded absolute eosinophil count was 7.63 x 109/L (normal range < 0.5 x 109/L), but the level returned to normal over a 4-week period after stopping quetiapine and no myocardial damage was observed. This patient’s dramatic eosinophilia did not have any associated clinical symptoms; it was only identified as part of a routine blood test a few weeks after starting quetiapine. This is a reminder that all clinicians who treat patients with antipsychotic medications must be vigilant about the occurrence of such rare but life-threatening adverse events. PMID:27199530

  7. Role of leukotrienes in airway hyperresponsiveness in guinea-pigs.

    PubMed Central

    Ishida, K.; Thomson, R. J.; Schellenberg, R. R.

    1993-01-01

    1. Repeated aerosolization of leukotriene C4 (LTC4) to guinea-pigs produced leftward shift in their pulmonary resistance (RL) dose-response curves to inhaled acetylcholine (ACh) without increasing the maximum responses. 2. Repeated LTC4 aerosolization did not increase airway eosinophils. 3. The 5-lipoxygenase-activating protein (FLAP) inhibitor, MK-886, prevented the leftward shift in RL dose-response curves to ACh following repeated antigen challenge in guinea-pigs. 4. MK-886 did not inhibit the increased maximal RL produced by repeated antigen challenge, nor inhibit the airway eosinophilia induced by repeated antigen challenge. 5. Our findings suggest that leukotrienes may account for the leftward shift in pulmonary resistance responses caused by antigen but do not cause the airway eosinophilia nor enhanced maximum broncho-constrictor response to antigen. PMID:8467358

  8. Treatment with Pyranopyran-1, 8-Dione Attenuates Airway Responses in Cockroach Allergen Sensitized Asthma in Mice

    PubMed Central

    Jung, Kyung-Hwa; Song, Joohyun; Kim, You Ah; Cho, Hi Jae; Min, Byung-Il; Bae, Hyunsu

    2014-01-01

    Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. Viticis Fructus (VF) has long been used in China and Korea as a traditional herbal remedy for treating various inflammatory diseases. Previously, we have isolated a novel phytochemical, pyranopyran-1, 8-dione (PPY), from VF. This study was conducted to evaluate the ability of PPY to prevent airway inflammation and to attenuate airway responses in a cockroach allergen-induced asthma model in mice. The mice sensitized to and challenged with cockroach allergen were treated with oral administration of PPY. The infiltration of total cells, eosinophils and lymphocytes into the BAL fluid was significantly inhibited in cockroach allergen-induced asthma mice treated with PPY (1, 2, or 10 mg/kg). Th2 cytokines and chemokine, such as IL-4, IL-5, IL-13 and eotaxin in BAL fluid were also reduced to normal levels following treatment with PPY. In addition, the levels of IgE were also markedly suppressed after PPY treatment. Histopathological examination demonstrated that PPY substantially inhibited eosinophil infiltration into the airway, goblet cell hyperplasia and smooth muscle hypertrophy. Taken together, these results demonstrate that PPY possesses a potent efficacy on controlling allergic asthma response such as airway inflammation and remodeling. PMID:24489937

  9. Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice

    PubMed Central

    1995-01-01

    Allergic asthma is characterized by airway hyperresponsiveness and pulmonary eosinophilia, and may be mediated by T helper (Th) lymphocytes expressing a Th2 cytokine pattern. Interleukin (IL) 12 suppresses the expression of Th2 cytokines and their associated responses, including eosinophilia, serum immunoglobulin E, and mucosal mastocytosis. We have previously shown in a murine model that antigen- induced increases in airway hyperresponsiveness and pulmonary eosinophilia are CD4+ T cell dependent. We used this model to determine the ability of IL-12 to prevent antigen-induced increases in airway hyperresponsiveness, bronchoalveolar lavage (BAL) eosinophils, and lung Th2 cytokine expression. Sensitized A/J mice developed airway hyperresponsiveness and increased numbers of BAL eosinophils and other inflammatory cells after single or repeated intratracheal challenges with sheep red blood cell antigen. Pulmonary mRNA and protein levels of the Th2 cytokines IL-4 and IL-5 were increased after antigen challenge. Administration of IL-12 (1 microgram/d x 5 d) at the time of a single antigen challenge abolished the airway hyperresponsiveness and pulmonary eosinophilia and promoted an increase in interferon (IFN) gamma and decreases in IL-4 and IL-5 expression. The effects of IL-12 were partially dependent on IFN-gamma, because concurrent treatment with IL-12 and anti-IFN-gamma monoclonal antibody partially reversed the inhibition of airway hyperresponsiveness and eosinophilia by IL-12. Treatment of mice with IL-12 at the time of a second antigen challenge also prevented airway hyperresponsiveness and significantly reduced numbers of BAL inflammatory cells, reflecting the ability of IL-12 to inhibit responses associated with ongoing antigen-induced pulmonary inflammation. These data show that antigen-induced airway hyperresponsiveness and inflammation can be blocked by IL-12, which suppresses Th2 cytokine expression. Local administration of IL-12 may provide a novel

  10. Cerebrospinal fluid eosinophilia associated with intraventricular shunts.

    PubMed

    Bezerra, Sofia; Frigeri, Thomas More; Severo, Carlos Marcelo; Santana, João Carlos Batista; Graeff-Teixeira, Carlos

    2011-06-01

    CSF eosinophilia (CSF-eo) is uncommon and is usually caused by helminthic infections. However, it has also been found in ∼30% of patients experiencing intraventricular shunt malfunctions. We present a case report and review the conditions associated with CSF-eo and their prophylaxis. An 8 year-old boy with tetraventricular hydrocephalus has had several shunt malfunctions over the last three years. During hospitalization in January 2009 for shunt revision, a transient 30% eosinophilia was detected in his cerebral spinal fluid (CSF) concomitant with Staphylococcus epidermidis infection and long term vancomycin administration. After several shunt replacements and antibiotic treatment, CSF-eo eventually disappeared with good overall clinical response. CSF-eo is a transient and focal event mainly associated with infection, reactions to foreign substances, particles or blood, or obstruction of tubing by normal or fibro-granulomatous tissues. Infection associated with CSF-eo is usually caused by S. epidermidis and Propioniumbacterium acnes. In addition to infection, allergy to silicone and other foreign materials may also be a cause of CSF-eo. We review the diversity of conditions and proposed mechanisms associated with CSF-eo, as well as recommendations for the care of patients with shunts. Detection of CSF-eo has been shown to be a useful indicator of shunt malfunction. As such, it provides physicians with an indicator of a hypersensitivity reaction that is underway or the need to identify bacterial infection. We also highlight the need for improved biocompatibility of shunt hardware and describe strategies to avoid conditions leading to shunt malfunction.

  11. The effect of marimastat, a metalloprotease inhibitor, on allergen-induced asthmatic hyper-reactivity

    SciTech Connect

    Bruce, Colleen; Thomas, Paul S. . E-mail: paul.thomas@unsw.edu.au

    2005-06-01

    This pilot study was designed to assess whether a synthetic matrix metalloproteinase (MMP) inhibitor has anti-inflammatory properties in mild asthma. Tumor necrosis factor alpha (TNF{alpha}) has been shown to be an important cytokine in the pathogenesis of allergic airway inflammatory responses, and its release can be inhibited by MMP inhibitors. Twelve atopic asthmatic subjects received the MMP inhibitor marimastat (5 mg) or placebo, twice daily for 3 weeks, separated by a 6-week washout period in a randomized, double-blind, cross-over manner. All subjects underwent an allergen inhalation provocation test to Dermatophagoides pteronyssinus before and after each study phase. Spirometry, exhaled NO (eNO) levels, differential sputum cell counts, an asthma symptom questionnaire, peak flow, and {beta}{sub 2}-agonist usage were measured. Nine subjects completed the study, and, when compared with placebo, marimastat reduced bronchial hyper-responsiveness to inhaled allergen in these subjects from an allergen PC{sub 20} of 22.2 AU/ml (95%CI 11.7-32.6) to 17.0 AU/ml (95%CI 7.6-26.4, P = 0.02). The marimastat phase showed a nonsignificant fall in sputum inflammatory cells. Marimastat did not modify eNO, FEV{sub 1}, asthma symptoms, or albuterol usage. In conclusion, airway responsiveness to allergen may be modified by a MMP inhibitor, perhaps via TNF{alpha} playing a role in airway inflammation and remodeling.

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

    PubMed

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

    2006-10-01

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

  13. Ambient particulate matter induces an exacerbation of airway inflammation in experimental asthma: role of interleukin-33.

    PubMed

    Shadie, A M; Herbert, C; Kumar, R K

    2014-08-01

    High levels of ambient environmental particulate matter (PM10 i.e. < 10 μm median aerodynamic diameter) have been linked to acute exacerbations of asthma. We examined the effects of delivering a single dose of Sydney PM10 by intranasal instillation to BALB/c mice that had been sensitized to ovalbumin and challenged repeatedly with a low (≈3 mg/m(3)) mass concentration of aerosolized ovalbumin for 4 weeks. Responses were compared to animals administered carbon black as a negative control, or a moderate (≈30 mg/m(3)) concentration of ovalbumin to simulate an allergen-induced acute exacerbation of airway inflammation. Delivery of PM10 to mice, in which experimental mild chronic asthma had previously been established, elicited characteristic features of enhanced allergic inflammation of the airways, including eosinophil and neutrophil recruitment, similar to that in the allergen-induced exacerbation. In parallel, there was increased expression of mRNA for interleukin (IL)-33 in airway tissues and an increased concentration of IL-33 in bronchoalveolar lavage fluid. Administration of a monoclonal neutralizing anti-mouse IL-33 antibody prior to delivery of particulates significantly suppressed the inflammatory response induced by Sydney PM10, as well as the levels of associated proinflammatory cytokines in lavage fluid. We conclude that IL-33 plays a key role in driving airway inflammation in this novel experimental model of an acute exacerbation of chronic allergic asthma induced by exposure to PM10.

  14. Ambient particulate matter induces an exacerbation of airway inflammation in experimental asthma: role of interleukin-33

    PubMed Central

    Shadie, A M; Herbert, C; Kumar, R K

    2014-01-01

    High levels of ambient environmental particulate matter (PM10 i.e. < 10 μm median aerodynamic diameter) have been linked to acute exacerbations of asthma. We examined the effects of delivering a single dose of Sydney PM10 by intranasal instillation to BALB/c mice that had been sensitized to ovalbumin and challenged repeatedly with a low (≈3 mg/m3) mass concentration of aerosolized ovalbumin for 4 weeks. Responses were compared to animals administered carbon black as a negative control, or a moderate (≈30 mg/m3) concentration of ovalbumin to simulate an allergen-induced acute exacerbation of airway inflammation. Delivery of PM10 to mice, in which experimental mild chronic asthma had previously been established, elicited characteristic features of enhanced allergic inflammation of the airways, including eosinophil and neutrophil recruitment, similar to that in the allergen-induced exacerbation. In parallel, there was increased expression of mRNA for interleukin (IL)-33 in airway tissues and an increased concentration of IL-33 in bronchoalveolar lavage fluid. Administration of a monoclonal neutralizing anti-mouse IL-33 antibody prior to delivery of particulates significantly suppressed the inflammatory response induced by Sydney PM10, as well as the levels of associated proinflammatory cytokines in lavage fluid. We conclude that IL-33 plays a key role in driving airway inflammation in this novel experimental model of an acute exacerbation of chronic allergic asthma induced by exposure to PM10. PMID:24730559

  15. The herbal medicine shoseiryu-to inhibits allergen-induced synthesis of tumour necrosis factor alpha by peripheral blood mononuclear cells in patients with perennial allergic rhinitis.

    PubMed

    Tanaka, A; Ohashi, Y; Kakinoki, Y; Washio, Y; Yamada, K; Nakai, Y; Nakano, T; Nakai, Y; Ohmoto, Y

    1998-01-01

    The herbal medicine shoseiryu-to is an effective agent in the treatment of allergic rhinitis. However, the mechanism by which it exerts its action in improving patient symptoms remains unclear. It might affect the allergen-induced TH1 and/or TH2 responses. This study investigated whether the herbal medicine could affect cytokine synthesis by peripheral blood mononuclear cells (PBMCs) in response to the major Dermatophagoides farinae (D. farinae) allergen, Der f 1. PBMCs were obtained from 15 patients with perennial allergic rhinitis due to D. farinae, and were stimulated for 96 h with 10 micrograms/ml Der f 1 in the presence or absence of 45 mg/ml shoseiryu-to. The culture supernatants were harvested to determine the synthesis of IgE, interleukin 5 (IL-5), IL-6, IL-10, interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha). The agent did not affect the allergen-induced synthesis of IL-5, IL-6 and IFN-gamma, but somewhat decreased the synthesis of IgE and IL-10. This study highlighted an interesting pharmacological action of shoseiryu-to to substantially inhibit the allergen-induced synthesis of TNF-alpha. Our study suggests that the shoseiryu-to may alleviate nasal symptoms in allergic rhinitis through control of the allergen-induced inflammatory process.

  16. Comparison of cetirizine with astemizole in the treatment of perennial allergic rhinitis and study of the concomitant effect on histamine and allergen-induced wheal responses.

    PubMed

    Lobaton, P; Moreno, F; Coulie, P

    1990-11-01

    Thirty patients suffering from perennial allergic rhinitis took astemizole and cetirizine, 10 mg/d, under double-blind, crossover randomized conditions for 4 weeks. Four weeks washout separated the two periods. Nasal condition was improved, histamine and allergen-induced wheal responses were inhibited by both treatments with a slight advantage for cetirizine. Both treatments were well tolerated.

  17. Primary Colonic Eosinophilia and Eosinophilic Colitis in Adults.

    PubMed

    Turner, Kevin O; Sinkre, Richa A; Neumann, William L; Genta, Robert M

    2017-02-01

    The normal content of eosinophils in the adult colon and the criteria for the histopathologic diagnosis of eosinophilic colitis remain undefined. This study aimed at: (1) establishing the numbers of eosinophils in the normal adult colon; and (2) proposing a clinicopathologic framework for the diagnosis of primary colonic eosinophilia and eosinophilic colitis. To accomplish these goals, we counted the eosinophils in the right, transverse, and left colon of 159 adults with normal colonic histology. Using a database of 1.2 million patients with colonic biopsies, we extracted all adults with a diagnosis of colonic eosinophilia. We reviewed the slides from all cases and captured demographic, clinical, and pathologic data, including information about eosinophilia in other organs. We then compared the clinical manifestations of the study patients (those with no identifiable cause of eosinophilia) to those of patients with other types of colitis. The normal eosinophil counts (per mm) were 55.7±23.4 in the right, 41.0±18.6 in the transverse, and 28.6±17.2 in the left colon. Of the 194 study patients (eosinophil counts 166-5050/mm), 63 were asymptomatic and had a normal colonoscopy. Diarrhea and abdominal pain were the commonest indications for colonoscopy (38% and 27%, respectively) among the 131 patients who had symptoms, endoscopic abnormalities, or both. Neither clinical manifestations nor endoscopic appearance were sufficiently characteristic to elicit the suspicion of colonic eosinophilia. In conclusion, primary colonic eosinophilia was extremely rare in this series (<1 in 6000 patients); one third of these patients were asymptomatic. Their clinical manifestations were not distinctive and could not have led clinicians to suspect this condition; one third of the patients were asymptomatic. We suggest that regularly reporting high colonic eosinophilia may result in increased opportunities for clinicopathologic studies that might lead to a better definition of this

  18. Glutathione redox regulates airway hyperresponsiveness and airway inflammation in mice.

    PubMed

    Koike, Yoko; Hisada, Takeshi; Utsugi, Mitsuyoshi; Ishizuka, Tamotsu; Shimizu, Yasuo; Ono, Akihiro; Murata, Yukie; Hamuro, Junji; Mori, Masatomo; Dobashi, Kunio

    2007-09-01

    Glutathione is the major intracellular redox buffer. We have shown that glutathione redox status, which is the balance between intracellular reduced (GSH) and oxidized (GSSG) glutathione, in antigen-presenting cells (APC) regulates the helper T cell type 1 (Th1)/Th2 balance due to the production of IL-12. Bronchial asthma is a typical Th2 disease. Th2 cells and Th2 cytokines are characteristic of asthma and trigger off an inflammation. Accordingly, we studied the effects of the intracellular glutathione redox status on airway hyperresponsiveness (AHR) and allergen-induced airway inflammation in a mouse model of asthma. We used gamma-Glutamylcysteinylethyl ester (gamma-GCE), which is a membrane-permeating GSH precursor, to elevate the intracellular GSH level and GSH/GSSG ratio of mice. In vitro, gamma-GCE pretreatment of human monocytic THP-1 cells elevated the GSH/GSSG ratio and enhanced IL-12(p70) production induced by LPS. In the mouse asthma model, intraperitoneal injection of gamma-GCE elevated the GSH/GSSG ratio of lung tissue and reduced AHR. gamma-GCE reduced levels of IL-4, IL-5, IL-10, and the chemokines eotaxin and RANTES (regulated on activation, normal T cell expressed and secreted) in bronchoalveolar lavage fluid, whereas it enhanced the production of IL-12 and IFN-gamma. Histologically, gamma-GCE suppressed eosinophils infiltration. Interestingly, we also found that gamma-GCE directly inhibited chemokine-induced eosinophil chemotaxis without affecting eotaxin receptor chemokine receptor 3 (CCR3) expressions. Taken together, these findings suggest that changing glutathione redox balance, increase in GSH level, and the GSH/GSSG ratio by gamma-GCE, ameliorate bronchial asthma by altering the Th1/Th2 imbalance through IL-12 production from APC and suppressing chemokine production and eosinophil migration itself.

  19. Persistent Marked Peripheral Eosinophilia due to Tuberculosis: A Case Report

    PubMed Central

    Garg, Gunjan; Gogia, Atul; Kakar, Atul; Miglani, Pratyush

    2017-01-01

    We report a case of a 68-year-old female who was a known case of diabetes mellitus and chronic liver disease and presented with complaints of dry cough and other constitutional symptoms since one month. During initial investigations, the patient was found to have peripheral blood eosinophilia. Upon investigating further,the patient was found to have mediastinal lymphadenopathy and fine-needle aspiration of mediastinal lymph nodes showed features of tuberculosis. The patient was started on anti-tubercular treatment and her eosinophil counts returned to normal levels. Correlation between eosinophilia and tuberculosis has not been established in classical literature. This case highlights the same association and raises awareness on this crucial finding. Coexistence of eosinophilia and tuberculosis in our patient is suggested since peripheral blood eosinophilia improved with anti-tubercular treatment. The exact pathogenesis of coexistence of tuberculosis and peripheral blood eosinophilia yet remains to be deciphered, but tissue pathology is mainly associated with the discharge of toxic eosinophil products. PMID:28293059

  20. Eosinophilia in Patients Infected with Human Immunodeficiency Virus

    PubMed Central

    Chou, Andrew; Serpa, Jose A.

    2015-01-01

    Eosinophilia is not uncommonly encountered in patients infected with human immunodeficiency virus (HIV); particularly at initiation of care or among those with advanced disease. The clinical manifestation most commonly associated with eosinophilia in this patient population is skin rash. Management of these patients is challenging due to a paucity of data evaluating diagnostic testing and therapeutic strategies. Patients born in or with significant travel to parasite-endemic countries are more likely to have tissue-invasive helminthes, such as Strongyloides or Schistosoma. Patients without such risk factors are unlikely to have parasitic infections and frequently will have self-resolution of eosinophilia. When a detailed history, physical exam and diagnostic work-up is unrevealing, we sometimes consider empirical therapy with ivermectin. Praziquantel may also be considered for those at risk for schistosomiasis. PMID:26126686

  1. Allergens stimulate store-operated calcium entry and cytokine production in airway epithelial cells

    PubMed Central

    Jairaman, Amit; Maguire, Chelsea H.; Schleimer, Robert P.; Prakriya, Murali

    2016-01-01

    Aberrant immune responses to environmental allergens including insect allergens from house dust mites and cockroaches contribute to allergic inflammatory diseases such as asthma in susceptible individuals. Airway epithelial cells (AECs) play a critical role in this process by sensing the proteolytic activity of allergens via protease-activated receptors (PAR2) to initiate inflammatory and immune responses in the airway. Elevation of cytosolic Ca2+ is an important signaling event in this process, yet the fundamental mechanism by which allergens induce Ca2+ elevations in AECs remains poorly understood. Here we find that extracts from dust mite and cockroach induce sustained Ca2+ elevations in AECs through the activation of Ca2+ release-activated Ca2+ (CRAC) channels encoded by Orai1 and STIM1. CRAC channel activation occurs, at least in part, through allergen mediated stimulation of PAR2 receptors. The ensuing Ca2+ entry then activates NFAT/calcineurin signaling to induce transcriptional production of the proinflammatory cytokines IL-6 and IL-8. These findings highlight a key role for CRAC channels as regulators of allergen induced inflammatory responses in the airway. PMID:27604412

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

    PubMed

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

    2007-01-01

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

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

    PubMed

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

    2010-12-01

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

  4. Marked eosinophilia in a patient with history of severe atypical Kawasaki disease.

    PubMed

    O'Byrne, Michael L; Cohen, Meryl S

    2013-01-01

    An infant with recent atypical, treatment-refractory Kawasaki disease presented with marked eosinophilia. Workup failed to identify an etiology. The eosinophilia spontaneously resolved. Eosinophilia has been observed in the acute phase of Kawasaki disease, but has not been reported following recovery.

  5. Effects of two Asian sand dusts transported from the dust source regions of Inner Mongolia and northeast China on murine lung eosinophilia

    SciTech Connect

    He, Miao; Ichinose, Takamichi; Song, Yuan; Yoshida, Yasuhiro; Arashidani, Keiichi; Yoshida, Seiichi; Liu, Boying; Nishikawa, Masataka; Takano, Hirohisa; and others

    2013-11-01

    The quality and quantity of toxic materials adsorbed onto Asian sand dust (ASD) are different based on dust source regions and passage routes. The aggravating effects of two ASDs (ASD1 and ASD2) transported from the source regions of Inner Mongolia and northeast China on lung eosinophilia were compared to clarify the role of toxic materials in ASD. The ASDs contained different amounts of lipopolysaccharides (LPS) and β-glucan (ASD1 < ASD2) and SiO{sub 2} (ASD1 > ASD2). CD-1 mice were instilled intratracheally with ASD1, ASD2 and/or ovalbumin (OVA) four times at 2-week intervals. ASD1 and ASD2 enhanced eosinophil recruitment induced by OVA in the submucosa of the airway, with goblet cell proliferation in the bronchial epithelium. ASD1 and ASD2 synergistically increased OVA-induced eosinophil-relevant cytokines interleukin-5 (IL-5), IL-13 (ASD1 < ASD2) and chemokine eotaxin (ASD1 > ASD2) in bronchoalveolar lavage fluid. ASD2 aggravating effects on lung eosinophilia were greater than ASD1. The role of LPS and β-glucan in ASD2 on the production of pro-inflammatory mediators was assessed using in vitro bone marrow-derived macrophages (BMDMs) from wild type, Toll-like receptor 2-deficient (TLR2 −/−), TLR4 −/−, and MyD88 −/− mice (on Balb/c background). ASD2-stimulated TLR2 −/− BMDMs enhanced IL-6, IL-12, TNF-α, MCP-1 and MIP-1α secretion compared with ASD2-stimulated TLR4 −/− BMDMs. Protein expression from ASD2-stimulated MyD88 −/− BMDM were very low or undetectable. The in vitro results indicate that lung eosinophilia caused by ASD is TLR4 dependent. Therefore, the aggravation of OVA-related lung eosinophilia by ASD may be dependent on toxic substances derived from microbes, such as LPS, rather than SiO{sub 2}. - Highlights: • Asian sand dust (ASD) from the deserts of China causes serious respiratory problems. • The aggravating effects of two ASDs on lung eosinophilia were compared. • The ASDs contained different LPS and β-glucan (ASD1

  6. Eosinophilia and Fever with Levetiracetam: A Case Report.

    PubMed

    Flannery, Alexander H; Willey, Maria D; Thompson Bastin, Melissa L; Buch, Ketan P; Bensadoun, Eric S

    2015-08-01

    Levetiracetam is considered by many clinicians to be one of the most benign antiepileptic medications available. We report the case of a 24-year-old man presenting with seizures for which he was started on levetiracetam. Despite an extensive work-up and treatment of possible infectious and noninfectious issues, the patient remained intermittently febrile. When a marked peripheral eosinophilia was noted, the patient's levetiracetam was discontinued and phenytoin prescribed. The fever resolved within 24 hours, and the patient's eosinophilia count returned to normal limits following discharge back to his long-term care facility. We estimate the probability of this reaction related to levetiracetam as probable based on a score of 7 on the Naranjo scale. Clinicians should be aware of the possibility that levetiracetam may be an offending agent in a patient with unexplained fever and eosinophilia. These may be early signs of the progression to a more serious drug hypersensitivity reaction, such as drug rash, eosinophilia, and systemic symptoms (DRESS) syndrome.

  7. Renal allograft eosinophilia: An unusual presentation of sudden graft dysfunction

    PubMed Central

    Yuvaraj, A.; Ghosh, S.; Abraham, G.; Koshy, P.

    2017-01-01

    We present a case of sudden allograft dysfunction 11 months after renal transplantation which presented as severe peripheral and allograft eosinophilia and was managed as a case of an acute cellular rejection with significant interstitial graft eosinophilic infiltration. Patient had partial response to antirejection therapy and eventually ended up in a chronic allograft dysfunction. PMID:28356665

  8. Seroprevalence of Toxocariasis among Healthy People with Eosinophilia

    PubMed Central

    Kim, Yong-Hun; Chung, Young-Bae

    2008-01-01

    The aim of this study is to determine the Toxocara seropositive rate among healthy people with eosinophilia. A total of 97 people residing in Seoul who were healthy and whose blood eosinophilia was over 10%, as shown by regular health check-ups in 2004, were subjected to this study. Their sera were tested by immunoblotting and ELISA with the antigen of larval Toxocara canis excretory-secretory (ES) protein. Sixty-five sera were band-positive (67.0%). The seropositve control sera were positive to band sizes of 66 kDa, 56 kDa, 32 kDa, and 13 kDa. In ELISA, 63 sera (65.0%) were positive to T. canis ES protein. There was no significant correlation between the IgG ELISA titer and the level of eosinophilia (r = 0.156, P = 0.156). As there were insufficient data to determine whether there were cross-reactions with other helminthic infections, or whether atopy occurred, further studies are required to verify the cause of the seropositive reactions against T. canis ES antigen. Toxocariasis seropositivity is suggested to be the major cause of eosinophilia, since the Toxocara seroprevalence among Korean rural adults was shown to be approximately 5%. PMID:18344674

  9. Regulatory T cells prevent Th2 immune responses and pulmonary eosinophilia during respiratory syncytial virus infection in mice.

    PubMed

    Durant, Lydia R; Makris, Spyridon; Voorburg, Cornelia Maaike; Loebbermann, Jens; Johansson, Cecilia; Openshaw, Peter J M

    2013-10-01

    During viral infection, inflammation and recovery are tightly controlled by competing proinflammatory and regulatory immune pathways. Respiratory syncytial virus (RSV) is the leading global cause of infantile bronchiolitis, which is associated with recurrent wheeze and asthma diagnosis in later life. Th2-driven disease has been well described under some conditions for RSV-infected mice. In the present studies, we used the Foxp3(DTR) mice (which allow specific conditional depletion of Foxp3(+) T cells) to investigate the functional effects of regulatory T cells (Tregs) during A2-strain RSV infection. Infected Treg-depleted mice lost significantly more weight than wild-type mice, indicating enhanced disease. This enhancement was characterized by increased cellularity in the bronchoalveolar lavage (BAL) fluid and notable lung eosinophilia not seen in control mice. This was accompanied by abundant CD4(+) and CD8(+) T cells exhibiting an activated phenotype and induction of interleukin 13 (IL-13)- and GATA3-expressing Th2-type CD4(+) T cells that remained present in the airways even 14 days after infection. Therefore, Treg cells perform vital anti-inflammatory functions during RSV infection, suppressing pathogenic T cell responses and inhibiting lung eosinophilia. These findings provide additional evidence that dysregulation of normal immune responses to viral infection may contribute to severe RSV disease.

  10. Regulatory T Cells Prevent Th2 Immune Responses and Pulmonary Eosinophilia during Respiratory Syncytial Virus Infection in Mice

    PubMed Central

    Durant, Lydia R.; Makris, Spyridon; Voorburg, Cornelia Maaike; Loebbermann, Jens

    2013-01-01

    During viral infection, inflammation and recovery are tightly controlled by competing proinflammatory and regulatory immune pathways. Respiratory syncytial virus (RSV) is the leading global cause of infantile bronchiolitis, which is associated with recurrent wheeze and asthma diagnosis in later life. Th2-driven disease has been well described under some conditions for RSV-infected mice. In the present studies, we used the Foxp3DTR mice (which allow specific conditional depletion of Foxp3+ T cells) to investigate the functional effects of regulatory T cells (Tregs) during A2-strain RSV infection. Infected Treg-depleted mice lost significantly more weight than wild-type mice, indicating enhanced disease. This enhancement was characterized by increased cellularity in the bronchoalveolar lavage (BAL) fluid and notable lung eosinophilia not seen in control mice. This was accompanied by abundant CD4+ and CD8+ T cells exhibiting an activated phenotype and induction of interleukin 13 (IL-13)- and GATA3-expressing Th2-type CD4+ T cells that remained present in the airways even 14 days after infection. Therefore, Treg cells perform vital anti-inflammatory functions during RSV infection, suppressing pathogenic T cell responses and inhibiting lung eosinophilia. These findings provide additional evidence that dysregulation of normal immune responses to viral infection may contribute to severe RSV disease. PMID:23926350

  11. Involvement of PTEN in airway hyperresponsiveness and inflammation in bronchial asthma.

    PubMed

    Kwak, Yong-Geun; Song, Chang H; Yi, Ho K; Hwang, Pyoung H; Kim, Jong-Suk; Lee, Kyung S; Lee, Yong C

    2003-04-01

    Phosphatase and tensin homologue deleted on chromosome ten (PTEN) is part of a complex signaling system that affects a variety of important cell functions. PTEN blocks the action of PI3K by dephosphorylating the signaling lipid phosphatidylinositol 3,4,5-triphosphate. We have used a mouse model for asthma to determine the effect of PI3K inhibitors and PTEN on allergen-induced bronchial inflammation and airway hyperresponsiveness. PI3K activity increased significantly after allergen challenge. PTEN protein expression and PTEN activity were decreased in OVA-induced asthma. Immunoreactive PTEN localized in epithelial layers around the bronchioles in control mice. However, this immunoreactive PTEN dramatically disappeared in allergen-induced asthmatic lungs. The increased IL-4, IL-5, and eosinophil cationic protein levels in bronchoalveolar lavage fluids after OVA inhalation were significantly reduced by the intratracheal administration of PI3K inhibitors or adenoviruses carrying PTEN cDNA (AdPTEN). Intratracheal administration of PI3K inhibitors or AdPTEN remarkably reduced bronchial inflammation and airway hyperresponsiveness. These findings indicate that PTEN may play a pivotal role in the pathogenesis of the asthma phenotype.

  12. Proton pump inhibitor responsive esophageal eosinophilia, a distinct disease entity?

    PubMed

    Munday, William; Zhang, Xuchen

    2014-08-14

    Recent studies have suggested the existence of a patient population with esophageal eosinophilia that responds to proton pump inhibitor therapy. These patients are being referred to as having proton pump inhibitor responsive esophageal eosinophilia (PPI-REE), which is currently classified as a distinct and separate disease entity from both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE). The therapeutic effect of proton pump inhibitor (PPI) on PPI-REE is thought to act directly at the level of the esophageal mucosa with an anti-inflammatory capacity, and completely independent of gastric acid suppression. The purpose of this manuscript is to review the mechanistic data of the proposed immune modulation/anti-inflammatory role of the PPI at the esophageal mucosa, and the existence of PPI-REE as a distinct disease entity from GERD and EoE.

  13. Aeroallergen challenge promotes dendritic cell proliferation in the airways.

    PubMed

    Veres, Tibor Z; Voedisch, Sabrina; Spies, Emma; Valtonen, Joona; Prenzler, Frauke; Braun, Armin

    2013-02-01

    Aeroallergen provocation induces the rapid accumulation of CD11c(+)MHC class II (MHC II)(+) dendritic cells (DCs) in the lungs, which is driven by an increased recruitment of blood-derived DC precursors. Recent data show, however, that well-differentiated DCs proliferate in situ in various tissues. This may also contribute to their allergen-induced expansion; therefore, we studied DC proliferation in the airways of mice in the steady state and after local aeroallergen provocation. Confocal whole-mount microscopy was used to visualize proliferating DCs in different microanatomical compartments of the lung. We demonstrate that in the steady state, CD11c(+)MHC II(+) DCs proliferate in both the epithelial and subepithelial layers of the airway mucosa as well as in the lung parenchyma. A 1-h pulse of the nucleotide 5-ethynyl-2'-deoxyuridine was sufficient to label 5% of DCs in both layers of the airway mucosa. On the level of whole-lung tissue, 3-5% of both CD11b(+) and CD11b(-) DC populations and 0.3% of CD11c(+)MHC II(low) lung macrophages incorporated 5-ethynyl-2'-deoxyuridine. Aeroallergen provocation caused a 3-fold increase in the frequency of locally proliferating DCs in the airway mucosa. This increase in mucosal DC proliferation was later followed by an elevation in the number of DCs. The recruitment of monocyte-derived inflammatory DCs contributed to the increasing number of DCs in the lung parenchyma, but not in the airway mucosa. We conclude that local proliferation significantly contributes to airway DC homeostasis in the steady state and that it is the major mechanism underlying the expansion of the mucosal epithelial/subepithelial DC network in allergic inflammation.

  14. Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children

    PubMed Central

    Steerenberg, P; Janssen, N; de Meer, G; Fischer, P; Nierkens, S; van Loveren, H; Opperhuizen, A; Brunekreef, B; van Amsterdam, J G C

    2003-01-01

    Methods: Levels of eNO in a sample of 450 children aged 7–12 years out of a total sample of 2504 school children living in different urban areas near motorways were determined. The aim of this cross-sectional study was to explore the relationship between eNO, impairment of lung function (PEF, FVC, FEV1 and MMEF), bronchial hyperresponsiveness (BHR), and blood eosinophilia in children with and without atopy as assessed by skin prick testing. Results: Regression analysis showed that wheezing and nasal discharge and conjunctivitis that had occurred during the previous 12 months were positively associated with eNO levels in atopic children (relative increase of 1.48 and 1.41, respectively; p<0.05) but not in non-atopic children. Similarly, BHR and the number of blood eosinophils per ml were positively associated with eNO levels in atopic children (relative increase of 1.55 and 2.29, respectively; p<0.05) but not in non-atopic children. The lung function indices PEF, FVC, FEV1 and MMEF were not associated with eNO levels. Conclusions: In addition to conventional lung function tests and symptom questionnaires, eNO is a suitable measure of airway inflammation and its application may reinforce the power of epidemiological surveys on respiratory health. PMID:12612304

  15. B cells play key roles in th2-type airway immune responses in mice exposed to natural airborne allergens.

    PubMed

    Drake, Li Yin; Iijima, Koji; Hara, Kenichiro; Kobayashi, Takao; Kephart, Gail M; Kita, Hirohito

    2015-01-01

    Humans are frequently exposed to various airborne allergens. In addition to producing antibodies, B cells participate in immune responses via various mechanisms. The roles of B cells in allergic airway inflammation and asthma have been controversial. We examined the functional importance of B cells in a mouse model of asthma, in which mice were exposed repeatedly to common airborne allergens. Naïve wild-type BALB/c mice or B cell-deficient JH-/- mice were exposed intranasally to a cocktail of allergen extracts, including Alternaria, Aspergillus, and house dust mite, every other day for two weeks. Ovalbumin was included in the cocktail to monitor the T cell immune response. Airway inflammation, lung pathology, and airway reactivity were analyzed. The airway exposure of naïve wild type mice to airborne allergens induced robust eosinophilic airway inflammation, increased the levels of Th2 cytokines and chemokines in the lung, and increased the reactivity to inhaled methacholine. These pathological changes and immune responses were attenuated in B cell-deficient JH-/- mice. The allergen-induced expansion of CD4+ T cells was impaired in the lungs and draining lymph nodes of JH-/- mice. Furthermore, lymphocytes from JH-/- mice failed to produce Th2 cytokines in response to ovalbumin re-stimulation in vitro. Our results suggest that B cells are required for the optimal development of Th2-type immune responses and airway inflammation when exposed to common airborne allergens. The therapeutic targeting of B cells may be beneficial to treat asthma in certain patients.

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

    PubMed

    Agua-Doce, Ana; Graca, Luis

    2011-01-01

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

  17. Nebulized lidocaine blunts airway hyper-responsiveness in experimental feline asthma.

    PubMed

    Nafe, Laura A; Guntur, Vamsi P; Dodam, John R; Lee-Fowler, Tekla M; Cohn, Leah A; Reinero, Carol R

    2013-08-01

    Nebulized lidocaine may be a corticosteroid-sparing drug in human asthmatics, reducing airway resistance and peripheral blood eosinophilia. We hypothesized that inhaled lidocaine would be safe in healthy and experimentally asthmatic cats, diminishing airflow limitation and eosinophilic airway inflammation in the latter population. Healthy (n = 5) and experimentally asthmatic (n = 9) research cats were administered 2 weeks of nebulized lidocaine (2 mg/kg q8h) or placebo (saline) followed by a 2-week washout and crossover to the alternate treatment. Cats were anesthetized to measure the response to inhaled methacholine (MCh) after each treatment. Placebo and doubling doses of methacholine (0.0625-32.0000 mg/ml) were delivered and results were expressed as the concentration of MCh increasing baseline airway resistance by 200% (EC200Raw). Bronchoalveolar lavage was performed after each treatment and eosinophil numbers quantified. Bronchoalveolar lavage fluid (BALF) % eosinophils and EC200Raw within groups after each treatment were compared using a paired t-test (P <0.05 significant). No adverse effects were noted. In healthy cats, lidocaine did not significantly alter BALF eosinophilia or the EC200Raw. There was no difference in %BALF eosinophils in asthmatic cats treated with lidocaine (36±10%) or placebo (33 ± 6%). However, lidocaine increased the EC200Raw compared with placebo 10 ± 2 versus 5 ± 1 mg/ml; P = 0.043). Chronic nebulized lidocaine was well-tolerated in all cats, and lidocaine did not induce airway inflammation or airway hyper-responsiveness in healthy cats. Lidocaine decreased airway response to MCh in asthmatic cats without reducing airway eosinophilia, making it unsuitable for monotherapy. However, lidocaine may serve as a novel adjunctive therapy in feline asthmatics with beneficial effects on airflow obstruction.

  18. Eosinophilia predicts poor clinical outcomes in recent-onset arthritis: results from the ESPOIR cohort

    PubMed Central

    Guellec, Dewi; Milin, Morgane; Cornec, Divi; Tobon, Gabriel J; Marhadour, Thierry; Jousse-Joulin, Sandrine; Chiocchia, Gilles; Vittecocq, Olivier; Devauchelle-Pensec, Valérie; Saraux, Alain

    2015-01-01

    Objectives To determine the prevalence of eosinophilia in patients with recent-onset arthritis suggestive of rheumatoid arthritis (RA) and to describe their features and outcomes. Methods We performed an ancillary study of data from a French prospective multicentre cohort study monitoring clinical, laboratory and radiographic data in patients with inflammatory arthritis of 6 weeks to 6 months duration. We determined the proportion of patients with eosinophilia, defined as a count >500/mm3, at baseline and after 3 years. Features of patients with and without baseline eosinophilia were compared. Results Baseline eosinophilia was evidenced in 26 of 804 (3.2%) patients; their mean eosinophil count was 637.7±107/mm3. Baseline eosinophilia was ascribed to atopic syndrome in 6 of 26 (23.1%) patients. After 3 years, patients with eosinophilia had higher Health Assessment Questionnaire scores (0.9 vs 0.5, p=0.004), higher patient visual analogue scale activity score and morning stiffness intensity (p=0.05), and were more often taking disease-modifying antirheumatic drugs (p=0.02). Baseline eosinophilia was not associated with presence of extra-articular manifestations. Conclusions Eosinophilia is rare in recent-onset arthritis suggestive of RA, and is usually directly related to the rheumatic disease. Our data suggest that patients with mild eosinophilia at diagnosis could respond worse to the treatment than those without. PMID:26509068

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

    PubMed Central

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

    2017-01-01

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

  20. Mast Cell Hyperplasia and Eosinophilia Induced by Ascaris Body Fluid

    PubMed Central

    Archer, G. T.; Binet, J.-L.

    1971-01-01

    Daily i.p. injections of dilute Ascaris body fluid into rats induced peritoneal eosinophilia and the formation of pin-point follicles in the omentum. The follicles comprised plasma cells, macrophages and fibroblasts together with large numbers of eosinophils and mast cells. Electron microscopy of eosinophils in the follicles revealed loss of cytoplasmic granules and numerous vesicular and tubular structures in the cytoplasm. The mast cells showed clear areas round the granules, suggesting dissolution of granule components. ImagesFigs. 4-6Figs. 7-8Figs. 13-14Figs. 9-10Figs. 1-3Figs. 11-12 PMID:5135540

  1. Evaluation of the common conditions associated with eosinophilia.

    PubMed Central

    Teo, C G; Singh, M; Ting, W C; Ho, L C; Ong, Y W; Seet, L C

    1985-01-01

    In an eosinophilic population of 47 boys of the same age, a large proportion (92%) were helminth infested or atopic, or both, compared with 36% of 36 controls. The methods used to detect these conditions were not costly or elaborate, except for the radioallergosorbent test, which was used to measure concentrations of circulating IgE antibodies to atopic allergens. It is suggested that an economical approach to detect helminthiasis and atopy in cases of eosinophilia is adopted using the methods employed here, with skin prick tests replacing the radioallergosorbent test. PMID:3973055

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

    NASA Astrophysics Data System (ADS)

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

    2004-04-01

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

  3. The Phillips airway.

    PubMed

    Haridas, R P; Wilkinson, D J

    2012-07-01

    The Phillips airway was developed by George Ramsay Phillips. There is no known original description of the airway and the earliest known reference to it is from 1919. The airway and its modifications are described.

  4. Strongyloides stercoralis, Eosinophilia, and Type 2 Diabetes Mellitus: The Predictive Value of Eosinophilia in the Diagnosis of S stercoralis Infection in an Endemic Community

    PubMed Central

    Hays, Russell; Thompson, Fintan; Esterman, Adrian; McDermott, Robyn

    2016-01-01

    Background. This study examines the predictive value of eosinophilia for Strongyloides stercoralis infection, as measured by enzyme-linked immunosorbent assay (ELISA) testing, in an endemic community. In remote communities, eosinophilia is frequently used as a proxy test for the presence of helminth infections. Past studies of eosinophilia and Strongyloides infection have been conducted in specific groups such as immigrants and refugees, or in subpopulations of nonendemic communities, rather than in endemic communities. Methods. We conducted a cross-sectional study of the relationship between eosinophilia and Strongyloides ELISA serology, as part of a study into the relationship between S stercoralis infection and type 2 diabetes mellitus (T2DM) in an Indigenous community in northern Australia. Results. Two hundred thirty-nine adults had their eosinophil count and S stercoralis ELISA serology measured in 2012 and 2013, along with other biometric and metabolic data. Eosinophilia was found to have a relatively poor sensitivity (60.9%), specificity (71.1%), positive predictive value (54.6%), and negative predictive value (76.1%) for S stercoralis ELISA positivity in this group. However, there was a more constant relationship between eosinophilia and S Stercoralis ELISA positivity in patients with T2DM (negative predictive value 87.5%). Conclusion. This study suggests that the presence or absence of eosinophilia is not an adequate proxy test for S stercoralis infection in a community where the infection is prevalent, and that the association between eosinophilia and S stercoralis ELISA positivity is more constant in patients with T2DM. PMID:26989753

  5. Effect of a single dose of salmeterol on the increase in airway eosinophils induced by allergen challenge in asthmatic subjects

    PubMed Central

    Dente, F.; Bancalari, L.; Bacci, E.; Bartoli, M.; Carnevali, S.; Cianchetti, S.; Di, F; Giannini, D.; Vagaggini, B.; Testi, R.; Paggiaro, P.

    1999-01-01

    BACKGROUND—The long acting β2 agonist salmeterol is very effective in preventing asthmatic responses to specific stimuli, and this effect could theoretically be due to some anti-inflammatory property in addition to bronchodilator property.
METHODS—The protective effect of a single dose of salmeterol (50 µg) on allergen induced early and late responses and on the associated airway inflammation was investigated in a double blind, placebo controlled, crossover study in 11 atopic asthmatic subjects. Eosinophil percentages and concentrations of eosinophil cationic protein (ECP) in peripheral blood and in hypertonic saline induced sputum were measured 24 hours after allergen inhalation.
RESULTS—Salmeterol effectively inhibited both early and late asthmatic responses in comparison with placebo. Salmeterol also inhibited the increase in the percentage of eosinophils in the sputum 24hours after allergen inhalation (median (range) baseline 6% (1-36), after placebo 31% (5-75), after salmeterol 12% (1-63)). However, the increase in both sputum and serum ECP concentrations 24 hours after allergen challenge was not affected by pretreatment with salmeterol.
CONCLUSIONS—A single dose of salmeterol inhibits the allergen induced airway responses and the increase in sputum eosinophils after allergen challenge.

 PMID:10377209

  6. Enhancement of intestinal eosinophilia during Hymenolepis nana infection in mice.

    PubMed

    Niwa, A; Miyazato, T

    1996-03-01

    The ability of Hymenolepis nana oncosphere extract to induce eosinophil chemotactic response was examined in vitro and in vivo. The extract showed a chemotactic activity specific for eosinophils but not for neutrophils. Partially purified eosinophil chemotactic factors (ECFs) from the oncosphere extract showed apparent molecular mass from 5.5 to 9.6kDa and 30 to 40kDa. These were resistant to heating and proteinase K digestion but sensitive to periodate oxidation. Peritoneal injection of the crude extract or partially purified ECFs to mice resulted in a preferential eosinophil infiltration. The chemotactic activity for eosinophils was not separable from the adhesion molecule expression or oxygen radical-inducing activity by means of chromatography or chemical treatments. Furthermore, histological examination demonstrated a marked tissue eosinophilia around H. nana larvae in the intestinal lamina propria of both humoral and cell-mediated immunodeficiency mice. The present findings suggest that H. nana oncosphere-derived molecules facilitate in vivo the intestinal eosinophilia during the infection.

  7. Blockage of upper airway

    MedlinePlus

    ... Airway obstruction - acute upper Images Throat anatomy Choking Respiratory system References Cukor J, Manno M. Pediatric respiratory emergencies: upper airway obstruction and infections. In: Marx ...

  8. Host lung immunity is severely compromised during tropical pulmonary eosinophilia: role of lung eosinophils and macrophages.

    PubMed

    Sharma, Pankaj; Sharma, Aditi; Vishwakarma, Achchhe Lal; Agnihotri, Promod Kumar; Sharma, Sharad; Srivastava, Mrigank

    2016-04-01

    Eosinophils play a central role in the pathogenesis of tropical pulmonary eosinophilia, a rare, but fatal, manifestation of filariasis. However, no exhaustive study has been done to identify the genes and proteins of eosinophils involved in the pathogenesis of tropical pulmonary eosinophilia. In the present study, we established a mouse model of tropical pulmonary eosinophilia that mimicked filarial manifestations of human tropical pulmonary eosinophilia pathogenesis and used flow cytometry-assisted cell sorting and real-time RT-PCR to study the gene expression profile of flow-sorted, lung eosinophils and lung macrophages during tropical pulmonary eosinophilia pathogenesis. Our results show that tropical pulmonary eosinophilia mice exhibited increased levels of IL-4, IL-5, CCL5, and CCL11 in the bronchoalveolar lavage fluid and lung parenchyma along with elevated titers of IgE and IgG subtypes in the serum. Alveolar macrophages from tropical pulmonary eosinophilia mice displayed decreased phagocytosis, attenuated nitric oxide production, and reduced T-cell proliferation capacity, and FACS-sorted lung eosinophils from tropical pulmonary eosinophilia mice upregulated transcript levels of ficolin A and anti-apoptotic gene Bcl2,but proapoptotic genes Bim and Bax were downregulated. Similarly, flow-sorted lung macrophages upregulated transcript levels of TLR-2, TLR-6, arginase-1, Ym-1, and FIZZ-1 but downregulated nitric oxide synthase-2 levels, signifying their alternative activation. Taken together, we show that the pathogenesis of tropical pulmonary eosinophilia is marked by functional impairment of alveolar macrophages, alternative activation of lung macrophages, and upregulation of anti-apoptotic genes by eosinophils. These events combine together to cause severe lung inflammation and compromised lung immunity. Therapeutic interventions that can boost host immune response in the lungs might thus provide relief to patients with tropical pulmonary eosinophilia.

  9. Allergen-induced resistin-like molecule-α promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis

    PubMed Central

    Mavi, Parm; Niranjan, Rituraj; Dutt, Parmesh; Zaidi, Asifa; Shukla, Jai Shankar; Korfhagen, Thomas

    2014-01-01

    Resistin-like molecule (Relm)-α is a secreted, cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-β, and Relm-γ. Although resistin was initially defined based on its insulin-resistance activity, the family members are highly induced in various inflammatory states. Earlier studies implicated Relm-α in insulin resistance, asthmatic responses, and intestinal inflammation; however, its function still remains an enigma. We now report that Relm-α is strongly induced in the esophagus in an allergen-challenged murine model of eosinophilic esophagitis (EoE). Furthermore, to understand the in vivo role of Relm-α, we generated Relm-α gene-inducible bitransgenic mice by using lung-specific CC-10 promoter (CC10-rtTA-Relm-α). We found Relm-α protein is significantly induced in the esophagus of CC10-rtTA-Relm-α bitransgenic mice exposed to doxycycline food. The most prominent effect observed by the induction of Relm-α is epithelial cell hyperplasia, basal layer thickness, accumulation of activated CD4+ and CD4− T cell subsets, and eosinophilic inflammation in the esophagus. The in vitro experiments further confirm that Relm-α promotes primary epithelial cell proliferation but has no chemotactic activity for eosinophils. Taken together, our studies report for the first time that Relm-α induction in the esophagus has a major role in promoting epithelial cell hyperplasia and basal layer thickness, and the accumulation of activated CD4+ and CD4− T cell subsets may be responsible for partial esophageal eosinophilia in the mouse models of EoE. Notably, the epithelial cell hyperplasia and basal layer thickness are the characteristic features commonly observed in human EoE. PMID:24994859

  10. Allergen-induced resistin-like molecule-α promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis.

    PubMed

    Mavi, Parm; Niranjan, Rituraj; Dutt, Parmesh; Zaidi, Asifa; Shukla, Jai Shankar; Korfhagen, Thomas; Mishra, Anil

    2014-09-01

    Resistin-like molecule (Relm)-α is a secreted, cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-β, and Relm-γ. Although resistin was initially defined based on its insulin-resistance activity, the family members are highly induced in various inflammatory states. Earlier studies implicated Relm-α in insulin resistance, asthmatic responses, and intestinal inflammation; however, its function still remains an enigma. We now report that Relm-α is strongly induced in the esophagus in an allergen-challenged murine model of eosinophilic esophagitis (EoE). Furthermore, to understand the in vivo role of Relm-α, we generated Relm-α gene-inducible bitransgenic mice by using lung-specific CC-10 promoter (CC10-rtTA-Relm-α). We found Relm-α protein is significantly induced in the esophagus of CC10-rtTA-Relm-α bitransgenic mice exposed to doxycycline food. The most prominent effect observed by the induction of Relm-α is epithelial cell hyperplasia, basal layer thickness, accumulation of activated CD4(+) and CD4(-) T cell subsets, and eosinophilic inflammation in the esophagus. The in vitro experiments further confirm that Relm-α promotes primary epithelial cell proliferation but has no chemotactic activity for eosinophils. Taken together, our studies report for the first time that Relm-α induction in the esophagus has a major role in promoting epithelial cell hyperplasia and basal layer thickness, and the accumulation of activated CD4(+) and CD4(-) T cell subsets may be responsible for partial esophageal eosinophilia in the mouse models of EoE. Notably, the epithelial cell hyperplasia and basal layer thickness are the characteristic features commonly observed in human EoE.

  11. Angiolymphoid hyperplasia with eosinophilia: a clinicopathologic study of 9 cases.

    PubMed

    Guinovart, R M; Bassas-Vila, J; Morell, L; Ferrándiz, C

    2014-03-01

    Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare disease characterized by single or multiple angiomatous lesions typically located on the scalp and the face. We present a retrospective analysis of 9 cases of ALHE. The lesions appeared largely as multiple grouped papules or, in some cases, subcutaneous nodules, located mainly on the scalp, particularly around the ear. We also observed lesions in atypical locations, such as areas of the head other than the scalp, and the shoulder, neck, and forearm. At these sites the lesions had an atypical clinical appearance that made diagnosis difficult; this should be borne in mind in patients with single, well-delimited lesions with a vascular appearance and superficial ulceration or crusting. Surgery was the most common treatment in our series, and even though ALHE is considered a benign condition, recurrence was common.

  12. Eosinophilia and thrombosis in parasitic diseases: an overview.

    PubMed

    Ames, Paul R J; Aloj, Giuseppina; Gentile, Fabrizio

    2011-02-01

    It is known that peripheral blood eosinophilia (PBE) is a normal hematopoietic response to several parasitic diseases, but it is less known that PBE promotes a hypercoagulable state that may favor thrombosis. Scope of this article is to explore which parasitic infestations are most likely to be complicated by thrombosis and to highlight the pathogenetic contribution of PBE to vascular occlusions in this setting. A review of the world literature revealed 18 cases in which PBE was associated with vascular occlusion though no specific surveys were dedicated to this topic. The eosinophil exerts its thrombogenic potential by inhibition of the natural anticoagulant pathways and release of tissue factor with enhanced coagulation activation leading to vascular occlusion. It is hoped that this review contributes to the awareness of the link between PBE and thrombosis in parasitic disorders to foster research in this area.

  13. Drug rash with eosinophilia and systemic symptoms due to telaprevir.

    PubMed

    Montaudié, H; Passeron, T; Cardot-Leccia, N; Sebbag, N; Lacour, J P

    2010-01-01

    We report a case of drug rash with eosinophilia and systemic symptoms (DRESS) due to telaprevir (VX-950), a specific inhibitor of the hepatitis C virus (HCV) serine protease. A 57-year-old woman with chronic hepatitis C was included in a phase 2 rollover study of VX-950. She received VX-950 in combination with pegylated interferon alfa-2a and ribavirin. Six weeks later, she developed a generalized pruritic maculopapular exanthema with malaise, fever, dyspnoea and lymph node swelling. She had an eosinophilia (up to 2.7 × 109 cells/l), large activated lymphocytes and increased concentrations of aminotransferases. Histological examination of a cutaneous biopsy was consistent with a drug rash reaction. The HCV treatment was stopped, and she was treated with topical and oral steroids. Cutaneous and systemic symptoms disappeared within 1 month. Telaprevir was considered the culprit drug. We report to our knowledge the first case of DRESS syndrome due to telaprevir. The safety data of telaprevir is derived mainly from the PROVE1, PROVE2 and PROVE3 studies. They showed a high frequency of cutaneous side effects reported under the imprecise terms of pruritus and rash, leading to an increased rate of treatment discontinuation. Telaprevir, due to its efficacy, is probably on the way to obtaining regulatory approval in the near future. It is therefore important to be aware of the high incidence of cutaneous side effects and better describe them. Our observation suggests that potentially severe hypersensitivity reactions may belong to the spectrum of rashes induced by this drug.

  14. “Auto-anti-IgE”: Naturally occurring IgG anti-IgE antibodies may inhibit allergen-induced basophil activation

    PubMed Central

    Chan, Yih-Chih; Ramadani, Faruk; Santos, Alexandra F.; Pillai, Prathap; Ohm-Laursen, Line; Harper, Clare E.; Fang, Cailong; Dodev, Tihomir S.; Wu, Shih-Ying; Ying, Sun; Corrigan, Christopher J.; Gould, Hannah J.

    2014-01-01

    Background Naturally occurring IgE-specific IgG autoantibodies have been identified in patients with asthma and other diseases, but their spectrum of functions is poorly understood. Objective Address the hypothesis that: (i) IgG anti-IgE autoantibodies are detectable in the serum of all subjects but elevated in asthmatic patients regardless of atopic status as compared with controls; (ii) some activate IgE-sensitized basophils; and (iii) some inhibit allergen-induced basophil activation. Methods IgE-specific IgG autoantibodies were detected and quantified in sera using ELISA. Sera were examined for their ability to activate IgE-sensitized human blood basophils in the presence and absence of allergen using a basophil activation test, and to inhibit allergen binding to specific IgE on a rat basophilic cell line stably expressing human FcεRI. Results IgG autoantibodies binding to both free and FcεRI-bound IgE were detected in patients with atopic and non-atopic asthma, as well as controls. While some were able to activate IgE-sensitised basophils, others inhibited allergen-induced basophil activation, at least partly by inhibiting binding of IgE to specific allergen. Conclusion Naturally occurring IgG anti-IgE autoantibodies may inhibit, as well as induce, basophil activation. They act in a manner distinct from therapeutic IgG anti-IgE antibodies such as omalizumab. They may at least partly explain why atopic subjects who make allergen-specific IgE never develop clinical symptoms, and why omalizumab therapy is of variable clinical benefit in severe atopic asthma. PMID:25112697

  15. Soluble toll-like receptor 4 reversed attenuating effect of Chinese herbal Xiao-Qing-Long-Tang on allergen induced nerve growth factor and thymic stromal lymphopoietin

    PubMed Central

    CHANG, REN-SHIU; WANG, YU-CHIN; KAO, SHUNG-TE

    2013-01-01

    Xiao-Qing-Long-Tang (XQLT) is known to regulate allergic immune reactions. The aim of this study was to investigate the effects of XQLT on allergen-induced cytokines and associated signaling pathways. An acute allergic mouse model was used to investigate the effects of XQLT on nerve growth factor (NGF) during an allergic reaction, while human pulmonary alveolar epithelial cells (HPAEpiCs) were used to investigate the effects of XQLT on Dermatophagoides pteronyssinus group 2 (Der p 2)-induced NGF, p75 neurotrophin receptor (p75NTR) and thymic stromal lymphopoietin (TSLP) expression. XQLT was demonstrated to inhibit NGF- and p75NTR-related allergic reactions in the mouse model. XQLT also reduced the expression of Toll-like receptor 4 (TLR4) in the lungs of the model mice. XQLT inhibited Der p 2-induced NGF, TSLP and p75NTR expression in the HPAEpiC cell line. The use of recombinant soluble TLR4 (sTLR4) in a competitive assay partially attenuated the inhibitory effect of XQLT on NGF, TSLP and p75NTR expression in HPAEpiC cells. The inhibitory effect of XQLT on the Ser536 phosphorylation of p65 (nuclear factor-κB; NF-κB), a TLR4-induced factor, was also attenuated by sTLR4. In conclusion, XQLT inhibited Der p allergen-induced NGF, p75NTR and TSLP expression. This inhibition was attenuated by sTLR4. The mechanism of action of XQLT may be correlated with TLR4, a primary receptor in the innate immune system. The findings of this study may focus the search for pharmacological targets of XQLT onto TLR4, which is important in the allergen presentation pathway. PMID:24223644

  16. EGFR signaling blunts allergen-induced IL-6 production and Th17 responses in the skin and attenuates development and relapse of atopic dermatitis.

    PubMed

    Zhang, Zhonghua; Xiao, Chang; Gibson, Aaron M; Bass, Stacey A; Khurana Hershey, Gurjit K

    2014-02-01

    Despite the important role for epidermal growth factor (EGF) in epithelial homeostasis and wound healing, it has not been investigated in atopic dermatitis (AD). We used AD animal models to explore the role of EGF in AD. In an acute AD model, skin transepidermal water loss was significantly attenuated in EGF-treated mice. Blockade of EGFR signaling genetically or pharmacologically confirms a protective role for EGFR signaling in AD. In a chronic/relapsing AD model, EGF treatment of mice with established AD resulted in an attenuation of AD exacerbation (skin epithelial thickness, cutaneous inflammation, and total and allergen specific IgE) following cutaneous allergen rechallenge. EGF treatment did not alter expression of skin barrier junction proteins or antimicrobial peptides in the AD model. However, EGF treatment attenuated allergen-induced expression of IL-17A, CXCL1, and CXCL2 and neutrophil accumulation in AD skin following cutaneous allergen exposure. IL-17A production was decreased in the in vitro restimulated skin-draining lymph node cells from the EGF-treated mice. Similarly, IL-17A was increased in waved-2 mice skin following allergen exposure. Whereas IL-6 and IL-1β expression was attenuated in the skin of EGF-treated mice, EGF treatment also suppressed allergen-induced IL-6 production by keratinocytes. Given the central role of IL-6 in priming Th17 differentiation in the skin, this effect of EGF on keratinocytes may contribute to the protective roles for EGFR in AD pathogenesis. In conclusion, our study provides evidence for a previously unrecognized protective role for EGF in AD and a new role for EGF in modulating IL-17 responses in the skin.

  17. Functional response to inhaled salbutamol and/or ipratropium bromide in Ascaris suum-sensitised cats with allergen-induced bronchospasms.

    PubMed

    Leemans, Jérôme; Kirschvink, Nathalie; Clercx, Cécile; Cambier, Carole; Gustin, Pascal

    2010-10-01

    Knowledge about the use of inhaled bronchodilators in cats with so-called 'feline asthma' is limited and relies on the experience of clinicians treating these patients. A randomised controlled four-way crossover study was therefore designed to compare the effects of salbutamol (SAL, 100 μg), ipratropium bromide (IB, 20 μg) and a combination of both (SAL/IB, 100 μg/20 μg), delivered through a pressurised metered-dose inhaler (pMDI) connected to a spacing chamber, on allergen-induced bronchospasms in five Ascaris suum (AS)-sensitised cats. Four AS bronchial provocation challenges were carried out at 1 week intervals, followed by one of four treatment protocols: SAL, IB, SAL/IB or control (untreated). Enhanced pause (Penh), an estimator of airflow limitation measured by barometric whole-body plethysmography, was repeatedly assessed within 120 min following the administration of each treatment protocol. Responses to inhaled medications were evaluated by calculating the area under the time-response curves (AUC) from 0 to 60 or 120 min after drug administration (AUC(0-60), AUC(0-120)), as well as the times required for half-recovery (T(50%)) or for returning to nearly basal conditions (T(20%)). No significant differences were found among the four study groups, with reference to the mean AUC(0-60), T(20%) and T(50%) values of Penh (P>0.05). Mean AUC(0-120) values of Penh were similar between the bronchodilators tested, but were significantly lower than those in the untreated group. It was concluded that inhalation of SAL, IB and SAL/IB via pMDI failed to improve most Penh-derived parameters, which suggested that these bronchodilators were of limited efficacy in reversing allergen-induced bronchospasm in cats. However, further studies using a larger number of animals are warranted to investigate if different drugs or delivery devices or higher dosages may be more effective.

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

    PubMed

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

    1994-04-01

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

  19. Triggers of airway inflammation.

    PubMed

    Kerrebijn, K F

    1986-01-01

    Most asthmatics have hyperresponsive airways. This makes them more sensitive than non-asthmatics to bronchoconstricting environmental exposures which, in their turn, may enhance responsiveness. Airway inflammation is considered to be a key determinant of airway hyperresponsiveness: the fact that chronic airway inflammation in cystic fibrosis does not lead to airway hyperresponsiveness of any importance indicates, however, that the role of airway inflammation is complex and incompletely elucidated. The main inducers of airway inflammation are viral infections, antigens, occupational stimuli and pollutants. Although exercise, airway cooling and hyper- or hypotonic aerosols are potent stimuli of bronchoconstriction, it is questionable if airway inflammation is involved in their mode of action. Each of the above-mentioned stimuli is discussed, with emphasis laid on the relation of symptoms to mechanisms.

  20. Eosinophilia as the presenting sign in pancreatic cancer: an extremely rare occurrence.

    PubMed

    Ibrahim, Uroosa; Asti, Divya; Saqib, Amina; Mudduluru, Bindu Madhavi; Ayaz, Sadaf; Odaimi, Marcel

    2017-04-01

    A case of pancreatic adenocarcinoma diagnosed following work up for eosinophilia is reported. A 68-year-old female was referred to our Hematology clinic for an absolute eosinophil count of 1869 per microliter. No allergic signs or symptoms were reported. Laboratory studies for parasitic infestations autoimmune disease and collagen vascular disease were negative. Computed tomography of the abdomen revealed a mass in the neck of the pancreas with fine needle aspiration biopsy consistent with adenocarcinoma. The patient received one cycle of modified FOLFIRINOX with complete resolution of the eosinophilia. There are rare case reports of tumor-associated blood eosinophilia in solid malignancies. The finding may be indicative of rapid disease progression and poor prognosis. Our case is the third in published English literature with eosinophilia being the initial finding in pancreatic cancer.

  1. A seroepidemiological survey of toxocariasis among eosinophilia patients in Chungcheongnam-do.

    PubMed

    Seo, Min; Yoon, Sung Chul

    2012-09-01

    There have been several reports on the relationship between toxocariasis and eosinophilia, but all have been limited to the areas of Seoul or Gangwon-do. In the present study, we investigated the seroprevalence of toxocariasis among eosinophilia patients in Chungcheongnam-do, the central district of Korea. Among the 101 patients tested, 51 (50.5%) were identified as positive by Toxocara ELISA, and 46 (45.5%) were confidently diagnosed with toxocariasis because of absence of any other cause of eosinophilia. Whereas 22 of 42 seropositive patients (52.3%) had a recent history of consuming raw livers, especially the cow liver, only 1 of 25 seronegative patients (4%) had done so (P<0.01). From these results, we could confirm that toxocariasis is related to eosinophilia, and infer that ingestion of raw cow liver plays a vital role in the transmission of toxocariasis in Chungcheongnam-do.

  2. A Seroepidemiological Survey of Toxocariasis among Eosinophilia Patients in Chungcheongnam-do

    PubMed Central

    Seo, Min

    2012-01-01

    There have been several reports on the relationship between toxocariasis and eosinophilia, but all have been limited to the areas of Seoul or Gangwon-do. In the present study, we investigated the seroprevalence of toxocariasis among eosinophilia patients in Chungcheongnam-do, the central district of Korea. Among the 101 patients tested, 51 (50.5%) were identified as positive by Toxocara ELISA, and 46 (45.5%) were confidently diagnosed with toxocariasis because of absence of any other cause of eosinophilia. Whereas 22 of 42 seropositive patients (52.3%) had a recent history of consuming raw livers, especially the cow liver, only 1 of 25 seronegative patients (4%) had done so (P<0.01). From these results, we could confirm that toxocariasis is related to eosinophilia, and infer that ingestion of raw cow liver plays a vital role in the transmission of toxocariasis in Chungcheongnam-do. PMID:22949755

  3. Acute synovial fluid eosinophilia associated with delayed pressure urticaria: a role for mast cells?

    PubMed

    Miossec, P; Sullivan, T J; Tharp, M D; Volant, A; Le Goff, P

    1987-04-01

    We report a case of exercise induced joint effusion with synovial fluid (SF) eosinophilia of 9,540/mm3 in a patient with delayed pressure urticaria. The SF eosinophilia was an acute but transient event associated with some evidence of local complement activation. Histologic assessment revealed a normal synovial membrane but with no detectable intact mast cells. These observations suggest that mast cells and eosinophils acting in concert can cause joint inflammation.

  4. Relevance of eosinophilia and hyper-IgE in immigrant children.

    PubMed

    Belhassen-García, Moncef; Pardo-Lledías, Javier; Pérez del Villar, Luis; Muro, Antonio; Velasco-Tirado, Virginia; Blázquez de Castro, Ana; Vicente, Belen; García García, Ma Inmaculada; Luis Muñoz Bellido, Juan; Cordero-Sánchez, Miguel

    2014-07-01

    Immigrants from undeveloped countries are a growing problem in Europe. Spain has become a frequent destination for immigrants (20% of whom are children) because of its geographic location and its historic and cultural links with Africa and Latin America. Eosinophilia is frequent in adult immigrants, travelers and expatriates coming from tropical areas. However, there are few studies that focus on the incidence and causes of tropical eosinophilia and hyper-IgE in immigrant children.We evaluated, prospectively, the prevalence and causes of eosinophilia and hyper-immunoglobulin E (IgE) in 362 immigrant children coming from Sub-Saharan Africa, Northern Africa and Latin America to Salamanca, Spain, between January 2007 and December 2011.Absolute eosinophilia and hyper-IgE were present in 22.9% and 56.8% of the analyzed children, respectively. The most frequent causes of absolute eosinophilia were filariasis (52.6%), strongyloidiasis (46.8%) and schistosomiasis (28.9%). Filariasis (41.9%), strongyloidiasis (29.6%) and schistosomiasis (22.2%) were the most frequent causes of increased levels of IgE. The area under the ROC curve showed similar values between eosinophil count and IgE levels in the diagnosis of helminthiasis (69% [95% confidence interval (CI) 63%-74%] vs 67% [95% CI 60%-72%], P = 0.24). Eosinophilia and hyper-IgE have a high value as biomarkers of helminthiasis in children coming from tropical and subtropical areas.

  5. Traumatic ulcerative granuloma with stromal eosinophilia - Mystery of pathogenesis revisited.

    PubMed

    Sarangarajan, R; Vaishnavi Vedam, V K; Sivadas, G; Sarangarajan, Anuradha; Meera, S

    2015-08-01

    Oral ulcers are a common symptom in clinical practice. Among various causative factors, different types of ulcers in oral cavity exist. Among this, traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) appears to be quite neglected by the clinicians due to the limited knowledge and awareness. On reviewing with a detailed approach to titles and abstracts of articles eliminating duplicates, 40 relevant articles were considered. Randomized studies, review articles, case reports and abstracts were included while conference papers and posters were excluded. Of importance, TUGSE cases been reported only to a minimal extent in the literature. Lack of its awareness tends to lead clinicians to a misconception of cancer. Thus, this particular lesion needs to be differentiated from other malignant lesions to provide a proper mode of treatment. The present article reviews various aspects of the TUGSE with emphasis on the clinical manifestation, pathogenesis, histological, and immunohistochemical study. This study provides the clinician contemporaries, a humble expansion to their knowledge of the disease, based on the searched literature, enabling a more comprehensive management of this rare occurrence.

  6. Angiolymphoid Hyperplasia with Eosinophilia of the Orbit and Adnexa

    PubMed Central

    Mukherjee, Bipasha; Kadaskar, Jayant; Priyadarshini, Omega; Krishnakumar, Subramanian; Biswas, Jyotirmay

    2015-01-01

    Purpose Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare disorder presenting with solitary or multiple nodules in the dermis or subcutaneous tissues. ALHE shares clinical as well as histopathological characteristics with Kimura disease (KD), but they have been considered to be two distinct entities based on their histological features. Orbital and adnexal involvement in ALHE is rare. The published literature is limited to few case reports featuring single cases. Methods We report a series of 5 cases of ALHE presenting with diverse clinical features seen at a tertiary referral care centre in India. We also review the published literature with a special emphasis on the treatment modalities for orbital and adnexal ALHE. Results Three patients of this series presented with orbital involvement, while the remaining 2 had involvement of the eyelid. Three patients underwent incisional and/or excisional biopsy, whereas 2 were managed conservatively. There were no recurrences seen on follow-up. Conclusions ALHE can rarely involve the orbit and adnexa. There is no consensus on the best modality of management of this rare entity. ALHE and KD have often been considered variations of the same disease, but it is important to differentiate between the two entities for optimal patient management. PMID:27171790

  7. Angiolymphoid hyperplasia with eosinophilia and entrapment of the ulnar nerve

    PubMed Central

    Di Vitantonio, Hambra; De Paulis, Danilo; Ricci, Alessandro; Raysi, Soheila Dehcordi; Marzi, Sara; Del Maestro, Mattia; Galzio, Renato Juan

    2016-01-01

    Background: The angiolymphoid hyperplasia with eosinophilia (ALHE) is a sporadic vasoproliferative lesion of uncertain etiology involving the skin and the subcutaneous tissue. Occasionally, it involves also the large arteries compressing the near nerves. ALHE is commonly confused with Kimura's disease because of their clinical and histological similarities. Case Description: We report a case of a 52-year-old female suffering from a 6-month pain and paresthesias in the fourth and fifth finger of the right hand. The angiography showed a pseudoaneurysm in the proximal third of the right ulnar artery. A complete surgical excision of the vascular lesion was undertaken. The lesion forced the right ulnar nerve. The histopathological diagnosis deposed for ALHE. Conclusion: Up to now, literature has described 8 cases of ALHE involving the arteries, and only one case originating from the ulnar nerve. The authors report a case of a female with ALHE involving the ulnar artery that compressed the ulnar nerve. Clinical aspects, radiological features, surgical treatment, and operative findings are discussed reviewing the pertinent literature. PMID:27069750

  8. Eosinophil activation of fibroblasts from chronic allergen-induced disease utilizes stem cell factor for phenotypic changes.

    PubMed

    Dolgachev, Vladislav; Berlin, Aaron A; Lukacs, Nicholas W

    2008-01-01

    In the present studies the role of stem cell factor (SCF) in mediating eosinophil and fibroblast activation during their interaction was investigated. SCF was significantly higher in fibroblasts grown from lungs of chronic allergen-challenged mice compared to fibroblasts grown from normal mice. When eosinophils were layered onto fibroblasts from allergic mice, a significant increase in SCF was detected compared to fibroblasts from nonallergic mice. The interaction of fibroblasts with eosinophils also increased the production of asthma-associated chemokines, CCL5 and CCL6, was dependent on cell-to-cell interaction, and was observed only with fibroblasts derived from lungs of chronic allergen-challenged mice and not from those derived from unchallenged normal mice. Chemokine production was significantly decreased when anti-SCF antibodies were added during eosinophil-fibroblast interaction. The interaction of fibroblasts from chronic allergen-challenged mice with eosinophils also increased alpha-smooth muscle cell actin and procollagen I expression as well as induced transforming growth factor-beta. The changes in myofibroblast activation were dependent on SCF-mediated pathways because anti-SCF antibody treatment reduced the expression of all three of these latter fibrosis-associated markers. Thus, our data suggest that SCF mediates an important activation pathway for fibroblasts during chronic allergic responses on interaction with recruited eosinophils and suggest a potential mechanism of airway remodeling during chronic disease.

  9. Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation

    PubMed Central

    Miyahara, Nobuaki; Matsubara, Shigeki; Taube, Christian; Kitamura, Kenichi; Hirano, Astushi; Tanimoto, Mitsune; Gelfand, Erwin W.

    2016-01-01

    Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways. PMID:27340385

  10. Emergency airway puncture

    MedlinePlus

    ... support for only a very short period of time. Alternative Names Needle cricothyrotomy Images Emergency airway puncture Cricoid cartilage Emergency airway puncture - series References Hebert RB, Bose S, Mace SE. Cricothyrotomy and ...

  11. Upper airway biopsy

    MedlinePlus

    ... upper airway Images Upper airway test Bronchoscopy Throat anatomy References Yung RC, Boss EF. Tracheobronchial endoscopy. In: Flint PW, Haughey BH, Lund LJ, et al, eds. Cummings Otolaryngology: Head & Neck Surgery. 5th ed. Philadelphia, PA: Elsevier Mosby; ...

  12. 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

  13. Careers in Airway Science.

    ERIC Educational Resources Information Center

    Federal Aviation Administration (DOT), Washington, DC.

    The Federal Aviation Administration (FAA) has initiated the Airway Science curriculum as a method of preparing the next generation of aviation technicians and managers. This document: (1) discusses the FAA's role in the Airway Science program; (2) describes some of the career fields that FAA offers to Airway Science graduates (air traffic control…

  14. Endomyocardial involvement in asymptomatic sub-Saharan immigrants with helminth-related eosinophilia

    PubMed Central

    Marrero-Santiago, Héctor; Hernández-Cabrera, Michele; Gil-Guillén, Carlos; Pisos-Álamo, Elena; Jaén-Sánchez, Nieves; Pérez-Arellano, José-Luis

    2017-01-01

    Background Among immigrants of sub-Saharan origin, parasitic infection is the leading cause of eosinophilia, which is generally interpreted as a defense mechanism. A side effect of the inflammatory mediators released by eosinophils is damage to host organs, especially the heart. The main objectives of this study were to i) assess cardiac involvement in asymptomatic sub-Saharan immigrants with eosinophilia, ii) relate the presence of lesions with the degree of eosinophilia, and iii) study the relationship between cardiac involvement and the type of causative parasite. Methodology/Principle findings In total, the study included 50 black immigrants (37 patients and 13 controls) from sub-Saharan Africa. In all subjects, heart structure and function were evaluated in a blinded manner using Sonos 5500 echocardiographic equipment. The findings were classified and described according to established criteria. The diagnostic criteria for helminthosis were those reported in the literature. Serum eosinophil-derived neurotoxin levels were measured using enzyme-linked immunosorbent assay. A significant association was found between the presence of eosinophilia and structural alterations (mitral valve thickening). However, the lack of an association between the degree of eosinophilia and heart valve disease and the absence of valve involvement in some patients with eosinophilia suggest the role of other factors in the appearance of endocardial lesions. There was also no association between the type of helminth and valve involvement. Conclusions We, therefore, suggest that transthoracic echocardiography be performed in every sub-Saharan individual with eosinophilia in order to rule out early heart valve lesions. PMID:28234952

  15. A comparison of the in vivo effects of ketotifen, clemastine, chlorpheniramine and sodium cromoglycate on histamine and allergen induced weals in human skin.

    PubMed Central

    Phillips, M J; Meyrick Thomas, R H; Moodley, I; Davies, R J

    1983-01-01

    The effect of ketotifen was compared with that of clemastine and chlorpheniramine, known antihistamines, and sodium cromoglycate, a drug considered to have mast cell "stabilizing' properties on histamine and allergen wealing reactions in human skin, in random order, double-blind, placebo controlled studies. Ketotifen was significantly more potent in the inhibition of both histamine (P less than 0.001) and allergen (P less than 0.001) skin wealing reactions than either clemastine or chlorpheniramine. Sodium cromoglycate had no significant effect on either histamine or allergen skin wealing reactions in any of the concentrations tested. However ketotifen, like clemastine, had a significantly greater inhibitory effect on histamine than on allergen induced weals (P less than 0.001) and both drugs were shown to act as competitive antagonists of histamine. Ketotifen has been shown to be a potent anti-histamine but there is no evidence from these in vivo studies to suggest that it has any additional inhibitory activity on release of mediators from mast cells in human skin. PMID:6405771

  16. Circulating histamine and neutrophil chemotactic activity during allergen-induced asthma: the effect of inhaled antihistamines and anti-allergic compounds.

    PubMed

    Morgan, D J; Moodley, I; Cundell, D R; Sheinman, B D; Smart, W; Davies, R J

    1985-07-01

    Plasma histamine and serum neutrophil chemotactic activity (S-NCA) were measured in ten atopic asthmatic patients on four separate occasions after allergen bronchial provocation testing (BPT). Single doses of inhaled sodium cromoglycate (SCG; 20 mg), clemastine (0.5 mg), ketotifen (0.5 mg) and isotonic saline (0.9% NaCl) placebo were administered 30 min before bronchial provocation testing in random order and double-blind. The airflow obstruction after BPT was monitored by measurement of forced expiratory volume in 1 s (FEV1). Plasma histamine was measured by the double-isotope radioenzymatic assay and S-NCA by a modified Boyden chamber technique. A highly significant decrease in FEV1 after BPT occurred on the placebo pre-treatment visit (P less than 0.001). Prior administration of inhaled SCG, clemastine and ketotifen significantly reduced the decrease in airflow obstruction seen after BPT when compared with placebo treatment (P less than 0.01, P less than 0.02, P less than 0.05 respectively). No significant alteration in plasma histamine was detected during allergen-induced airflow obstruction. Levels of S-NCA were significantly higher 5, 10 and 15 min after BPT when compared with the pre-challenge level (P less than 0.01, P less than 0.01, P less than 0.001 respectively). These levels were not significantly decreased when airflow obstruction was inhibited by the prior inhalation of SCG, clemastine or ketotifen.

  17. Increased prevalence of eosinophilia in a hemodialysis population: Longitudinal and case control studies.

    PubMed

    Hildebrand, Sarah; Corbett, Richard; Duncan, Neill; Ashby, Damien

    2016-07-01

    Eosinophilia is commonly found in patients with clinical reactions to the hemodialysis circuit. With modern membranes, such reactions have become less common, but they may be under diagnosed in patients with subtle symptoms, in whom the presence of eosinophilia is an important diagnostic feature. Two case reports are presented, along with a hemodialysis study of the frequency and clinical associations of eosinophilia. In three hemodialysis facilities, all current hemodialysis patients with persistent eosinophilia (greater than 1 × 10(9) /L for 3 months) were identified. Control patients without eosinophilia (less than 0.5 × 10(9) /L for 3 months) matched for age, gender, and ethnicity were identified from the same facilities. A historical cohort of patients, dialyzing at the same facilities 5 years ago, was screened for the presence of persistent eosinophilia. From 510 patients, 24 cases of persistent eosinophilia were identified (4.7%). The median eosinophil count was 1.75 × 10(9) /L (range 1.1-7.5 × 10(9) /L). The prevalence in a historical cohort 5 years previously was significantly less at 1.5% (P = 0.046). Compared to controls, patients with eosinophilia were more likely to be on an angiotensin converting enzyme inhibitor (41.7% vs. 12.5%, P = 0.049), had a lower C-reactive protein (10 vs. 24 mg/L, P = 0.02) and were more likely to be using a fistula for access (P = 0.049). Over the following 12 months, there was no difference in the mean number of hospital admission days between cases and controls (7.6 vs. 11.5 days, P = 0.54), and no difference in mortality over 29 months (25.0% vs. 29.2%, P = 1.00). Eosinophilia remains not uncommon in hemodialysis patients, and in most cases reflects allergy to components of the dialysis circuit, which is usually subclinical. The overall prognosis for asymptomatic patients appears to be favourable.

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

    PubMed Central

    Wang, Xiaoyun; Li, Yin; Luo, Deyu; Wang, Xing; Zhang, Yun; Liu, Zhigang; Zhong, Nanshan; Wu, Min; Li, Guoping

    2017-01-01

    Hypersecretion of mucus is an important component of airway remodeling and contributes to the mucus plugs and airflow obstruction associated with severe asthma phenotypes. Lyn has been shown to down-regulate allergen-induced airway inflammation. However, the role of Lyn in mucin gene expression remains unresolved. In this study, we first demonstrate that Lyn overexpression decreased the mucus hypersecretion and levels of the muc5ac transcript in mice exposed to ovalbumin (OVA). Lyn overexpression also decreased the infiltration of inflammatory cells and the levels of IL-13 and IL-4 in OVA-challenged airways. Whereas Lyn knockdown increased the IL-4 or IL-13-induced MUC5AC transcript and protein levels in the human bronchial epithelial cell line, 16HBE, Lyn overexpression decreased IL-4- or IL-13-induced MUC5AC transcript and protein levels. Overexpression of Lyn also decreased the expression and phosphorylation of STAT6 in OVA-exposed mice, whereas Lyn knockdown increased STAT6 and MUC5AC levels in 16HBE cells. Finally, chromatin immunoprecipitation analysis confirmed that Lyn overexpression decreased the binding of STAT6 to the promoter region of Muc5ac in mice exposed to OVA. Collectively, these findings demonstrated that Lyn overexpression ameliorated airway mucus hypersecretion by down-regulating STAT6 and its binding to the MUC5AC promoter. PMID:28205598

  19. Myocardial infarction associated with eosinophilia and plasma extravasation at multiple sites. A variant of Kounis syndrome

    PubMed Central

    Gunawardena, Mudalige Don Vajira Malin; Weerasinghe, Anura; Herath, Jagath; Amarasena, Naomali

    2015-01-01

    Myocardial infarction occurring during the course of type I hypersensitivity constitutes Kounis syndrome. We report a case of a 38-year-old man who presented with anterior ST elevation myocardial infarction and peripheral blood eosinophilia. He had rhinitis and malaise for several days prior to presentation. There was no urticarial rash or pruritus to suggest hypersensitivity. Coronary angiogram revealed only mild plaque disease. Blood investigations revealed moderate eosinophilia and elevated IgE levels. CT of the thorax revealed fluid extravasation at multiple sites. Screening for a possible secondary cause for eosinophilia revealed hypersensitivity to multiple antigens. A diagnosis of Kounis syndrome was made. Within days of starting steroids and antihistamines, the patient's eosinophil count returned to normal with improvement of clinical picture. This case differs from classical Kounis syndrome as there was no acute allergic reaction (except atopic rhinitis). Fluid extravasation at multiple sites has not been described in previous cases. PMID:25608982

  20. In vivo imaging of tissue eosinophilia and eosinopoietic responses to schistosome worms and eggs

    PubMed Central

    Davies, Stephen J.; Smith, Steven J.; Lim, K.C.; Zhang, Hongbing; Purchio, Anthony F.; McKerrow, James H.; West, David B.

    2010-01-01

    Using a sensitive transgenic reporter mouse system and in vivo biophotonic imaging techniques, we present a dynamic analysis of eosinophil responses to schistosome infection. Use of this methodology provided previously unattainable detail on the spatial and temporal distribution of tissue eosinophilia and eosinopoietic responses to schistosome worms and eggs. Dramatic hepatic and intestinal eosinophilia in response to the deposition of schistosome eggs, with accompanying eosinopoiesis in the bone marrow, was observed between weeks 8 and 10 p.i., with subsequent downregulation evident by week 11. Contrary to expectations, we also demonstrate that schistosome parasites themselves induce significant intestinal eosinophilia and eosinopoiesis in the bone marrow at very early stages during prepatent infection. PMID:15950229

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

    PubMed Central

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

    2015-01-01

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

  2. 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

  3. Upper-airway cough syndrome with latent eosinophilic bronchitis.

    PubMed

    Yu, Li; Wei, Weili; Wang, Lan; Huang, Yang; Shi, Cuiqin; Lü, Hanjing; Qiu, Zhongmin

    2010-01-01

    Upper-airway cough syndrome often coexists with other diseases that elicit chronic cough. However, the concomitant conditions are not always relevant to chronic cough, which complicates the cause diagnosis of chronic cough. The objective of this study was to explore the diagnosis and clinical implication of upper-airway cough syndrome with latent eosinophilic bronchitis. Eleven patients with upper-airway cough syndrome and latent eosinophilic bronchitis were retrospectively analyzed for their clinical manifestations, changes of eosinophilia in induced sputum, and cough threshold with capsaicin defined as capsaicin concentration that elicits two or more coughs (C2) and five or more coughs (C5) between pretreatment and post-treatment. All patients reported a history of allergic rhinitis, showed persistent dry cough or small amounts of viscid sputum with a time course of 2-60 months (median = 7 months), and presented with symptoms and signs of rhinitis, normal lung function, and airway responsiveness. Initial eosinophil percentage in induced sputum was 3.5-8.0%. Cough disappeared after 2-5 (3 +/- 1) weeks of only oral antihistamine. With successful treatment, cough threshold C2 increased from 1.73 +/- 1.45 to 4.43 +/- 4.50 micromol/L (t = 2.64, P = 0.025) and C5 increased from 2.79 +/- 2.16 to 10.10 +/- 8.22 micromol/L (t = 3.10, P = 0.011). However, there was no significant change of eosinophil percentage in induced sputum (4.8 +/- 1.5% vs. 4.4 +/- 1.4%, t = 0.84, P = 0.427). Upper-airway cough syndrome with latent eosinophilic bronchitis is a unique condition. The recognition of the entity may avoid unnecessary use of corticosteroids.

  4. Metal allergens induce nitric oxide production by mouse dermal fibroblasts via the hypoxia-inducible factor-2α-dependent pathway.

    PubMed

    Kuroishi, Toshinobu; Bando, Kanan; Endo, Yasuo; Sugawara, Shunji

    2013-09-01

    Nickel (Ni) has been shown to be one of the most frequent metal allergens. We have already reported a murine metal allergy model with pathogen-associated molecular patterns (PAMPs) as adjuvants. Interleukin (IL)-1β plays a critical role in our mouse model. Because nonimmune cells, including fibroblasts, play important roles in local allergic inflammation, we investigated whether Ni induces inflammatory responses in mouse dermal fibroblasts (MDF). We also analyzed the synergistic effects between Ni, PAMPs, and IL-1β. MDF stimulated with Ni produced a significantly higher amount of nitric oxide (NO) in a dose-dependent manner. NO production was augmented by costimulation with IL-1β but not with PAMPs. On the other hand, IL-1β or PAMPs induced a significantly higher amount of IL-6 production by MDF, but no augmentation was detected in the presence of Ni. A specific inhibitor for inducible nitric oxide synthase (iNOS) inhibited Ni-induced NO production. iNOS mRNA expression was significantly higher in MDF stimulated with Ni, IL-1β, or both. A specific inhibitor for hypoxia-inducible factor (HIF)-2α, but not HIF-1α, inhibited NO production. Another frequent metal allergen, cobalt, also induced iNOS expression and NO production by MDF via the HIF-2α-dependent pathway. The inhibitor for iNOS augmented ear swelling in Ni allergy mouse model. On the other hand, HIF-2α inhibitor attenuates allergic inflammation. These results indicate that metal allergens induce NO production in MDF via the HIF-2α-dependent pathway and IL-1β augments NO production, which suggests that the NO induced by metal allergens plays a pathological role in metal allergies.

  5. Inhibition airway remodeling and transforming growth factor-β1/Smad signaling pathway by astragalus extract in asthmatic mice

    PubMed Central

    QU, ZHENG-HAI; YANG, ZHAO-CHUAN; CHEN, LEI; LV, ZHI-DONG; YI, MING-JI; RAN, NI

    2012-01-01

    Airway remodeling is characterized by airway wall thickening, subepithelial fibrosis, increased smooth muscle mass, angiogenesis and increased mucous glands, which can lead to a chronic and obstinate asthma with pulmonary function depression. In the present study, we investigated whether the astragalus extract inhibits airway remodeling in a mouse asthma model and observed the effects of astragalus extract on the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway in ovalbumin-sensitized mice. Mice were sensitized and challenged by ovalbumin to establish a model of asthma. Treatments included the astragalus extract and budesonide. Lung tissues were obtained for hematoxylin and eosin staining and Periodic acid-Schiff staining after the final ovalbumin challenge. Levels of TGF-β1 were assessed by immunohistology and ELISA, levels of TGF-β1 mRNA were measured by RT-PCR, and levels of P-Smad2/3 and T-Smad2/3 were assessed by western blotting. Astragalus extract and budesonide reduced allergen-induced increases in the thickness of bronchial airway and mucous gland hypertrophy, goblet cell hyperplasia and collagen deposition. Levels of lung TGF-β1, TGF-β1 mRNA and P-Smad2/3 were significantly reduced in mice treated with astragalus extract and budesonide. Astragalus extract improved asthma airway remodeling by inhibiting the expression of the TGF-β1/Smad signaling pathway, and may be a potential drug for the treatment of patients with a severe asthma airway. PMID:22200784

  6. Persistent eosinophilia and Strongyloides infection in Montagnard refugees after presumptive albendazole therapy.

    PubMed

    Goswami, Neela D; Shah, J Jina; Corey, G Ralph; Stout, Jason E

    2009-08-01

    Chronic helminth infections are common in refugee populations and may persist years after immigration. Asymptomatic Strongyloides stercoralis infection raises particular concern because of its potential for complications in immunosuppressed patients. We examined 172 Montagnard refugees resettled to Wake County, North Carolina from 2002 through 2003. Refugees were pretreated with albendazole for five days and screened for health conditions after arrival. Eosinophilia was present in 41 of 171 refugees at the first blood draw. Only 1 of 172 had a stool helminth (Fasciola) identified by microscopy. On repeat testing, 13 people had persistent eosinophilia. Results of serologic analysis for Strongyloides were available in 24 persons. Eosinophil counts decreased significantly after treatment with ivermectin in nine refugees (P = 0.039). Persistent eosinophilia, likely caused by Strongyloides infection, was common in this cohort of Montagnard refugees. Clinicians should understand the limitations of stool microscopy in diagnosis of strongyloidiasis, the limited effectiveness of albendazole in treating strongyloidiasis, and the importance of following-up refugees with persistent eosinophilia.

  7. Elevated serum IgE, eosinophilia, and lung function in rubber workers

    SciTech Connect

    Bascom, R.; Baser, M.E.; Thomas, R.J.; Fisher, J.F.; Yang, W.N.; Baker, J.H. )

    1990-01-01

    We previously reported an outbreak of acute respiratory illness associated with eosinophilia in a group of rubber workers who performed a thermoinjection process in which synthetic rubber was heated and then injected onto metal molds. This study was conducted to determine if persistent respiratory health effects were associated with this work area and to explore the possible allergic etiology of this syndrome. A survey was performed 1 mo after a major improvement in area ventilation and consisted of baseline, cross-shift, and cross-week spirometry; diffusing capacity; serum immunoglobulin E (IgE), total eosinophil count; and skin patch testing. Baseline lung function, cross-shift, and cross-week spirometry were not significantly worse in the exposed group as compared to the control group. However, either eosinophilia (greater than 450/mm3) or elevated serum IgE (greater than 470 ng/ml) were present in 44% of exposed workers vs. 11% of the control group (p = .003). Nine months later, neither eosinophilia nor elevated IgE were associated with employment in this work area. We conclude that employment in the thermoinjection process was associated with eosinophilia and elevated IgE, which suggests sensitization to one of the components of the rubber, although no effect on pulmonary function could be demonstrated.

  8. Peripheral T-cell lymphoma with eosinophilia presenting as monoarthritis: a case study.

    PubMed

    Daneshpouy, Marjan; Bataille, Dominique; Rivet, Jacqueline; Riviere, Olivier; Morel, Pierre; Amouroux, Jacques; Briere, Josette; Sigaux, Francois; Janin, Anne

    2002-09-01

    Direct involvement of the joints is unusual in patients with non-Hodgkin's lymphoma (NHL). This may pose a diagnostic problem for pathologists, especially since synovial localization can disclose NHL. In the following case of T-cell NHL with eosinophilia, we point out the essential importance of clonality analysis on frozen tissue to distinguish between synovial NHL and specific inflammatory damage.

  9. TRIMELLITIC ANHYDRIDE-INDUCED EOSINOPHILIA IN A MURINE MODEL OF OCCUPATIONAL ASTHMA

    EPA Science Inventory

    TRIMELLITIC ANHYDRIDE-INDUCED EOSINOPHILIA IN A MURINE MODEL OF OCCUPATIONAL ASTHMA. J F Regal, ME Mohrman, E Boykin and D Sailstad. Dept. of Pharmacology, University of Minnesota, Duluth, MN, USA and NHEERL, ORD, US EPA, RTP, NC, USA.
    Trimellitic anhydride (TMA) is a small m...

  10. Controversies in Pediatric Perioperative Airways

    PubMed Central

    Klučka, Jozef; Štourač, Petr; Štoudek, Roman; Ťoukálková, Michaela; Harazim, Hana; Kosinová, Martina

    2015-01-01

    Pediatric airway management is a challenge in routine anesthesia practice. Any airway-related complication due to improper procedure can have catastrophic consequences in pediatric patients. The authors reviewed the current relevant literature using the following data bases: Google Scholar, PubMed, Medline (OVID SP), and Dynamed, and the following keywords: Airway/s, Children, Pediatric, Difficult Airways, and Controversies. From a summary of the data, we identified several controversies: difficult airway prediction, difficult airway management, cuffed versus uncuffed endotracheal tubes for securing pediatric airways, rapid sequence induction (RSI), laryngeal mask versus endotracheal tube, and extubation timing. The data show that pediatric anesthesia practice in perioperative airway management is currently lacking the strong evidence-based medicine (EBM) data that is available for adult subpopulations. A number of procedural steps in airway management are derived only from adult populations. However, the objective is the same irrespective of patient age: proper securing of the airway and oxygenation of the patient. PMID:26759809

  11. Persistence of Serotonergic Enhancement of Airway Response in a Model of Childhood Asthma

    PubMed Central

    Moore, Brian D.; Hyde, Dallas M.; Miller, Lisa A.; Wong, Emily M.

    2014-01-01

    The persistence of airway hyperresponsiveness (AHR) and serotonergic enhancement of airway smooth muscle (ASM) contraction induced by ozone (O3) plus allergen has not been evaluated. If this mechanism persists after a prolonged recovery, it would indicate that early-life exposure to O3 plus allergen induces functional changes predisposing allergic individuals to asthma-related symptoms throughout life, even in the absence of environmental insult. A persistent serotonergic mechanism in asthma exacerbations may offer a novel therapeutic target, widening treatment options for patients with asthma. The objective of this study was to determine if previously documented AHR and serotonin-enhanced ASM contraction in allergic monkeys exposed to O3 plus house dust mite allergen (HDMA) persist after prolonged recovery. Infant rhesus monkeys sensitized to HDMA were exposed to filtered air (FA) (n = 6) or HDMA plus O3 (n = 6) for 5 months. Monkeys were then housed in a FA environment for 30 months. At 3 years, airway responsiveness was assessed. Airway rings were then harvested, and ASM contraction was evaluated using electrical field stimulation with and without exogenous serotonin and serotonin-subtype receptor antagonists. Animals exposed to O3 plus HDMA exhibited persistent AHR. Serotonin exacerbated the ASM contraction in the exposure group but not in the FA group. Serotonin subtype receptors 2, 3, and 4 appear to drive the response. Our study shows that AHR and serotonin-dependent exacerbation of cholinergic-mediated ASM contraction induced by early-life exposure to O3 plus allergen persist for at least 2.5 years and may contribute to a persistent asthma phenotype. PMID:24484440

  12. Prediction of drug-induced eosinophilia adverse effect by using SVM and naïve Bayesian approaches.

    PubMed

    Zhang, Hui; Yu, Peng; Xiang, Ming-Li; Li, Xi-Bo; Kong, Wei-Bao; Ma, Jun-Yi; Wang, Jun-Long; Zhang, Jin-Ping; Zhang, Ji

    2016-03-01

    Drug-induced eosinophilia is a potentially life-threatening adverse effect; clinical manifestations, eosinophilia-myalgia syndrome, mainly include severe skin eruption, fever, hematologic abnormalities, and organ system dysfunction. Using experimental methods to evaluate drug-induced eosinophilia is very complicated, time-consuming, and costly in the early stage of drug development. Thus, in this investigation, we established computational prediction models of drug-induced eosinophilia using SVM and naïve Bayesian approaches. For the SVM modeling, the overall prediction accuracy for the training set by means of fivefold cross-validation is 91.6 and for the external test set is 82.9 %. For the naïve Bayesian modeling, the overall prediction accuracy for the training set is 92.5 and for the external test set is 85.4 %. Moreover, some molecular descriptors and substructures considered as important for drug-induced eosinophilia were identified. Thus, we hope the prediction models of drug-induced eosinophilia built in this work should be applied to filter early-stage molecules for potential eosinophilia adverse effect, and the selected molecular descriptors and substructures of toxic compounds should be taken into consideration in the design of new candidate drugs to help medicinal chemists rationally select the chemicals with the best prospects to be effective and safe.

  13. Retrospective Study of Incidence and Prognostic Significance of Eosinophilia after Allogeneic Hematopoietic Stem Cell Transplantation: Influence of Corticosteroid Therapy

    PubMed Central

    Yamamoto, Wataru; Ogusa, Eriko; Matsumoto, Kenji; Maruta, Atsuo; Ishigatsubo, Yoshiaki; Kanamori, Heiwa

    2016-01-01

    Objective: The clinical significance of eosinophilia after allogeneic hematopoietic stem cell transplantation is controversial. This study aimed to retrospectively study the impact of eosinophilia on the outcome of allogeneic hematopoietic stem cell transplantation by taking into account the influence of corticosteroid therapy. Materials and Methods: We retrospectively studied 204 patients with acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome who underwent allogeneic hematopoietic stem cell transplantation from January 2001 to December 2010. Results: The median age was 43 years (minimum-maximum: 17-65 years). Myeloablative conditioning was used in 153 patients and reduced intensity conditioning was employed in 51 patients. Donor cells were from bone marrow in 132 patients, peripheral blood in 34, and cord blood in 38. Eosinophilia was detected in 71 patients and there was no significant predictor of eosinophilia by multivariate analysis. There was no relationship between occurrence of eosinophilia and the incidence or grade of acute graft-versus-host disease when the patients were stratified according to corticosteroid treatment. Although eosinophilia was a prognostic factor for 5-year overall survival by univariate analysis, it was not a significant indicator by multivariate analysis. Conclusion: These results suggest that the clinical significance of eosinophilia in patients receiving allogeneic hematopoietic stem cell transplantation should be assessed with consideration of systemic corticosteroid administration. PMID:27094383

  14. Eosinophilia of dystrophin-deficient muscle is promoted by perforin-mediated cytotoxicity by T cell effectors

    NASA Technical Reports Server (NTRS)

    Cai, B.; Spencer, M. J.; Nakamura, G.; Tseng-Ong, L.; Tidball, J. G.

    2000-01-01

    Previous investigations have shown that cytotoxic T lymphocytes (CTLs) contribute to muscle pathology in the dystrophin-null mutant mouse (mdx) model of Duchenne muscular dystrophy through perforin-dependent and perforin-independent mechanisms. We have assessed whether the CTL-mediated pathology includes the promotion of eosinophilia in dystrophic muscle, and thereby provides a secondary mechanism through which CTLs contribute to muscular dystrophy. Quantitative immunohistochemistry confirmed that eosinophilia is a component of the mdx dystrophy. In addition, electron microscopic observations show that eosinophils traverse the basement membrane of mdx muscle fibers and display sites of close apposition of eosinophil and muscle membranes. The close membrane apposition is characterized by impingement of eosinophilic rods of major basic protein into the muscle cell membrane. Transfer of mdx splenocytes and mdx muscle extracts to irradiated C57 mice by intraperitoneal injection resulted in muscle eosinophilia in the recipient mice. Double-mutant mice lacking dystrophin and perforin showed less eosinophilia than was displayed by mdx mice that expressed perforin. Finally, administration of prednisolone, which has been shown previously to reduce the concentration of CTLs in dystrophic muscle, produced a significant reduction in eosinophilia. These findings indicate that eosinophilia is a component of the mdx pathology that is promoted by perforin-dependent cytotoxicity of effector T cells. However, some eosinophilia of mdx muscle is independent of perforin-mediated processes.

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

    PubMed

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

    2013-01-01

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

  16. Arginase inhibition in airways from normal and nitric oxide synthase 2-knockout mice exposed to ovalbumin

    SciTech Connect

    Bratt, Jennifer M.; Franzi, Lisa M.; Linderholm, Angela L.; O'Roark, Erin M.; Kenyon, Nicholas J.; Last, Jerold A.

    2010-01-01

    Arginase1 and nitric oxide synthase2 (NOS2) utilize L-arginine as a substrate, with both enzymes expressed at high levels in the asthmatic lung. Inhibition of arginase in ovalbumin-exposed C57BL/6 mice with the transition state inhibitor N{sup o}mega-hydroxy-nor-L-arginine (nor-NOHA) significantly increased total L-arginine content in the airway compartment. We hypothesized that such an increase in L-arginine content would increase the amount of nitric oxide (NO) being produced in the airways and thereby decrease airway hyperreactivity and eosinophilic influx. We further hypothesized that despite arginase inhibition, NOS2 knockout (NOS2-/-) mice would be unable to up-regulate NO production in response to allergen exposure and would demonstrate higher amounts of airway hyperreactivity and eosinophilia under conditions of arginase inhibition than C57BL/6 animals. We found that administration of nor-NOHA significantly decreased airway hyperreactivity and eosinophilic airway inflammation in ovalbumin-exposed C57BL/6 mice, but these parameters were unchanged in ovalbumin-exposed NOS2-/- mice. Arginase1 protein content was increased in mice exposed to ovalbumin, an effect that was reversed upon nor-NOHA treatment in C57BL/6 mice. Arginase1 protein content in the airway compartment directly correlated with the degree of airway hyperreactivity in all treatment groups. NOS2-/- mice had significantly greater arginase1 and arginase2 concentrations compared to their respective C57BL/6 groups, indicating that inhibition of arginase may be dependent upon NOS2 expression. Arginase1 and 2 content were not affected by nor-NOHA administration in the NOS2-/- mice. We conclude that L-arginine metabolism plays an important role in the development of airway hyperreactivity and eosinophilic airway inflammation. Inhibition of arginase early in the allergic inflammatory response decreases the severity of the chronic inflammatory phenotype. These effects appear to be attributable to NOS2

  17. Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor

    PubMed Central

    Wang, Xiaoqin; Xu, Weidong; Mohapatra, Subhra; Kong, Xiaoyuan; Li, Xu; Lockey, Richard F; Mohapatra, Shyam S

    2008-01-01

    Background Asthma is a complex disease, characterized by reversible airway obstruction, hyperresponsiveness and chronic inflammation. Principle pharmacologic treatments for asthma include bronchodilating beta2-agonists and anti-inflammatory glucocorticosteroids; but these agents do not target the main cause of the disease, the generation of pathogenic Th2 cells. We previously reported reduction in allergic inflammation in mice deficient in the ANP receptor NPRA. Here we determined whether siRNA for natriuretic peptide receptor A (siNPRA) protected against asthma when administered transdermally. Methods Imiquimod cream mixed with chitosan nanoparticles containing either siRNA green indicator (siGLO) or siNPRA was applied to the skin of mice. Delivery of siGLO was confirmed by fluorescence microscopy. The anti-inflammatory activity of transdermal siNPRA was tested in OVA-sensitized mice by measuring airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines. Results SiGLO appearing in the lung proved the feasibility of transdermal delivery. In a mouse asthma model, BALB/c mice treated with imiquimod cream containing siNPRA chitosan nanoparticles showed significantly reduced airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines IL-4 and IL-5 in lung homogenates compared to controls. Conclusion These results demonstrate that topical cream containing imiquimod and siNPRA nanoparticles exerts an anti-inflammatory effect and may provide a new and simple therapy for asthma. PMID:18279512

  18. Chronic myelogenous leukaemia with persistent neutrophilia, eosinophilia and basophilia in a cat.

    PubMed

    Mochizuki, Hiroyuki; Seki, Takahiro; Nakahara, Yoshitaka; Tomita, Akitada; Takahashi, Masashi; Fujino, Yasuhito; Ohno, Koichi; Tsujimoto, Hajime

    2014-06-01

    Chronic myelogenous leukaemia was diagnosed in a 7-year-old male neutered domestic shorthair cat. Leukocytosis (74,900/µl)--mature neutrophilia, eosinophilia and basophilia--was observed. Bone marrow aspiration revealed hypercellularity with proliferation of cells of myeloid lineage. An underlying condition leading to leukocytosis was not identified. The severe leukocytosis did not respond to antibiotic therapy. Based on these findings, chronic myelogenous leukaemia was diagnosed. Because of the absence of clinical signs, the cat was monitored without treatment until 7 months after diagnosis, when it developed pruritic skin lesions. Pruritus was controlled with oral prednisolone. Forty-two months after diagnosis, the cat developed nasal lymphoma, which was treated with radiation therapy, resulting in complete remission. The cat was still in good physical condition 63 months after diagnosis, despite the persistence of marked neutrophilia, eosinophilia and basophilia.

  19. A rare presentation of hydropneumothorax in tropical pulmonary eosinophilia: cavitation and pneumonic consolidation in a child.

    PubMed

    Kumar, Saurabh; Beri, Rajbeer Singh

    2016-04-01

    Tropical pulmonary eosinophilia (TPE) is a syndrome of wheezing, fever and eosinophilia seen predominantly in the Indian subcontinent and other tropical areas. The pathogenesis is due to an exaggerated immune response to the filarial antigens which includes type I, type III and type IV reactions with eosinophils playing a pivotal role. Leucocytosis with an absolute increase in eosinophils in the peripheral blood is the hallmark of TPE. Other criteria for the diagnosis of TPE include high titres of antifilarial antibodies, raised serum total IgE > 1000 ku/L and a favourable response to the antifilarial agent, diethyl-carbamazine. Although TPE runs a benign course, if left untreated, it could result in a fair degree of respiratory morbidity.

  20. Drug Reaction with Eosinophilia and Systemic Symptom Syndrome Induced by Lamotrigine

    PubMed Central

    Han, Song Hee; Hur, Min Seok; Youn, Hae Jeong; Roh, Nam Kyung; Lee, Yang Won; Choe, Yong Beom

    2017-01-01

    Drug reaction with eosinophilia and systemic symptom (DRESS) syndrome is a type of severe adverse drug-induced reaction. Dermatologists should make a quick diagnosis and provide appropriate treatment for DRESS syndrome to reduce mortality rates, which can be as high as 10%. We present the case of a 47-year-old man with schizoaffective disorder treated with lamotrigine who developed DRESS syndrome to emphasize the importance of close observation of patients with drug eruption. He was consulted for erythematous maculopapular rashes on the trunk that developed 3 weeks after starting lamotrigine. A few days later, he developed generalized influenza-like symptoms. The skin rashes spread over his entire body, and the sense of itching was rapidly aggravated within a few days. Increased liver enzyme levels and significant eosinophilia were found on laboratory test results. His condition was diagnosed as DRESS syndrome, and he was treated with systemic and topical corticosteroids for 2 weeks.

  1. Cranial Sixth-Nerve Palsy and Eosinophilia in an Outbreak of Mycoplasma Pneumonia

    PubMed Central

    Wing, Howard J.; Lindzon, Martin

    1987-01-01

    The authors discuss a case in which three siblings presented with Mycoplasma pneumonia. All three had a typical rise in complement fixation antibody titres. However, the sibling with the highest titre also developed cranial sixth-nerve palsy; in addition, she was the only one of the three who did not have an eosinophilia. The authors review the symptomatology of Mycoplasma pneumonia and the involvement of the central nervous system. PMID:21263943

  2. Drug reaction with eosinophilia and systemic symptoms (DRESS): a clinical update and review of current thinking.

    PubMed

    Walsh, S A; Creamer, D

    2011-01-01

    Summary Drug reaction with eosinophilia and systemic symptoms (DRESS) describes a severe medication-induced adverse reaction, which has cutaneous, haematological and solid-organ features. It is one of the triad of life-threatening drug hypersensitivity dermatoses, along with acute generalized exanthematous pustulosis (AGEP) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). In this article, we discuss several controversies that surround DRESS, including problems with nomenclature and the lack of consensus in diagnostic criteria.

  3. Eosinophilia in an Acutely Limping Child: An Easy Guess of Rare Systemic Aetiology!

    PubMed Central

    Sharma, Harshita; Ahmed, Maaz; Rathi, Surbhi

    2016-01-01

    Painful limping child is often considered due to septic arthritis. Iliopsoas abscess (IPA) is rare in adults and children. The aetiology is often related to tuberculosis of spine. Hereby we report a case of staphylococcal IPA where incidental evaluations led to obvious diagnosis of a rare primary immunodeficiency syndrome called Job syndrome or hyperimmunoglobulin E and Eosinophilia Syndrome (HIES). This was the first case of IPA in a case of immunodeficiency syndrome including HIES. PMID:27504370

  4. Targeted therapy of bronchitis in obstructive airway diseases.

    PubMed

    Dasgupta, Angira; Neighbour, Helen; Nair, Parameswaran

    2013-12-01

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

  5. Multisystemic Eosinophilia Resembling Hypereosinophilic Syndrome in a Colony-Bred Owl Monkey (Aotus vociferans)

    PubMed Central

    Gozalo, Alfonso S; Rosenberg, Helene F; Elkins, William R; Montoya, Enrique J; Weller, Richard E

    2009-01-01

    In animals, multisystemic eosinophilic disease is a rare condition characterized by eosinophilic and lymphoplasmacytic infiltrates in various organs. This disorder resembles the human disease known as hypereosinophilic syndrome, a condition defined by prolonged peripheral eosinophilia in the absence of recognizable etiology and associated with end-organ damage. In this report we describe a research-naïve, colony-born, juvenile female owl monkey (Aotus vociferans) who presented clinically with severe respiratory distress and histologically with multiple end-organ infiltration with phenotypically mature eosinophils, plasma cells, and lymphocytes. No tumors or infectious agents were noted either macroscopically or microscopically. Cultures from lung samples revealed no bacteria or fungi. Histologic examination of lung, heart, thymus, liver, spleen, kidney, adrenal, pancreas, stomach, small intestine, and colon revealed no migrating nematode larvae, other parasites, or foreign material that might trigger eosinophilia, nor was there any evidence of or history consistent with an allergic etiology. Given that we ruled out most exogenous and endogenous triggers of eosinophilia, the signs, symptoms, and pathologic findings support the diagnosis of multisystemic eosinophilic disease. To our knowledge, this report is the first description of presumptive hypereosinophilic syndrome in a nonhuman primate. PMID:19476722

  6. Increased circulating IL-9-producing CD8+ T cells are associated with eosinophilia and high FeNO in allergic asthmatics

    PubMed Central

    Wang, Wei; Cheng, Zhen-Shun; Chen, Yi-Fei; Lin, Yu-Hui

    2016-01-01

    Allergic asthma is a chronic airway disorder mediated by Th2 cells. It has been shown that IL-9-producing CD8+ cytotoxic T (Tc9) cells promote the subsequent onset of allergic airway inflammation in mice mediated by abnormal Th2 immunity. Whether Tc9 cells are associated with the immunopathogenesis of asthmatic patients remains unknown. In the present study, peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Hypaque gradient centrifugation from all subjects. The frequency of Tc9 cells was measured by flow cytometry. Serum IL-9 levels were assessed by enzyme-linked immunosorbent assay (ELISA). mRNA expression levels of IL-9, STAT6, and IRF4 in PBMCs from healthy controls and asthmatic patients were detected by reverse transcription-quantitative polymerase chain reaction. The results showed that the numbers of Tc9 cells in allergic asthmatics were significantly increased, compared with healthy controls (P<0.0001). Notably, IL-9 protein and mRNA levels were increased in allergic asthmatics and STAT6 and IRF4 mRNA levels were elevated, as compared with healthy controls. In addition, circulating numbers of Tc9 cells were positively correlated with blood eosinophil counts and fractioned exhaled nitric oxide (FeNO) levels in asthmatic patients. Moreover, the number of Tc9 cells and serum IL-9 levels in asthmatic patients were significantly decreased after treatment with glucocorticoids (P<0.05). These findings suggest that increased circulating Tc9 cells are associated with eosinophilia and high FeNO of allergic asthma, and that abnormal Tc9 immunity may contribute to the pathogenesis of allergic asthmatics. PMID:28105134

  7. Sinomenine attenuates airway inflammation and remodeling in a mouse model of asthma

    PubMed Central

    BAO, HAI-RONG; LIU, XIAO-JU; LI, YUN-LIN; MEN, XIANG; ZENG, XIAO-LI

    2016-01-01

    Asthma is an inflammatory disease that involves airway inflammation and remodeling. Sinomenine (SIN) has been demonstrated to have immunosuppressive and anti-inflammatory properties. The aim of the present study was to investigate the inhibitory effects of SIN on airway inflammation and remodeling in an asthma mouse model and observe the effects of SIN on the transforming growth factor-β1 (TGF-β1)/connective tissue growth factor (CTGF) pathway and oxidative stress. Female BALB/c mice were sensitized by repetitive ovalbumin (OVA) challenge for 6 weeks in order to develop a mouse model of asthma. OVA-sensitized animals received SIN (25, 50 and 75 mg/kg) or dexamethasone (2 mg/kg). A blank control group received saline only. The area of smooth muscle and collagen, levels of mucus secretion and inflammatory cell infiltration were evaluated 24 h subsequent to the final OVA challenge. mRNA and protein levels of TGF-β1 and CTGF were determined by reverse transcription-quantitative polymerase chain reaction and immunohistology, respectively. The indicators of oxidative stress were detected by spectrophotometry. SIN significantly reduced allergen-induced increases in smooth muscle thickness, mucous gland hypertrophy, goblet cell hyperplasia, collagen deposition and eosinophilic inflammation. The levels of TGF-β1 and CTGF mRNA and protein were significantly reduced in the lungs of mice treated with SIN. Additionally, the total antioxidant capacity was increased in lungs following treatment with SIN. The malondialdehyde content and myeloperoxidase activities in the lungs from OVA-sensitized mice were significantly inhibited by SIN. In conclusion, SIN may inhibit airway inflammation and remodeling in asthma mouse models, and may have therapeutic efficacy in the treatment of asthma. PMID:26820806

  8. Airway Inflammatory Biomarker: Could It Tailor the Right Medications for the Right Asthmatic Patient?

    PubMed

    Zedan, Magdy Mohamed; Osman, Amal Mohamed; Laimon, Wafaa Nabil; Zedan, Mohamed Magdy; Abo-Elkheir, Nermin Youssef; Zaki, Ahmed

    2016-06-01

    Asthma is a heterogeneous disease, in which asthmatic patients present with different clinical phenotypes, variable endotypes, and different response to asthma medicines. Thus, we are faced with an asthma paradox; asthma is diagnosed subjectively by clinical history and treated with biologically active drugs. To solve this paradox, we need objective airway biomarkers to tailor the proper medications to the proper patient. Biomarkers should have one or more of the following characteristics:1) A biomarker that could differentiate poor symptoms perceivers from over perceivers, 2) A biomarker that could predict disease activity and hence disease outcome, 3) A biomarker that could clarify responders from non-responders asthma phenotypes, and finally 4) A biomarker that could characterize different clinical asthma phenotypes. In conclusion, we have conducted a review of literature trying to apply those four parameters to different airway inflammatory biomarkers. We found that FeNO fulfilled the four proposed clinical parameters of airway inflammatory biomarkers whereas; serum periostin was the single best systemic biomarker of airway luminal and tissue eosinophilia in severe uncontrolled TH2 asthma phenotype. Thus, this may be considered a trial towards tailoring the proper medication to the proper patient. However, application of biomarkers in clinical practice requires easier and cheaper techniques together with standardized methods for sample collection and analysis.

  9. Involvement of cysteinyl leukotrienes in airway smooth muscle cell DNA synthesis after repeated allergen exposure in sensitized Brown Norway rats

    PubMed Central

    Salmon, Michael; Walsh, David A; Huang, Tung-Jung; Barnes, Peter J; Leonard, Thomas B; Hay, Douglas W P; Chung, K Fan

    1999-01-01

    Airway smooth muscle thickening is a characteristic feature of airway wall remodelling in chronic asthma. We have investigated the role of the leukotrienes in airway smooth muscle (ASM) and epithelial cell DNA synthesis and ASM thickening following repeated allergen exposure in Brown Norway rats sensitized to ovalbumin. There was a 3 fold increase in ASM cell DNA synthesis, as measured by percentage bromodeoxyuridine (BrdU) incorporation, in repeatedly ovalbumin-exposed (4.1%, 3.6–4.6; mean, 95% c.i.) compared to chronically saline-exposed rats (1.3%, 0.6–2.1; P<0.001). Treatment with a 5-lipoxygenase enzyme inhibitor (SB 210661, 10 mg kg−1, p.o.) and a specific cysteinyl leukotriene (CysLT1) receptor antagonist, pranlukast (SB 205312, 30 mg kg−1, p.o.), both attenuated ASM cell DNA synthesis. Treatment with a specific leukotriene B4 (BLT) receptor antagonist (SB 201146, 15 mg kg−1, p.o.) had no effect. There was also a significant, 2 fold increase in the number of epithelial cells incorporating BrdU per unit length of basement membrane after repeated allergen exposure. This response was not inhibited by treatment with SB 210661, pranlukast or SB 201146. A significant increase in ASM thickness was identified following repeated allergen exposure and this response was attenuated significantly by SB 210661, pranlukast and SB 201146. Rats exposed to chronic allergen exhibited bronchial hyperresponsiveness to acetylcholine and had significant eosinophil recruitment into the lungs. Treatment with SB 210661, pranlukast or SB 201146 significantly attenuated eosinophil recruitment into the lungs, whilst having no significant effect on airway hyperresponsiveness. These data indicate that the cysteinyl leukotrienes are important mediators in allergen-induced ASM cell DNA synthesis in rats, while both LTB4 and cysteinyl leukotrienes contribute to ASM thickening and eosinophil recruitment following repeated allergen exposure. PMID:10455261

  10. The effects of dietary supplementation with fish oil lipids on the airways response to inhaled allergen in bronchial asthma.

    PubMed

    Arm, J P; Horton, C E; Spur, B W; Mencia-Huerta, J M; Lee, T H

    1989-06-01

    The effects of dietary supplementation with fish oil lipids on the airways responses to allergen and neutrophil biochemistry and function have been studied in 17 atopic asthmatic subjects. Nine subjects received 18 capsules of Max-EPA (3.2 g eicosapentaenoic acid and 2.2 g docosahexaenoic acid) a day and eight subjects received identical capsules containing olive oil, for 10 wk in a double-blind fashion. There were no differences between prediet values and those observed after dietary supplementation with Max-EPA or placebo in the dose of allergen causing an acute asthmatic response as assessed by a 35% fall in specific airways conductance (PD35), the extinction dose of allergen on skin prick testing, the histamine PD35, or the total serum IgE concentrations. Twelve of the 17 subjects developed late asthmatic responses after allergen challenge prediet. Six of these subjects received Max-EPA, and six received placebo capsules. As compared to prediet values, the magnitude of the allergen-induced late asthmatic response was significantly attenuated from 2 to 7 h after allergen challenge following dietary supplementation with Max-EPA (p less than 0.005) but not with placebo. The attenuation of the late response was not accompanied by any significant change in the clinical severity of disease as assessed by diurnal peak expiratory flow rates, symptom scores, or bronchodilator drug usage.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Upper airway radiographs in infants with upper airway insufficiency.

    PubMed Central

    Tonkin, S L; Davis, S L; Gunn, T R

    1994-01-01

    Upper airway measurements in nine infants considered to be at risk of upper airway insufficiency, six of whom presented after an apnoeic episode, were compared with measurements taken in two age groups of healthy infants. Paired, inspiratory and expiratory, lateral upper airway radiographs were obtained while the infants were awake and breathing quietly. The radiographs of all nine infants demonstrated narrowing in the oropharyngeal portion of the airway during inspiration and in six infants there was ballooning of the upper airway during expiration. Seven of the nine infants subsequently experienced recurrent apnoeic episodes which required vigorous stimulation to restore breathing. Experience suggests that respiratory phase timed radiographs are a useful adjunct to the evaluation of infants who are suspected of having upper airway dysfunction. They provide information regarding both the dimensions and compliance of the upper airway as well as the site of any restriction. Images PMID:8048825

  12. The diagnosis of esophageal eosinophilia is not increased in the summer months.

    PubMed

    Elias, Martha K; Kopacova, Jana; Arora, Amindra S; Dierkhising, Ross A; Enders, Felicity T; Katzka, David A; Kryzer, Lori A; Halland, Magnus; Smyrk, Thomas C; Talley, Nicholas J; Alexander, Jeffrey A

    2015-02-01

    Smaller studies have suggested seasonal variation of the diagnosis of eosinophilic esophagitis with more patients being diagnosed in the aeroallergen season. We evaluated a large group of adult patients for a seasonal variation of the diagnosis of symptomatic eosinophilic esophageal infiltration. We performed a retrospective review of adult patients from a large Eosinophilic esophagitis database at the Mayo Clinic Rochester. We only included patients from three states in the upper Midwest, who had 15 or more eosinophils per high-power field on esophageal biopsy, symptomatic dysphagia, and were seen, in our Gastroenterology Clinic between 2000 and 2008. Clinical data were abstracted and the month of diagnosis was determined. The Rayleigh circular test and the Chi-square goodness-of-fit test were used to detect seasonality of symptomatic esophageal eosinophilia diagnosis and seasonality corrected for esophagogastroduodenoscopy monthly volume. The diagnosis of symptomatic eosinophilic esophageal infiltration was made in 372 patients. The mean number of eosinophils was 39.6 per high-power field. The December/January and May/June periods seem to have an increased presentation rate (p = 0.014). Of those tested, reactions to any aeroallergen was present in 69 % (48/70), reactions to >4 aeroallergens in 47 % (33/70) and reactions to any food allergen in 63 % (50/80) of patients. There was no evidence of monthly concentration of symptomatic esophageal eosinophilia diagnosis in the subgroups of patients with any positive aeroallergen, >4 positive aeroallergens, or history of atopy. The diagnosis of symptomatic esophageal eosinophilia is not made more frequently in the summer months.

  13. Supraglottic airway devices in children

    PubMed Central

    Ramesh, S; Jayanthi, R

    2011-01-01

    Modern anaesthesia practice in children was made possible by the invention of the endotracheal tube (ET), which made lengthy and complex surgical procedures feasible without the disastrous complications of airway obstruction, aspiration of gastric contents or asphyxia. For decades, endotracheal intubation or bag-and-mask ventilation were the mainstays of airway management. In 1983, this changed with the invention of the laryngeal mask airway (LMA), the first supraglottic airway device that blended features of the facemask with those of the ET, providing ease of placement and hands-free maintenance along with a relatively secure airway. The invention and development of the LMA by Dr. Archie Brain has had a significant impact on the practice of anaesthesia, management of the difficult airway and cardiopulmonary resuscitation in children and neonates. This review article will be a brief about the clinical applications of supraglottic airways in children. PMID:22174464

  14. Angiolymphoid hyperplasia with eosinophilia presenting multinucleated cells in histology: an ultrastructural study.

    PubMed

    Sakamoto, F; Hashimoto, T; Takenouchi, T; Ito, M; Nitto, H

    1998-07-01

    A case of angiolymphoid hyperplasia with eosinophilia arising on the face of a woman is reported. Histologically, the uniqueness of this case is the presence of multinucleated cells (MNCs), besides the conventional dermal changes. Electron microscopy showed that some of the apparent MNCs are clusters of endothelial cells forming immature vascular lumens with numerous microvilli, and the other MNCs displayed the recognized features of fibrohistiocytic or myofibroblastic cells. Immunohistochemically, some MNCs were positive for Ulex europaeus agglutinin and Factor VIII-related antigen. From these findings, some of the MNCs are histologically endothelial sprouts, and the others are fibrohistiocytic cells in the present case.

  15. Evaluation of effects of Bauhinia variegata stem bark extracts against milk-induced eosinophilia in mice.

    PubMed

    Mali, Ravindra G; Dhake, Avinash S

    2011-04-01

    Bauhinia variegata Linn (family: Caesalpiniaceae), popularly known as Rakta Kanchnar, is a medium-sized tree found throughout India. The stem bark of B. variegata (BV) is used traditionally in the treatment of asthma, jaundice, tuberculosis, leprosy, and skin diseases. In the present study, we have investigated the role of aqueous (BVA) and ethanol (BVE) extracts of the plant against milk-induced leukocytosis and eosinophilia in albino mice. The results of the study revealed that pretreatment with both the extracts caused significant reduction in the total leukocyte and eosinophil counts in animals in dose-dependent manner. From these results, it can be concluded that the plant BV is having antieosinophilic activity.

  16. Oxcarbazepine-induced drug rash with eosinophilia and systemic symptoms syndrome presenting as exfoliative dermatitis.

    PubMed

    Saha, Mahimanjan; Gorai, Surajit; Madhab, Vaswatee

    2016-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a type of severe adverse cutaneous drug reaction characterized by fever, skin eruption, hematological abnormalities, and internal organ involvement. Although anticonvulsant drugs are mainly implicated in DRESS, newer anticonvulsants such as oxcarbazepine-induced definite cases of DRESS syndrome are rare and oxcarbazepine-induced DRESS syndrome presenting as exfoliative dermatitis is even rarer. We report a case of a 35-year-old male who developed DRESS syndrome presenting as exfoliative dermatitis after taking oxcarbazepine for 3 weeks.

  17. Localization of human T-cell lymphotropic virus-1 gag proviral sequences in dermato-immunological disorders with eosinophilia.

    PubMed

    Nagy, K; Marschalkó, Márta; Kemény, B; Horváth, A

    2005-01-01

    The mechanisms leading to the development of eosinophilia were investigated in 65 patients with immunodermatological disorders, including the role of eosinophilotactic cytokines and the possible involvement of human T-cell leukemia virus, HTLV. HTLV-1 gag proviral sequences were revealed in two cases of lymphoproliferative disorders such as angiolymphoid hyperplasia with eosinophilia (ALHE) and CD4+ cutaneous lymphoma, respectively. Increased level of GM-CSF was detected in 33% of disorders studied. Elevated level of IL-5 and eotaxin was detected in 27% and 30%, respectively, of patients with bullous diseases. Elevated level of GM-CSF and eotaxin was found in 33% and 46%, respectively, of patients with inflammatory diseases. Neither of the four cytokines, however proved to be responsible alone or together for the induction of eosinophilia. The possible indirect role of human retroviruses through induction of eosinophilic chemotactic cytokines is hypothesized.

  18. High rate of strongyloidosis infection, out of endemic area, in patients with eosinophilia and without risk of exogenous reinfections.

    PubMed

    Repetto, Silvia A; Durán, Pablo A; Lasala, María B; González-Cappa, Stella M

    2010-06-01

    Strongyloides stercoralis chronic infections are usually asymptomatic and underestimated. We used direct fresh stool examination, Ritchie's method, and agar plate culture for diagnosis in patients with eosinophilia and previous residence in endemic areas. The frequency of strongyloidosis detected among these patients was high: 21 of 42 were positive. Among them, 10 were positive only by agar plate culture. After ivermectin treatment, patients resulted negative for parasitological tests and reduced their eosinophil counts. Half of the submitted patients that were followed 4-12 months after treatment remained negative without eosinophilia, except one who showed an eosinophil ascending curve before reappearance of larvae in stools. The high frequency of strongyloidosis found in this group emphasizes the relevance of including this parasitosis among differential diagnosis in patients with eosinophilia and past risk of S. stercoralis infection to prevent disseminated infections secondary to corticoid therapy.

  19. Drug reaction with eosinophilia and systemic symptoms (DRESS) and its relation with autoimmunity in a reference center in Mexico*

    PubMed Central

    Matta, Juan Manuel Ruiz; Flores, Silvia Méndez; Cherit, Judith Domínguez

    2017-01-01

    BACKGROUND Drug reaction with eosinophilia and systemic symptoms is a severe adverse drug reaction, with a reported mortality of 10%. Long-term outcomes involve organic failure and autoimmune diseases in some populations. OBJECTIVE To evaluate the clinical prognosis of patients with drug reaction with eosinophilia and systemic symptoms. METHODS We conducted a retrospective review at a referral hospital in Mexico City in a period of 22 years (1992-2013), looking up for records with diagnosis of DRESS according to RegiSCAR criteria. Clinical characteristics, organ failures, culprit drugs, treatment, and short and long-term sequelae were analyzed. RESULTS We found 11 patients with diagnosis of drug reaction with eosinophilia and systemic symptoms syndrome, 7 female and 4 male, with a median age of 22 years-old; 9 had maculopapular rash and 2 were erythrodermic. Affected organs were liver (8/11), kidney (6/11) and hematologic disorders (8/11). The most common culprit drugs were antiepileptic (63%). Systemic corticosteroids were given to 8 patients, being pyelonephritis (1/8) and pneumonia (2/8) the adverse events of this therapy. Long-term sequelae were 1 patient with renal failure, 1 patient with chronic anemia; and 2 patients developed autoimmune diseases (one autoimmune thyroid disease and another one with autoimmune thyroid disease and autoimmune hemolytic anemia). Study limitations: The retrospective nature of the study and the limited number of patients with drug reaction with eosinophilia and systemic symptoms. CONCLUSIONS Drug reaction with eosinophilia and systemic symptoms syndrome has been linked to the development of chronic organ failure. We found two young patients who developed autoimmune diseases in the short term. Patients with drug reaction with eosinophilia and systemic symptoms should have a long-term monitoring for signs or symptoms suggestive of an autoimmune disease. PMID:28225953

  20. [Acute lymphatic leukaemia with eosinophilia in a younger man returning from a travel in the tropics--case report].

    PubMed

    Larsen, Mette Vang; Karstoft, Kristian; Andersen, Mette Klarskov

    2011-05-09

    A 22-year-old man presented with severe back pain and 60% eosinophilia after returning from the tropics. An extensive investigation for parasitic diseases was negative. Over time, his haemoglobin level and thrombocyte count fell, and the spleen and several lymph nodes were enlarged. The patient was diagnosed with acute lymphatic leukaemia with eosinophilia by bone marrow microscopy and flow cytometry. Chromosome analysis detected clonal abnormalities including t(5;14)(q31;q32). He initially responded to chemotherapy, but due to residual disease, he now awaits allogeneic bone marrow transplantation.

  1. Peripheral eosinophilia and respiratory symptoms in rubber injection press operators: a case-control study.

    PubMed

    Thomas, R J; Bascom, R; Yang, W N; Fisher, J F; Baser, M E; Greenhut, J; Baker, J H

    1986-01-01

    To evaluate a suspected association between an outbreak of acute respiratory illness and eosinophilia and employment as a rubber worker, we performed a retrospective review of medical records of rubber workers employed from September 1983 to July 1984 in a plant housing a thermoinjection process. Twenty-five workers met the case definition of a respiratory illness requiring a physician visit. The predominant respiratory illness was acute in onset with cough, chest tightness, and dyspnea. Peripheral eosinophilia, up to 40% of white blood cells in a peripheral smear, was seen in 10 of 18 (56%) cases. Twenty-one of 25 white males with respiratory symptoms were employed in the thermoinjection process (odds ratio = 22, p less than .001). Smoking and employment in this process contributed independently to an increased risk of being a case as determined by a logistic regression analysis. Return to the plant building caused recurrence of symptoms in most cases, and these workers have been transferred or left the company. We conclude that a strong previously unrecognized association exists between employment in this neoprene rubber thermoinjection process and the development of an acute respiratory illness.

  2. Cutaneous Gnathostomiasis with Recurrent Migratory Nodule and Persistent Eosinophilia: a Case Report from China

    PubMed Central

    Cui, Jing; Wang, Ye

    2013-01-01

    The present study reports a human case of cutaneous gnathostomiasis with recurrent migratory nodule and persistent eosinophilia in China. A 52-year-old woman from Henan Province, central China, presented with recurrent migratory reddish swelling and subcutaneous nodule in the left upper arm and on the back for 3 months. Blood examination showed eosinophila (21.2%), and anti-sparganum antibodies were positive. Skin biopsy of the lesion and histopathological examinations revealed dermal infiltrates of eosinophils but did not show any parasites. Thus, the patient was first diagnosed as sparganosis; however, new migratory swellings occurred after treatment with praziquantel for 3 days. On further inquiring, she recalled having eaten undercooked eels and specific antibodies to the larvae of Gnathostoma spinigerum were detected. The patient was definitely diagnosed as cutaneous gnathostomiasis caused by Gnathostoma sp. and treated with albendazole (1,000 mg/day) for 15 days, and the subsequent papule and blister developed after the treatment. After 1 month, laboratory findings indicated a reduced eosinophil count (3.3%). At her final follow-up 18 months later, the patient had no further symptoms and anti-Gnathostoma antibodies became negative. Conclusively, the present study is the first report on a human case of cutaneous gnathostomiasis in Henan Province, China, based on the past history (eating undercooked eels), clinical manifestations (migratory subcutaneous nodule and persistent eosinophilia), and a serological finding (positive for specific anti-Gnathostoma antibodies). PMID:24039291

  3. Drug-reaction eosinophilia and systemic symptoms and drug-induced hypersensitivity syndrome.

    PubMed

    Fernando, Suran L

    2014-02-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a rare, severe cutaneous adverse reaction characterised by fever, rash, lymphadenopathy, eosinophilia and/or other leukocyte abnormalities, and internal organ involvement and often has a relapsing-remitting course despite withdrawal of the drug. The drugs that are most implicated include aromatic anticonvulsants, allopurinol, sulphonamides, antiretrovirals (abacavir and nevirapine), and minocycline. The pathogenesis of DRESS/DIHS is far from clear but probably involves a combination of impaired pharmacokinetics and the accumulation of drug metabolites, the sequential reactivation of the herpesvirus family and genetic susceptibility conferred by the association with certain human leukocyte antigen (HLA) class I alleles. The strong association between abacavir and HLA-B*5701 has enabled pharmacogenetics screening to be employed successfully to minimise the occurrence of hypersensitivity. A prolonged course of oral corticosteroids is required to treat DRESS/DIHS, given the relapsing-remitting nature of the condition with i.v. immunoglobulin and valgangciclovir reserved for refractory or life-threatening cases.

  4. 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

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

    PubMed

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

    2003-06-01

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

  6. Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa

    SciTech Connect

    Chou, Debbie L.; Gerriets, Joan E.; Schelegle, Edward S.; Hyde, Dallas M.; Miller, Lisa A.

    2011-12-15

    Epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. We have previously reported that ozone exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. To test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys following cyclical ozone and house dust mite (HDM) aerosol exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are associated with eosinophil location in response to exposures. In lavage, eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone + HDM animals showed significantly increased CCL24 and CCL26 protein in lavage, but the concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM alone; comparatively, ozone and ozone + HDM resulted in reduced eosinophils. CCL26 mRNA and immunofluorescence staining increased in airway mucosa of HDM alone animals and correlated with eosinophil volume. In ozone + HDM animal groups, CCL24 mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate with airway mucosa eosinophils. Cumulatively, our data indicate that ozone exposure results in a profile of airway eosinophil migration that is distinct from HDM mediated pathways. CCL24 was found to be induced only by combined ozone and HDM exposure, however expression was not associated with the presence of eosinophils within the airway mucosa. -- Highlights: Black-Right-Pointing-Pointer Ozone can modulate the localization of eosinophils in infant allergic airways. Black-Right-Pointing-Pointer Expression of eotaxins within the lung is affected by ozone and allergen exposure. Black-Right-Pointing-Pointer CCL24 induction by

  7. Prenatal secondhand cigarette smoke promotes Th2 polarization and impairs goblet cell differentiation and airway mucus formation.

    PubMed

    Singh, Shashi P; Gundavarapu, Sravanthi; Peña-Philippides, Juan C; Rir-Sima-ah, Jules; Mishra, Neerad C; Wilder, Julie A; Langley, Raymond J; Smith, Kevin R; Sopori, Mohan L

    2011-11-01

    Parental, particularly maternal, smoking increases the risk for childhood allergic asthma and infection. Similarly, in a murine allergic asthma model, prenatal plus early postnatal exposure to secondhand cigarette smoke (SS) exacerbates airways hyperreactivity and Th2 responses in the lung. However, the mechanism and contribution of prenatal versus early postnatal SS exposure on allergic asthma remain unresolved. To identify the effects of prenatal and/or early postnatal SS on allergic asthma, BALB/c dams and their offspring were exposed gestationally and/or 8-10 wk postbirth to filtered air or SS. Prenatal, but not postnatal, SS strongly increased methacholine and allergen (Aspergillus)-induced airway resistance, Th2 cytokine levels, and atopy and activated the Th2-polarizing pathway GATA3/Lck/ERK1/2/STAT6. Either prenatal and/or early postnatal SS downregulated the Th1-specific transcription factor T-bet and, surprisingly, despite high levels of IL-4/IL-13, dramatically blocked the allergen-induced mucous cell metaplasia, airway mucus formation, and the expression of mucus-related genes/proteins: Muc5ac, γ-aminobutyric acid A receptors, and SAM pointed domain-containing Ets-like factor. Given that SS/nicotine exposure of normal adult mice promotes mucus formation, the results suggested that fetal and neonatal lung are highly sensitive to cigarette smoke. Thus, although the gestational SS promotes Th2 polarization/allergic asthma, it may also impair and/or delay the development of fetal and neonatal lung, affecting mucociliary clearance and Th1 responses. Together, this may explain the increased susceptibility of children from smoking parents to allergic asthma and childhood respiratory infections.

  8. Protective effect of Bifidobacterium infantis CGMCC313-2 on ovalbumin-induced airway asthma and β-lactoglobulin-induced intestinal food allergy mouse models

    PubMed Central

    Liu, Meng-Yun; Yang, Zhen-Yu; Dai, Wen-Kui; Huang, Jian-Qiong; Li, Yin-Hu; Zhang, Juan; Qiu, Chuang-Zhao; Wei, Chun; Zhou, Qian; Sun, Xin; Feng, Xin; Li, Dong-Fang; Wang, He-Ping; Zheng, Yue-Jie

    2017-01-01

    AIM To determine whether oral administration of Bifidobacterium infantis CGMCC313-2 (B. infantis CGMCC313-2) inhibits allergen-induced airway inflammation and food allergies in a mouse model. METHODS Ovalbumin (OVA)-induced allergic asthma and β-lactoglobulin-induced food allergy mouse models were used in this study. Following oral administration of B. infantis CGMCC313-2 during or after allergen sensitization, histopathologic changes in the lung and intestine were evaluated by hematoxylin and eosin (HE) staining. In the allergic asthma mouse model, we evaluated the proportion of lung-infiltrating inflammatory cells. OVA-specific IgE and IgG1 levels in serum and cytokine levels in bronchoalveolar lavage fluid (BALF) were also assessed. In the food allergy mouse model, the levels of total IgE and cytokines in serum were measured. RESULTS Oral administration of B. infantis CGMCC313-2 during or after allergen sensitization suppressed allergic inflammation in lung and intestinal tissues, while the proportion of infiltrating inflammatory cells was significantly decreased in the BALF of allergic asthma mice. Moreover, B. infantis CGMCC313-2 decreased the serum levels of total IgE in food allergy mice, and reductions in IgE and IgG1 were also observed in OVA-induced allergic asthma mice. The expression of interleukin-4 (IL-4) and IL-13 in both serum and BALF was suppressed following the administration of B. infantis CGMCC313-2, while an effect on serum IL-10 levels was not observed. CONCLUSION B. infantis CGMCC313-2 inhibits the secretion of allergen-induced IgE, IL-4 and IL-13, and attenuates allergic inflammation.

  9. Impact of chemotherapy on eosinophilia-associated advanced rectal cancer: A case report and review of the literature

    PubMed Central

    Inoue, Maki; Kadono, Jun; Sugita, Hiroshi; Nakazono, Toshihiro; Motoi, Shunsuke; Kitazono, Iwao; Goto, Yuko; Fukukura, Yoshihiko; Yoshimitsu, Makoto; Misaka, Takaharu; Imoto, Yutaka

    2016-01-01

    The present study reports a case of eosinophilia-associated rectal cancer that was successfully stabilized using chemotherapy, and reviews the mechanisms of eosinophilia and the importance of chemotherapy. A 65-year-old man, who had previously been diagnosed with suspected rectal cancer, presented with the chief complaint of melena. Eosinophilia, abnormal blood coagulation, and elevated carcinoembryonic antigen and carbohydrate antigen 19–9 tumor marker levels were observed, and the patient was subsequently diagnosed with advanced rectal cancer accompanied by multiple lymph node metastases that extended from the para-aortic lymph nodes to the left axillary lymph nodes. The complication of deep vein thrombosis was also observed. Tumor hemorrhage was exacerbated, and thus, Hartmann's procedure was performed. Pathological findings included poorly- to moderately-differentiated adenocarcinoma; however, no eosinophil infiltration was observed within the tumor. Following surgery, the eosinophilia and lymph node metastasis were exacerbated, and an oxaliplatin plus capecitabine chemotherapy regimen was initiated. The patient's eosinophil count and tumor marker levels normalized, and the lymph nodes decreased in size; however, re-enlargement of the lymph nodes was observed 6 months after surgery. The patient was then administered a chemotherapeutic regimen of irinotecan/fluorouracil/folinic acid + bevacizumab, and stable disease was maintained until pleural and peritoneal dissemination were observed at 22 months post-surgery. Following a rapid deterioration in condition, the patient succumbed to the disease at 23 months post-surgery. The present case indicates that although eosinophilia-associated colon cancer exhibits a poor prognosis, early chemotherapeutic intervention may improve this. PMID:28105235

  10. Eosinophilia-myalgia syndrome case-associated contaminants in commercially available 5-hydroxytryptophan.

    PubMed

    Klarskov, K; Johnson, K L; Benson, L M; Gleich, G J; Naylor, S

    1999-01-01

    Recently, 5-hydroxy-L-tryptophan (5-OHTrp) has been promoted as an alternative to banned L-tryptophan as a dietary supplement. It has been claimed to help alleviate obesity, insomnia, depression, and headaches. However, eosinophilia-myalgia syndrome (EMS)-like symptoms have also been associated with ingestion or exposure to 5-OHTrp. HPLC-UV analysis of EMS-implicated 5-OHTrp revealed the presence of peak X, described as case-implicated. We show that peak X is actually a family of contaminants with the same molecular weight (234 Da) and similar HPLC retention times. We also demonstrate that all eight samples of commercially available 5-OHTrp analyzed by HPLC-MS contained three or more contaminants of the peak X family. The significance of these findings is discussed.

  11. Management of proton pump inhibitor responsive-esophageal eosinophilia and eosinophilic esophagitis: controversies in treatment approaches.

    PubMed

    Kochar, Bharati; Dellon, Evan S

    2015-01-01

    Eosinophilic esophagitis (EoE) is a chronic immune-mediated clinicopathologic disease. The prevalence of EoE is approximately 1/2000 persons, EoE is now the most common cause of food impactions, with healthcare expenditures approaching US$ 1 billion annually. This article will discuss challenges related to proton pump inhibitor responsive esophageal eosinophilia, including distinguishing this condition from EoE and understanding the mechanisms behind the PPI response. For EoE, we will review multiple ongoing debates about treatment and monitoring strategies, including selecting treatment outcomes, optimizing medication formulations, approaching the steroid-refractory patient, conducting dietary elimination, prescribing long-term maintenance therapy and performing esophageal dilation.

  12. Distribution and variability of esophageal eosinophilia in patients undergoing upper endoscopy.

    PubMed

    Dellon, Evan S; Speck, Olga; Woodward, Kimberly; Covey, Shannon; Rusin, Spencer; Shaheen, Nicholas J; Woosley, John T

    2015-03-01

    The variability of eosinophilic infiltrates in eosinophilic esophagitis is not well described. This study aimed to determine the distribution of esophageal eosinophilia and the utility of histologic cut-points for eosinophilic esophagitis diagnosis in subjects undergoing endoscopy. We performed a prospective study of adults undergoing outpatient endoscopy. Research protocol esophageal biopsies were obtained from all subjects. Incident cases of eosinophilic esophagitis were diagnosed per consensus guidelines. Biopsies were interpreted following a validated protocol, and maximum eosinophil counts (eosinophils per high-power field; eos/hpf) were determined. Histologic analyses were performed on a per-patient, per-biopsy, and per-hpf basis. There were 213 patients, yielding 923 esophageal biopsies with 4588 hpfs. Overall, 48 patients (23%), 165 biopsy fragments (18%), and 449 hpfs (10%) had ≥15 eos/hpf; most subjects had no or low levels of eosinophils. In the eosinophilic esophagitis cases, 119 biopsy fragments (63%) and 332 hpfs (36%) had ≥15 eos/hpf. There was a mean 104-fold difference between the lowest and highest hpf eosinophil count for the eosinophilic esophagitis patients; 85% of the biopsies from eosinophilic esophagitis cases also had at least one hpf with <15 eos/hpf. The cut-point of 15 eos/hpf had a sensitivity of 100% and a specificity of 96% for diagnosis of eosinophilic esophagitis. In conclusion, most patients have little to no esophageal eosinophilia. In patients with eosinophilic esophagitis, there was marked variability in the eosinophil counts by biopsy and by hpf within a given biopsy. Additionally, the 15 eos/hpf cut-point was highly sensitive and specific for eosinophilic esophagitis. Multiple esophageal biopsies from different locations should be obtained to optimize eosinophilic esophagitis diagnosis.

  13. Operative endoscopy of the airway

    PubMed Central

    Walters, Dustin M.

    2016-01-01

    Airway endoscopy has long been an important and useful tool in the management of thoracic diseases. As thoracic specialists have gained experience with both flexible and rigid bronchoscopic techniques, the technology has continued to evolve so that bronchoscopy is currently the foundation for diagnosis and treatment of many thoracic ailments. Airway endoscopy plays a significant role in the biopsy of tumors within the airways, mediastinum, and lung parenchyma. Endoscopic methods have been developed to treat benign and malignant airway stenoses and tracheomalacia. And more recently, techniques have been conceived to treat end-stage emphysema and prolonged air leaks in select patients. This review describes the abundant uses of airway endoscopy, as well as technical considerations and limitations of the current technologies. PMID:26981263

  14. 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.

  15. Recurrent airway obstruction: a review.

    PubMed

    Pirie, R S

    2014-05-01

    Recurrent airway obstruction is a widely recognised airway disorder, characterised by hypersensitivity-mediated neutrophilic airway inflammation and lower airway obstruction in a subpopulation of horses when exposed to suboptimal environments high in airborne organic dust. Over the past decade, numerous studies have further advanced our understanding of different aspects of the disease. These include clarification of the important inhaled airborne agents responsible for disease induction, improving our understanding of the underlying genetic basis of disease susceptibility and unveiling the fundamental immunological mechanisms leading to establishment of the classic disease phenotype. This review, as well as giving a clinical overview of recurrent airway obstruction, summarises much of the work in these areas that have culminated in a more thorough understanding of this debilitating disease.

  16. The airway microbiome and disease.

    PubMed

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

    2013-08-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2007-02-01

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

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

    PubMed

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

    2010-11-15

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

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

    PubMed

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

    2009-11-01

    studies, rats were killed 24 hours after the last OVA challenge, bronchoalveolar lavage fluid (BALF) was collected and analyzed for cellularity and secreted mediators, and lungs and nose were processed for histopathologic examination and morphometric analysis of intraepithelial mucosubstances (IM). The results of our animal inhalation studies in the southwest (SW) Detroit community, an area with elevated ambient PM2.5 concentrations, suggested that, during allergen challenge, exposure to CAPs that were predominantly associated with emissions from combustion sources markedly enhanced the OVA-induced allergic airway disease, which was characterized by an increased infiltration in the lungs of eosinophilic and lymphocytic inflammation, increased IM in conducting airways, and increased concentrations in BALF of mucin-specific proteins and inflammatory cytokines. These findings suggest that urban airborne PM2.5 derived from stationary combustion sources (e.g., refineries, coal-burning power plants, waste-treatment plants) may enhance the development of human allergic airway diseases like childhood asthma. Previous animal inhalation studies in this community have also suggested that these fine, ambient combustion-derived particles may also exacerbate preexisting allergic airway disease. In contrast to our CAPs studies in Detroit, the controlled DEE exposures of allergen-sensitized BN rats, during either allergen sensitization or challenge periods, caused only a few mild modifications in the character of the allergen-induced disease. This finding contrasts with other reported studies that indicate that DEPs at relatively higher exposure doses do enhance allergic airway disease in some rodent models. The reasons for these disparities between studies likely reflect differences in exposure dose, animal models, the timing of exposures to the allergens and DEP exposures, the methods of allergen sensitization and challenge, or physicochemical differences among DEEs.

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

    PubMed Central

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

    2014-01-01

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

  2. Antibody to very late activation antigen 4 prevents interleukin-5-induced airway hyperresponsiveness and eosinophil infiltration in the airways of guinea pigs.

    PubMed

    Kraneveld, A D; van Ark, I; Van Der Linde, H J; Fattah, D; Nijkamp, F P; Van Oosterhout, A J

    1997-08-01

    This study examines the effect of monoclonal antibody to very late activation antigen-4 (VLA-4) on IL5-induced airway hyperresponsiveness in vivo and eosinophil accumulation into guinea pig airways. IL5 has been shown to be important in the development of airway hyperresponsiveness and eosinophil accumulation in the guinea pig. Eosinophils, unlike neutrophils, express VLA-4 which mediates the adhesion to vascular cell adhesion molecule-1 on endothelial cells. Thus VLA-4 seems to be an important adhesion molecule in the infiltration of eosinophils from the vasculature into the airway tissue. In addition, it has been shown that IL5 activates VLA-4 on eosinophils to facilitate their adhesion. In the present study, IL5 (1 microg, twice on one day) or vehicle were administered intranasally. Monoclonal antibody (mAb) to VLA-4 (HP1/2) or the isotype-matched control mAb (1E6) were injected 1 hour before each IL5 or vehicle treatment at a dose of 2.5 mg/kg body weight. The next day in vivo bronchial reactivity, eosinophil number in bronchoalveolar lavage (BAL) fluid, and eosinophil peroxidase (EPO) activity in cell-free BAL fluid were determined. IL5 induces an increase in bronchial reactivity to histamine, which is associated with an accumulation of eosinophils into BAL fluid (control: 12 (5 to 42) x 10(5) cells and IL5: 69 (11 to 99) x 10(5) cells, p < 0.05) and an increase of 35% +/- 14% in EPO activity in cell-free BAL fluid. Intravenous administration of anti-VLA-4 mAb, but not of the control antibody, completely inhibits the bronchial hyperresponsiveness as well as the airway eosinophilia found after intraairway application of IL5. HP1/2 also suppresses the IL5-induced increase in EPO activity in cell-free BAL fluid. In conclusion, for the development of IL5-induced airway hyperresponsiveness in the guinea pig, the VLA-4-dependent infiltration and activation of eosinophils in the bronchial tissue seems to be essential.

  3. Putting the Squeeze on Airway Epithelia

    PubMed Central

    Park, Jin-Ah; Fredberg, Jeffrey J.

    2015-01-01

    Asthma is characterized by chronic inflammation, airway hyperresponsiveness, and progressive airway remodeling. The airway epithelium is known to play a critical role in the initiation and perpetuation of these processes. Here, we review how excessive epithelial stress generated by bronchoconstriction is sufficient to induce airway remodeling, even in the absence of inflammatory cells. PMID:26136543

  4. Airway complications after lung transplantation.

    PubMed

    Machuzak, Michael; Santacruz, Jose F; Gildea, Thomas; Murthy, Sudish C

    2015-01-01

    Airway complications after lung transplantation present a formidable challenge to the lung transplant team, ranging from mere unusual images to fatal events. The exact incidence of complications is wide-ranging depending on the type of event, and there is still evolution of a universal characterization of the airway findings. Management is also wide-ranging. Simple observation or simple balloon bronchoplasty is sufficient in many cases, but vigilance following more severe necrosis is required for late development of both anastomotic and nonanastomotic airway strictures. Furthermore, the impact of coexisting infection, rejection, and medical disease associated with high-level immunosuppression further complicates care.

  5. Gene Delivery to the Airway

    PubMed Central

    Keiser, Nicholas W.; Engelhardt, John F.

    2013-01-01

    This unit describes generation of and gene transfer to several commonly used airway models. Isolation and transduction of primary airway epithelial cells are first described. Next, the preparation of polarized airway epithelial monolayers is outlined. Transduction of these polarized cells is also described. Methods are presented for generation of tracheal xenografts as well as both ex vivo and in vivo gene transfer to these xenografts. Finally, a method for in vivo gene delivery to the lungs of rodents is included. Methods for evaluating transgene expression are given in the support protocols. PMID:23853081

  6. 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

  7. Apoptosis and the Airway Epithelium

    PubMed Central

    White, Steven R.

    2011-01-01

    The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases. PMID:22203854

  8. Extraglottic airway devices: A review

    PubMed Central

    Ramaiah, Ramesh; Das, Debasmita; Bhananker, Sanjay M; Joffe, Aaron M

    2014-01-01

    Extraglottic airway devices (EAD) have become an integral part of anesthetic care since their introduction into clinical practice 25 years ago and have been used safely hundreds of millions of times, worldwide. They are an important first option for difficult ventilation during both in-hospital and out-of-hospital difficult airway management and can be utilized as a conduit for tracheal intubation either blindly or assisted by another technology (fiberoptic endoscopy, lightwand). Thus, the EAD may be the most versatile single airway technique in the airway management toolbox. However, despite their utility, knowledge regarding specific devices and the supporting data for their use is of paramount importance to patient's safety. In this review, number of commercially available EADs are discussed and the reported benefits and potential pitfalls are highlighted. PMID:24741502

  9. An Overlap of Angiolymphoid Hyperplasia with Eosinophilia and Kimura's Disease: Successful Treatment of Skin Lesions with Cryotherapy

    PubMed Central

    Reddy, Praveen Kumar S; Prasad, Arakali Lakshminarayana Shyam; Sumathy, Tharayil Kunneth; Shivaswamy, Kanakapura Nanjundaswamy; Ranganathan, Chandrasekaran

    2015-01-01

    Kimura's disease is characterized by a triad of painless subcutaneous masses, eosinophilia in the peripheral blood and in tissues with marked increase in Serum Ig E. Angiolymphoid hyperplasia with eosinophilia (ALHE) manifests with the presence of dermal papules and nodules. Unique clinical, histopathological, and biochemical findings are noted in these individual entities. A 32-year-female presented with multiple nodules in the axillae for 2 years. Peripheral smear showed eosinophilia with AEC of 6080. Histopathological examination showed features of overlap. Antinuclear antibody immunoflorescence was was negative. CD31, CD34, and FVIII were positive in vascular component. A CT chest revealed left axillary lymphadenopathy. The patient was treated with Cryotherapy and there was complete regression of skin lesions, with no recurrence after 1 year of follow-up. ALHE and KD are common in the head and neck region, but no reports of an overlap, presenting with lesions in the axillae are available to date, to the best of our knowledge. Response of skin lesions to cryotherapy is highlighted. PMID:25814755

  10. Fascioliasis and eosinophilia in the highlands of Cuzco, Peru and their association with water and socioeconomic factors.

    PubMed

    Cabada, Miguel M; Goodrich, Mary R; Graham, Brittany; Villanueva-Meyer, Pablo G; Lopez, Martha; Arque, Eulogia; White, A Clinton

    2014-11-01

    There are limited data about the epidemiology of fascioliasis in Cuzco, Peru. We studied children 3-12 years old from six communities in the highlands of Cuzco to evaluate the epidemiology of fascioliasis; 227 children were included, one-half were female, the mean age was 7.5 (±2.6) years, and 46.2±% had one or more parasites, including Fasciola (9.7%), Ascaris (12.8%), Hymenolepis (9.3%), Trichuris (1.3%), hookworm (1.8%), Strongyloides (0.9%), and Giardia (27.8%). Fasciola was associated with the number of siblings in the household, drinking untreated water, and giardiasis. Eosinophilia was encountered in 21% of children and more common in those drinking untreated water at home and those infected with a parasite, but the differences were not significant. Eating water plants was not associated with Fasciola or eosinophilia. Fascioliasis and eosinophilia were common in the highlands of Cuzco. Fascioliasis was associated with socioeconomic factors and drinking water.

  11. Significance of serum antibody test for toxocariasis in healthy healthcare examinees with eosinophilia in Seoul and Gyeongsangnam-do, Korea.

    PubMed

    Kim, Hong Seok; Jin, Yan; Choi, Min-Ho; Kim, Jae-Hwan; Lee, Young Ha; Yoon, Cheong Ha; Hwang, Eui-Hyuk; Kang, Hun; Ahn, Sang-Yong; Kim, Gi Jin; Hong, Sung-Tae

    2014-12-01

    There have been numerous reports on the relationship between eosinophilia and toxocariasis. The present study investigated seropositive rates of toxocariasis among healthy people with or without eosinophilia in urban and rural areas, and assessed risk factors for positive antibody test. A total of 610 healthy people, who visited health check-up (Medicheck®, Korea Association of Health Promotion), 310 from Seoul and 300 from Gyeongsangnam-do, were subjected for this study. Their serum samples were tested by ELISA with the crude antigen of Toxocara canis larvae. Cross-reactions with other tissue invading helminth antigens were also investigated. Total antibody positive rate of toxocariasis was 8.7% of the 610 subjects. When the subjects were grouped into 3 by their eosinophil counts, the antibody positive rates significantly differed by the groups; 5.9% (18/306) in the group<350/µL, 10.0% (11/110) in the group 350-500/µL, and 12.4% (24/194) in the group>500/µL (P=0.028). A total of 22 serum samples cross-reacted with other tissue-invading helminth antigens. A questionnaire analysis recognized drinking alcohol and smoking as significant risk factors of toxocariasis. In conclusion, toxocariasis antibody positive rate is correlated with eosinophil counts. It is recommended that healthy subjects with eosinophilia by routine health examination and risk factors undergo Toxocara serology by multiantigen ELISA to investigate etiology.

  12. PDGFRβ-Rearranged Myeloid Neoplasm with Marked Eosinophilia in a 37-Year-Old Man; And a Literature Review

    PubMed Central

    Andrei, Mirela; Bandarchuk, Andrei; Abdelmalek, Cherif; Kundra, Ajay; Gotlieb, Vladimir; Wang, Jen Chin

    2017-01-01

    Patient: Male, 37 Final Diagnosis: PDGFRβ-rearranged myeloid neoplasm with eosinophilia Symptoms: Night sweats • weight loss Medication: — Clinical Procedure: — Specialty: Hematology Objective: Rare disease Background: PDGFRβ-positive myeloid neoplasms are rare. Marked leukocytosis (over 100×109/L) with marked eosinophilia (over 10%) has been rarely described in myeloid neoplasms associated with PDGFRβ rearrangement. Case report: We report a case of 37-year-old man with myeloid neoplasm associated with PDGFRβ rearrangement who presented with marked eosinophilia of 13.3% and leukocytosis with WBC count of 189×109/L. He was found to have PDGFRβ locus rearrangement at 5q32-33 by fluorescent in situ hybridization (FISH). He responded very well to low-dose imatinib therapy. To the best of our knowledge this degree of hypereosinophilia and leukocytosis in a young adult was reported only once previously. Using low dose therapy in treating this condition has rarely been reported and has not been clearly defined. Our case demonstrated that low dose imatinib therapy can be as effective as high dose imatinib therapy in treating PDGFRβ-positive myeloid neoplasms. Conclusions: The patient presented with very high WBC and eosinophil count rarely reported in a young adult with PDGFRβ-rearranged myeloid neoplasm. The recognition of this rare presentation as a manifestation of PDGFRβ-gene translocation is important, and equally important that low-dose imatinib (100 mg/day) might have the same effect as higher dose imatinib (400 mg/day). PMID:28209946

  13. Fascioliasis and Eosinophilia in the Highlands of Cuzco, Peru and Their Association with Water and Socioeconomic Factors

    PubMed Central

    Cabada, Miguel M.; Goodrich, Mary R.; Graham, Brittany; Villanueva-Meyer, Pablo G.; Lopez, Martha; Arque, Eulogia; White, A. Clinton

    2014-01-01

    There are limited data about the epidemiology of fascioliasis in Cuzco, Peru. We studied children 3–12 years old from six communities in the highlands of Cuzco to evaluate the epidemiology of fascioliasis; 227 children were included, one-half were female, the mean age was 7.5 (±2.6) years, and 46.2±% had one or more parasites, including Fasciola (9.7%), Ascaris (12.8%), Hymenolepis (9.3%), Trichuris (1.3%), hookworm (1.8%), Strongyloides (0.9%), and Giardia (27.8%). Fasciola was associated with the number of siblings in the household, drinking untreated water, and giardiasis. Eosinophilia was encountered in 21% of children and more common in those drinking untreated water at home and those infected with a parasite, but the differences were not significant. Eating water plants was not associated with Fasciola or eosinophilia. Fascioliasis and eosinophilia were common in the highlands of Cuzco. Fascioliasis was associated with socioeconomic factors and drinking water. PMID:25200257

  14. A new removable airway stent

    PubMed Central

    Amundsen, Tore; Sørhaug, Sveinung; Leira, Håkon Olav; Tyvold, Stig Sverre; Langø, Thomas; Hammer, Tommy; Manstad-Hulaas, Frode; Mattsson, Erney

    2016-01-01

    Background Malignant airway obstruction is a feared complication and will most probably occur more frequently in the future because of increasing cancer incidence and increased life expectancy in cancer patients. Minimal invasive treatment using airway stents represents a meaningful and life-saving palliation. We present a new removable airway stent for improved individualised treatment. Methods To our knowledge, the new airway stent is the world's first knitted and uncovered self-expanding metal stent, which can unravel and be completely removed. In an in vivo model using two anaesthetised and spontaneously breathing pigs, we deployed and subsequently removed the stents by unravelling the device. The procedures were executed by flexible bronchoscopy in an acute and a chronic setting – a ‘proof-of-principle’ study. Results The new stent was easily and accurately deployed in the central airways, and it remained fixed in its original position. It was easy to unravel and completely remove from the airways without clinically significant complications. During the presence of the stent in the chronic study, granulation tissue was induced. This tissue disappeared spontaneously with the removal. Conclusions The new removable stent functioned according to its purpose and unravelled easily, and it was completely removed without significant technical or medical complications. Induced granulation tissue disappeared spontaneously. Further studies on animals and humans are needed to define its optimal indications and future use. PMID:27608269

  15. Role of oxidants in interstitial lung diseases: pneumoconioses, constrictive bronchiolitis, and chronic tropical pulmonary eosinophilia.

    PubMed

    Rom, William N

    2011-01-01

    Oxidants such as superoxide anion, hydrogen peroxide, and myeloperoxidase from activated inflammatory cells in the lower respiratory tract contribute to inflammation and injury. Etiologic agents include inorganic particulates such as asbestos, silica, or coal mine dust or mixtures of inorganic dust and combustion materials found in World Trade Center dust and smoke. These etiologic agents are phagocytosed by alveolar macrophages or bronchial epithelial cells and release chemotactic factors that recruit inflammatory cells to the lung. Chemotactic factors attract and activate neutrophils, eosinophils, mast cells, and lymphocytes and further activate macrophages to release more oxidants. Inorganic dusts target alveolar macrophages, World Trade Center dust targets bronchial epithelial cells, and eosinophils characterize tropical pulmonary eosinophilia (TPE) caused by filarial organisms. The technique of bronchoalveolar lavage in humans has recovered alveolar macrophages (AMs) in dust diseases and eosinophils in TPE that release increased amounts of oxidants in vitro. Interestingly, TPE has massively increased eosinophils in the acute form and after treatment can still have ongoing eosinophilic inflammation. A course of prednisone for one week can reduce the oxidant burden and attendant inflammation and may be a strategy to prevent chronic TPE and interstitial lung disease.

  16. Drug Reaction With Eosinophilia and Systemic Symptoms Induced by Valproic Acid: A Case Report

    PubMed Central

    Darban, Mahboubeh; Bagheri, Bahador

    2016-01-01

    Introduction Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but life-threatening reaction to drugs such as carbamazepine and allopurinol. The condition is characterized by skin rashes, fever, hematological disturbances, lymphadenopathy, and organ failure, most probably hepatic dysfunction. To date, only a few cases of valproate-induced DRESS syndrome have been reported. Case Presentation We report on the case of a 60-year-old man who had been treated with valproic acid some time before being referred to Kowsar Hospital, Semnan, Iran in December 2015. He was given valproic acid 1000 mg PO, and after 20 days, he had developed widespread rashes, fever, esophagitis, cervical lymphadenopathy, and tender hepatomegaly. Laboratory results at Kowsar showed a drop in hemoglobin, in addition to lymphocytosis, thrombocytopenia, and elevated serum transaminases. DRESS was diagnosed, and corticosteroid therapy was initiated. Administration of the culprit drug to the patient was also stopped. Intravenous immunoglobulin (IVIG) improved the general condition of the patient. Conclusions Only a small number of case reports have described valproic acid-induced DRESS syndrome; therefore, the condition is difficult to prevent. Rechallenge with valproic acid should be avoided in patients with a history of reaction to the drug. PMID:28144463

  17. Tumor Associated Tissue Eosinophilia in Oral Squamous Cell Carcinoma: A Histo-Chemical Analysis

    PubMed Central

    Sahni, Priya; Patel, Anil; Md, Shylaja; Hallur, Jayadeva; Gujjar, Pavan Kumar

    2015-01-01

    Background Tumor associated tissue eosinophilia (TATE) is believed to play a significant role in biological behavior of the carcinoma. Eosinophils are involved in immune reaction. Various studies have been carried out regarding their role in tumor progression or regulation. In oral squamous cell carcinoma (OSCC), eosinophils are associated with favourable or unfavourable prognosis and hence their role is yet unclear. To compare the tissue eosinophils in OSCC and normal tissue and to correlate the expression of TATE in different grades of OSCC. Method Study comprised 30 cases, 6 normal and 24 histopathologically diagnosed with OSCC. 4 micron thick sections were stained using 1% congo red solution. The sections were examined under high power (×40) and 10 consecutive microscopic fields were studied. The average number of eosinophils were statistically analysed. Results The tabulated results showed that the median value of tissue eosinophils, increased in OSCC compared to normal mucosa. Analysis on different grades of carcinoma showed a higher TATE in Well differentiated squamous cell carcinoma as compared to other grades. Conclusion The higher eosinophil count in OSCC compare to normal tissue might have a role in stromal invasion and infiltration. TATE can be used as an indicator of favourable prognosis in OSCC. PMID:28223881

  18. Larva Migration and Eosinophilia in Mice Experimentally Infected With Gnathostoma spinigerum

    PubMed Central

    Saksirisampant, W.; Choomchuay, N.; Kraivichian, K.; Thanomsub, B. Wongsatayanon

    2012-01-01

    Background Gnathostoma spinigerum causes larva migran in human which is endemic in Southeast Asia. Information regarding larva migration is limited. In this study, we investigated the parasite migration by recovery of worms from the whole body of mouse after oral infection with advanced third stage larvae (AL3). The percentage of blood eosinophils was examined in parallel. Methods Mice were orally infected with AL3 and histological study of organs was investigated in order to study the migration of AL3, along with blood eosinophilia. Results At 1 hr post infection (PI), the larvae remained in the stomach, thereafter at 3, 5, 7, 10 and 24 hr PI; they were recovered from various organs including liver, mesentery, esophagus, diaphragm, lung, heart and dorsal fat. At day 15 PI, they were mostly found in muscles (76.47%). The average worm recovery (5 months) was 78.03%. The worms were found in the liver at every time point. Larva encystment was detected. There was a significant difference in blood eosinophils between the 8 larvae- (average 9.33% + 6.25%) and the 15 larvae-infected groups (average 22.66% + 11.03%). Surprisingly, the blood eosinophils (average 19.00% + 2.92%) were not higher in the higher infective dose- group (25 larvae). Conclusion Liver was involved by G. spinigerum throughout the study. We detected larva encystment which had never been reported in human gnathostomiasis. The highest percentage of eosinophil occurred during the invasive stage. PMID:23109965

  19. Combined pulsed dye and CO2 lasers in the treatment of angiolymphoid hyperplasia with eosinophilia.

    PubMed

    Sagi, Lior; Halachmi, Shlomit; Levi, Assi; Amitai, Dan Ben; Enk, Claes D; Lapidoth, Moshe

    2016-08-01

    Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon dermatosis of unknown etiology that manifests as characteristic red nodules and papules with a predilection for the scalp and periauricular region. Treatment is required for both esthetic and functional reasons, as lesions may ulcerate and bleed. Many treatment approaches have been reported, including excision, systemic medical approaches, topical or intralesional therapies, and non-invasive modalities including cryotherapy, electrosurgery, and laser. Treatments have exhibited variable efficacy, and the recurrence rate is 100 %. We report the combination of pulsed dye laser and CO2 laser in the treatment of ALHE in 14 patients. All patients exhibited clinical response after a mean of 2.4 ± 0.4 treatment sessions. The clinical efficacy of the combined treatment, together with its well-tolerated nature, render the use of pulsed dye laser in combination with CO2 laser, a viable treatment for debulking ALHE lesions. Ongoing maintenance treatments are needed to due to the high degree of relapse.

  20. Shock state: an unrecognized and underestimated presentation of drug reaction with eosinophilia and systemic symptoms.

    PubMed

    Kimmoun, Antoine; Dubois, Elsa; Perez, Pierre; Barbaud, Annick; Levy, Bruno

    2013-11-01

    Some patients with drug reaction with eosinophilia and systemic symptoms (DRESS) are probably admitted in intensive care unit (ICU), but data concerning their clinical features at admission are scarce. Therefore, in the present study, we used a clinical network of French intensivists to study the clinical features and evolution of DRESS patients hospitalized in ICU. A national, retrospective, multicenter study collected DRESS cases hospitalized in ICU for DRESS from 2000 to end of 2011. All files were analyzed through the RegiSCAR scoring system as "no," "possible," "probable," or "definite" DRESS. Patients were included only if they had a probable or definite DRESS. Demographic, hemodynamic, biological, and infectious data were recorded. Twenty-one patients were included. Hospital mortality was 10 (47%) of 21, and 16 of 21 patients had on admission a shock state necessitating vasopressor agents. Echocardiographic ejection fraction in shock patients was depressed (47% ± 13%). Mechanical ventilation was required in 13 of 21 cases. Hepatic failure was observed in 11 of 21 cases, acute renal failure in 18 of 20 cases, and lactic acidosis in 12 of 20 patients. Initial bacteriology was negative in all patients. Human herpesvirus reactivations were found in five of 15 cases. In conclusion, shock without bacteriological documentation associated with multiple organ failure is the most common presentation of DRESS at admission in ICU and is associated with a higher mortality than previously described.

  1. Fatal hepatic sarcocystosis in a puppy with eosinophilia and eosinophilic peritoneal effusion.

    PubMed

    Allison, Robin; Williams, Philip; Lansdowne, Jennifer; Lappin, Michael; Jensen, Tracey; Lindsay, David

    2006-09-01

    A 3-month-old male Golden Retriever puppy was evaluated for lethargy and fever of 2-days duration. Results of a CBC and biochemical profile revealed marked eosinophilia (6.3 X 10(3)/microL; reference interval 0.1-1.2 X 10(3)/microL), moderate thrombocytopenia, and increased activities of alanine aminotransferase, aspartate aminotransferase, and creatine kinase. Hepatomegaly and peritoneal effusion were found using abdominal ultrasound. Peritoneal fluid analysis revealed eosinophilic inflammation (23,000 nucleated cells/microL with 88% eosinophils). Despite supportive treatment the puppy's condition deteriorated rapidly; euthanasia was requested, and a necropsy performed. Microscopically, there was marked necrosuppurative and eosinophilic hepatitis with vasculitis. Numerous hepatocytes contained protozoal organisms suspected to be Toxoplasma gondii or Neospora caninum. However, serum was negative for both T gondii and N caninum antibodies; polymerase chain reaction assay on hepatic tissue was negative for both organisms; and immunohistochemical evaluation of hepatic tissue using serum raised against T gondii, N caninum, and Sarcocystis neurona also was negative. Schizont morphology suggested that merozoites replicated by endopolygeny, forming rosettes around a central residual body. Transmission electron microscopy revealed that merozoites lacked rhoptries. These findings were consistent with a diagnosis of Sarcocystis canis, an apicomplexan parasite with an unknown life cycle.

  2. Immunity to Brugia pahangi in athymic nude and normal mice: eosinophilia, antibody and hypersensitivity responses.

    PubMed

    Vickery, A C; Vincent, A L

    1984-11-01

    Congenitally athymic nude (nu/nu) mice, immunologically reconstituted by thymus grafting before inoculation with infective larvae, and mice heterozygous for the nu gene (nu/+), mounted potent protective humoral and cellular immune responses to Brugia pahangi. Although responses were not identical, both groups of mice produced IgM, IgG and IgE antibodies specific for adult worm antigen (S-Ag) present in a crude aqueous extract, made immediate and delayed hypersensitivity footpad swelling responses when challenged with S-Ag and eliminated their infection in the early larval stages. Heterozygotes also exhibited a marked eosinophilia which peaked coincident with larval killing. In contrast, thymus grafting of patent nudes had no effect upon microfilaraemias or adult worm burdens and did not completely protect against a challenge larval inoculum although antibodies specific for S-Ag were produced. With the occasional exceptions of moderate immediate footpad swelling and very low titres of IgM specific for S-Ag, no specific immune responses to B. pahangi were found in ungrafted nude mice which allowed full development of adult worms and supported patent infections.

  3. IL-5-overexpressing mice exhibit eosinophilia and altered wound healing through mechanisms involving prolonged inflammation.

    PubMed

    Leitch, Victoria D; Strudwick, Xanthe L; Matthaei, Klaus I; Dent, Lindsay A; Cowin, Allison J

    2009-02-01

    Leucocytes are essential in healing wounds and are predominantly involved in the inflammatory and granulation stages of wound repair. Eosinophils are granulocytic leucocytes and are specifically regulated by interleukin-5 (IL-5), a cytokine produced by T helper 2 (Th2) cells. To characterize more clearly the role of the IL-5 and eosinophils in the wound healing process, IL-5-overexpressing and IL-5-deficient mice were used as models of eosinophilia and eosinophil depletion, respectively. Our results reveal a significantly altered inflammatory response between IL-5-overexpressing and IL-5 knockout mice post-wounding. Healing was significantly delayed in IL-5-overexpressing mice with wounds gaping wider and exhibiting impaired re-epithelialization. A delay in collagen deposition was observed suggesting a direct effect on matrix synthesis. A significant increase in inflammatory cell infiltration, particularly eosinophils and CD4(+) cells, one of the main cell types which secrete IL-5, was observed in IL-5-overexpressing mice wounds suggesting that one of the main roles of IL-5 in wound repair may be to promote the infiltration of eosinophils into healing wounds. Healing is delayed in IL-5-overexpressing mice and this corresponds to significantly increased levels of eosinophils and CD4(+) cells within the wound site that may contribute to and exacerbate the inflammatory response, resulting in detrimental wound repair.

  4. Eosinophilia-myalgia syndrome: selective cognitive impairment, longitudinal effects, and neuroimaging findings

    PubMed Central

    Armstrong, C.; Lewis, T.; D'Esposito, M.; Freundlich, B.

    1997-01-01

    OBJECTIVE—To identify the specific nature of the neurocognitive impairments of eosinophilia-myalgia syndrome (EMS) in an unselected population, and to present longitudinal patterns.
METHODS—A consecutive sample of 23 patients with EMS and 18 age and education matched control subjects were assessed on a comprehensive neuropsycho- logical battery. Longitudinal results were gathered from six patients.
RESULTS—Neurocognitive impairments were found which represent a subset of deficits reported in previous group and case study reports. Deficits were limited to complex visual memory, conceptual set shifting, and attention, which suggest a selective dysexecutive syndrome. The motor slowing and verbal memory deficits previously reported were not found. Although depression, fatigue, sleep deprivation, and pain were significant symptoms, they were unassociated with deficits with the exception of an association of depression with one deficit. There was no pattern of overall decline over time in a subset of the group, although considerable heterogeneity in the longitudinal patterns of neurocognitive tests was found. Abnormalities of white matter appeared in the MRI of eight of 12patients.
CONCLUSIONS—The neurocognitive and neuroimaging findings contribute to the evidence which indicates that the neural substrate of EMS is white matter damage.

 PMID:9408106

  5. Some enzymatic characteristics of eosinophil peroxidase from patients with eosinophilia and from healthy donors.

    PubMed

    Bos, A J; Wever, R; Hamers, M N; Roos, D

    1981-05-01

    Some enzymatic characteristics of human eosinophil peroxidase were compared with those of human myeloperoxidase. Both enzymes catalyzed the oxidation of iodide by hydrogen peroxide. This assay proved to be very sensitive; the activity of 100 eosinophils/ml could be measured. The position of the pH optimum of this reaction was linearly dependent on the logarithm of the iodide/H2O2 ratio. At the same substrate ratio, this optimum was about 1 pH unit higher for eosinophil peroxidase than for myeloperoxidase. This difference may be related to the action of myeloperoxidase inside an acidified phagolysosome as opposed to the extracellular action of eosinophil peroxidase on the surface of certain parasites. Under defined conditions (KI, 1.4 mM; H2O2, 0.18 mM; cetyltrimethylammonium bromide, 0.008% [wt/vol]; pH 6), the activity of eosinophil peroxidase could be measured in a mixed granulocyte suspension independently of myeloperoxidase. Eosinophils from patients with eosinophilia were found to contain as much peroxidase activity as did eosinophils from healthy donors. No enzymatic differences in eosinophil peroxidase were found between the two types of donors.

  6. Significance of para-esophageal lymph nodes in food or aeroallergen-induced iNKT cell-mediated experimental eosinophilic esophagitis.

    PubMed

    Rajavelu, Priya; Rayapudi, Madhavi; Moffitt, Matthew; Mishra, Akanksha; Mishra, Anil

    2012-04-01

    Eosinophilic esophagitis (EoE) is a recently recognized inflammatory disorder driven by food hypersensitivity; however, the specific foods and mechanisms involved are unclear. In patients with EoE, we have found that hypersensitivities to corn and peanuts are the most common. Accordingly, we sensitized and exposed mice either intranasally or intragastrically with corn or peanut extract or saline. Esophageal eosinophilia, the genes of eosinophil-directed cytokines, and allergen-induced antibodies were examined in mice challenged with corn or peanut extract or saline. A high number of esophageal lamina propria eosinophils as well as eosinophilic microabscesses, intraepithelial eosinophils, extracellular eosinophilic granules, thickened and disrupted epithelial mucosa, and mast cell hyperplasia were observed in the esophagus of peanut or corn allergen-challenged mice. Mechanistic analysis indicated that para-esophageal lymph nodes might be critical in the trafficking of eosinophils to the esophagus and in EoE association to airway eosinophilia. Furthermore, experimentation with gene-targeted mice revealed that peanut allergen-induced EoE was dependent on eotaxin and invariant natural killer T (iNKT) cells, as CD1d and eotaxin-1/2 gene-deficient mice were protected from disease induction. Thus we provide evidence that para-esophageal lymph nodes are involved in food- or aeroallergen-induced eosinophilia and patchy EoE pathogenesis, likely a mechanism dependent on eotaxins and iNKT cells.

  7. 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.

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

    PubMed Central

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

    2015-01-01

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

  9. Human airway ciliary dynamics

    PubMed Central

    Thompson, Kristin; Knowles, Michael R.; Davis, C. William

    2013-01-01

    Airway cilia depend on precise changes in shape to transport the mucus gel overlying mucosal surfaces. The ciliary motion can be recorded in several planes using video microscopy. However, cilia are densely packed, and automated computerized systems are not available to convert these ciliary shape changes into forms that are useful for testing theoretical models of ciliary function. We developed a system for converting planar ciliary motions recorded by video microscopy into an empirical quantitative model, which is easy to use in validating mathematical models, or in examining ciliary function, e.g., in primary ciliary dyskinesia (PCD). The system we developed allows the manipulation of a model cilium superimposed over a video of beating cilia. Data were analyzed to determine shear angles and velocity vectors of points along the cilium. Extracted waveforms were used to construct a composite waveform, which could be used as a standard. Variability was measured as the mean difference in position of points on individual waveforms and the standard. The shapes analyzed were the end-recovery, end-effective, and fastest moving effective and recovery with mean (± SE) differences of 0.31(0.04), 0.25(0.06), 0.50(0.12), 0.50(0.10), μm, respectively. In contrast, the same measures for three different PCD waveforms had values far outside this range. PMID:23144323

  10. Airway Hydration and COPD

    PubMed Central

    Ghosh, Arunava; Boucher, R.C.; Tarran, Robert

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the prevalent causes of worldwide mortality and encompasses two major clinical phenotypes, i.e., chronic bronchitis (CB) and emphysema. The most common cause of COPD is chronic tobacco inhalation. Research focused on the chronic bronchitic phenotype of COPD has identified several pathological processes that drive disease initiation and progression. For example, the lung’s mucociliary clearance (MCC) system performs the critical task of clearing inhaled pathogens and toxic materials from the lung. MCC efficiency is dependent on: (i) the ability of apical plasma membrane ion channels such as the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na+ channel (ENaC) to maintain airway hydration; (ii) ciliary beating; and, (iii) appropriate rates of mucin secretion. Each of these components is impaired in CB and likely contributes to the mucus stasis/accumulation seen in CB patients. This review highlights the cellular components responsible for maintaining MCC and how this process is disrupted following tobacco exposure and with CB. We shall also discuss existing therapeutic strategies for the treatment of chronic bronchitis and how components of the MCC can be used as biomarkers for the evaluation of tobacco or tobacco-like-product exposure. PMID:26068443

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

    PubMed

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

    2010-04-01

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

  12. Efficacy of Surgical Airway Plasty for Benign Airway Stenosis

    PubMed Central

    Takahama, Makoto; Nakajima, Ryu; Kimura, Michitaka; Inoue, Hidetoshi; Yamamoto, Ryoji

    2015-01-01

    Background: Long-term patency is required during treatment for benign airway stenosis. This study investigated the effectiveness of surgical airway plasty for benign airway stenosis. Methods: Clinical courses of 20 patients, who were treated with surgical plasty for their benign airway stenosis, were retrospectively investigated. Results: Causes of stenosis were tracheobronchial tuberculosis in 12 patients, post-intubation stenosis in five patients, malacia in two patients, and others in one patient. 28 interventional pulmonology procedures and 20 surgical plasty were performed. Five patients with post-intubation stenosis and four patients with tuberculous stenosis were treated with tracheoplasty. Eight patients with tuberculous stenosis were treated with bronchoplasty, and two patients with malacia were treated with stabilization of the membranous portion. Anastomotic stenosis was observed in four patients, and one to four additional treatments were required. Performance status, Hugh–Jones classification, and ventilatory functions were improved after surgical plasty. Outcomes were fair in patients with tuberculous stenosis and malacia. However, efficacy of surgical plasty for post-intubation stenosis was not observed. Conclusion: Surgical airway plasty may be an acceptable treatment for tuberculous stenosis. Patients with malacia recover well after surgical plasty. There may be untreated patients with malacia who have the potential to benefit from surgical plasty. PMID:26567879

  13. Airway management in emergency situations.

    PubMed

    Dörges, Volker

    2005-12-01

    Securing and monitoring the airway are among the key requirements of appropriate therapy in emergency patients. Failures to secure the airways can drastically increase morbidity and mortality of patients within a very short time. Therefore, the entire range of measures needed to secure the airway in an emergency, without intermediate ventilation and oxygenation, is limited to 30-40 seconds. Endotracheal intubation is often called the 'gold standard' for airway management in an emergency, but multiple failed intubation attempts do not result in maintaining oxygenation; instead, they endanger the patient by prolonging hypoxia and causing additional trauma to the upper airways. Thus, knowledge and availability of alternative procedures are also essential in every emergency setting. Given the great variety of techniques available, it is important to establish a well-planned, methodical protocol within the framework of an algorithm. This not only facilitates the preparation of equipment and the training of personnel, it also ensures efficient decision-making under time pressure. Most anaesthesia-related deaths are due to hypoxaemia when difficulty in securing the airway is encountered, especially in obstetrics during induction of anaesthesia for caesarean delivery. The most commonly occurring adverse respiratory events are failure to intubate, failure to recognize oesophageal intubation, and failure to ventilate. Thus, it is essential that every anaesthesiologist working on the labour and delivery ward is comfortable with the algorithm for the management of failed intubation. The algorithm for emergency airway management describing the sequence of various procedures has to be adapted to internal standards and to techniques that are available.

  14. The Airway Microbiome at Birth

    PubMed Central

    Lal, Charitharth Vivek; Travers, Colm; Aghai, Zubair H.; Eipers, Peter; Jilling, Tamas; Halloran, Brian; Carlo, Waldemar A.; Keeley, Jordan; Rezonzew, Gabriel; Kumar, Ranjit; Morrow, Casey; Bhandari, Vineet; Ambalavanan, Namasivayam

    2016-01-01

    Alterations of pulmonary microbiome have been recognized in multiple respiratory disorders. It is critically important to ascertain if an airway microbiome exists at birth and if so, whether it is associated with subsequent lung disease. We found an established diverse and similar airway microbiome at birth in both preterm and term infants, which was more diverse and different from that of older preterm infants with established chronic lung disease (bronchopulmonary dysplasia). Consistent temporal dysbiotic changes in the airway microbiome were seen from birth to the development of bronchopulmonary dysplasia in extremely preterm infants. Genus Lactobacillus was decreased at birth in infants with chorioamnionitis and in preterm infants who subsequently went on to develop lung disease. Our results, taken together with previous literature indicating a placental and amniotic fluid microbiome, suggest fetal acquisition of an airway microbiome. We speculate that the early airway microbiome may prime the developing pulmonary immune system, and dysbiosis in its development may set the stage for subsequent lung disease. PMID:27488092

  15. Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation

    PubMed Central

    Uller, Lena; Mathiesen, Jesper Mosolff; Alenmyr, Lisa; Korsgren, Magnus; Ulven, Trond; Högberg, Thomas; Andersson, Gunnar; Persson, Carl GA; Kostenis, Evi

    2007-01-01

    Background Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit asthma-like pathology. Methods Affinity for and antagonistic potency of TM30089 on many mouse receptors including thromboxane A2 receptor mTP, CRTH2 receptor, and selected anaphylatoxin and chemokines receptors were determined in recombinant expression systems in vitro. In vivo effects of TM30089 and ramatroban on tissue eosinophilia and mucus cell histopathology were examined in a mouse asthma model. Results TM30089, displayed high selectivity for and antagonistic potency on mouse CRTH2 but lacked affinity to TP and many other receptors including the related anaphylatoxin C3a and C5a receptors, selected chemokine receptors and the cyclooxygenase isoforms 1 and 2 which are all recognized players in allergic diseases. Furthermore, TM30089 and ramatroban, the latter used as a reference herein, similarly inhibited asthma pathology in vivo by reducing peribronchial eosinophilia and mucus cell hyperplasia. Conclusion This is the first report to demonstrate anti-allergic efficacy in vivo of a highly selective small molecule CRTH2 antagonist. Our data suggest that CRTH2 antagonism alone is effective in mouse allergic airway inflammation even to the extent that this mechanism can explain the efficacy of ramatroban. PMID:17328802

  16. Cystic Fibrosis Transmembrane Conductance Regulator in Sarcoplasmic Reticulum of Airway Smooth Muscle. Implications for Airway Contractility

    PubMed Central

    Cook, Daniel P.; Rector, Michael V.; Bouzek, Drake C.; Michalski, Andrew S.; Gansemer, Nicholas D.; Reznikov, Leah R.; Li, Xiaopeng; Stroik, Mallory R.; Ostedgaard, Lynda S.; Abou Alaiwa, Mahmoud H.; Thompson, Michael A.; Prakash, Y. S.; Krishnan, Ramaswamy; Meyerholz, David K.; Seow, Chun Y.

    2016-01-01

    Rationale: An asthma-like airway phenotype has been described in people with cystic fibrosis (CF). Whether these findings are directly caused by loss of CF transmembrane conductance regulator (CFTR) function or secondary to chronic airway infection and/or inflammation has been difficult to determine. Objectives: Airway contractility is primarily determined by airway smooth muscle. We tested the hypothesis that CFTR is expressed in airway smooth muscle and directly affects airway smooth muscle contractility. Methods: Newborn pigs, both wild type and with CF (before the onset of airway infection and inflammation), were used in this study. High-resolution immunofluorescence was used to identify the subcellular localization of CFTR in airway smooth muscle. Airway smooth muscle function was determined with tissue myography, intracellular calcium measurements, and regulatory myosin light chain phosphorylation status. Precision-cut lung slices were used to investigate the therapeutic potential of CFTR modulation on airway reactivity. Measurements and Main Results: We found that CFTR localizes to the sarcoplasmic reticulum compartment of airway smooth muscle and regulates airway smooth muscle tone. Loss of CFTR function led to delayed calcium reuptake following cholinergic stimulation and increased myosin light chain phosphorylation. CFTR potentiation with ivacaftor decreased airway reactivity in precision-cut lung slices following cholinergic stimulation. Conclusions: Loss of CFTR alters porcine airway smooth muscle function and may contribute to the airflow obstruction phenotype observed in human CF. Airway smooth muscle CFTR may represent a therapeutic target in CF and other diseases of airway narrowing. PMID:26488271

  17. Hypereosinophilic syndrome, Churg-Strauss syndrome and parasitic diseases: possible links between eosinophilia and thrombosis.

    PubMed

    Maino, Alberto; Rossio, Raffaella; Cugno, Massimo; Marzano, Angelo V; Tedeschi, Alberto

    2012-09-01

    Throughout the past decade, a possible role of eosinophils in blood coagulation and thrombosis has been suggested. We conducted a Pubmed (MEDLINE) search of case and series referring to any kind of thrombotic events described in three conditions characterised by persistent blood eosinophilia, i.e. the hypereosinophilic syndrome (HES), the Churg Strauss syndrome (CSS), and parasitic infestations from 1966 to date. One hundred and ninety-two articles were found regarding thrombotic events in HES and CSS, and 209 cases of thrombosis were extracted. One hundred and seventy- seven articles dealing with parasitic diseases and thrombosis were found, but only 15 manuscripts reporting thrombosis of unknown origin in 22 patients were selected. In HES, arterial thromboses were more frequent than in CSS (p=0.006), representing almost half of the cases (45%), while venous and mixed artero-venous thrombosis were respectively 28% and 27%. In contrast, in CSS there was a predominance of venous thrombosis (56%, p=0.006), with arterial thrombosis representing 38% of total thrombotic events, and mixed thrombosis being the least frequent (4%). The higher incidence of arterial thrombosis in HES patients can be explained by the common cardiac involvement (64% of patients). In the 22 patients with parasitoses and thrombosis, 15 had arterial thrombosis (68%) and 7 had venous thrombosis (32 %). Literature analysis shows that there are numerous reports of thrombotic events in patients with eosinophil-related disorders supporting a role for eosinophils in thrombosis. This observation raises the problem of prevention and treatment of thromboembolism particularly in HES and CSS patients.

  18. [Orthodontics and the upper airway].

    PubMed

    Cobo Plana, J; de Carlos Villafranca, F; Macías Escalada, E

    2004-03-01

    One of the general aims of orthodontic treatment and of the combination of orthodontics and orthognathic surgery is to achieve good occlusion and aesthetic improvement, especially in cases of severe dentoskeletal deformities. However, on many occasions, the parameters of the upper airways are not taken into account when the aims of conventional treatment are fulfilled. Patients with obstructive alterations during sleep represent for the orthodontist a type of patient who differs from the normal; for them, treatment should include the objective of improving oxygen saturation. Here, functional considerations should outweigh purely aesthetic ones. It is important, when making an orthodontic, surgical or combined diagnosis for a patient, to bear in mind the impact that treatment may have on the upper airways. Good aesthetics should never be achieved for some of our patients at the expense of diminishing the capacity of their upper airways.

  19. Myeloid cell HIF-1α regulates asthma airway resistance and eosinophil function

    PubMed Central

    Akong-Moore, Kathryn; Feldstein, Stephanie; Johansson, Per; Nyugen, Anh; McEachern, Elisa K.; Nicatia, Shari; Cowburn, Andrew S.; Olson, Joshua; Cho, Jae Youn; Isaacs, Hart; Johnson, Randall S.; Broide, David H.; Nizet, Victor

    2013-01-01

    Hypoxia-inducible factor (HIF)-1α is a master regulator of inflammatory activities of myeloid cells, including neutrophils and macrophages. These studies examine the role of myeloid cell HIF-1α in regulating asthma induction and pathogenesis, and for the first time, evaluate the roles of HIF-1α and HIF-2α in the chemotactic properties of eosinophils, the myeloid cells most associated with asthma. Wild-type (WT) and myeloid cell-specific HIF-1α knockout (KO) C57BL/6 mice were studied in an ovalbumin (OVA) model of asthma. Administration of the pharmacological HIF-1α antagonist YC-1 was used to corroborate findings from the genetic model. WT, HIF-1α, and HIF-2α KO eosinophils underwent in vitro chemotaxis assays. We found that deletion of HIF-1α in myeloid cells and systemic treatment with YC-1 during asthma induction decreased airway hyperresponsiveness (AHR). Deletion of HIF-1α in myeloid cells in OVA-induced asthma also reduced eosinophil infiltration, goblet cell hyperplasia, and levels 34 of cytokines IL-4, IL-5, and IL-13 in the lung. HIF-1α inhibition with YC-1 during asthma induction decreased eosinophilia in bronchoalveolar lavage, lung parenchyma, and blood, as well as decreased total lung inflammation, IL-5, and serum OVA-specific IgE levels. Deletion of HIF-1α in eosinophils decreased their chemotaxis, while deletion of the isoform HIF-2α led to increased chemotaxis. This work demonstrates that HIF-1α in myeloid cells plays a role in asthma pathogenesis, particularly in AHR development. Additionally, treatment with HIF-1α inhibitors during asthma induction decreases AHR and eosinophilia. Finally, we show that HIF- 1α and HIF-2α regulate eosinophil migration in opposing ways. PMID:23250618

  20. Endogenous airway mucins carry glycans that bind Siglec-F and induce eosinophil apoptosis

    PubMed Central

    Evans, Christopher M.; Janssen, William J.; Brummet, Mary E.; Hudson, Sherry A.; Zhu, Zhou

    2014-01-01

    Background Siglec-F is a glycan binding protein selectively expressed on mouse eosinophils. Its engagement induces apoptosis, suggesting a pathway for ameliorating eosinophilia in asthma and other eosinophil-associated diseases. Siglec-F recognizes sialylated, sulfated glycans in glycan binding assays, but the identities of endogenous sialoside ligands and their glycoprotein carriers in vivo are unknown. Methods Lungs from normal and mucin-deficient mice, as well as mouse tracheal epithelial cells from mice, were interrogated in vitro and in vivo for the expression of Siglec-F ligands. Western blotting and immunocytochemistry used Siglec-F-Fc as a probe for directed purification, followed by liquid chromatography-tandem mass spectrometric analysis of recognized glycoproteins. Purified components were tested in mouse eosinophil binding assays and flow cytometry-based cell death assays. Results We detected mouse lung glycoproteins that bound to Siglec-F; binding was sialic-acid dependent. Proteomic analysis of Siglec-F binding material identified Muc5b and Muc4. Cross-affinity enrichment and histochemical analysis of lungs from mucin-deficient mice assigned and validated the identity of Muc5b as one glycoprotein ligand for Siglec-F. Purified mucin preparations carried sialylated and sulfated glycans, bound to eosinophils and induced their death in vitro. Mice conditionally deficient in Muc5b displayed exaggerated eosinophilic inflammation in response to intratracheal installation of IL-13. Conclusions These data identify a previously unrecognized endogenous anti-inflammatory property of airway mucins by which their glycans can control lung eosinophilia through engagement of Siglec-F. PMID:25497369

  1. Potential Masking of Airway Eosinophilic Inflammation by Combination Therapy in Asthma

    PubMed Central

    Lee, Byung-Jae; Jeung, Yun-Jin; Lee, Jin-Young; Oh, Mi-Jung

    2014-01-01

    Purpose Long-acting β2 agonists (LABA) may mask ongoing bronchial inflammation, leaving asthmatic patients at greater risk of severe complications. The aim of this study was to compare the effect of combination therapy using low-dose inhaled corticosteroids (ICS) plus LABA on airway inflammation in asthma to the effect of medium-dose ICS alone. Methods Twenty-four patients with asthma not controlled by low-dose (400 µg per day) budesonide alone were enrolled in this prospective crossover study. Patients were randomized into 2 treatment phases: one receiving medium-dose (800 µg per day) budesonide (ICS phase), and the other receiving a combination therapy of low-dose budesonide/formoterol (360 µg/9 µg per day) delivered by a single inhaler (LABA phase). Each treatment phase lasted for 6 week, after which patients were crossed over. Asthma symptoms, lung function, and airway inflammation were compared between the 2 phases. Results Twenty-three patients completed the study; adequate sputum samples were collected from 17 patients. Asthma symptoms and lung function remained similar between the 2 phases. However, the mean sputum eosinophil percentage was higher in the LABA phase than in the ICS phase (5.07±3.82% vs. 1.02±1.70%; P<0.01). Sputum eosinophilia (≥3%) was more frequently observed in the LABA phase than in the ICS phase (six vs. two). Conclusion Addition of LABA may mask airway eosinophilic inflammation in asthmatic patients whose symptoms are not controlled with low-dose ICS. PMID:24587956

  2. Airway Assessment for Office Sedation/Anesthesia.

    PubMed

    Rosenberg, Morton B; Phero, James C

    2015-01-01

    Whenever a patient is about to receive sedation or general anesthesia, no matter what the technique, the preoperative assessment of the airway is one of the most important steps in ensuring patient safety and positive outcomes. This article, Part III in the series on airway management, is directed at the ambulatory office practice and focuses on predicting the success of advanced airway rescue techniques.

  3. Comments to Role of upper airway ultrasound in airway management.

    PubMed

    Lien, Wan-Ching

    2017-01-01

    Tracheal ultrasound can be an alternative diagnostic tool in airway management, besides traditional confirmatory methods such as capnography and auscultation. The standard image is a hyperechoic air-mucosa (A-M) interface with a reverberation artifact posteriorly (comet-tail artifact). If the second A-M interface appears, which we call a "double-tract sign," esophageal intubation is considered.

  4. Eosinophilia and biotoxin exposure in bottlenose dolphins (Tursiops truncatus) from a coastal area impacted by repeated mortality events

    SciTech Connect

    Schwacke, Lori H.; Twiner, Michael J.; De Guise, Sylvain; Balmer, Brian C.; Wells, Randall S.; Rotstein, David C.; Varela, Rene A.; Hansen, Larry J.; Zolman, Eric S.; Spradlin, Trevor R.; and others

    2010-08-15

    Bottlenose dolphins (Tursiops truncatus) inhabiting coastal waters in the northern Gulf of Mexico have been impacted by recurrent unusual mortality events over the past few decades. Several of these mortality events along the Florida panhandle have been tentatively attributed to poisoning from brevetoxin produced by the dinoflagellate Karenia brevis. While dolphins in other regions of the Florida coast are often exposed to K. brevis blooms, large-scale dolphin mortality events are relatively rare and the frequency and magnitude of die-offs along the Panhandle raise concern for the apparent vulnerability of dolphins in this region. We report results from dolphin health assessments conducted near St. Joseph Bay, Florida, an area impacted by 3 unusual die-offs within a 7-year time span. An eosinophilia syndrome, manifested as an elevated blood eosinophil count without obvious cause, was observed in 23% of sampled dolphins. Elevated eosinophil counts were associated with decreased T-lymphocyte proliferation and increased neutrophil phagocytosis. In addition, indication of chronic low-level exposure to another algal toxin, domoic acid produced by the diatom Pseudo-nitzschia spp., was determined. Previous studies of other marine mammal populations exposed recurrently to Pseudo-nitzschia blooms have suggested a possible link between the eosinophilia and domoic acid exposure. While the chronic eosinophilia syndrome could over the long-term produce organ damage and alter immunological status and thereby increase vulnerability to other challenges, the significance of the high prevalence of the syndrome to the observed mortality events in the St. Joseph Bay area is unclear. Nonetheless, the unusual immunological findings and concurrent evidence of domoic acid exposure in this sentinel marine species suggest a need for further investigation to elucidate potential links between chronic, low-level exposure to algal toxins and immune health.

  5. Intra-Arterial Angiolymphoid Hyperplasia with Eosinophilia: A Rare Case Report of Peripheral Medium Sized Muscular Artery Involvement.

    PubMed

    Amin, Ashima; Umashankar, T; Dsouza, Chryselle Olive

    2015-08-01

    Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign vasoproliferative disease with distinct clinical and histopathological features. The most common clinical presentation is dermal and subcutaneous painless nodules in the head and neck region. The involvement of medium sized peripheral muscular artery is uncommon. It predominantly affects Caucasian adults during the third and fourth decades, but is also known to occur in Asians and it very rarely occurs in children. We here by present a case of intravascular ALHE in a 46-year-old female presenting with subcutaneous forearm nodule clinically diagnosed as ulnar artery thrombosis.

  6. [DRESS syndrome or reaction to drugs with eosinophilia and systemic symptoms associated to anti-tuberculosis drugs].

    PubMed

    Fernández de Córdova-Rodríguez1, Luis René; Guzmán-Guillén, Karol Andrea; Fernández de Córdova-Aguirre, Juan Carlos

    2015-01-01

    Tuberculosis has increased all over the world. This paper reports the case of a male patient with tuberculous meningitis, spinal tuberculosis (Pott's disease) and severe adverse reactions to antituberculosis drugs. He had skin rash, hepatitis, eosinophilia and fever; all these signs make the diagnosis of DRESS syndrome. This syndrome is caused by a severe hypersensitivity reaction to different drugs. It is usually caused by anticonvulsants, sulfonamides and some antiviral drugs, among other drugs. Anti-tuberculosis drugs can also cause this potentially fatal syndrome. The importance of surveillance for early detection and treatment of adverse drug reactions is emphasized.

  7. The Lung Microbiome and Airway Disease.

    PubMed

    Lynch, Susan V

    2016-12-01

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

  8. Airway nerves: in vitro electrophysiology.

    PubMed

    Fox, Alyson

    2002-06-01

    Recording the activity of single airway sensory fibres or neuronal cell bodies in vitro has allowed detailed characterisation of fibre types and membrane properties. Fibre types can be identified by their conduction velocities and further studied by the application of drugs to their receptive field. C-fibres are sensitive to mechanical stimuli and a range of irritant chemicals (bradykinin, capsaicin, low pH, platelet-activating factor), whereas Adelta-fibres are relatively insensitive to chemical stimuli and appear to correlate to the rapidly adapting receptors identified in airways in vivo. Their site of origin also differs: upper airway C-fibres arise predominantly from the jugular ganglion and Adelta-fibres from the jugular and nodose ganglia. Intracellular recording from cell bodies in the ganglia has revealed a calcium-dependent potassium current common to many putative C-fibre cell bodies. This slow after hyperpolarisation current may be inhibited by stimuli that excite and sensitise C-fibres - this could be an important mechanism underlying the sensitisation of C-fibres in airway irritability.

  9. Airway malacia in children with achondroplasia.

    PubMed

    Dessoffy, Kimberly E; Modaff, Peggy; Pauli, Richard M

    2014-02-01

    This study was undertaken to assess the frequency of airway malacia in infants and young children with achondroplasia, a population well known to be at risk for a variety of respiratory problems. We also wished to evaluate what, if any, contribution airway malacia makes to the complex respiratory issues that may be present in those with achondroplasia. Retrospective chart review of all infants and young children with achondroplasia who were assessed through the Midwest Regional Bone Dysplasia Clinics from 1985 through 2012 (n = 236) was completed. Records of comprehensive clinical examinations, polysomnographic assessments, and airway visualization were reviewed and abstracted using a data collection form. Analyses were completed comparing the group with and those without evidence for airway malacia. Thirteen of 236 patients (5.5%) were found to have airway malacia. Most of those affected had lower airway involvement (9/13). The presence of airway malacia was correlated with an increased occurrence of obstructive sleep apnea as well as need for oxygen supplementation, airway surgeries and tracheostomy placement. Although estimates of the frequency of airway malacia in the general population are limited, its frequency in children with achondroplasia appears to be much higher than any published general population estimate. The presence of airway malacia appears to confound other breathing abnormalities in this population and results in the need for more invasive airway treatments.

  10. Native Small Airways Secrete Bicarbonate

    PubMed Central

    Quinton, Paul M.

    2014-01-01

    Since the discovery of Cl− impermeability in cystic fibrosis (CF) and the cloning of the responsible channel, CF pathology has been widely attributed to a defect in epithelial Cl− transport. However, loss of bicarbonate (HCO3−) transport also plays a major, possibly more critical role in CF pathogenesis. Even though HCO3− transport is severely affected in the native pancreas, liver, and intestines in CF, we know very little about HCO3− secretion in small airways, the principle site of morbidity in CF. We used a novel, mini-Ussing chamber system to investigate the properties of HCO3− transport in native porcine small airways (∼ 1 mm φ). We assayed HCO3− transport across small airway epithelia as reflected by the transepithelial voltage, conductance, and equivalent short-circuit current with bilateral 25-mM HCO3− plus 125-mM NaGlu Ringer’s solution in the presence of luminal amiloride (10 μM). Under these conditions, because no major transportable anions other than HCO3− were present, we took the equivalent short-circuit current to be a direct measure of active HCO3− secretion. Applying selective agonists and inhibitors, we show constitutive HCO3− secretion in small airways, which can be stimulated significantly by β-adrenergic– (cAMP) and purinergic (Ca2+) -mediated agonists, independently. These results indicate that two separate components for HCO3− secretion, likely via CFTR- and calcium-activated chloride channel–dependent processes, are physiologically regulated for likely roles in mucus clearance and antimicrobial innate defenses of small airways. PMID:24224935

  11. Sarcoidosis of the upper and lower airways.

    PubMed

    Morgenthau, Adam S; Teirstein, Alvin S

    2011-12-01

    Sarcoidosis is a systemic granulomatous disease of undetermined etiology characterized by a variable clinical presentation and disease course. Although clinical granulomatous inflammation may occur within any organ system, more than 90% of sarcoidosis patients have lung disease. Sarcoidosis is considered an interstitial lung disease that is frequently characterized by restrictive physiologic dysfunction on pulmonary function tests. However, sarcoidosis also involves the airways (large and small), causing obstructive airways disease. It is one of a few interstitial lung diseases that affects the entire length of the respiratory tract - from the nose to the terminal bronchioles - and causes a broad spectrum of airways dysfunction. This article examines airway dysfunction in sarcoidosis. The anatomical structure of the airways is the organizational framework for our discussion. We discuss sarcoidosis involving the nose, sinuses, nasal passages, larynx, trachea, bronchi and small airways. Common complications of airways disease, such as, atelectasis, fibrosis, bullous leions, bronchiectasis, cavitary lesions and mycetomas, are also reviewed.

  12. Saponins, especially platyconic acid A, from Platycodon grandiflorum reduce airway inflammation in ovalbumin-induced mice and PMA-exposed A549 cells.

    PubMed

    Choi, Jae Ho; Jin, Sun Woo; Kim, Hyung Gyun; Choi, Chul Yung; Lee, Hyun Sun; Ryu, Shi Yong; Chung, Young Chul; Hwang, Young Jung; Um, Yeon Ji; Jeong, Tae Cheon; Jeong, Hye Gwang

    2015-02-11

    We investigated the inhibitory effects of Platycodon grandiflorum root-derived saponins (Changkil saponins: CKS) on ovalbumin-induced airway inflammation in mice. CKS suppressed leukocytes number, IgE, Th1/Th2 cytokines, and MCP-1 chemokine secretion in bronchoalveolar lavage fluid. Also, ovalbumin-increased MUC5AC, MMP-2/9, and TIMP-1/-2 mRNA expression, NF-κB activation, leukocytes recruitment, and mucus secretion were inhibited by CKS treatment. Moreover, the active component of CKS, platyconic acid A (PA), suppressed PMA-induced MUC5AC mRNA expression (from 2.1 ± 0.2 to 1.1 ± 0.1) by inhibiting NF-κB activation (from 2.3 ± 0.2 to 1.2 ± 0.1) via Akt (from 3.7 ± 0.3 to 2.1 ± 0.2) (p < 0.01) in A549 cells. Therefore, we demonstrate that CKS or PA suppressed the development of respiratory inflammation, hyperresponsiveness, and remodeling by reducing allergic responses, and they may be potential herbal drugs for allergen-induced respiratory disease prevention.

  13. Airway remodeling in asthma: what really matters.

    PubMed

    Fehrenbach, Heinz; Wagner, Christina; Wegmann, Michael

    2017-03-01

    Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and "endotyped" human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.

  14. [Diagnosis and treatment of imported eosinophilia in travellers and immigrants: Recommendations of the Spanish Society of Tropical Medicine and International Health (SEMTSI)].

    PubMed

    Salas-Coronas, J; Ramírez-Olivencia, G; Pérez-Arellano, J L; Belhassen-García, M; Carranza-Rodríguez, C; García-Rodríguez, M; Villar-Garcia, J; Treviño-Maruri, B; Serre-Delcor, N; López-Vélez, R; Norman, F; Gómez-Junyent, J; Soriano-Pérez, M J; Rojo-Marcos, G; Rodríguez de Las Parras, E; Lago-Núñez, M M; Muro, A; Muñoz, J

    2017-02-01

    According to published data, prevalence of imported eosinophilia among travellers and immigrants is set between 8% and 28.5%. Etiological diagnosis is often troublesome, and depending on the depth of the study and on the population analyzed, a parasitic cause is identified in 17% to 75.9% of the individuals. Among the difficulties encountered to compare studies are the heterogeneity of the studied populations, the type of data collection (prospective/retrospective) and different diagnostic protocols. In this document the recommendations of the expert group of the Spanish Society of Tropical Medicine and International Health (SEMTSI) for the diagnosis and treatment of imported eosinophilia are detailed.

  15. Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) / Drug-induced Hypersensitivity Syndrome (DIHS): a review of current concepts.

    PubMed

    Criado, Paulo Ricardo; Criado, Roberta Fachini Jardim; Avancini, João de Magalhães; Santi, Claudia Giuli

    2012-01-01

    The Drug Reaction with Eosinophilia and Systemic Symptoms syndrome, also known as Drug Induced Hypersensitivity Syndrome presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, causing damage to several systems, especially to the kidneys, heart, lungs, and pancreas. Recognition of this syndrome is of paramount importance, since the mortality rate is about 10% to 20%, and a specific therapy may be necessary. The pathogenesis is related to specific drugs, especially the aromatic anticonvulsants, altered immune response, sequential reactivation of herpes virus and association with HLA alleles. Early recognition of the syndrome and withdrawal of the offending drug are the most important and essential steps in the treatment of affected patients. Corticosteroids are the basis of the treatment of the syndrome, which may be associated with intravenous immunoglobulin and, in selected cases, Ganciclovir. The article reviews the current concepts involving this important manifestation of adverse drug reaction.

  16. Genetic control of eosinophilia in mice: gene(s) expressed in bone marrow-derived cells control high responsiveness

    SciTech Connect

    Vadas, M.A.

    1982-02-01

    A heterogeneity in the capacity of strains of mice to mount eosinophilia is described. BALB/c and C3H are eosinophil high responder strains (EO-HR) and CBA and A/J are eosinophil low responder strains (EO-LR), judged by the response of blood eosinophils to Ascaris suum, and the response of blood, bone marrow, and spleen eosinophils to keyhole limpet hemocyanin given 2 days after 150 mg/kg cyclophosphamide. Some of the gene(s) for high responsiveness appear to be dominant because (EO-HR x EO-LR)F/sub 1/ mice were intermediate to high responders. This gene is expressed in bone marrow-derived cells because radiation chimeras of the type EO-HR..-->..F/sub 1/ were high responders and EO-LR..-->..F/sub 1/ were low responders. This description of a genetic control of eosinophilia in mice may be useful in understanding the role of this cell in parasite immunity and allergy.

  17. 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).

  18. Generation of Pig Airways using Rules Developed from the Measurements of Physical Airways

    PubMed Central

    Azad, Md Khurshidul; Mansy, Hansen A.

    2017-01-01

    Background A method for generating bronchial tree would be helpful when constructing models of the tree for benchtop experiments as well as for numerical modeling of flow or sound propagation in the airways. Early studies documented the geometric details of the human airways that were used to develop methods for generating human airway tree. However, methods for generating animal airway tree are scarcer. Earlier studies suggested that the morphology of animal airways can be significantly different from that of humans. Hence, using algorithms for the human airways may not be accurate in generating models of animal airway geometry. Objective The objective of this study is to develop an algorithm for generating pig airway tree based on the geometric details extracted from the physical measurements. Methods In the current study, measured values of branch diameters, lengths and bifurcation angles and rotation of bifurcating planes were used to develop an algorithm that is capable of generating a realistic pig airway tree. Results The generation relations between parent and daughter branches were found to follow certain trends. The diameters and the length of different branches were dependent on airway generations while the bifurcation angles were primarily dependent on bifurcation plane rotations. These relations were sufficient to develop rules for generating a model of the pig large airways. Conclusion The results suggested that the airway tree generated from the algorithm can provide an approximate geometric model of pig airways for computational and benchtop studies. PMID:28255517

  19. Recent trends in airway management

    PubMed Central

    Karlik, Joelle; Aziz, Michael

    2017-01-01

    Tracheal intubation remains a life-saving procedure that is typically not difficult for experienced providers in routine conditions. Unfortunately, difficult intubation remains challenging to predict and intubation conditions may make the event life threatening. Recent technological advances aim to further improve the ease, speed, safety, and success of intubation but have not been fully investigated. Video laryngoscopy, though proven effective in the difficult airway, may result in different intubation success rates in various settings and in different providers’ hands. The rescue surgical airway remains a rarely used but critical skill, and research continues to investigate optimal techniques. This review highlights some of the new thoughts and research on these important topics. PMID:28299194

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

    PubMed Central

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

    2005-01-01

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

  1. Partial airway obstruction following manufacturing defect in laryngeal mask airway (Laryngeal Mask Silken™).

    PubMed

    Jangra, Kiran; Malhotra, Surender Kumar; Saini, Vikas

    2014-10-01

    Laryngeal mask (LM) airway is commonly used for securing airway in day-care surgeries. Various problems have been described while using LM airway. Out of those, mechanical obstruction causing airway compromise is most common. Here, we describe a case report of 4-year-old child who had partial upper airway obstruction due to LM manufacturer's defect. There was a silicon band in upper one-third of shaft of LM airway. This band was made up of the same material as that of LM airway so it was not identifiable on external inspection of transparent shaft. We suggest that such as non-transparent laryngeal mask, a transparent LM airway should also be inspected looking inside the lumen with naked eyes or by using a probe to rule out any manufacturing defect before its insertion.

  2. Method for 3D Airway Topology Extraction

    PubMed Central

    Grothausmann, Roman; Kellner, Manuela; Heidrich, Marko; Lorbeer, Raoul-Amadeus; Ripken, Tammo; Meyer, Heiko; Kuehnel, Mark P.; Ochs, Matthias; Rosenhahn, Bodo

    2015-01-01

    In lungs the number of conducting airway generations as well as bifurcation patterns varies across species and shows specific characteristics relating to illnesses or gene variations. A method to characterize the topology of the mouse airway tree using scanning laser optical tomography (SLOT) tomograms is presented in this paper. It is used to test discrimination between two types of mice based on detected differences in their conducting airway pattern. Based on segmentations of the airways in these tomograms, the main spanning tree of the volume skeleton is computed. The resulting graph structure is used to distinguish between wild type and surfactant protein (SP-D) deficient knock-out mice. PMID:25767561

  3. Automated Lobe-Based Airway Labeling

    PubMed Central

    Gu, Suicheng; Wang, Zhimin; Siegfried, Jill M.; Wilson, David; Bigbee, William L.; Pu, Jiantao

    2012-01-01

    Regional quantitative analysis of airway morphological abnormalities is of great interest in lung disease investigation. Considering that pulmonary lobes are relatively independent functional unit, we develop and test a novel and efficient computerized scheme in this study to automatically and robustly classify the airways into different categories in terms of pulmonary lobe. Given an airway tree, which could be obtained using any available airway segmentation scheme, the developed approach consists of four basic steps: (1) airway skeletonization or centerline extraction, (2) individual airway branch identification, (3) initial rule-based airway classification/labeling, and (4) self-correction of labeling errors. In order to assess the performance of this approach, we applied it to a dataset consisting of 300 chest CT examinations in a batch manner and asked an image analyst to subjectively examine the labeled results. Our preliminary experiment showed that the labeling accuracy for the right upper lobe, the right middle lobe, the right lower lobe, the left upper lobe, and the left lower lobe is 100%, 99.3%, 99.3%, 100%, and 100%, respectively. Among these, only two cases are incorrectly labeled due to the failures in airway detection. It takes around 2 minutes to label an airway tree using this algorithm. PMID:23093951

  4. Anatomic Optical Coherence Tomography of Upper Airways

    NASA Astrophysics Data System (ADS)

    Chin Loy, Anthony; Jing, Joseph; Zhang, Jun; Wang, Yong; Elghobashi, Said; Chen, Zhongping; Wong, Brian J. F.

    The upper airway is a complex and intricate system responsible for respiration, phonation, and deglutition. Obstruction of the upper airways afflicts an estimated 12-18 million Americans. Pharyngeal size and shape are important factors in the pathogenesis of airway obstructions. In addition, nocturnal loss in pharyngeal muscular tone combined with high pharyngeal resistance can lead to collapse of the airway and periodic partial or complete upper airway obstruction. Anatomical optical coherence tomography (OCT) has the potential to provide high-speed three-dimensional tomographic images of the airway lumen without the use of ionizing radiation. In this chapter we describe the methods behind endoscopic OCT imaging and processing to generate full three dimensional anatomical models of the human airway which can be used in conjunction with numerical simulation methods to assess areas of airway obstruction. Combining this structural information with flow dynamic simulations, we can better estimate the site and causes of airway obstruction and better select and design surgery for patients with obstructive sleep apnea.

  5. Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland in a male patient: a case report and literature review.

    PubMed

    Lai, Chi-Yun; Chao, Tzu-Chieh; Lin, Jen-Der; Hsueh, Chuen

    2015-01-01

    Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) was first described by Chan et al in 1991. It is characterized by nest or strands of epidermoid tumor cells with squamous differentiation, rare mucous cells, prominent sclerotic stroma, eosinophilic and lymphoplasmacytic infiltration, and a background of chronic lymphocytic thyroiditis in the non-neoplastic thyroid gland. It is important to recognize SMECE of thyroid and differentiate it from squamous cell carcinoma or other neoplasms with squamous differentiation/metaplasia. In published cases, the SMECE of thyroid gland predominantly occurs in women. We report a case of SMECE of thyroid in a 45-year-old male patient. All cases in male patients were Caucasian described in English literature, and our case is the first one in Asian.

  6. Pattern of airway inflammation and its determinants in children with acute severe asthma.

    PubMed

    Gibson, P G; Norzila, M Z; Fakes, K; Simpson, J; Henry, R L

    1999-10-01

    The aim of this study was to examine the relationship between sputum cell counts and clinical variables in children with an acute exacerbation of asthma. Sputum was successfully obtained from 37 of 42 children presenting to the Emergency Department with acute asthma, using ultrasonically nebulized normal saline (n = 19) or spontaneous expectoration (n = 18). Sputum portions were selected and dispersed, and total and differential cell counts were performed. Sputum supernatant was assessed for eosinophil cationic protein (ECP), interleukin (IL)-5, and IL-8. The exacerbations were of 3 inflammatory cell patterns: eosinophilic (n = 16 or 43% of total), combined eosinophilic/neutrophilic (E/N; n = 13.3 or 35% of total), or noneosinophilic (n = 8 or 22% of total). IL-5 was highest in eosinophilic exacerbations. Combined E/N exacerbations had increased mast cells (77%) and higher sputum ECP levels than eosinophilic exacerbations: 2,146 ng/mL vs. 666 ng/mL (P = 0.04). The speed of onset of the exacerbation was not related to the inflammatory cell profile. Logistic regression identified maintenance asthma treatment (odds ratio (OR), 5.9; 95% confidence interval (CI), 1.3-26.8) and lung function during the acute episode (OR, 4.0; 95% CI, 1.7-93) as significantly associated with the intensity of sputum eosinophilia. Eosinophils were lowest in children who received maintenance treatment with oral corticosteroids compared to those with no background asthma preventer therapy (P = 0.001). In conclusion, we identified three distinct patterns of airway inflammation in children with acute asthma; they included increased eosinophils, combined eosinophilic-neutrophilic infiltration, and a noneosinophilic pattern. Eosinophil degranulation was greatest with the combined eosinophilic/neutrophilic pattern of airway inflammation. Sputum eosinophils were associated with clinical severity, and background asthma therapy, but not with outcome, nor with speed of onset of exacerbations. These

  7. Recombinase Activating Gene 1 Deficiencies Without Omenn Syndrome May Also Present With Eosinophilia and Bone Marrow Fibrosis

    PubMed Central

    Ulusoy, Ezgi; Karaca, Neslihan Edeer; Azarsiz, Elif; Berdeli, Afig; Aksu, Guzide; Kutukculer, Necil

    2016-01-01

    Background Severe combined immunodeficiency (SCID) syndromes are a heterogenous group of diseases characterized by impairment in both cellular and humoral immunity with a range of genetic disorders. Complete recombinase activating gene (RAG) deficiency is associated with classical T-B-NK+ SCID which is the most common phenotype of Turkish SCID patients. There is a broad spectrum of hypomorfic RAG mutations including Omenn syndrome, leaky or atypical SCID with expansion of γδ T cells, autoimmunity and cytomegalovirus (CMV) infections. Methods Twenty-one (44%) patients had RAG1 deficiency of all 44 SCID patients followed up by pediatric immunology department. A retrospective analysis was conducted on the medical records of all SCID patients with RAG1 deficiency. Results Eight patients were classified as T-B-NK+ SCID, five patients as T+B-NK+ SCID (three of these were Omenn phenotype), and eight patients as T+B+NK+ SCID phenotype. Mean age of the whole study group, mean age at onset of symptoms and mean age at diagnosis were 87.7 ± 73.8 (12 - 256), 4.4 ± 8.2 (1 - 36) and 29.1 ± 56.8 (1 - 244) months, respectively. Consanguinity was present in 11 (52%) of 21 patients. Autoimmunity was found in six patients (28%). Ten patients (47%) had CMV infection, four (19%) had Epstein-Barr virus (EBV) infections and three (14%) had Bacillus Calmette-Guerin (BCG) infections. Seven patients who had refractory cytopenia (two pancytopenia and five bicytopenia) underwent bone marrow biopsy, three of whom had bone marrow fibrosis. Future evaluations must be considered about bone marrow fibrosis in RAG1 deficiency patients. Eosinophilia was observed in 10 patients, seven of whom did not have Omenn phenotype. Conclusion Non-Omenn phenotype RAG1 deficiencies can also present with eosinophilia. This report is presented to emphasize that RAG1 mutations may lead to diverse clinical phenotypes. PMID:27081423

  8. Airway management: induced tension pneumoperitoneum

    PubMed Central

    Ahmed, Khedher; Amine, El Ghali Mohamed; Abdelbaki, Azouzi; Jihene, Ayachi; Khaoula, Meddeb; Yamina, Hamdaoui; Mohamed, Boussarsar

    2016-01-01

    Pneumoperitoneum is not always associated with hollow viscus perforation. Such condition is called non-surgical or spontaneous pneumoperitoneum. Intrathoracic causes remain the most frequently reported mechanism inducing this potentially life threatening complication. This clinical condition is associated with therapeutic dilemma. We report a case of a massive isolated pneumoperitoneum causing acute abdominal hypertension syndrome, in a 75 year female, which occurred after difficult airway management and mechanical ventilation. Emergent laparotomy yielded to full recovery. The recognition of such cases for whom surgical management can be avoided is primordial to avoid unnecessary laparotomy and its associated morbidity particularly in the critically ill.

  9. Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma.

    PubMed

    An, S S; Bai, T R; Bates, J H T; Black, J L; Brown, R H; Brusasco, V; Chitano, P; Deng, L; Dowell, M; Eidelman, D H; Fabry, B; Fairbank, N J; Ford, L E; Fredberg, J J; Gerthoffer, W T; Gilbert, S H; Gosens, R; Gunst, S J; Halayko, A J; Ingram, R H; Irvin, C G; James, A L; Janssen, L J; King, G G; Knight, D A; Lauzon, A M; Lakser, O J; Ludwig, M S; Lutchen, K R; Maksym, G N; Martin, J G; Mauad, T; McParland, B E; Mijailovich, S M; Mitchell, H W; Mitchell, R W; Mitzner, W; Murphy, T M; Paré, P D; Pellegrino, R; Sanderson, M J; Schellenberg, R R; Seow, C Y; Silveira, P S P; Smith, P G; Solway, J; Stephens, N L; Sterk, P J; Stewart, A G; Tang, D D; Tepper, R S; Tran, T; Wang, L

    2007-05-01

    Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma. As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series of events leading to asthmatic symptoms is not clear. It is not certain whether, in asthma, there is a change in the intrinsic properties of ASM, a change in the structure and mechanical properties of the noncontractile components of the airway wall, or a change in the interdependence of the airway wall with the surrounding lung parenchyma. All these potential changes could result from acute or chronic airway inflammation and associated tissue repair and remodelling. Anti-inflammatory therapy, however, does not "cure" asthma, and airway hyperresponsiveness can persist in asthmatics, even in the absence of airway inflammation. This is perhaps because the therapy does not directly address a fundamental abnormality of asthma, that of exaggerated airway narrowing due to excessive shortening of ASM. In the present study, a central role for airway smooth muscle in the pathogenesis of airway hyperresponsiveness in asthma is explored.

  10. Mechanisms of inflammation-mediated airway smooth muscle plasticity and airways remodeling in asthma.

    PubMed

    Halayko, Andrew J; Amrani, Yassine

    2003-09-16

    Recent evidence points to progressive structural change in the airway wall, driven by chronic local inflammation, as a fundamental component for development of irreversible airway hyperresponsiveness. Acute and chronic inflammation is orchestrated by cytokines from recruited inflammatory cells, airway myofibroblasts and myocytes. Airway myocytes exhibit functional plasticity in their capacity for contraction, proliferation, and synthesis of matrix protein and cytokines. This confers a principal role in driving different components of the airway remodeling process, and mediating constrictor hyperresponsiveness. Functional plasticity of airway smooth muscle (ASM) is regulated by an array of environmental cues, including cytokines, which mediate their effects through receptors and a number of intracellular signaling pathways. Despite numerous studies of the cellular effects of cytokines on cultured airway myocytes, few have identified how intracellular signaling pathways modulate or induce these cellular responses. This review summarizes current understanding of these concepts and presents a model for the effects of inflammatory mediators on functional plasticity of ASM in asthma.

  11. 21 CFR 868.5110 - Oropharyngeal airway.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Oropharyngeal airway. 868.5110 Section 868.5110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5110 Oropharyngeal airway....

  12. 21 CFR 868.5100 - Nasopharyngeal airway.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway....

  13. 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 ...

  14. Upper airway resistance: species-related differences.

    PubMed

    Kirschvink, N; Reinhold, P

    2010-07-01

    In veterinary medicine, upper airway resistance deserves a particular attention in equines athletes and brachycephalic dogs. Due to the anatomical peculiarities of the upper airway and/or pathological conditions, significant alterations of performance and/or well being might occur in horses and dogs. Physiological specificities and pathological changes of the lower respiratory tract deserve a major attention in other species.

  15. Airway and Extracellular Matrix Mechanics in COPD

    PubMed Central

    Bidan, Cécile M.; Veldsink, Annemiek C.; Meurs, Herman; Gosens, Reinoud

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases worldwide, and is characterized by airflow obstruction that is not fully reversible with treatment. Even though airflow obstruction is caused by airway smooth muscle contraction, the extent of airway narrowing depends on a range of other structural and functional determinants that impact on active and passive tissue mechanics. Cells and extracellular matrix in the airway and parenchymal compartments respond both passively and actively to the mechanical stimulation induced by smooth muscle contraction. In this review, we summarize the factors that regulate airway narrowing and provide insight into the relative contributions of different constituents of the extracellular matrix and their biomechanical impact on airway obstruction. We then review the changes in extracellular matrix composition in the airway and parenchymal compartments at different stages of COPD, and finally discuss how these changes impact airway narrowing and the development of airway hyperresponsiveness. Finally, we position these data in the context of therapeutic research focused on defective tissue repair. As a conclusion, we propose that future works should primarily target mild or early COPD, prior to the widespread structural changes in the alveolar compartment that are more characteristic of severe COPD. PMID:26696894

  16. Difficult Airway Response Team: A Novel Quality Improvement Program for Managing Hospital-Wide Airway Emergencies

    PubMed Central

    Mark, Lynette J.; Herzer, Kurt R.; Cover, Renee; Pandian, Vinciya; Bhatti, Nasir I.; Berkow, Lauren C.; Haut, Elliott R.; Hillel, Alexander T.; Miller, Christina R.; Feller-Kopman, David J.; Schiavi, Adam J.; Xie, Yanjun J.; Lim, Christine; Holzmueller, Christine; Ahmad, Mueen; Thomas, Pradeep; Flint, Paul W.; Mirski, Marek A.

    2015-01-01

    Background Difficult airway cases can quickly become emergencies, increasing the risk of life-threatening complications or death. Emergency airway management outside the operating room is particularly challenging. Methods We developed a quality improvement program—the Difficult Airway Response Team (DART)—to improve emergency airway management outside the operating room. DART was implemented by a team of anesthesiologists, otolaryngologists, trauma surgeons, emergency medicine physicians, and risk managers in 2005 at The Johns Hopkins Hospital in Baltimore, Maryland. The DART program had three core components: operations, safety, and education. The operations component focused on developing a multidisciplinary difficult airway response team, standardizing the emergency response process, and deploying difficult airway equipment carts throughout the hospital. The safety component focused on real-time monitoring of DART activations and learning from past DART events to continuously improve system-level performance. This objective entailed monitoring the paging system, reporting difficult airway events and DART activations to a web-based registry, and using in situ simulations to identify and mitigate defects in the emergency airway management process. The educational component included development of a multispecialty difficult airway curriculum encompassing case-based lectures, simulation, and team building/communication to ensure consistency of care. Educational materials were also developed for non-DART staff and patients to inform them about the needs of patients with difficult airways and ensure continuity of care with other providers after discharge. Results Between July 2008 and June 2013, DART managed 360 adult difficult airway events comprising 8% of all code activations. Predisposing patient factors included body mass index > 40, history of head and neck tumor, prior difficult intubation, cervical spine injury, airway edema, airway bleeding, and previous

  17. The critical airway in adults: The facts

    PubMed Central

    Bonanno, Fabrizio Giuseppe

    2012-01-01

    An algorithm on the indications and timing for a surgical airway in emergency as such cannot be drawn due to the multiplicity of variables and the inapplicability in the context of life-threatening critical emergency, where human brain elaborates decisions better in cluster rather than in binary fashion. In particular, in emergency or urgent scenarios, there is no clear or established consensus as to specifically who should receive a tracheostomy as a life-saving procedure; and more importantly, when. The two classical indications for emergency tracheostomy (laryngeal injury and failure to secure airway with endotracheal intubation or cricothyroidotomy) are too generic and encompass a broad spectrum of possibilities. In literature, specific indications for emergency tracheostomy are scattered and are biased, partially comprehensive, not clearly described or not homogeneously gathered. The review highlights the indications and timing for an emergency surgical airway and gives recommendations on which surgical airway method to use in critical airway. PMID:22787346

  18. Investigating the geometry of pig airways using computed tomography

    NASA Astrophysics Data System (ADS)

    Mansy, Hansen A.; Azad, Md Khurshidul; McMurray, Brandon; Henry, Brian; Royston, Thomas J.; Sandler, Richard H.

    2015-03-01

    Numerical modeling of sound propagation in the airways requires accurate knowledge of the airway geometry. These models are often validated using human and animal experiments. While many studies documented the geometric details of the human airways, information about the geometry of pig airways is scarcer. In addition, the morphology of animal airways can be significantly different from that of humans. The objective of this study is to measure the airway diameter, length and bifurcation angles in domestic pigs using computed tomography. After imaging the lungs of 3 pigs, segmentation software tools were used to extract the geometry of the airway lumen. The airway dimensions were then measured from the resulting 3 D models for the first 10 airway generations. Results showed that the size and morphology of the airways of different animals were similar. The measured airway dimensions were compared with those of the human airways. While the trachea diameter was found to be comparable to the adult human, the diameter, length and branching angles of other airways were noticeably different from that of humans. For example, pigs consistently had an early airway branching from the trachea that feeds the superior (top) right lung lobe proximal to the carina. This branch is absent in the human airways. These results suggested that the human geometry may not be a good approximation of the pig airways and may contribute to increasing the errors when the human airway geometric values are used in computational models of the pig chest.

  19. Intrathoracic airway measurement: ex-vivo validation

    NASA Astrophysics Data System (ADS)

    Reinhardt, Joseph M.; Raab, Stephen A.; D'Souza, Neil D.; Hoffman, Eric A.

    1997-05-01

    High-resolution x-ray CT (HRCT) provides detailed images of the lungs and bronchial tree. HRCT-based imaging and quantitation of peripheral bronchial airway geometry provides a valuable tool for assessing regional airway physiology. Such measurements have been sued to address physiological questions related to the mechanics of airway collapse in sleep apnea, the measurement of airway response to broncho-constriction agents, and to evaluate and track the progression of disease affecting the airways, such as asthma and cystic fibrosis. Significant attention has been paid to the measurements of extra- and intra-thoracic airways in 2D sections from volumetric x-ray CT. A variety of manual and semi-automatic techniques have been proposed for airway geometry measurement, including the use of standardized display window and level settings for caliper measurements, methods based on manual or semi-automatic border tracing, and more objective, quantitative approaches such as the use of the 'half-max' criteria. A recently proposed measurements technique uses a model-based deconvolution to estimate the location of the inner and outer airway walls. Validation using a plexiglass phantom indicates that the model-based method is more accurate than the half-max approach for thin-walled structures. In vivo validation of these airway measurement techniques is difficult because of the problems in identifying a reliable measurement 'gold standard.' In this paper we report on ex vivo validation of the half-max and model-based methods using an excised pig lung. The lung is sliced into thin sections of tissue and scanned using an electron beam CT scanner. Airways of interest are measured from the CT images, and also measured with using a microscope and micrometer to obtain a measurement gold standard. The result show no significant difference between the model-based measurements and the gold standard; while the half-max estimates exhibited a measurement bias and were significantly

  20. Educating the Educator: Teaching Airway Adjunct Techniques in Athletic Training

    ERIC Educational Resources Information Center

    Berry, David C.; Seitz, S. Robert

    2011-01-01

    The 5th edition of the "Athletic Training Education Competencies" ("Competencies") now requires athletic training educators (ATEs) to introduce into the curriculum various types of airway adjuncts including: (1) oropharyngeal airways (OPA), (2) nasopharyngeal airways (NPA), (3) supraglottic airways (SGA), and (4) suction. The addition of these…

  1. Airway adequacy, head posture, and craniofacial morphology.

    PubMed

    Solow, B; Siersbaek-Nielsen, S; Greve, E

    1984-09-01

    Previous studies of different samples have demonstrated associations between craniocervical angulation and craniofacial morphology, between airway obstruction by adenoids and craniofacial morphology, and between airway obstruction and craniocervical angulation. A hypothesis to account for the different sets of associations was suggested by Solow and Kreiborg in 1977. In the present study, the three sets of associations were examined in a single group of nonpathologic subjects with no history of airway obstruction. Cephalometric radiographs taken in the natural head position and rhinomanometric recordings were obtained from twenty-four children 7 to 9 years of age. Correlations were calculated between twenty-seven morphologic, eight postural, and two airway variables. A large craniocervical angle was, on the average, seen in connection with small mandibular dimensions, mandibular retrognathism, and a large mandibular inclination. Obstructed nasopharyngeal airways (defined as a small pm-ad 2 radiographic distance and a large nasal respiratory resistance, NRR, determined rhinomanometrically) were, on the average, seen in connection with a large craniocervical angle and with small mandibular dimensions, mandibular retrognathism, a large mandibular inclination, and retroclination of the upper incisors. The observed correlations were in agreement with the predicted pattern of associations between craniofacial morphology, craniocervical angulation, and airway resistance, thus suggesting the simultaneous presence of such associations in the sample of nonpathologic subjects with no history of airway obstruction.

  2. Comparison of analysis methods for airway quantification

    NASA Astrophysics Data System (ADS)

    Odry, Benjamin L.; Kiraly, Atilla P.; Novak, Carol L.; Naidich, David P.

    2012-03-01

    Diseased airways have been known for several years as a possible contributing factor to airflow limitation in Chronic Obstructive Pulmonary Diseases (COPD). Quantification of disease severity through the evaluation of airway dimensions - wall thickness and lumen diameter - has gained increased attention, thanks to the availability of multi-slice computed tomography (CT). Novel approaches have focused on automated methods of measurement as a faster and more objective means that the visual assessment routinely employed in the clinic. Since the Full-Width Half-Maximum (FWHM) method of airway measurement was introduced two decades ago [1], several new techniques for quantifying airways have been detailed in the literature, but no approach has truly become a standard for such analysis. Our own research group has presented two alternative approaches for determining airway dimensions, one involving a minimum path and the other active contours [2, 3]. With an increasing number of techniques dedicated to the same goal, we decided to take a step back and analyze the differences of these methods. We consequently put to the test our two methods of analysis and the FWHM approach. We first measured a set of 5 airways from a phantom of known dimensions. Then we compared measurements from the three methods to those of two independent readers, performed on 35 airways in 5 patients. We elaborate on the differences of each approach and suggest conclusions on which could be defined as the best one.

  3. Airway smooth muscle growth in asthma: proliferation, hypertrophy, and migration.

    PubMed

    Bentley, J Kelley; Hershenson, Marc B

    2008-01-01

    Increased airway smooth muscle mass is present in fatal and non-fatal asthma. However, little information is available regarding the cellular mechanism (i.e., hyperplasia vs. hypertrophy). Even less information exists regarding the functional consequences of airway smooth muscle remodeling. It would appear that increased airway smooth muscle mass would tend to increase airway narrowing and airflow obstruction. However, the precise effects of increased airway smooth muscle mass on airway narrowing are not known. This review will consider the evidence for airway smooth muscle cell proliferation and hypertrophy in asthma, potential functional effects, and biochemical mechanisms.

  4. An unusual case of splenomegaly and increased lactate dehydrogenase heralding acute myeloid leukemia with eosinophilia and RUNX1–MECOM fusion transcripts

    PubMed Central

    Forghieri, Fabio; Bigliardi, Sara; Morselli, Monica; Potenza, Leonardo; Fantuzzi, Valeria; Faglioni, Laura; Nasillo, Vincenzo; Messerotti, Andrea; Paolini, Ambra; Luppi, Mario

    2014-01-01

    We report the first case of acute myeloid leukemia (AML) with RUNX1–MECOM fusion transcripts, showing marked eosinophilia. A 63-year old man admitted in August 2013, had previously been observed in April 2013, because of persisting homogeneous splenomegaly and increased LDH, which were initially attributed to both minor β-thalassemia and previous acute myocardial infarction. However, based upon the retrospective analysis of clinical features combined with the documentation of both JAK2 V617F and c-KIT D816V mutations at AML diagnosis, an aggressive leukemic transformation with eosinophilia of a previously unrecognized myeloproliferative neoplasm, rather than the occurrence of de novo AML, may be hypothesized. PMID:25379409

  5. Myeloid sarcoma causing airway obstruction

    PubMed Central

    Krause, John R.

    2017-01-01

    Myeloid sarcoma is an extramedullary collection of blasts of the myeloid series that partially or totally effaces the architecture of the tissue in which it is found. These tumors have been described in many sites of the body, but the skin, lymph nodes, gastrointestinal tract, bone, soft tissue, and testes are most common. They can arise in a patient following the diagnosis of acute myeloid leukemia, but they may also be precursors of leukemia and should be considered diagnostic for acute myeloid leukemia. The differential diagnosis of this neoplasm includes malignant lymphoma, with which it is often mistaken, leading to diagnostic and therapeutic delays. We present the case of an 84-year-old African American man with a history of renal disease secondary to hypertension and coronary artery disease without any prior history of malignancies who presented with airway obstruction. He was diagnosed with a myeloid sarcoma of the mediastinum compressing his trachea.

  6. The Development and Application of Airway Devices in China

    PubMed Central

    Chen, Xiangdong; Ma, Wuhua; Liu, Renyu; Yao, Shanglong

    2017-01-01

    Airway management is one of the most important tasks for anesthesiologists. Anesthesiologists are experts in airway management and have made tremendous contribution to the development of the airway devices. Chinese anesthesiologists have made significant contribution in introducing advanced airway management and developing innovative techniques and devices for airway management in China. This article overviews the development and application of airway devices in China as well as the dedication and contribution of Chinese experts in the development of novel airway devices. With the development of science and technology accompanied by the advanced knowledge in airway management, more effective and safe artificial airways will be developed for clinical practice. The authors believe that Chinese experts will continue their outstanding contribution to the development of innovative airway devices, systems and knowledge. PMID:28191485

  7. Pharmacology of airway afferent nerve activity

    PubMed Central

    Undem, Bradley J; Carr, Michael J

    2001-01-01

    Afferent nerves in the airways serve to regulate breathing pattern, cough, and airway autonomic neural tone. Pharmacologic agents that influence afferent nerve activity can be subclassified into compounds that modulate activity by indirect means (e.g. bronchial smooth muscle spasmogens) and those that act directly on the nerves. Directly acting agents affect afferent nerve activity by interacting with various ion channels and receptors within the membrane of the afferent terminals. Whether by direct or indirect means, most compounds that enter the airspace will modify afferent nerve activity, and through this action alter airway physiology. PMID:11686889

  8. Firefighting acutely increases airway responsiveness.

    PubMed

    Sherman, C B; Barnhart, S; Miller, M F; Segal, M R; Aitken, M; Schoene, R; Daniell, W; Rosenstock, L

    1989-07-01

    The acute effects of the products of combustion and pyrolysis on airway responsiveness among firefighters are poorly documented. To study this relationship, spirometry and methacholine challenge testing (MCT) were performed on 18 active Seattle firefighters before and 5 to 24 h after firefighting. Body plethysmography was used to measure changes in specific airway conductance (SGaw), and results of MCT were analyzed using PD35-SGaw, the cumulative dose causing a 35% decrease in SGaw. Subjects who did not react by the end of the protocol were assigned a value of 640 inhalational units, the largest cumulative dose. Fire exposure was defined as the total time (hours) spent without a self-contained breathing apparatus at the firesite and was categorized as mild (less than 1 h, n = 7), moderate (1 to 2 h, n = 5), or severe (greater than 2 h, n = 6). Mean age of the 18 firefighters was 36.7 +/- 6.7 yr (range, 25 to 51), with a mean of 9.1 +/- 7.9 active years in the trade (range, zero to 22). None was known to be asthmatic. After firefighting, FEV1 % predicted (%pred) and FEF25-75 %pred significantly decreased by means of 3.4 +/- 1.1% and 5.6 +/- 2.6%, respectively. The mean decline in PD35-SGaw after firefighting was 184.5 +/- 53.2 units (p = 0.003). This observed decline in PD35-SGaw could not be explained by decrements in prechallenge SGaw, FEV1, or FVC.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident postinfectious glomerulonephritis

    PubMed Central

    Kim, Kyung Min; Sung, Kyoung; Yang, Hea Koung; Kim, Seong Heon; Kim, Hye Young; Ban, Gil Ho; Park, Su Eun; Lee, Hyoung Doo

    2016-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature. PMID:27186222

  10. Assessment of Tissue Eosinophilia as a Prognosticator in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma—An Image Analysis Study

    PubMed Central

    Jain, Megha; Kasetty, Sowmya; Sudheendra, U. S.; Tijare, Manisha; Khan, Samar; Desai, Ami

    2014-01-01

    Association of tissue eosinophilia with oral squamous cell carcinoma has shown variable results ranging from favourable to unfavourable or even having no influence on prognosis. Also, very few studies have been done to know the role of eosinophils in premalignancy. So the present study investigated role of eosinophilic infiltration in oral precancer and cancer and its possible use as a prognosticator. 60 histopathologically proven cases (20 cases each of metastatic and nonmetastatic oral squamous cell carcinoma and oral leukoplakia with dysplasia of various grades) were included. Congo red is used as a special stain for eosinophils. Each specimen slide was viewed under high power in 10 consecutive microscopic fields for counting of eosinophils. As a result, a significant increase in eosinophil count was found in oral carcinomas compared to dysplasia. Nonmetastatic cases showed higher counts than metastatic carcinomas. So, it is concluded that eosinophilia is a favourable histopathological prognostic factor in oral cancer. Moreover, higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion thus suggesting that quantitative assessment of tissue eosinophilia should become a part of the routine histopathological diagnosis for oral precancer and OSCC. PMID:24693457

  11. Diesel exhaust particles and airway inflammation

    EPA Science Inventory

    Purpose of review. Epidemiologic investigation has associated traffic-related air pollution with adverse human health outcomes. The capacity ofdiesel exhaust particles (DEP), a major emission source air pollution particle, to initiate an airway inflammation has subsequently been ...

  12. Airway management for cervical spine surgery.

    PubMed

    Farag, Ehab

    2016-03-01

    Cervical spine surgery is one of the most commonly performed spine surgeries in the United States, and 90% of the cases are related to degenerative cervical spine disease (the rest to cervical spine trauma and/or instability). The airway management for cervical spine surgery represents a crucial step in the anesthetic management to avoid injury to the cervical cord. The crux for upper airway management for cervical spine surgery is maintaining the neck in a neutral position with minimal neck movement during endotracheal intubation. Therefore, the conventional direct laryngoscopy (DL) can be unsuitable for securing the upper airway in cervical spine surgery, especially in cases of cervical spine instability and myelopathy. This review discusses the most recent evidence-based facts of the main advantages and limitations of different techniques available for upper airway management for cervical spine surgery.

  13. Therapeutic bronchoscopic interventions for malignant airway obstruction

    PubMed Central

    Dalar, Levent; Özdemir, Cengiz; Abul, Yasin; Karasulu, Levent; Sökücü, Sinem Nedime; Akbaş, Ayşegül; Altın, Sedat

    2016-01-01

    Abstract There is no definitive consensus about the factors affecting the choice of interventional bronchoscopy in the management of malignant airway obstruction. The present study defines the choice of the interventional bronchoscopic modality and analyzes the factors influencing survival in patients with malignant central airway obstruction. Totally, over 7 years, 802 interventional rigid bronchoscopic procedures were applied in 547 patients having malignant airway obstruction. There was a significant association between the type of stent and the site of the lesion in the present study. Patients with tracheal involvement and/or involvement of the main bronchi had the worst prognosis. The sites of the lesion and endobronchial treatment modality were independent predictors of survival in the present study. The selection of different types of airway stents can be considered on the base of site of the lesion. Survival can be estimated based on the site of the lesion and endobronchial brochoscopic modality used. PMID:27281104

  14. Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review

    PubMed Central

    EL Omairi, Nissrine; Abourazzak, Sanae; Chaouki, Sanae; Atmani, Samir; Hida, Moustapha

    2014-01-01

    Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug. PMID:25360193

  15. The pan-B cell marker CD22 is expressed on gastrointestinal eosinophils and negatively regulates tissue eosinophilia

    PubMed Central

    Wen, Ting; Mingler, Melissa K.; Blanchard, Carine; Wahl, Benjamin; Pabst, Oliver; Rothenberg, Marc E.

    2011-01-01

    CD22 is currently recognized as a B cell-specific Siglec and has been exploited therapeutically with humanized anti-CD22 monoclonal antibody having been used against B cell leukemia. Herein, tissue-specific eosinophil mRNA microarray analysis identified that CD22 transcript levels of murine gastrointestinal (GI) eosinophils are 10-fold higher than those of lung eosinophils. In order to confirm the mRNA data at the protein level, we developed a FACS-based protocol designed to phenotype live GI eosinophils isolated from the murine lamina propria. Indeed, we found that jejunum eosinophils expressed remarkably high levels of surface CD22, similar to levels found in B cells across multiple mouse strains. In contrast, CD22 was undetectable on eosinophils from the colon, blood, thymus, spleen, uterus, peritoneal cavity and allergen-challenged lung. Eosinophils isolated from newborn mice did not express CD22 but subsequently upregulated CD22 expression to adult levels within the first 10 days after birth. The GI lamina propria from CD22 gene-targeted mice harbored more eosinophils than wild-type control mice, while the GI eosinophil turnover rate was unaltered in the absence of CD22. Our findings identify a novel expression pattern and tissue eosinophilia-regulating function for the “B cell-specific” inhibitory molecule CD22 on GI eosinophils. PMID:22190185

  16. Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review.

    PubMed

    E L omairi, Nissrine; Abourazzak, Sanae; Chaouki, Sanae; Atmani, Samir; Hida, Moustapha

    2014-01-01

    Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug.

  17. Comparison of the Causes and Clinical Features of Drug Rash With Eosinophilia and Systemic Symptoms and Stevens-Johnson Syndrome

    PubMed Central

    Jeung, Yun-Jin; Lee, Jin-Young; Oh, Mi-Jung; Choi, Dong-Chull

    2010-01-01

    Purpose Drug rash with eosinophilia and systemic symptoms (DRESS) and the Stevens-Johnson syndrome (SJS) are both severe drug reactions. Their pathogenesis and clinical features differ. This study compared the causes and clinical features of SJS and DRESS. Methods We enrolled 31 patients who were diagnosed with DRESS (number=11) and SJS (number=20). We retrospectively compared the clinical and laboratory data of patients with the two disorders. Results In both syndromes, the most common prodromal symptoms were itching, fever, and malaise. The liver was commonly involved in DRESS. The mucosal membrane of the oral cavity and eyes was often affected in SJS. The most common causative agents in both diseases were antibiotics (DRESS 4/11 (37%), SJS 8/20 (40%)), followed by anticonvulsants (DRESS 3/11 (27%), SJS 7/20 (35%)). In addition, dapsone, allopurinol, clopidogrel, sulfasalazine and non-steroidal anti-inflammatory drugs (NSAIDs) were sporadic causes. Conclusions The most common causes of DRESS and SJS were antibiotics, followed by anticonvulsants, NSAIDs and sulfonamides. The increase in the use of antibiotics in Korea might explain this finding. PMID:20358026

  18. Taste Receptors in Upper Airway Immunity.

    PubMed

    Carey, Ryan M; Lee, Robert J; Cohen, Noam A

    2016-01-01

    Taste receptors are well known for their role in communicating information from the tongue to the brain about nutritional value or potential toxicity of ingested substances. More recently, it has been shown that taste receptors are expressed in other locations throughout the body, including the airway, gastrointestinal tract, brain and pancreas. The roles of some 'extraoral' taste receptors are largely unknown, but emerging research suggests that bitter and sweet taste receptors in the airway are capable of sensing bacteria and modulating innate immunity. This chapter focuses on the role of bitter and sweet taste receptors in human airway innate immunity and their clinical relevance to rhinosinusitis. The bitter taste receptor T2R38 expressed in sinonasal cilia detects bitter bacterial quorum-sensing molecules and activates a nitric oxide-dependent innate immune response; moreover, there are polymorphisms in T2R38 that underlie susceptibility to chronic rhinosinusitis (CRS). Bitter and sweet receptors in sinonasal solitary chemosensory cells control secretion of antimicrobial peptides in the upper airway and may have a profound impact on airway infections in patients with CRS and diabetes. Future research on taste receptors in the airway has enormous potential to expand our understanding of host-pathogen immune interactions and provide novel therapeutic targets.

  19. Sensory nerves in lung and airways.

    PubMed

    Lee, Lu-Yuan; Yu, Jerry

    2014-01-01

    Sensory nerves innervating the lung and airways play an important role in regulating various cardiopulmonary functions and maintaining homeostasis under both healthy and disease conditions. Their activities conducted by both vagal and sympathetic afferents are also responsible for eliciting important defense reflexes that protect the lung and body from potential health-hazardous effects of airborne particulates and chemical irritants. This article reviews the morphology, transduction properties, reflex functions, and respiratory sensations of these receptors, focusing primarily on recent findings derived from using new technologies such as neural immunochemistry, isolated airway-nerve preparation, cultured airway neurons, patch-clamp electrophysiology, transgenic mice, and other cellular and molecular approaches. Studies of the signal transduction of mechanosensitive afferents have revealed a new concept of sensory unit and cellular mechanism of activation, and identified additional types of sensory receptors in the lung. Chemosensitive properties of these lung afferents are further characterized by the expression of specific ligand-gated ion channels on nerve terminals, ganglion origin, and responses to the action of various inflammatory cells, mediators, and cytokines during acute and chronic airway inflammation and injuries. Increasing interest and extensive investigations have been focused on uncovering the mechanisms underlying hypersensitivity of these airway afferents, and their role in the manifestation of various symptoms under pathophysiological conditions. Several important and challenging questions regarding these sensory nerves are discussed. Searching for these answers will be a critical step in developing the translational research and effective treatments of airway diseases.

  20. Regulation of Airway Mucin Gene Expression

    PubMed Central

    Thai, Philip; Loukoianov, Artem; Wachi, Shinichiro; Wu, Reen

    2015-01-01

    Mucins are important components that exert a variety of functions in cell-cell interaction, epidermal growth factor receptor signaling, and airways protection. In the conducting airways of the lungs, mucins are the major contributor to the viscoelastic property of mucous secretion, which is the major barrier to trapping inhaled microbial organism, particulates, and oxidative pollutants. The homeostasis of mucin production is an important feature in conducting airways for the maintenance of mucociliary function. Aberrant mucin secretion and accumulation in airway lumen are clinical hallmarks associated with various lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, and lung cancer. Among 20 known mucin genes identified, 11 of them have been verified at either the mRNA and/or protein level in airways. The regulation of mucin genes is complicated, as are the mediators and signaling pathways. This review summarizes the current view on the mediators, the signaling pathways, and the transcriptional units that are involved in the regulation of airway mucin gene expression. In addition, we also point out essential features of epigenetic mechanisms for the regulation of these genes. PMID:17961085

  1. Nitrogen Dioxide Exposure and Airway Responsiveness in ...

    EPA Pesticide Factsheets

    Controlled human exposure studies evaluating the effect of inhaled NO2 on the inherent responsiveness of the airways to challenge by bronchoconstricting agents have had mixed results. In general, existing meta-analyses show statistically significant effects of NO2 on the airway responsiveness of individuals with asthma. However, no meta-analysis has provided a comprehensive assessment of clinical relevance of changes in airway responsiveness, the potential for methodological biases in the original papers, and the distribution of responses. This paper provides analyses showing that a statistically significant fraction, 70% of individuals with asthma exposed to NO2 at rest, experience increases in airway responsiveness following 30-minute exposures to NO2 in the range of 200 to 300 ppb and following 60-minute exposures to 100 ppb. The distribution of changes in airway responsiveness is log-normally distributed with a median change of 0.75 (provocative dose following NO2 divided by provocative dose following filtered air exposure) and geometric standard deviation of 1.88. About a quarter of the exposed individuals experience a clinically relevant reduction in their provocative dose due to NO2 relative to air exposure. The fraction experiencing an increase in responsiveness was statistically significant and robust to exclusion of individual studies. Results showed minimal change in airway responsiveness for individuals exposed to NO2 during exercise. A variety of fa

  2. Mechanical Properties of the Upper Airway

    PubMed Central

    Strohl, Kingman P.; Butler, James P.; Malhotra, Atul

    2013-01-01

    The importance of the upper airway (nose, pharynx, and larynx) in health and in the pathogenesis of sleep apnea, asthma, and other airway diseases, discussed elsewhere in the Comprehensive Physiology series, prompts this review of the biomechanical properties and functional aspects of the upper airway. There is a literature based on anatomic or structural descriptions in static circumstances, albeit studied in limited numbers of individuals in both health and disease. As for dynamic features, the literature is limited to studies of pressure and flow through all or parts of the upper airway and to the effects of muscle activation on such features; however, the links between structure and function through airway size, shape, and compliance remain a topic that is completely open for investigation, particularly through analyses using concepts of fluid and structural mechanics. Throughout are included both historically seminal references, as well as those serving as signposts or updated reviews. This article should be considered a resource for concepts needed for the application of biomechanical models of upper airway physiology, applicable to understanding the pathophysiology of disease and anticipated results of treatment interventions. PMID:23723026

  3. Slowly Adapting Sensory Units Have More Receptors in Large Airways than in Small Airways in Rabbits

    PubMed Central

    Liu, Jun; Song, Nana; Guardiola, Juan; Roman, Jesse; Yu, Jerry

    2016-01-01

    Sensory units of pulmonary slowly adapting receptors (SARs) are more active in large airways than in small airways. However, there is no explanation for this phenomenon. Although sensory structures in large airways resemble those in small airways, they are bigger and more complex. Possibly, a larger receptor provides greater surface area for depolarization, and thus has a lower activating threshold and/or a higher sensitivity to stretch, leading to more nerve electrical activities. Recently, a single sensory unit has been reported to contain multiple receptors. Therefore, sensory units in large airways may contain more SARs, which may contribute to high activities. To test this hypothesis, we used a double staining technique to identify sensory receptor sizes. We labeled the sensory structure with Na+/K+-ATPase antibodies and the myelin sheath with myelin basic protein (MBP) antibodies. A SAR can be defined as the end formation beyond MBP labeling. Thus, we are able to compare sizes of sensory structures and SARs in large (trachea and bronchi) vs. small (bronchioles <500 μm in diameter) airways in the rabbit. We found that even though the sensory structure was bigger in large airways than in small airways (3340 ± 223 vs. 1168 ± 103 μm2; P < 0.0001), there was no difference in receptor sizes (349 ± 14 vs. 326 ± 16 μm2; > 0.05). However, the sensory structure contains more SARs in large airways than in small airways (9.6 ± 0.6 vs. 3.6 ± 0.3; P < 0.0001). Thus, our data support the hypothesis that greater numbers of SARs in sensory units of large airways may contribute to higher activities. PMID:28018231

  4. Slowly Adapting Sensory Units Have More Receptors in Large Airways than in Small Airways in Rabbits.

    PubMed

    Liu, Jun; Song, Nana; Guardiola, Juan; Roman, Jesse; Yu, Jerry

    2016-01-01

    Sensory units of pulmonary slowly adapting receptors (SARs) are more active in large airways than in small airways. However, there is no explanation for this phenomenon. Although sensory structures in large airways resemble those in small airways, they are bigger and more complex. Possibly, a larger receptor provides greater surface area for depolarization, and thus has a lower activating threshold and/or a higher sensitivity to stretch, leading to more nerve electrical activities. Recently, a single sensory unit has been reported to contain multiple receptors. Therefore, sensory units in large airways may contain more SARs, which may contribute to high activities. To test this hypothesis, we used a double staining technique to identify sensory receptor sizes. We labeled the sensory structure with Na(+)/K(+)-ATPase antibodies and the myelin sheath with myelin basic protein (MBP) antibodies. A SAR can be defined as the end formation beyond MBP labeling. Thus, we are able to compare sizes of sensory structures and SARs in large (trachea and bronchi) vs. small (bronchioles <500 μm in diameter) airways in the rabbit. We found that even though the sensory structure was bigger in large airways than in small airways (3340 ± 223 vs. 1168 ± 103 μm(2); P < 0.0001), there was no difference in receptor sizes (349 ± 14 vs. 326 ± 16 μm(2); > 0.05). However, the sensory structure contains more SARs in large airways than in small airways (9.6 ± 0.6 vs. 3.6 ± 0.3; P < 0.0001). Thus, our data support the hypothesis that greater numbers of SARs in sensory units of large airways may contribute to higher activities.

  5. Intradermal cytosine-phosphate-guanosine treatment reduces lung inflammation but induces IFN-γ-mediated airway hyperreactivity in a murine model of natural rubber latex allergy.

    PubMed

    Haapakoski, Rita; Karisola, Piia; Fyhrquist, Nanna; Savinko, Terhi; Wolff, Henrik; Turjanmaa, Kristiina; Palosuo, Timo; Reunala, Timo; Lauerma, Antti; Alenius, Harri

    2011-05-01

    Asthma and other allergic diseases are continuously increasing, causing considerable economic and sociologic burden to society. The hygiene hypothesis proposes that lack of microbial T helper (Th) 1-like stimulation during early childhood leads to increased Th2-driven allergic disorders later in life. Immunostimulatory cytosine-phosphate-guanosine (CpG)-oligodeoxynucleotide motifs are candidate molecules for immunotherapeutic studies, as they have been shown to shift the Th2 response toward the Th1 direction and reduce allergic symptoms. Using natural rubber latex (NRL)-induced murine model of asthma, we demonstrated that intradermal CpG administration with allergen reduced pulmonary eosinophilia, mucus production, and Th2-type cytokines, but unexpectedly induced airway hyperreactivity (AHR) to inhaled methacholine, one of the hallmarks of asthma. We found that induction in AHR was dependent on STAT4, but independent of STAT6 signaling. CpG treatment increased production of IFN-γ in the airways and shifted the ratio of CD4(+):CD8(+) T cells toward CD8(+) dominance. By blocking soluble IFN-γ with neutralizing antibody, AHR diminished and the CD4(+):CD8(+) ratio returned to CD4(+) dominance. These results indicate that increased production of IFN-γ in the lungs may lead to severe side effects, such as enhancement of bronchial hyperreactivity to inhaled allergen. This finding should be taken into consideration when planning prophylaxis treatment of asthma with intradermal CpG injections.

  6. Promotion of airway anastomotic microvascular regeneration and alleviation of airway ischemia by deferoxamine nanoparticles

    PubMed Central

    Tian, Wen; Sung, Yon K.; Sun, Wenchao; Hsu, Joe L.; Manickam, Sathish; Wagh, Dhananjay; Joubert, Lydia-Marie; Semenza, Gregg L.; Rajadas, Jayakumar; Nicolls, Mark R.

    2014-01-01

    Airway tissue ischemia and hypoxia in human lung transplantation is a consequence of the sacrifice of the bronchial circulation during the surgical procedure and is a major risk factor for the development of airway anastomotic complications. Augmented expression of hypoxia-inducible factor (HIF)-1α promotes microvascular repair and alleviates allograft ischemia and hypoxia. Deferoxamine mesylate (DFO) is an FDA-approved iron chelator which has been shown to upregulate cellular HIF-1α. Here, we developed a nanoparticle formulation of DFO that can be topically applied to airway transplants at the time of surgery. In a mouse orthotopic tracheal transplant (OTT) model, the DFO nanoparticle was highly effective in enhancing airway microvascular perfusion following transplantation through the production of the angiogenic factors, placental growth factor (PLGF) and stromal cell-derived factor (SDF)-1. The endothelial cells in DFO treated airways displayed higher levels of p-eNOS and Ki67, less apoptosis, and decreased production of perivascular reactive oxygen species (ROS) compared to vehicle-treated airways. In summary, a DFO formulation topically-applied at the time of surgery successfully augmented airway anastomotic microvascular regeneration and the repair of alloimmune-injured microvasculature. This approach may be an effective topical transplant-conditioning therapy for preventing airway complications following clinical lung transplantation. PMID:24161166

  7. Airway smooth muscle in airway reactivity and remodeling: what have we learned?

    PubMed Central

    2013-01-01

    It is now established that airway smooth muscle (ASM) has roles in determining airway structure and function, well beyond that as the major contractile element. Indeed, changes in ASM function are central to the manifestation of allergic, inflammatory, and fibrotic airway diseases in both children and adults, as well as to airway responses to local and environmental exposures. Emerging evidence points to novel signaling mechanisms within ASM cells of different species that serve to control diverse features, including 1) [Ca2+]i contractility and relaxation, 2) cell proliferation and apoptosis, 3) production and modulation of extracellular components, and 4) release of pro- vs. anti-inflammatory mediators and factors that regulate immunity as well as the function of other airway cell types, such as epithelium, fibroblasts, and nerves. These diverse effects of ASM “activity” result in modulation of bronchoconstriction vs. bronchodilation relevant to airway hyperresponsiveness, airway thickening, and fibrosis that influence compliance. This perspective highlights recent discoveries that reveal the central role of ASM in this regard and helps set the stage for future research toward understanding the pathways regulating ASM and, in turn, the influence of ASM on airway structure and function. Such exploration is key to development of novel therapeutic strategies that influence the pathophysiology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. PMID:24142517

  8. Two-dimensional airway analysis using probabilistic neural networks

    NASA Astrophysics Data System (ADS)

    Tan, Jun; Zheng, Bin; Park, Sang Cheol; Pu, Jiantao; Sciurba, Frank C.; Leader, Joseph K.

    2010-03-01

    Although 3-D airway tree segmentation permits analysis of airway tree paths of practical lengths and facilitates visual inspection, our group developed and tested an automated computer scheme that was operated on individual 2-D CT images to detect airway sections and measure their morphometry and/or dimensions. The algorithm computes a set of airway features including airway lumen area (Ai), airway cross-sectional area (Aw), the ratio (Ra) of Ai to Aw, and the airway wall thickness (Tw) for each detected airway section depicted on the CT image slice. Thus, this 2-D based algorithm does not depend on the accuracy of 3-D airway tree segmentation and does not require that CT examination encompasses the entire lung or reconstructs contiguous images. However, one disadvantage of the 2-D image based schemes is the lack of the ability to identify the airway generation (Gb) of the detected airway section. In this study, we developed and tested a new approach that uses 2-D airway features to assign a generation number to an airway. We developed and tested two probabilistic neural networks (PNN) based on different sets of airway features computed by our 2-D based scheme. The PNNs were trained and tested on 12 lung CT examinations (8 training and 4 testing). The accuracy for the PNN that utilized Ai and Ra for identifying the generation of airway sections varies from 55.4% - 100%. The overall accuracy of the PNN for all detected airway sections that are spread over all generations is 76.7%. Interestingly, adding wall thickness feature (Tw) to PNN did not improve identification accuracy. This preliminary study demonstrates that a set of 2-D airway features may be used to identify the generation number of an airway with reasonable accuracy.

  9. The relation of airway size to lung function

    NASA Astrophysics Data System (ADS)

    Leader, J. Ken; Zheng, Bin; Sciurba, Frank C.; Fuhrman, Carl R.; Bon, Jessica M.; Park, Sang C.; Pu, Jiantao; Gur, David

    2008-03-01

    Chronic obstructive pulmonary disease may cause airway remodeling, and small airways are the mostly likely site of associated airway flow obstruction. Detecting and quantifying airways depicted on a typical computed tomography (CT) images is limited by spatial resolution. In this study, we examined the association between lung function and airway size. CT examinations and spirometry measurement of forced expiratory volume in one second as a percent predicted (FEV I%) from 240 subjects were used in this study. Airway sections depicted in axial CT section were automatically detected and quantified. Pearson correlation coefficients (PCC) were computed to compare lung function across three size categories: (1) all detected airways, (2) the smallest 50% of detected airways, and (3) the largest 50% of detected airways using the CORANOVA test. The mean number of all airways detected per subject was 117.4 (+/- 40.1) with mean size ranging from 20.2 to 50.0 mm2. The correlation between lung function (i.e., FEV I) and airway morphometry associated with airway remodeling and airflow obstruction (i.e., lumen perimeter and wall area as a percent of total airway area) was significantly stronger for smaller compared to larger airways (p < 0.05). The PCCs between FEV I and all airways, the smallest 50%, and the largest 50% were 0.583, 0.617, 0.523, respectively, for lumen perimeter and -0.560, -0.584, and -0.514, respectively, for wall area percent. In conclusion, analyzing a set of smaller airways compared to larger airways may improve detection of an association between lung function and airway morphology change.

  10. Airway pressure with chest compressions versus Heimlich manoeuvre in recently dead adults with complete airway obstruction.

    PubMed

    Langhelle, A; Sunde, K; Wik, L; Steen, P A

    2000-04-01

    In a previous case report a standard chest compression successfully removed a foreign body from the airway after the Heimlich manoeuvre had failed. Based on this case, standard chest compressions and Heimlich manoeuvres were performed by emergency physicians on 12 unselected cadavers with a simulated complete airway obstruction in a randomised crossover design. The mean peak airway pressure was significantly lower with abdominal thrusts compared to chest compressions, 26.4+/-19.8 cmH(2)O versus 40.8+/-16.4 cmH(2)O, respectively (P=0.005, 95% confidence interval for the mean difference 5.3-23.4 cmH(2)O). Standard chest compressions therefore have the potential of being more effective than the Heimlich manoeuvre for the management of complete airway obstruction by a foreign body in an unconscious patient. Removal of the Heimlich manoeuvre from the resuscitation algorithm for unconscious patients with suspected airway obstruction will also simplify training.

  11. Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways

    PubMed Central

    Gilley, Sandra K.; Stenbit, Antine E.; Pasek, Raymond C.; Sas, Kelli M.; Steele, Stacy L.; Amria, May; Bunni, Marlene A.; Estell, Kimberly P.; Schwiebert, Lisa M.; Flume, Patrick; Gooz, Monika; Haycraft, Courtney J.; Yoder, Bradley K.; Miller, Caroline; Pavlik, Jacqueline A.; Turner, Grant A.; Sisson, Joseph H.

    2013-01-01

    The mechanisms for the development of bronchiectasis and airway hyperreactivity have not been fully elucidated. Although genetic, acquired diseases and environmental influences may play a role, it is also possible that motile cilia can influence this disease process. We hypothesized that deletion of a key intraflagellar transport molecule, IFT88, in mature mice causes loss of cilia, resulting in airway remodeling. Airway cilia were deleted by knockout of IFT88, and airway remodeling and pulmonary function were evaluated. In IFT88− mice there was a substantial loss of airway cilia on respiratory epithelium. Three months after the deletion of cilia, there was clear evidence for bronchial remodeling that was not associated with inflammation or apparent defects in mucus clearance. There was evidence for airway epithelial cell hypertrophy and hyperplasia. IFT88− mice exhibited increased airway reactivity to a methacholine challenge and decreased ciliary beat frequency in the few remaining cells that possessed cilia. With deletion of respiratory cilia there was a marked increase in the number of club cells as seen by scanning electron microscopy. We suggest that airway remodeling may be exacerbated by the presence of club cells, since these cells are involved in airway repair. Club cells may be prevented from differentiating into respiratory epithelial cells because of a lack of IFT88 protein that is necessary to form a single nonmotile cilium. This monocilium is a prerequisite for these progenitor cells to transition into respiratory epithelial cells. In conclusion, motile cilia may play an important role in controlling airway structure and function. PMID:24213915

  12. Preparation of the patient and the airway for awake intubation

    PubMed Central

    Ramkumar, Venkateswaran

    2011-01-01

    Awake intubation is usually performed electively in the presence of a difficult airway. A detailed airway examination is time-consuming and often not feasible in an emergency. A simple 1-2-3 rule for airway examination allows one to identify potential airway difficulty within a minute. A more detailed airway examination can give a better idea about the exact nature of difficulty and the course of action to be taken to overcome it. When faced with an anticipated difficult airway, the anaesthesiologist needs to consider securing the airway in an awake state without the use of anaesthetic agents or muscle relaxants. As this can be highly discomforting to the patient, time and effort must be spent to prepare such patients both psychologically and pharmacologically for awake intubation. Psychological preparation is best initiated by an anaesthesiologist who explains the procedure in simple language. Sedative medications can be titrated to achieve patient comfort without compromising airway patency. Additional pharmacological preparation includes anaesthetising the airway through topical application of local anaesthetics and appropriate nerve blocks. When faced with a difficult airway, one should call for the difficult airway cart as well as for help from colleagues who have interest and expertise in airway management. Preoxygenation and monitoring during awake intubation is important. Anxious patients with a difficult airway may need to be intubated under general anaesthesia without muscle relaxants. Proper psychological and pharmacological preparation of the patient by an empathetic anaesthesiologist can go a long way in making awake intubation acceptable for all concerned. PMID:22174458

  13. Macrophage adaptation in airway inflammatory resolution.

    PubMed

    Kaur, Manminder; Bell, Thomas; Salek-Ardakani, Samira; Hussell, Tracy

    2015-09-01

    Bacterial and viral infections (exacerbations) are particularly problematic in those with underlying respiratory disease, including post-viral infection, asthma, chronic obstructive pulmonary disease and pulmonary fibrosis. Patients experiencing exacerbations tend to be at the more severe end of the disease spectrum and are often difficult to treat. Most of the unmet medical need remains in this patient group. Airway macrophages are one of the first cell populations to encounter airborne pathogens and, in health, exist in a state of reduced responsiveness due to interactions with the respiratory epithelium and specific factors found in the airway lumen. Granulocyte-macrophage colony-stimulating factor, interleukin-10, transforming growth factor-β, surfactant proteins and signalling via the CD200 receptor, for example, all raise the threshold above which airway macrophages can be activated. We highlight that following severe respiratory inflammation, the airspace microenvironment does not automatically re-set to baseline and may leave airway macrophages more restrained than they were at the outset. This excessive restraint is mediated in part by the clearance of apoptotic cells and components of extracellular matrix. This implies that one strategy to combat respiratory exacerbations would be to retune airway macrophage responsiveness to allow earlier bacterial recognition.

  14. Acoustic simulation of a patient's obstructed airway.

    PubMed

    van der Velden, W C P; van Zuijlen, A H; de Jong, A T; Lynch, C T; Hoeve, L J; Bijl, H

    2016-01-01

    This research focuses on the numerical simulation of stridor; a high pitched, abnormal noise, resulting from turbulent airflow and vibrating tissue through a partially obstructed airway. Characteristics of stridor noise are used by medical doctors as indication for location and size of the obstruction. The relation between type of stridor and the various diseases associated with airway obstruction is unclear; therefore, simply listening to stridor is an unreliable diagnostic tool. The overall aim of the study is to better understand the relationship between characteristics of stridor noise and localization and size of the obstruction. Acoustic analysis of stridor may then in future simplify the diagnostic process, and reduce the need for more invasive procedures such as laryngoscopy under general anesthesia. In this paper, the feasibility of a coupled flow, acoustic and structural model is investigated to predict the noise generated by the obstruction as well as the propagation of the noise through the airways, taking into account a one-way coupled fluid, structure, and acoustic interaction components. The flow and acoustic solver are validated on a diaphragm and a simplified airway model. A realistic airway model of a patient suffering from a subglottic stenosis, derived from a real computed tomography scan, is further analyzed. Near the mouth, the broadband noise levels at higher frequencies increased with approximately 15-20 dB comparing the stridorous model with the healthy model, indicating stridorous sound.

  15. 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.

  16. SPONTANEOUS AIRWAY HYPERRESPONSIVENESS IN ESTROGEN RECEPTOR-A DEFICIENT MICE

    EPA Science Inventory

    Rationale: Airway hyperresponsiveness is a critical feature of asthma. Substantial epidemiologic evidence supports a role for female sex hormones in modulating lung function and airway hyperresponsiveness in humans. Objectives: To examine the role of estrogen receptors in modulat...

  17. The Three A’s in Asthma – Airway Smooth Muscle, Airway Remodeling & Angiogenesis

    PubMed Central

    Keglowich, L.F; Borger, P

    2015-01-01

    Asthma affects more than 300 million people worldwide and its prevalence is still rising. Acute asthma attacks are characterized by severe symptoms such as breathlessness, wheezing, tightness of the chest, and coughing, which may lead to hospitalization or death. Besides the acute symptoms, asthma is characterized by persistent airway inflammation and airway wall remodeling. The term airway wall remodeling summarizes the structural changes in the airway wall: epithelial cell shedding, goblet cell hyperplasia, hyperplasia and hypertrophy of the airway smooth muscle (ASM) bundles, basement membrane thickening and increased vascular density. Airway wall remodeling starts early in the pathogenesis of asthma and today it is suggested that remodeling is a prerequisite for other asthma pathologies. The beneficial effect of bronchial thermoplasty in reducing asthma symptoms, together with the increased potential of ASM cells of asthmatics to produce inflammatory and angiogenic factors, indicate that the ASM cell is a major effector cell in the pathology of asthma. In the present review we discuss the ASM cell and its role in airway wall remodeling and angiogenesis. PMID:26106455

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

    PubMed

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

    2015-03-01

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

  19. 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

  20. Electrical stimulation of upper airway musculature.

    PubMed

    Smith, P L; Eisele, D W; Podszus, T; Penzel, T; Grote, L; Peter, J H; Schwartz, A R

    1996-12-01

    Investigators have postulated that pharyngeal collapse during sleep in patients with obstructive sleep apnea (OSA) may be alleviated by stimulating the genioglossus. The effect of electrical stimulation (ES) of the genioglossus on pharyngeal patency was examined in an isolated feline upper airway preparation and in apneic humans during sleep. We found that stimulation of the genioglossus (n = 8) and of the hypoglossal nerve (n = 1) increased maximum airflow through the isolated feline upper airway in humans during sleep. Additional findings in the isolated feline upper airway suggest that such increases in airflow were due to decreases in pharyngeal collapsibility. The evidence suggests that improvements in airflow dynamics with electrical stimulation are due to selective recruitment of the genioglossus, rather than due to nonspecific activation of the pharyngeal musculature or arousal from sleep. The implications of these results for future therapy with ES are discussed.

  1. Laser applications in pediatric airway surgery

    NASA Astrophysics Data System (ADS)

    Karamzadeh, Amir M.; Ahuja, Gurpreet S.; Nguyen, John D.; Crumley, Roger

    2003-06-01

    The smaller anatomy and limited access to instrumentation pose a challenge to the pediatric airway surgeon. The enhanced precision and ability to photocoagulate tissue while operating with the laser enhances the surgeon"s ability to successfully treat unique pediatric conditions such subglottic hemangiomas, congenital cysts, respiratory papillomatosis, and laryngeal or tracheal stenosis. Due to its shallow tissue penetration and thermal effect, the carbon dioxide (CO2) laser is generally considered the laser of choice for pediatric airway applications. The potential for increased scarring and damage to underlying tissue caused by the greater penetration depth and thermal effect of the Nd:YAG and KTP lasers preclude their use in this population. In this review, we will describe the specific advantages of using lasers in airway surgery, the current technology and where the current technology is deficient.

  2. Cold weather exercise and airway cytokine expression.

    PubMed

    Davis, Michael S; Malayer, Jerry R; Vandeventer, Lori; Royer, Christopher M; McKenzie, Erica C; Williamson, Katherine K

    2005-06-01

    Athletes who perform repeated exercise while breathing cold air have a high prevalence of asthmalike chronic airway disease, but the mechanism linking such activity to airway inflammation is unknown. We used a novel animal model (exercising horses) to test the hypothesis that exercise-induced chronic airway disease is caused by exposure of intrapulmonary airways to unconditioned air, resulting in the upregulation of cytokine expression. Bronchoalveolar lavage fluid (BALF) was obtained from eight horses 5 h after submaximal exercise while they breathed room temperature or subfreezing air in a random crossover design. BALF total and differential nucleated cell counts were determined, and relative cytokine mRNA expression in BALF nucleated cells was quantified by real-time RT-PCR using primer and probe sequences specific for equine targets. There were no significant changes in total or differential cell concentrations between BALF recovered after warm and cold air exercise, although there was a strong trend toward increased concentrations of airway epithelial cells after cold air exercise (P = 0.0625). T(H)2 cytokines IL-4, IL-5, and IL-10 were preferentially upregulated after cold air exercise 12-, 9-, and 10-fold, respectively, compared with warm air exercise. Other cytokines (IL-2 and IL-6) were upregulated to a lesser extent (6- and 3-fold, respectively) or not at all (IL-1, IL-8, IFN-gamma, and TNF-alpha). These results suggest that cold weather exercise can lead to asthmalike airway disease through the local induction of cytokines typical of the T(H)2 phenotype.

  3. Airway epithelium stimulates smooth muscle proliferation.

    PubMed

    Malavia, Nikita K; Raub, Christopher B; Mahon, Sari B; Brenner, Matthew; Panettieri, Reynold A; George, Steven C

    2009-09-01

    Communication between the airway epithelium and stroma is evident during embryogenesis, and both epithelial shedding and increased smooth muscle proliferation are features of airway remodeling. Hence, we hypothesized that after injury the airway epithelium could modulate airway smooth muscle proliferation. Fully differentiated primary normal human bronchial epithelial (NHBE) cells at an air-liquid interface were co-cultured with serum-deprived normal primary human airway smooth muscle cells (HASM) using commercially available Transwells. In some co-cultures, the NHBE were repeatedly (x4) scrape-injured. An in vivo model of tracheal injury consisted of gently denuding the tracheal epithelium (x3) of a rabbit over 5 days and then examining the trachea by histology 3 days after the last injury. Our results show that HASM cell number increases 2.5-fold in the presence of NHBE, and 4.3-fold in the presence of injured NHBE compared with HASM alone after 8 days of in vitro co-culture. In addition, IL-6, IL-8, monocyte chemotactic protein (MCP)-1 and, more markedly, matrix metalloproteinase (MMP)-9 concentration increased in co-culture correlating with enhanced HASM growth. Inhibiting MMP-9 release significantly attenuated the NHBE-dependent HASM proliferation in co-culture. In vivo, the injured rabbit trachea demonstrated proliferation in the smooth muscle (trachealis) region and significant MMP-9 staining, which was absent in the uninjured control. The airway epithelium modulates smooth muscle cell proliferation via a mechanism that involves secretion of soluble mediators including potential smooth muscle mitogens such as IL-6, IL-8, and MCP-1, but also through a novel MMP-9-dependent mechanism.

  4. Benign Nodular Goiter Causing Upper Airway Obstruction

    PubMed Central

    Başoğlu, Mahmut; Öztürk, Gürkan; Aydınlı, Bülent; Yıldırgan, M. İlhan; Atamanalp, S. Selçuk; Celebi, Fehmi

    2009-01-01

    Objective Benign nodular goiter (BNG) can cause narrowing of the upper airway. In some rare cases, obstruction of the upper airway also occurs. The following paper reports our experiences with regard to BNG patients who experienced obstruction of the upper airway. Materials and Methods. We retrospectively investigated the records of 13 patients with acute airway obstruction due to BNG who were admitted to the General Surgery Department of Ataturk University Medical School between January 2000 and December 2007. Results Thirteen patients with airway obstruction secondary to BNG were hospitalized during this period. There were two males and 11 females, and the mean age was 58.5 years (range 37–74 years). For all patients, the primary symptom upon admission was defined as respiratory distress; all patients had varying degrees of respiratory distress upon admission. Three of the patients underwent emergent endotracheal intubation in the emergency room. A preoperative radiological evaluation was performed with thyroid ultrasonography (US) and computed tomography (CT). There were retrosternal or substernal components of the BNG in nine patients. Twelve patients underwent operations, while one patient with mild respiratory distress elected not to be operated on. Ten patients underwent total thyroidectomies, while two patients underwent near-total thyroidectomies. One patient with retrosternal goiter also underwent a median sternotomy. Three patients received a tracheostomy after the operation. Suction drains were utilized in all operations. During the post-operative period, two patients suffered from voice impairment, and seven patients experienced hypocalcemia. Two patients died. Pathological examination of the thyroidectomy tissue revealed BNG in all cases. In addition, two patients had micropapillary carcinomas. Conclusion Although BNG causing upper airway obstruction is rare, it is an important clinical entity because of the need for emergent operation, the

  5. Autoimmune Limbic Encephalitis and Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Lamotrigine-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome.

    PubMed

    Ozisik, Lale; Tanriover, Mine Durusu; Saka, Esen

    2016-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug hypersensitivity reaction characterized by rash, fever and multi-organ failure. Limbic encephalitis (LE) is a rare disorder characterized by cognitive dysfunction with memory disturbance, seizures and psychiatric symptoms. We herein present an unusual case of DRESS syndrome due to lamotrigine with reactivation of Epstein-Barr virus, which developed autoimmune LE and syndrome of inappropriate antidiuretic hormone secretion. Discontinuation of lamotrigine, administration of methylprednisolone and intravenous immunoglobulin led to improvement. The LE in this case might have been caused by an autoimmune inflammatory mechanism associated with DRESS syndrome.

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

    PubMed Central

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

    2010-01-01

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

  7. Cine CT technique for dynamic airway studies

    SciTech Connect

    Ell, S.R.; Jolles, H.; Keyes, W.D.; Galvin, J.R.

    1985-07-01

    The advent of cine CT scanning with its 50-msec data acquisition time promises a much wider range of dynamic CT studies. The authors describe a method for dynamic evaluation of the extrathoracic airway, which they believe has considerable potential application in nonfixed upper-airway disease, such as sleep apnea and stridor of unknown cause. Conventional CT is limited in such studies by long data acquisition time and can be used to study only prolonged maneuvers such as phonation. Fluoroscopy and digital subtraction studies are limited by relatively high radiation dose and inability to image all wall motions simultaneously.

  8. 21 CFR 868.5090 - Emergency airway needle.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Emergency airway needle. 868.5090 Section 868.5090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... provide an emergency airway during upper airway obstruction. (b) Classification. Class II...

  9. 21 CFR 868.2600 - Airway pressure monitor.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Airway pressure monitor. 868.2600 Section 868.2600...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2600 Airway pressure monitor. (a) Identification. An airway pressure monitor is a device used to measure the pressure in a patient's upper...

  10. 21 CFR 868.1780 - Inspiratory airway pressure meter.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Inspiratory airway pressure meter. 868.1780... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1780 Inspiratory airway pressure meter. (a) Identification. An inspiratory airway pressure meter is a device used to measure the...

  11. 21 CFR 868.2600 - Airway pressure monitor.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Airway pressure monitor. 868.2600 Section 868.2600...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2600 Airway pressure monitor. (a) Identification. An airway pressure monitor is a device used to measure the pressure in a patient's upper...

  12. 21 CFR 868.2600 - Airway pressure monitor.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Airway pressure monitor. 868.2600 Section 868.2600...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2600 Airway pressure monitor. (a) Identification. An airway pressure monitor is a device used to measure the pressure in a patient's upper...

  13. 21 CFR 868.1780 - Inspiratory airway pressure meter.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Inspiratory airway pressure meter. 868.1780... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1780 Inspiratory airway pressure meter. (a) Identification. An inspiratory airway pressure meter is a device used to measure the...

  14. 21 CFR 868.2600 - Airway pressure monitor.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Airway pressure monitor. 868.2600 Section 868.2600...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2600 Airway pressure monitor. (a) Identification. An airway pressure monitor is a device used to measure the pressure in a patient's upper...

  15. 21 CFR 868.2600 - Airway pressure monitor.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Airway pressure monitor. 868.2600 Section 868.2600...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2600 Airway pressure monitor. (a) Identification. An airway pressure monitor is a device used to measure the pressure in a patient's upper...

  16. 21 CFR 868.1780 - Inspiratory airway pressure meter.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Inspiratory airway pressure meter. 868.1780... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1780 Inspiratory airway pressure meter. (a) Identification. An inspiratory airway pressure meter is a device used to measure the...

  17. 21 CFR 868.1780 - Inspiratory airway pressure meter.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Inspiratory airway pressure meter. 868.1780... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1780 Inspiratory airway pressure meter. (a) Identification. An inspiratory airway pressure meter is a device used to measure the...

  18. 21 CFR 868.1780 - Inspiratory airway pressure meter.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Inspiratory airway pressure meter. 868.1780... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1780 Inspiratory airway pressure meter. (a) Identification. An inspiratory airway pressure meter is a device used to measure the...

  19. Automated airway evaluation system for multi-slice computed tomography using airway lumen diameter, airway wall thickness and broncho-arterial ratio

    NASA Astrophysics Data System (ADS)

    Odry, Benjamin L.; Kiraly, Atilla P.; Novak, Carol L.; Naidich, David P.; Lerallut, Jean-Francois

    2006-03-01

    Pulmonary diseases such as bronchiectasis, asthma, and emphysema are characterized by abnormalities in airway dimensions. Multi-slice computed tomography (MSCT) has become one of the primary means to depict these abnormalities, as the availability of high-resolution near-isotropic data makes it possible to evaluate airways at oblique angles to the scanner plane. However, currently, clinical evaluation of airways is typically limited to subjective visual inspection only: systematic evaluation of the airways to take advantage of high-resolution data has not proved practical without automation. We present an automated method to quantitatively evaluate airway lumen diameter, wall thickness and broncho-arterial ratios. In addition, our method provides 3D visualization of these values, graphically illustrating the location and extent of disease. Our algorithm begins by automatic airway segmentation to extract paths to the distal airways, and to create a map of airway diameters. Normally, airway diameters decrease as paths progress distally; failure to taper indicates abnormal dilatation. Our approach monitors airway lumen diameters along each airway path in order to detect abnormal profiles, allowing even subtle degrees of pathologic dilatation to be identified. Our method also systematically computes the broncho-arterial ratio at every terminal branch of the tree model, as a ratio above 1 indicates potentially abnormal bronchial dilatation. Finally, the airway wall thickness is computed at corresponding locations. These measurements are used to highlight abnormal branches for closer inspection, and can be summed to compute a quantitative global score for the entire airway tree, allowing reproducible longitudinal assessment of disease severity. Preliminary tests on patients diagnosed with bronchiectasis demonstrated rapid identification of lack of tapering, which also was confirmed by corresponding demonstration of elevated broncho-arterial ratios.

  20. Prehospital endotracheal tube airway or esophageal gastric tube airway: a critical comparison.

    PubMed

    Shea, S R; MacDonald, J R; Gruzinski, G

    1985-02-01

    This study compares two similar groups of patients in cardiopulmonary arrest with ventricular fibrillation (VF). In the survival study group of 296 patients, 148 patients received an endotracheal tube airway (ETA) and 148 patients received an esophageal gastric tube airway (EGTA), the improved version of the esophageal obturator airway (EOA). Survival rates, both short term (ETA = 35.8%, EGTA = 39.1%) and long term (ETA = 11.5%, EGTA = 16.2%), and neurological sequelae of survivors showed no statistically significant difference between the two groups (P greater than .05). In addition, we found that success and complication rates of intubation were similar. Training time was longer for the ETA. We conclude that both airways have a place in the prehospital setting.

  1. Expression of ligands for Siglec-8 and Siglec-9 in human airways and airway cells

    PubMed Central

    Jia, Yi; Yu, Huifeng; Fernandes, Steve M.; Wei, Yadong; Gonzalez-Gil, Anabel; Motari, Mary G.; Vajn, Katarina; Stevens, Whitney W.; Peters, Anju T.; Bochner, Bruce S.; Kern, Robert C.; Schleimer, Robert P.; Schnaar, Ronald L.

    2015-01-01

    Background Balanced activation and inhibition of the immune system ensures pathogen clearance while avoiding hyperinflammation. Siglecs, sialic acid binding proteins found on subsets of immune cells, often inhibit inflammation: Siglec-8 on eosinophils and Siglec-9 on neutrophils engage sialoglycan ligands on airways to diminish ongoing inflammation. The identities of human siglec ligands and their expression during inflammation are largely unknown. Objective The histological distribution, expression and molecular characteristics of siglec ligands were explored in healthy and inflamed human upper airways and in a cellular model of airway inflammation. Methods Normal and chronically inflamed upper airway tissues were stained for siglec ligands. The ligands were extracted from normal and inflamed tissues and from human Calu-3 cells for quantitative analysis by siglec blotting and isolation by siglec capture. Results Siglec-8 ligands were expressed on a subpopulation of submucosal gland cells of human inferior turbinate, whereas Siglec-9 ligands were expressed more broadly (submucosal glands, epithelium, connective tissue); both were significantly upregulated in chronic rhinosinusitis patients. Human airway (Calu-3) cells expressed Siglec-9 ligands on mucin 5B under inflammatory control via the NF-κB pathway, and mucin 5B carried sialoglycan ligands of Siglec-9 on human upper airway tissue. Conclusion Inflammation results in upregulation of immune inhibitory Siglec-8 and Siglec-9 sialoglycan ligands on human airways. Siglec-9 ligands were upregulated via the NF-κB pathway resulting in their enhanced expression on mucin 5B. Siglec sialoglycan ligand expression in inflamed cells and tissues may contribute to the control of airway inflammation. PMID:25747723

  2. Complications of upper airway surgery in companion animals.

    PubMed

    Mercurio, Andrew

    2011-09-01

    Surgery of the upper airway is performed in dogs for the correction of brachycephalic airway syndrome and laryngeal paralysis and for temporary or permanent tracheostomy. Although technically simple to perform, upper airway surgeries can lead to the development of significant postoperative complications. This article reviews complications associated with common surgical conditions of the upper airway. It involves a discussion of brachycephalic airway syndrome and associated respiratory and gastrointestinal complications. It also covers laryngeal paralysis with a focus on unilateral arytenoid lateralization and the complication of aspiration pneumonia. The condition of acquired laryngeal webbing/stenosis and potential treatment options is also discussed. Finally, tracheostomies and associated complications in dogs and cats are reviewed.

  3. Techniques of assessing small airways dysfunction

    PubMed Central

    McNulty, William; Usmani, Omar S.

    2014-01-01

    The small airways are defined as those less than 2 mm in diameter. They are a major site of pathology in many lung diseases, not least chronic obstructive pulmonary disease (COPD) and asthma. The small airways are frequently involved early in the course of these diseases, with significant pathology demonstrable often before the onset of symptoms or changes in spirometry and imaging. Despite their importance, they have proven relatively difficult to study. This is in part due to their relative inaccessibility to biopsy and their small size which makes their imaging difficult. Traditional lung function tests may only become abnormal once there is a significant burden of disease within them. This has led to the term ‘the quiet zone’ of the lung. In recent years, more specialised tests have been developed which may detect these changes earlier, perhaps offering the possibility of earlier diagnosis and intervention. These tests are now moving from the realms of clinical research laboratories into routine clinical practice and are increasingly useful in the diagnosis and monitoring of respiratory diseases. This article gives an overview of small airways physiology and some of the routine and more advanced tests of airway function. PMID:26557240

  4. Reproducibility of airway wall thickness measurements

    NASA Astrophysics Data System (ADS)

    Schmidt, Michael; Kuhnigk, Jan-Martin; Krass, Stefan; Owsijewitsch, Michael; de Hoop, Bartjan; Peitgen, Heinz-Otto

    2010-03-01

    Airway remodeling and accompanying changes in wall thickness are known to be a major symptom of chronic obstructive pulmonary disease (COPD), associated with reduced lung function in diseased individuals. Further investigation of this disease as well as monitoring of disease progression and treatment effect demand for accurate and reproducible assessment of airway wall thickness in CT datasets. With wall thicknesses in the sub-millimeter range, this task remains challenging even with today's high resolution CT datasets. To provide accurate measurements, taking partial volume effects into account is mandatory. The Full-Width-at-Half-Maximum (FWHM) method has been shown to be inappropriate for small airways1,2 and several improved algorithms for objective quantification of airway wall thickness have been proposed.1-8 In this paper, we describe an algorithm based on a closed form solution proposed by Weinheimer et al.7 We locally estimate the lung density parameter required for the closed form solution to account for possible variations of parenchyma density between different lung regions, inspiration states and contrast agent concentrations. The general accuracy of the algorithm is evaluated using basic tubular software and hardware phantoms. Furthermore, we present results on the reproducibility of the algorithm with respect to clinical CT scans, varying reconstruction kernels, and repeated acquisitions, which is crucial for longitudinal observations.

  5. Airway-parenchyma uncoupling in nocturnal asthma.

    PubMed

    Irvin, C G; Pak, J; Martin, R J

    2000-01-01

    Airway flow resistance is well known to be dependent upon lung volume. The rise in lung volume that occurs in asthma is therefore thought to be an important mechanism that defends airway patency. The purpose of the current study was to investigate the interdependence or mechanical coupling between airways and lung parenchyma during the inflammatory processes that occur in the patient with nocturnal asthma. Five patients with documented nocturnal asthma were studied in both a vertical and a horizontal body plethysmograph. Lung volume was altered with continuous negative pressure as applied to the chest wall with a poncho cuirass in different postures and during sleep. We found during the awake phase that an increase in lung volume decreased lower pulmonary resistance (Rlp); however, within 30 min of sleep onset, functional residual capacity (FRC) fell and Rlp rose more than would be expected for the fall in FRC. Restoring FRC to presleep values either at an early (half-hour) or a late (3-h) time point did not cause Rlp to significantly fall. A second phase of the study showed that the loss of Rlp dependence on lung volume was not due to the assumption of the supine posture. Indirect measurements of lung compliance were consistent with a stiffening of the lung. We conclude that with sleep there is an immediate uncoupling of the parenchyma to the airway, resulting in a loss of interdependence that persists throughout sleep and may contribute to the morbidity and mortality associated with nocturnal asthma.

  6. Quercetin Blocks Airway Epithelial Cell Chemokine Expression

    PubMed Central

    Nanua, Suparna; Zick, Suzanna M.; Andrade, Juan E.; Sajjan, Umadevi S.; Burgess, John R.; Lukacs, Nicholas W.; Hershenson, Marc B.

    2006-01-01

    Quercetin (3,3′,4′,5,7-pentahydroxyflavone), a dietary flavonoid, is an inhibitor of phosphatidylinositol (PI) 3-kinase and potent antioxidant. We hypothesized that quercetin blocks airway epithelial cell chemokine expression via PI 3-kinase–dependent mechanisms. Pretreatment with quercetin and the PI 3–kinase inhibitor LY294002 each reduced TNF-α–induced IL-8 and monocyte chemoattractant protein (MCP)-1 (also called CCL2) expression in cultured human airway epithelial cells. Quercetin also inhibited TNF-α–induced PI 3-kinase activity, Akt phosphorylation, intracellular H2O2 production, NF-κB transactivation, IL-8 promoter activity, and steady-state mRNA levels, consistent with the notion that quercetin inhibits chemokine expression by attenuating NF-κB transactivation via a PI 3-kinase/Akt-dependent pathway. Quercetin also reduced TNF-α–induced chemokine secretion in the presence of the transcriptional inhibitor actinomycin D, while inducing phosphorylation of eukaryotic translation initiation factor (eIF)-2α, suggesting that quercetin attenuates chemokine expression by post-transcriptional as well as transcriptional mechanisms. Finally, we tested the effects of quercetin in cockroach antigen–sensitized and –challenged mice. These mice show MCP-1–dependent airways hyperresponsiveness and inflammation. Quercetin significantly reduced lung MCP-1 and methacholine responsiveness. We conclude that quercetin blocks airway cell chemokine expression via transcriptional and post-transcriptional pathways. PMID:16794257

  7. COLCHICINE DECREASES AIRWAY HYPERACTIVITY AFTER PHOSGENE EXPOSURE

    EPA Science Inventory

    Phosgene (COCl(2)) exposure affects an influx of inflammatory cells into the lung, which can be reduced in an animal model by pretreatment with colchicine. Inflammation in the respiratory tract can be associated with an increase in airway hyperreactivity. We tested the hypotheses...

  8. Osmotic regulation of airway reactivity by epithelium.

    PubMed

    Fedan, J S; Yuan, L X; Chang, V C; Viola, J O; Cutler, D; Pettit, L L

    1999-05-01

    Inhalation of nonisotonic solutions can elicit pulmonary obstruction in asthmatic airways. We evaluated the hypothesis that the respiratory epithelium is involved in responses of the airways to nonisotonic solutions using the guinea pig isolated, perfused trachea preparation to restrict applied agents to the mucosal (intraluminal) or serosal (extraluminal) surface of the airway. In methacholine-contracted tracheae, intraluminally applied NaCl or KCl equipotently caused relaxation that was unaffected by the cyclo-oxygenase inhibitor, indomethacin, but was attenuated by removal of the epithelium and Na+ and Cl- channel blockers. Na+-K+-2Cl- cotransporter and nitric oxide synthase blockers caused a slight inhibition of relaxation, whereas Na+,K+-pump inhibition produced a small potentiation. Intraluminal hyperosmolar KCl and NaCl inhibited contractions in response to intra- or extraluminally applied methacholine, as well as neurogenic cholinergic contractions elicited with electric field stimulation (+/- indomethacin). Extraluminally applied NaCl and KCl elicited epithelium-dependent relaxation (which for KCl was followed by contraction). In contrast to the effects of hyperosmolarity, intraluminal hypo-osmolarity caused papaverine-inhibitable contractions (+/- epithelium). These findings suggest that the epithelium is an osmotic sensor which, through the release of epithelium-derived relaxing factor, can regulate airway diameter by modulating smooth muscle responsiveness and excitatory neurotransmission.

  9. Quantitative analysis of airway abnormalities in CT

    NASA Astrophysics Data System (ADS)

    Petersen, Jens; Lo, Pechin; Nielsen, Mads; Edula, Goutham; Ashraf, Haseem; Dirksen, Asger; de Bruijne, Marleen

    2010-03-01

    A coupled surface graph cut algorithm for airway wall segmentation from Computed Tomography (CT) images is presented. Using cost functions that highlight both inner and outer wall borders, the method combines the search for both borders into one graph cut. The proposed method is evaluated on 173 manually segmented images extracted from 15 different subjects and shown to give accurate results, with 37% less errors than the Full Width at Half Maximum (FWHM) algorithm and 62% less than a similar graph cut method without coupled surfaces. Common measures of airway wall thickness such as the Interior Area (IA) and Wall Area percentage (WA%) was measured by the proposed method on a total of 723 CT scans from a lung cancer screening study. These measures were significantly different for participants with Chronic Obstructive Pulmonary Disease (COPD) compared to asymptomatic participants. Furthermore, reproducibility was good as confirmed by repeat scans and the measures correlated well with the outcomes of pulmonary function tests, demonstrating the use of the algorithm as a COPD diagnostic tool. Additionally, a new measure of airway wall thickness is proposed, Normalized Wall Intensity Sum (NWIS). NWIS is shown to correlate better with lung function test values and to be more reproducible than previous measures IA, WA% and airway wall thickness at a lumen perimeter of 10 mm (PI10).

  10. Access to the Airways: Rationale and Applications.

    ERIC Educational Resources Information Center

    Hanks, William; Longini, Peter

    Current movements toward greater public access to the airways are discussed. Traditional practices have limited access to journalists employed by stations and to those who purchase time and have allowed only limited responses to station-initiated editorials. Legal arguments that support citizen demands for more access arise from the First…

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

    PubMed Central

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

    2003-01-01

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

  12. Upper Airway Variation and Frequent Alcohol Consumption Can Affect Compliance With Continuous Positive Airway Pressure

    PubMed Central

    Jeong, Jong In; Kim, Hyo Yeol; Hong, Sang Duk; Ryu, Gwanghui; Kim, Su Jin; Lee, Kyung Eun; Dhong, Hun-Jong; Chung, Seung-Kyu

    2016-01-01

    Objectives Compliance with continuous positive airway pressure (CPAP) treatment remains a primary concern for improving treatment outcomes of obstructive sleep apnea. There are few studies that have considered the role of upper airway anatomy on the compliance with CPAP. We hypothesized that upper airway anatomy would influence the compliance with CPAP. Methods One hundred out of 161 consecutive patients were enrolled in this study. The following possible determinants were tested against CPAP use: demographic and anthropometric data, minimal cross-sectional area on acoustic rhinometry, cephalometric and polysomnographic data, questionnaires of Epworth sleepiness scale and Beck depression index, and histories of previous upper airway surgery, degree of nasal obstruction, daily cigarette consumption, and weekly frequency of alcohol intake. Results Univariate analysis showed that histories of previous upper airway surgery and less frequent alcohol consumption, and longer mandibular plane-hyoid length (MP-H) on cephalometry were associated with longer average daily CPAP use. After adjustment for the confounding factors with multiple linear regression analysis, alcohol consumption and MP-H were still associated with the compliance with CPAP significantly. Conclusion To improve compliance with CPAP, careful evaluations of upper airway problems and life style are important before initiating CPAP. PMID:27334512

  13. Estimation of airway obstruction using oximeter plethysmograph waveform data

    PubMed Central

    Arnold, Donald H; Spiro, David M; Desmond, Renee' A; Hagood, James S

    2005-01-01

    Background Validated measures to assess the severity of airway obstruction in patients with obstructive airway disease are limited. Changes in the pulse oximeter plethysmograph waveform represent fluctuations in arterial flow. Analysis of these fluctuations might be useful clinically if they represent physiologic perturbations resulting from airway obstruction. We tested the hypothesis that the severity of airway obstruction could be estimated using plethysmograph waveform data. Methods Using a closed airway circuit with adjustable inspiratory and expiratory pressure relief valves, airway obstruction was induced in a prospective convenience sample of 31 healthy adult subjects. Maximal change in airway pressure at the mouthpiece was used as a surrogate measure of the degree of obstruction applied. Plethysmograph waveform data and mouthpiece airway pressure were acquired for 60 seconds at increasing levels of inspiratory and expiratory obstruction. At each level of applied obstruction, mean values for maximal change in waveform area under the curve and height as well as maximal change in mouth pressure were calculated for sequential 7.5 second intervals. Correlations of these waveform variables with mouth pressure values were then performed to determine if the magnitude of changes in these variables indicates the severity of airway obstruction. Results There were significant relationships between maximal change in area under the curve (P < .0001) or height (P < 0.0001) and mouth pressure. Conclusion The findings suggest that mathematic interpretation of plethysmograph waveform data may estimate the severity of airway obstruction and be of clinical utility in objective assessment of patients with obstructive airway diseases. PMID:15985171

  14. Deposition of Graphene Nanoparticles in Human Upper Airways

    PubMed Central

    Su, Wei-Chung; Ku, Bon-Ki; Kulkarni, Pramod; Cheng, Yung Sung

    2016-01-01

    Graphene nanomaterials have attracted wide attention in recent years on their application to state-of-the-art technology due to their outstanding physical properties. On the other hand, the nanotoxicity of graphene materials also has rapidly become a serious concern especially in occupational health. Graphene materials inevitably could become airborne in the workplace during manufacturing processes. The inhalation and subsequent deposition of graphene nanoparticles in the human respiratory tract could potentially result in adverse health effects to exposed workers. Therefore, investigating the deposition of graphene nanoparticles in the human airways is considered essential for an integral graphene occupational health study. For this reason, this study carried out a series of airway replica deposition experiments to obtain original data of graphene nanoparticle airway deposition. In this study, size classified graphene nanoparticles were delivered into human airway replicas (both nasal and oral-to-lung airways). The deposition fraction and efficiency of graphene nanoparticle in the airway were obtained by a novel experimental approach. The experimental results acquired showed that the fractional deposition of graphene nanoparticles in airway sections studied were all less than 4%, and the deposition efficiencies in each airway section were generally lower than 0.03. These results implies that the majority of the graphene nanoparticles inhaled into the human respiratory tract could easily penetrate through the head airways as well as the upper part of the tracheobronchial airways and then transit down to the lower lung airways, where undesired biological responses might be induced. PMID:26317666

  15. Airway evaluation in obstructive sleep apnea.

    PubMed

    Stuck, Boris A; Maurer, Joachim T

    2008-12-01

    As the interest in sleep-disordered breathing has increased, various attempts have been made to assess upper airway anatomy in patients with this relatively frequent disorder. The aim is not only to reveal potential differences in upper airway anatomy to better understand origin and pathophysiology of the disease but also to improve patient management and treatment success. The present review is based on a systematic literature search with regard to upper airway evaluation in sleep-disordered breathing; the articles were selected and discussed in light of our clinical experiences. Based on clinical assessment including endoscopy during wakefulness, the value of the Mueller Maneuver, static radiologic imaging techniques (X-ray cephalometry, computed tomography (CT) scanning and magnetic resonance imaging (MRI)), dynamic scanning protocols (e.g. ultrafast CT or cine MRI), upper airway endoscopy during sleep and sedated sleep, pressure measurements and the assessment of the critical closing pressure are discussed. Each technique itself and its history in the field of sleep medicine are briefly reviewed and problems of standardization and interpretation are discussed when appropriate. Insights into the pathophysiology of the disease gained with the help of the investigational techniques are presented and the impact of the techniques on patient management is reported. Although all these additional techniques for upper airway assessment have substantially improved our understanding of sleep-disordered breathing, their significance in daily practice is limited. In contrast to the widespread use of the Mueller maneuver and sedated endoscopy, convincing data supporting their use in terms of treatment outcome are lacking. So far, there is only very limited evidence that selected techniques improve treatment outcome for selected indications. In general, there is not enough evidence that these techniques are superior to the routine clinical assessment.

  16. The Diagnosis and Management of Airway Complications Following Lung Transplantation.

    PubMed

    Mahajan, Amit K; Folch, Erik; Khandhar, Sandeep J; Channick, Colleen L; Santacruz, Jose F; Mehta, Atul C; Nathan, Steven D

    2017-03-05

    Airway complications following lung transplantation result in considerable morbidity and are associated with a mortality of 2-4 percent. The incidence of lethal and non-lethal airway complications has decreased since the early experiences with double- and single-lung transplantation. The most common risk factor associated with post-lung transplant airway complications is anastomotic ischemia. Airway complications include development of exophytic granulation tissue, bronchial stenosis, bronchomalacia, airway fistula, endobronchial infection, and anastomotic dehiscence. The broadening array of bronchoscopic therapies has enhanced treatment options for lung transplant recipients with airway complications. This article reviews the risk factors, clinical manifestations, and treatments of airway complications following lung transplantation, and provides our expert opinion where evidence is lacking.

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

    EPA Science Inventory

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

  18. Simple pulmonary eosinophilia

    MedlinePlus

    ... Pneumocystis jirovecii A parasite, including the roundworms Ascariasis lumbricoides , or Necator americanus , or the hookworm Ancylostoma duodenale ... contents ( gastric lavage ) may show signs of the Ascaris worm or another parasite. Treatment If you are ...

  19. Detection of Upper Airway Status and Respiratory Events by a Current Generation Positive Airway Pressure Device

    PubMed Central

    Li, Qing Yun; Berry, Richard B.; Goetting, Mark G.; Staley, Bethany; Soto-Calderon, Haideliza; Tsai, Sheila C.; Jasko, Jeffrey G.; Pack, Allan I.; Kuna, Samuel T.

    2015-01-01

    Study Objectives: To compare a positive airway pressure (PAP) device's detection of respiratory events and airway status during device-detected apneas with events scored on simultaneous polysomnography (PSG). Design: Prospective PSGs of patients with sleep apnea using a new-generation PAP device. Settings: Four clinical and academic sleep centers. Patients: Forty-five patients with obstructive sleep apnea (OSA) and complex sleep apnea (Comp SA) performed a PSG on PAP levels adjusted to induce respiratory events. Interventions: None. Measurements and Results: PAP device data identifying the type of respiratory event and whether the airway during a device-detected apnea was open or obstructed were compared to time-synced, manually scored respiratory events on simultaneous PSG recording. Intraclass correlation coefficients between device-detected and PSG scored events were 0.854 for apnea-hypopnea index (AHI), 0.783 for apnea index, 0.252 for hypopnea index, and 0.098 for respiratory event-related arousals index. At a device AHI (AHIFlow) of 10 events/h, area under the receiver operating characteristic curve was 0.98, with sensitivity 0.92 and specificity 0.84. AHIFlow tended to overestimate AHI on PSG at values less than 10 events/h. The device detected that the airway was obstructed in 87.4% of manually scored obstructive apneas. Of the device-detected apneas with clear airway, a minority (15.8%) were manually scored as obstructive apneas. Conclusions: A device-detected apnea-hypopnea index (AHIFlow) < 10 events/h on a positive airway pressure device is strong evidence of good treatment efficacy. Device-detected airway status agrees closely with the presumed airway status during polysomnography scored events, but should not be equated with a specific type of respiratory event. Citation: Li QY, Berry RB, Goetting MG, Staley B, Soto-Calderon H, Tsai SC, Jasko JG, Pack AI, Kuna ST. Detection of upper airway status and respiratory events by a current generation positive

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

    PubMed Central

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

    2017-01-01

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

  1. Does the length dependency of airway smooth muscle force contribute to airway hyperresponsiveness?

    PubMed

    Lee-Gosselin, Audrey; Pascoe, Chris D; Couture, Christian; Paré, Peter D; Bossé, Ynuk

    2013-11-01

    Airway wall remodeling and lung hyperinflation are two typical features of asthma that may alter the contractility of airway smooth muscle (ASM) by affecting its operating length. The aims of this study were as follows: 1) to describe in detail the "length dependency of ASM force" in response to different spasmogens; and 2) to predict, based on morphological data and a computational model, the consequence of this length dependency of ASM force on airway responsiveness in asthmatic subjects who have both remodeled airway walls and hyperinflated lungs. Ovine tracheal ASM strips and human bronchial rings were isolated and stimulated to contract in response to increasing concentrations of spasmogens at three different lengths. Ovine tracheal strips were more sensitive and generated greater force at longer lengths in response to acetylcholine (ACh) and K(+). Equipotent concentrations of ACh were approximately a log less for ASM stretched by 30% and approximately a log more for ASM shortened by 30%. Similar results were observed in human bronchi in response to methacholine. Morphometric and computational analyses predicted that the ASM of asthmatic subjects may be elongated by 6.6-10.4% (depending on airway generation) due to remodeling and/or hyperinflation, which could increase ACh-induced force by 1.8-117.8% (depending on ASM length and ACh concentration) and enhance the increased resistance to airflow by 0.4-4,432.8%. In conclusion, elongation of ASM imposed by airway wall remodeling and/or hyperinflation may allow ASM to operate at a longer length and to consequently generate more force and respond to lower concentration of spasmogens. This phenomenon could contribute to airway hyperresponsiveness.

  2. Airway acidification initiates host defense abnormalities in cystic fibrosis mice

    PubMed Central

    Shah, Viral S.; Meyerholz, David K.; Tang, Xiao Xiao; Reznikov, Leah; Alaiwa, Mahmoud Abou; Ernst, Sarah E.; Karp, Philip H.; Wohlford-Lenane, Christine L.; Heilmann, Kristopher P.; Leidinger, Mariah R.; Allen, Patrick D.; Zabner, Joseph; McCray, Paul B.; Ostedgaard, Lynda S.; Stoltz, David A.; Randak, Christoph O.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. In humans and pigs lacking CFTR, unchecked H+ secretion by the nongastric H+/K+ adenosine triphosphatase (ATP12A) acidified airway surface liquid, which impaired airway host defenses. In contrast, mouse airways expressed little ATP12A and secreted minimal H+; consequently, airway surface liquid in CF and non-CF mice had similar pH. Inhibiting ATP12A reversed host defense abnormalities in human and pig airways. Conversely, expressing ATP12A in CF mouse airways acidified airway surface liquid, impaired defenses, and increased airway bacteria. These findings help explain why CF mice are protected from infection and nominate ATP12A as a potential therapeutic target for CF. PMID:26823428

  3. Dynamics of Surfactant Liquid Plugs at Bifurcating Lung Airway Models

    NASA Astrophysics Data System (ADS)

    Tavana, Hossein

    2013-11-01

    A surfactant liquid plug forms in the trachea during surfactant replacement therapy (SRT) of premature babies. Under air pressure, the plug propagates downstream and continuously divides into smaller daughter plugs at continuously branching lung airways. Propagating plugs deposit a thin film on airway walls to reduce surface tension and facilitate breathing. The effectiveness of SRT greatly depends on the final distribution of instilled surfactant within airways. To understand this process, we investigate dynamics of splitting of surfactant plugs in engineered bifurcating airway models. A liquid plug is instilled in the parent tube to propagate and split at the bifurcation. A split ratio, R, is defined as the ratio of daughter plug lengths in the top and bottom daughter airway tubes and studied as a function of the 3D orientation of airways and different flow conditions. For a given Capillary number (Ca), orienting airways farther away from a horizontal position reduced R due to the flow of a larger volume into the gravitationally favored daughter airway. At each orientation, R increased with 0.0005 < Ca < 0.05. This effect diminished by decrease in airways diameter. This approach will help elucidate surfactant distribution in airways and develop effective SRT strategies.

  4. Airway Inflammation and Hypersensitivity Induced by Chronic Smoking

    PubMed Central

    Kou, Yu Ru; Kwong, Kevin; Lee, Lu-Yuan

    2011-01-01

    Airway hypersensitivity, characterized by enhanced excitability of airway sensory nerves, is a prominent pathophysiological feature in patients with airway inflammatory diseases. Although the underlying pathogenic mechanism is not fully understood, chronic airway inflammation is believed to be primarily responsible. Cigarette smoking is known to cause chronic airway inflammation, accompanied by airway hyperresponsiveness. Experimental evidence indicates that enhanced excitability of vagal bronchopulmonary sensory nerves and increased tachykinin synthesis in these nerves resulting from chronic inflammation are important contributing factors to the airway hyperresponsiveness. Multiple inflammatory mediators released from various types of structural and inflammatory cells are involved in the smoking-induced airway inflammation, which is mainly regulated by redox-sensitive signaling pathways and transcription factors. Furthermore, recent studies have reported potent sensitizing and stimulatory effects of these inflammatory mediators such as prostanoids and reactive oxygen species on these sensory nerves. In summary, these studies using cigarette smoking as an experimental approach have identified certain potentially important cell signaling pathways and underlying mechanisms of the airway hypersensitivity induced by chronic airway inflammation. PMID:21397052

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

    PubMed

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

    2017-03-01

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

  6. Comparison of laryngeal mask airway vs tracheal intubation: a systematic review on airway complications.

    PubMed

    van Esch, Babette F; Stegeman, Inge; Smit, Adriana L

    2017-02-01

    To determine whether the laryngeal mask airway (LMA) has advantages over the tracheal tube (TT) in terms of incidence of cough, sore throat, laryngospasm, dysphagia, dysphonia, and blood staining. This is a systematic literature review performed at the Universtity Medical Center of Utrecht. The online databases PubMed, Embase, and the Cochrane Library were searched for relevant randomized controlled trials. Two independent reviewers selected relevant articles after title, abstract, and full text screening. Articles were assessed on risk of bias in accordance with the Cochrane risk of bias tool. Study results of the LMA and the TT were related to the method of selection of the device size and the method for cuff inflation. Of the 1718 unique articles, we included 19 studies which used the LMA Classic, the LMA Proseal, the Flexible Reinforced LMA, and the LMA Supreme compared with TT. After methodological inspection, data could not be pooled due to heterogeneity among the selected studies. Overall, no clear advantage of the LMA over the TT was found but the LMA Supreme was related to the lowest incidence of airway complications. In this review, no clear difference in incidence of postoperative airway complications could be demonstrated between LMA and TT. The LMA Supreme may reduce the incidence of airway complication in comparison to the TT but high quality randomized trials are recommended to further objectify if use of the LMA decreases the risk on postoperative airway complications.

  7. Advances in upper airway cough syndrome.

    PubMed

    Yu, Li; Xu, Xianghuai; Lv, Hanjing; Qiu, Zhongmin

    2015-05-01

    Upper airway cough syndrome (UACS), previously referred to as postnasal drip syndrome, is one of the most common causes of chronic cough. However, the pathogenesis of UACS/postnasal drip syndrome remains unclear, and physicians in countries throughout the world have different definitions and ways of treating this disease. The various proposed pathogeneses of UACS include the early postnasal drip theory, subsequent chronic airway inflammation theory, and a recent sensory neural hypersensitivity theory. Additionally, some researchers suggest that UACS is a clinical phenotype of cough hypersensitivity syndrome. While the general principles involved in treating UACS are similar throughout the world, the specific details of treatment differ. This review summarizes the various definitions, pathogenic mechanisms, treatments, and other aspects of UACS, to aid clinicians in expanding their knowledge of how to diagnose and treat this syndrome.

  8. When continuous positive airway pressure (CPAP) fails

    PubMed Central

    Virk, Jagdeep S.

    2016-01-01

    Obstructive sleep apnoea (OSA) is increasingly prevalent, particularly in the context of the obesity epidemic, and is associated with a significant social, health and economic impact. The gold standard of treatment for moderate to severe OSA is continuous positive airway pressure (CPAP). However compliance rates can be low. Methodology to improve patient tolerance to CPAP alongside with alternative, non-surgical and surgical, management strategies are discussed. All patients that fail CPAP therapy would benefit from formal upper airway evaluation by the otolaryngologist to identify any obvious causes and consider site-specific surgical therapies. Patient selection is integral to ensuring successful outcomes. A multidisciplinary team is needed to manage these patients. PMID:27867577

  9. 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

  10. Mechanically patterning the embryonic airway epithelium.

    PubMed

    Varner, Victor D; Gleghorn, Jason P; Miller, Erin; Radisky, Derek C; Nelson, Celeste M

    2015-07-28

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo.

  11. Endoscopic low coherence interferometry in upper airways

    NASA Astrophysics Data System (ADS)

    Delacrétaz, Yves; Boss, Daniel; Lang, Florian; Depeursinge, Christian

    2009-07-01

    We introduce Endoscopic Low Coherence Interferometry to obtain topology of upper airways through commonly used rigid endoscopes. Quantitative dimensioning of upper airways pathologies is crucial to provide maximum health recovery chances, for example in order to choose the correct stent to treat endoluminal obstructing pathologies. Our device is fully compatible with procedures used in day-to-day examinations and can potentially be brought to bedside. Besides this, the approach described here can be almost straightforwardly adapted to other endoscopy-related field of interest, such as gastroscopy and arthroscopy. The principle of the method is first exposed, then filtering procedure used to extract the depth information is described. Finally, demonstration of the method ability to operate on biological samples is assessed through measurements on ex-vivo pork bronchi.

  12. Mechanically patterning the embryonic airway epithelium

    PubMed Central

    Varner, Victor D.; Gleghorn, Jason P.; Miller, Erin; Radisky, Derek C.; Nelson, Celeste M.

    2015-01-01

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  13. Liquid secretion properties of airway submucosal glands

    PubMed Central

    Ballard, Stephen T; Inglis, Sarah K

    2004-01-01

    The tracheobronchial submucosal glands secrete liquid that is important for hydrating airway surfaces, supporting mucociliary transport, and serving as a fluid matrix for numerous secreted macromolecules including the gel-forming mucins. This review details the essential structural elements of airway glands and summarizes what is currently known regarding the ion transport processes responsible for producing the liquid component of gland secretion. Liquid secretion most likely arises from serous cells and is principally under neural control with muscarinic agonists, substance P, and vasoactive intestinal peptide (VIP) functioning as effective secretogogues. Liquid secretion is driven by the active transepithelial secretion of both Cl− and HCO3− and at least a portion of this process is mediated by the cystic fibrosis transmembrane conductance regulator (CFTR), which is highly expressed in glands. The potential role of submucosal glands in cystic fibrosis lung disease is discussed. PMID:14660706

  14. Airway inflammation in aluminium potroom asthma

    PubMed Central

    Sjaheim, T; Halstensen, T; Lund, M; Bjortuft, O; Drablos, P; Malterud, D; Kongerud, J

    2004-01-01

    Aims: To examine whether asthma induced by exposure to aluminium potroom emissions (potroom asthma) is associated with inflammatory changes in the airways. Methods: Bronchial biopsy specimens from 20 asthmatic workers (8 non-smokers and 12 smokers), 15 healthy workers (8 non-smokers and 7 smokers), and 10 non-exposed controls (all non-smokers) were analysed. Immunohistofluorescent staining was performed to identify mucosal total leucocytes (CD45+ leucocytes), neutrophils, and mast cells. Results: Median RBM thickness was significantly increased in both asthmatic workers (8.2 µm) and healthy workers (7.4 µm) compared to non-exposed controls (6.7 µm). Non-smoking asthmatic workers had significantly increased median density of lamina propria CD45+ leucocytes (1519 cells/mm2v 660 and 887 cells/mm2) and eosinophils (27 cells/mm2v 10 and 3 cells/mm2) and significantly increased concentrations of exhaled NO (18.1 ppb v 6.5 and 5.1 ppb) compared to non-smoking healthy workers and non-exposed controls. Leucocyte counts and exhaled NO concentrations varied with smoking habits and fewer leucocytes were observed in asthmatic smokers than in non-smokers Asthmatic smokers had significantly increased numbers of eosinophils in lamina propria compared to non-exposed controls (10 v 3 cells/mm2). Both eosinophilic and non-eosinophilic phenotypes of asthma were recognised in the potroom workers and signs of airway inflammation were also observed in healthy workers. Conclusions: Airway inflammation is a central feature of potroom asthma and exposure to potroom emissions induces pathological alterations similar to those described in other types of asthma. Cigarette smoking seems to affect the underlying mechanisms involved in asthma, as the cellular composition of airway mucosa appears different in asthmatic smokers and non-smokers. PMID:15317920

  15. Airway wall stiffening increases peak wall shear stress: a fluid-structure interaction study in rigid and compliant airways.

    PubMed

    Xia, Guohua; Tawhai, Merryn H; Hoffman, Eric A; Lin, Ching-Long

    2010-05-01

    The airflow characteristics in a computed tomography (CT) based human airway bifurcation model with rigid and compliant walls are investigated numerically. An in-house three-dimensional (3D) fluid-structure interaction (FSI) method is applied to simulate the flow at different Reynolds numbers and airway wall stiffness. As the Reynolds number increases, the airway wall deformation increases and the secondary flow becomes more prominent. It is found that the peak wall shear stress on the rigid airway wall can be five times stronger than that on the compliant airway wall. When adding tethering forces to the model, we find that these forces, which produce larger airway deformation than without tethering, lead to more skewed velocity profiles in the lower branches and further reduced wall shear stresses via a larger airway lumen. This implies that pathologic changes in the lung such as fibrosis or remodeling of the airway wall-both of which can serve to restrain airway wall motion-have the potential to increase wall shear stress and thus can form a positive feed-back loop for the development of altered flow profiles and airway remodeling. These observations are particularly interesting as we try to understand flow and structural changes seen in, for instance, asthma, emphysema, cystic fibrosis, and interstitial lung disease.

  16. Catheter-Based Sensing In The Airways

    NASA Astrophysics Data System (ADS)

    Fouke, J. M.; Saunders, K. G.

    1988-04-01

    Studies attempting to define the role of the respiratory tract in heating and humidifying inspired air point to the need for sensing many variables including airway wall and airstream temperatures, humidity, and surface fluid pH and osmolarity. In order to make such measurements in vivo in human volunteers, catheter based technologies must be exploited both to assure subject safety and subject comfort. Miniturization of the electrodes or sensors becomes a top priority. This paper describes the use of thin-film microelectronic technology to fabricate a miniature, flexible sensor which can be placed directly onto the surface of the airway to measure the electrical conductance of the fluids present. From this information the osmolarity of the surface fluid was calculated. Physiologic evaluation of the device and corroboration of the calculations was performed in mongrel dogs. We also describe the successful application of current thermistor technology for the thermal mapping of the airways in humans in order to characterize the dynamic intrathoracic events that occur during breathing. The thermal probe consisted of a flexible polyvinyl tube that contained fourteen small thermistors fixed into the catheter. Data have been obtained in dozens of people, both normal subjects and asthmatic patients, under a variety of interventions. These data have substantively advanced the study of asthma, a particularly troublesome chronic obstructive pulmonary disorder.

  17. Techniques of endoscopic airway tumor treatment

    PubMed Central

    Mhanna, Laurent; Droneau, Sylvain; Plat, Gavin; Didier, Alain; Mazieres, Julien; Hermant, Christophe

    2016-01-01

    Interventional bronchoscopy has a predominant role in the management of both early and advanced-stage airway tumors. Given the very poor prognosis of lung cancer, there is a need for new tools to improve early detection and bronchoscopic treatment of endo-bronchial precancerous lesions. In more advanced stages, interventional bronchoscopy plays an important role, as nearly a third of lung cancers lead to proximal airway obstruction. This will cause great discomfort or even life-threatening symptoms related to local extension, such as dyspnea, post-obstructive pneumonia, and hemoptysis. Surgery for very locally advanced disease is only effective for a limited number of patients and the effects of conventional antitumor therapies, like radiation therapy or chemotherapy, are inconstant and are too delayed in a palliative context. In this review, we aim to provide pulmonologists with an exhaustive technical overview of (I) the bronchoscopic management of benign endobronchial lesions; (II) the bronchoscopic management of malignant tumors, including the curative treatment of localized lesions and palliative management of malignant proximal airway stenosis; and (III) descriptions of the emerging endoscopic techniques used to treat peripheral lung tumors. PMID:28066616

  18. Resting calcium influx in airway smooth muscle.

    PubMed

    Montaño, Luis M; Bazán-Perkins, Blanca

    2005-01-01

    Plasma membrane Ca2+ leak remains the most uncertain of the cellular Ca2+ regulation pathways. During passive Ca2+ influx in non-stimulated smooth muscle cells, basal activity of constitutive Ca2+ channels seems to be involved. In vascular smooth muscle, the 3 following Ca2+ entry pathways contribute to this phenomenon: (i) via voltage-dependent Ca2+ channels, (ii) receptor gated Ca2+ channels, and (iii) store operated Ca2+ channels, although, in airway smooth muscle it seems only 2 passive Ca2+ influx pathways are implicated, one sensitive to SKF 96365 (receptor gated Ca2+ channels) and the other to Ni2+ (store operated Ca2+ channels). Resting Ca2+ entry could provide a sufficient amount of Ca2+ and contribute to resting intracellular Ca2+ concentration ([Ca2+]i), maintenance of the resting membrane potential, myogenic tone, and sarcoplasmic reticulum-Ca2+ refilling. However, further research, especially in airway smooth muscle, is required to better explore the physiological role of this passive Ca2+ influx pathway as it could be involved in airway hyperresponsiveness.

  19. Surgery of the airway: historic notes

    PubMed Central

    2016-01-01

    Prior to the 20th century, the need for surgical procedures on the airway was infrequent and consisted mainly of tracheostomy to relieve airway obstruction or repair of tracheal injuries such as lacerations. Even the ability of tracheal suture lines to heal primarily was viewed with concern due to the rigidity of the tracheal wall, its precarious blood supply and uncertainty as to whether the cartilage components could heal without complications. In the 20th century the evolution of tracheal procedures on major airways evolved to meet the challenges provided by the expanding fields of thoracic surgery and advent of mechanical respiratory support with its associated complications. In the first half of the century lobar and lung resections done for tuberculosis and lung cancer required methods for safe closure of the resulting bronchial stumps and end-to-end bronchial anastomosis in the case of sleeve resections of the lung. Beginning in mid-century the advent of respiratory care units for the treatment of polio and for the expanding fields of thoracic and cardiac surgery resulted in a significant number of post-intubation tracheal stenosis requiring resection and primary repair. In the last 20 years of the century the development of lung transplantation with its requirement for successful bronchial anastomoses between the donor and recipient bronchi, created unique challenges including ischemia of the donor bronchus the adverse effects of immunosuppression, donor lung preservation and diagnosis and management of post-transplant infection and rejection. PMID:26981261

  20. Voxel classification based airway tree segmentation

    NASA Astrophysics Data System (ADS)

    Lo, Pechin; de Bruijne, Marleen

    2008-03-01

    This paper presents a voxel classification based method for segmenting the human airway tree in volumetric computed tomography (CT) images. In contrast to standard methods that use only voxel intensities, our method uses a more complex appearance model based on a set of local image appearance features and Kth nearest neighbor (KNN) classification. The optimal set of features for classification is selected automatically from a large set of features describing the local image structure at several scales. The use of multiple features enables the appearance model to differentiate between airway tree voxels and other voxels of similar intensities in the lung, thus making the segmentation robust to pathologies such as emphysema. The classifier is trained on imperfect segmentations that can easily be obtained using region growing with a manual threshold selection. Experiments show that the proposed method results in a more robust segmentation that can grow into the smaller airway branches without leaking into emphysematous areas, and is able to segment many branches that are not present in the training set.

  1. Airway mucus: From production to secretion.

    PubMed

    Williams, Olatunji W; Sharafkhaneh, Amir; Kim, Victor; Dickey, Burton F; Evans, Christopher M

    2006-05-01

    Mucus hypersecretion is a phenotype associated with multiple obstructive lung diseases. However, in spite of its nefarious reputation under pathologic conditions, there are significant benefits to having low levels of mucus present in the airways at baseline, such as the ability to trap and eliminate inhaled particles and to prevent desiccation of airway surfaces. Mucins are high-molecular-weight glycoproteins that are the chief components that render viscoelastic and gel-forming properties to mucus. Recent advances in animal models and in vitro systems have provided a wealth of information regarding the identification of the mucin genes that are expressed in the lungs, the signal transduction pathways that regulate the expression of these mucins, and the secretory pathways that mediate their release into the airways. In addition, the clinical and pathologic literature has corroborated many of the basic laboratory findings. As a result, mucin overproduction and hypersecretion are moving away from being markers of disease and toward being testable as functional components of lung disease processes.

  2. Exercise and airway injury in athletes.

    PubMed

    Couto, Mariana; Silva, Diana; Delgado, Luis; Moreira, André

    2013-01-01

    Olympic level athletes present an increased risk for asthma and allergy, especially those who take part in endurance sports, such as swimming or running, and in winter sports. Classical postulated mechanisms behind EIA include the osmotic, or airway-drying, hypothesis. Hyperventilation leads to evaporation of water and the airway surface liquid becomes hyperosmolar, providing a stimulus for water to move from any cell nearby, which results in the shrinkage of cells and the consequent release of inflammatory mediators that cause airway smooth muscle contraction. But the exercise-induced asthma/bronchoconstriction explanatory model in athletes probably comprises the interaction between environmental training factors, including allergens and ambient conditions such as temperature, humidity and air quality; and athlete's personal risk factors, such as genetic and neuroimmuneendocrine determinants. After the stress of training and competitions athletes experience higher rate of upper respiratory tract infections (URTI), compared with lesser active individuals. Increasing physical activity in non-athletes is associated with a decreased risk of URTI. Heavy exercise induces marked immunodepression which is multifactorial in origin. Prolonged, high intensity exercise temporarily impairs the immune competence while moderate activity may enhance immune function. The relationship between URTI and exercise is affected by poorly known individual determinants such genetic susceptibility, neurogenic mediated immune inflammation and epithelial barrier dysfunction. Further studies should better define the aetiologic factors and mechanisms involved in the development of asthma in athletes, and propose relevant preventive and therapeutic measures.

  3. Oral airway flow dynamics in healthy humans.

    PubMed

    Amis, T C; O'Neill, N; Wheatley, J R

    1999-02-15

    1. Oral airway resistance (RO) is an important determinant of oro-nasal partitioning of airflow (e.g. during exercise and sleep); however, little is known of factors influencing its magnitude and measurement. 2. We developed a non-invasive standardized technique for measuring RO (based on a modification of posterior rhinomanometry) and examined inspiratory RO in 17 healthy male subjects (age, 36 +/- 2 years (mean +/- s.e.m.); height, 177 +/- 2 cm; weight, 83 +/- 3 kg). 3. Inspiratory RO (at 0.4 l s-1) was 0.86 +/- 0.23 cmH2O l-1 s-1 during resting mouthpiece breathing in the upright posture. RO was unaffected by assumption of the supine posture, tended to decrease with head and neck extension and increased to 1.22 +/- 0.19 cmH2O l-1 s-1 (n = 10 subjects, P < 0.01) with 40-45 deg of head and neck flexion. When breathing via a mouth-mask RO was 2.98 +/- 0.42 cmH2O l-1 s-1 (n = 7) and not significantly different from nasal airway resistance. 4. Thus, in awake healthy male subjects with constant jaw position, RO is unaffected by body posture but increases with modest degrees of head and neck flexion. This influence on upper airway patency may be important when oral route breathing is associated with alterations in head and neck position, e.g. during sleep.

  4. Airways obstruction, coal mining, and disability.

    PubMed Central

    Lapp, N L; Morgan, W K; Zaldivar, G

    1994-01-01

    It has recently been suggested that the inhalation of coal in the absence of complicated coal workers' pneumoconiosis (CWP) or smoking can lead to disabling airways obstruction. The cause of such obstruction has been variously attributed to emphysema or bronchitis. The frequency of significant airways obstruction in a group of United States coal miners seeking compensation for occupationally induced pulmonary impairment was therefore determined. In a sample of 611 "Black Lung" claimants there was only one subject who was a non-smoker and who in the absence of other non-occupationally related diseases,--for example, asthma and bronchiectasis--had sufficient airways obstruction to render it difficult for him to carry out hard labour. An alternative explanation for his reduced ventilatory capacity other than coal dust or smoking may be available. If the inhalation of coal dust in the absence of smoking and complicated CWP ever induces sufficient ventilatory impairment to preclude a miner from working, it is indeed rare. PMID:8199664

  5. Impact of airway morphological changes on pulmonary flows in scoliosis

    NASA Astrophysics Data System (ADS)

    Farrell, James; Garrido, Enrique; Valluri, Prashant

    2016-11-01

    The relationship between thoracic deformity in scoliosis and lung function is poorly understood. In a pilot study, we reviewed computed tomography (CT) routine scans of patients undergoing scoliosis surgery. The CT scans were processed to segment the anatomy of the airways, lung and spine. A three-dimensional model was created to study the anatomical relationship. Preliminary analysis showed significant airway morphological differences depending on the anterior position of the spine. A computational fluid dynamics (CFD) study was also conducted on the airway geometry using the inspiratory scans. The CFD model assuming non-compliant airway walls was capable of showing pressure drops in areas of high airway resistance, but was unable to predict regional ventilation differences. Our results indicate a dependence between the dynamic deformation of the airway during breathing and lung function. Dynamic structural deformation must therefore be incorporated within any modelling approaches to guide clinicians on the decision to perform surgical correction of the scoliosis.

  6. A framework for understanding shared substrates of airway protection

    PubMed Central

    TROCHE, Michelle Shevon; BRANDIMORE, Alexandra Essman; GODOY, Juliana; HEGLAND, Karen Wheeler

    2014-01-01

    Deficits of airway protection can have deleterious effects to health and quality of life. Effective airway protection requires a continuum of behaviors including swallowing and cough. Swallowing prevents material from entering the airway and coughing ejects endogenous material from the airway. There is significant overlap between the control mechanisms for swallowing and cough. In this review we will present the existing literature to support a novel framework for understanding shared substrates of airway protection. This framework was originally adapted from Eccles' model of cough28 (2009) by Hegland, et al.42 (2012). It will serve to provide a basis from which to develop future studies and test specific hypotheses that advance our field and ultimately improve outcomes for people with airway protective deficits. PMID:25141195

  7. Central airway tumors: interventional bronchoscopy in diagnosis and management

    PubMed Central

    Lin, Chun-Yu

    2016-01-01

    The diagnosis of central airway tumors is usually challenging because of the vague presentations. Advances in visualization technology in bronchoscopy aid early detection of bronchial lesion. Cryotechnology has great impact on endobronchial lesion sampling and provides better diagnostic yield. Airway tumor involvements result in significant alteration in life quality and lead to poor life expectancy. Timely and efficiently use ablation techniques by heat or cold energy provide symptoms relief for central airway obstruction. Prostheses implantation is effective in maintaining airway patency after ablative procedure or external compression. Combined interventional bronchoscopy modalities and other adjunctive therapies have improvement in quality of life and further benefit in survival. This review aims to provide a diagnostic approach to central airway tumors and an overview of currently available techniques of interventional bronchoscopy in managing symptomatic central airway obstruction. PMID:27867582

  8. An anterior mediastinal mass: delayed airway compression and using a double lumen tube for airway patency.

    PubMed

    Lee, Jeounghyuk; Rim, Yong Chul; In, Junyong

    2014-06-01

    Perioperative management of patients with an anterior mediastinal mass is difficult. We present a 35-year-old woman who showed delayed compression of the carina and left main bronchus despite no preoperative respiratory signs, symptoms, or radiologic findings due to an anterior mediastinal mass and uneventful stepwise induction of general anesthesia. Even use of a fiberoptic bronchoscope (FB) after induction of anesthesia was not helpful to predict delayed compression of the airway. Therefore, the anesthesiologist and the cardiothoracic surgeon must prepare for unexpected delayed compression of the airway, even in low risk patients who are asymptomatic or mildly symptomatic without postural symptoms or radiographic evidence of significant compression of structures. We also describe successful management for the compressed carina and left main bronchus with a double lumen tube (DLT) as a stent during surgery. FB guided DLT intubation is a possible solution to maintain airway patency.

  9. Increased sensitivity to thyroid hormone replacement therapy followed by hyponatremia and eosinophilia in a patient with long-standing young-onset primary hypothyroidism.

    PubMed

    Fujikawa, M; Okamura, K; Sato, K; Mizokami, T; Shiratsuchi, M; Fujishima, M

    1999-06-01

    We describe a 51-year-old woman with long-standing young-onset primary hypothyroidism. Serum cortisol, adrenocorticotropin, and arginine vasopressin levels were normal, but urinary excretion of 17-hydroxycorticosteroid was decreased. Administration of a very small initial dose of thyroid hormone induced severe acute complications including fever, palpitation, and sweating associated with a rapid decrease in serum thyrotropin level, a dramatic increase in serum alkaline-phosphatase level, and a decrease in serum total cholesterol level. A week later, the late complications of nausea, severe hyponatremia, and eosinophilia occurred. Serum cortisol level decreased slightly but remained within normal limits during this hyponatremic period. This rare case suggests that increased sensitivity to thyroid hormone can occur in long-standing primary hypothyroidism with biphasic clinical course of acute thyrotoxic complications followed by severe hyponatremia resembling hypoadrenocorticism.

  10. Airway Epithelial Expression Quantitative Trait Loci Reveal Genes Underlying Asthma and Other Airway Diseases

    PubMed Central

    Luo, Wei; Obeidat, Ma’en; Di Narzo, Antonio Fabio; Chen, Rong; Sin, Don D.; Paré, Peter D.

    2016-01-01

    Genome-wide association studies (GWASs) have identified loci that are robustly associated with asthma and related phenotypes; however, the molecular mechanisms underlying these associations need to be explored. The most relevant tissues to study the functional consequences of asthma are the airways. We used publically available data to derive expression quantitative trait loci (eQTLs) for human epithelial cells from small and large airways and applied the eQTLs in the interpretation of GWAS results of asthma and related phenotypes. For the small airways (n = 105), we discovered 660 eQTLs at a 10% false discovery rate (FDR), among which 315 eQTLs were not previously reported in a large-scale eQTL study of whole lung tissue. A large fraction of the identified eQTLs is supported by data from Encyclopedia of DNA Elements (ENCODE) showing that the eQTLs reside in regulatory elements (57.5 and 67.6% of cis- and trans-eQTLs, respectively). Published pulmonary GWAS hits were enriched as airway epithelial eQTLs (9.2-fold). Further, genes regulated by asthma GWAS loci in epithelium are significantly enriched in immune response pathways, such as IL-4 signaling (FDR, 5.2 × 10−4). The airway epithelial eQTLs described in this study are complementary to previously reported lung eQTLs and represent a powerful resource to link GWAS-associated variants to their regulatory function and thus elucidate the molecular mechanisms underlying asthma and airway-related conditions. PMID:26102239

  11. Thick airway surface liquid volume and weak mucin expression in pendrin-deficient human airway epithelia

    PubMed Central

    Lee, Hyun Jae; Yoo, Jee Eun; Namkung, Wan; Cho, Hyung-Ju; Kim, Kyubo; Kang, Joo Wan; Yoon, Joo-Heon; Choi, Jae Young

    2015-01-01

    Pendrin is an anion exchanger whose mutations are known to cause hearing loss. However, recent data support the linkage between pendrin expression and airway diseases, such as asthma. To evaluate the role of pendrin in the regulation of the airway surface liquid (ASL) volume and mucin expression, we investigated the function and expression of pendrin and ion channels and anion exchangers. Human nasal epithelial cells were cultured from 16 deaf patients carrying pendrin mutations (DFNB4) and 17 controls. The cells were treated with IL-13 to induce mucus hypersecretion. Airway surface liquid thickness was measured and real-time polymerase chain reaction was performed targeting various transporters and MUC5AC. Anion exchanger activity was measured using a pH-sensitive fluorescent probe. Periodic acid-Schiff staining was performed on the cultured cells and inferior turbinate tissues. The ASL layer of the nasal epithelia from DFNB4 subjects was thicker than the controls, and the difference became more prominent following IL-13 stimulation. There was no difference in anion exchange activity after IL-13 treatment in the cells from DFNB4 patients, while it increased in the controls. Goblet cell metaplasia induced by IL-13 treatment seen in the controls was not observed in the DFNB4 cells. Furthermore, the periodic acid-Schiff staining-positive area was lesser in the inferior turbinate tissues from DFNB4 patients that those from controls. Pendrin plays a critical role in ASL volume regulation and mucin expression as pendrin-deficient airway epithelial cells are refractory to stimulation with IL-13. Specific blockers targeting pendrin in the airways may therefore have therapeutic potential in the treatment of allergic airway diseases. PMID:26243215

  12. Air-Q intubating laryngeal airway: A study of the second generation supraglottic airway device

    PubMed Central

    Attarde, Viren Bhaskar; Kotekar, Nalini; Shetty, Sarika M

    2016-01-01

    Background and Aims: Air-Q intubating laryngeal mask airway (ILA) is used as a supraglottic airway device and as a conduit for endotracheal intubation. This study aims to assess the efficacy of the Air-Q ILA regarding ease of insertion, adequacy of ventilation, rate of successful intubation, haemodynamic response and airway morbidity. Methods: Sixty patients presenting for elective surgery at our Medical College Hospital were selected. Following adequate premedication, baseline vital parameters, pulse rate and blood pressure were recorded. Air-Q size 3.5 for patients 50-70 kg and size 4.5 for 70-100 kg was selected. After achieving adequate intubating conditions, Air-Q ILA was introduced. Confirming adequate ventilation, appropriate sized endotracheal tube was advanced through the Air-Q blindly to intubate the trachea. Placement of the endotracheal tube in trachea was confirmed. Results: Air-Q ILA was successfully inserted in 88.3% of patients in first attempt and 11.7% patients in second attempt. Ventilation was adequate in 100% of patients. Intubation was successful in 76.7% of patients with Air-Q ILA. 23.3% of patients were intubated by direct laryngoscopy following failure with two attempts using Air-Q ILA. Post-intubation the change in heart rate was statistically significant (P < 0.0001). 10% of patients were noted to have a sore throat and 5% of patients had mild airway trauma. Conclusion: Air-Q ILA is a reliable device as a supraglottic airway ensuring adequate ventilation as well as a conduit for endotracheal intubation. It benefits the patient by avoiding the stress of direct laryngoscopy and is also superior alternative device for use in a difficult airway. PMID:27212722

  13. Improving the safety of remote site emergency airway management.

    PubMed

    Wijesuriya, Julian; Brand, Jonathan

    2014-01-01

    Airway management, particularly in non-theatre settings, is an area of anaesthesia and critical care associated with significant risk of morbidity & mortality, as highlighted during the 4th National Audit Project of the Royal College of Anaesthetists (NAP4). A survey of junior anaesthetists at our hospital highlighted a lack of confidence and perceived lack of safety in emergency airway management, especially in non-theatre settings. We developed and implemented a multifaceted airway package designed to improve the safety of remote site airway management. A Rapid Sequence Induction (RSI) checklist was developed; this was combined with new advanced airway equipment and drugs bags. Additionally, new carbon dioxide detector filters were procured in order to comply with NAP4 monitoring recommendations. The RSI checklists were placed in key locations throughout the hospital and the drugs and advanced airway equipment bags were centralised in the Intensive Care Unit (ICU). It was agreed with the senior nursing staff that an appropriately trained ICU nurse would attend all emergency situations with new airway resources upon request. Departmental guidelines were updated to include details of the new resources and the on-call anaesthetist's responsibilities regarding checks and maintenance. Following our intervention trainees reported higher confidence levels regarding remote site emergency airway management. Nine trusts within the Northern Region were surveyed and we found large variations in the provision of remote site airway management resources. Complications in remote site airway management due lack of available appropriate drugs, equipment or trained staff are potentially life threatening and completely avoidable. Utilising the intervention package an anaesthetist would be able to safely plan and prepare for airway management in any setting. They would subsequently have the drugs, equipment, and trained assistance required to manage any difficulties or complications

  14. Toll-like Receptor 7 Rapidly Relaxes Human Airways

    PubMed Central

    Scott, Gregory D.; Proskocil, Becky J.; Fryer, Allison D.; Jacoby, David B.; Kaufman, Elad H.

    2013-01-01

    Rationale: Toll-like receptors (TLRs) 7 and 8 detect respiratory virus single-stranded RNA and trigger an innate immune response. We recently described rapid TLR7-mediated bronchodilation in guinea pigs. Objectives: To characterize TLR7 expression and TLR7-induced airway relaxation in humans and in eosinophilic airway inflammation in guinea pigs. To evaluate the relaxant effects of other TLRs. Methods: Human airway smooth muscle strips were contracted with methacholine in vitro, and responses to TLR7 and TLR8 agonists were assessed. TLR7-mediated nitric oxide production was measured using a fluorescent indicator, and TLR7 expression was characterized using immunofluorescence. TLR7 signaling was also evaluated in ovalbumin-challenged guinea pigs. Measurements and Main Results: The TLR7 agonist imiquimod (R837) caused rapid dose-dependent relaxation of methacholine-contracted human airways in vitro. This was blocked by the TLR7 antagonist IRS661 and by inhibiting nitric oxide production but not by inhibiting prostaglandin production. TLR7 activation markedly increased fluorescence of a nitric oxide detector. TLR7 was expressed on airway nerves, but not airway smooth muscle, implicating airway nerves as the source of TLR7-induced nitric oxide production. TLR7-mediated relaxation persisted in inflamed guinea pigs airways in vivo. The TLR8 agonists polyuridylic acid and polyadenylic acid also relaxed human airways, and this was not blocked by the TLR7 antagonist or by blocking nitric oxide or prostaglandin production. No other TLRs relaxed the airways. Conclusions: TLR7 is expressed on airway nerves and mediates relaxation of human and animal airways through nitric oxide production. TLR7-mediated bronchodilation may be a new therapeutic strategy in asthma. PMID:23924358

  15. Investigation of the effects of intranasal botulinum toxin type A and ipratropium bromide nasal spray on nasal hypersecretion in idiopathic rhinitis without eosinophilia.

    PubMed

    Sapci, Tarik; Yazici, Sara; Evcimik, M Fatih; Bozkurt, Ziya; Karavus, Ahmet; Ugurlu, Bayram; Ozkurt, Emre

    2008-03-01

    Idiopathic rhinitis without eosinophilia is a group of frequently observed diseases, the aetiopathogenesis of which is not yet well known. One of the most disturbing symptoms for patients within this disease group is nasal hypersecretion. Although many different treatments have been tried for hypersecretion, nasal topical drugs form the basis of any such therapy today. Ipratropium bromide (IB) is a drug offirst choice in nasal hypersecretion therapy. It displays a parasympatholytic effect in topical use and antagonizes acetylcholine transport in efferent parasympathetic nerves, thus decreasing submucosal gland secretion, which is the cause of hypersecretion. Botulinum toxin type A (BTX-A) is among the alternative treatment choices that is increasingly used in symptomatic treatment of nasal hypersecretion. Our study was planned with the aim of comparing the effect of these two groups of drugs on nasal hypersecretion. Thirty-eight patients who were diagnosed with idiopathic rhinitis without eosinophilia were included in the study and were divided in 3 different groups: In the first group, a total of 10 units of BTX-A were injected into both nasal cavities. In the second group, 3x2 IB was injected into both nasal cavities for 4 weeks. The third group received intranasal physiologic saline as placebo. The patients were evaluated in terms of nasal hypersecretion with visual analogue scale prior to the treatment and at weeks 1, 2, 4, 8, and 12 during the follow-up period. Throughout the 8 weeks follow-up period, the patient complaints displayed a 41.2% decrease in the group that received BTX-A and a 61.4% decrease in the group which received IB, while no change was observed in the control group. Both drug groups were well tolerated by the patients, with no serious adverse or systemic effects. As a result, while IB and BTX-A differ in terms of method of application, they display a similar degree and duration of efficiency in hypersecretion therapy.

  16. Quantitative computed tomography imaging of airway remodeling in severe asthma

    PubMed Central

    Fetita, Catalin I.; Brillet, Pierre-Yves

    2016-01-01

    Asthma is a heterogeneous condition and approximately 5–10% of asthmatic subjects have severe disease associated with structure changes of the airways (airway remodeling) that may develop over time or shortly after onset of disease. Quantitative computed tomography (QCT) imaging of the tracheobronchial tree and lung parenchyma has improved during the last 10 years, and has enabled investigators to study the large airway architecture in detail and assess indirectly the small airway structure. In severe asthmatics, morphologic changes in large airways, quantitatively assessed using 2D-3D airway registration and recent algorithms, are characterized by airway wall thickening, luminal narrowing and bronchial stenoses. Extent of expiratory gas trapping, quantitatively assessed using lung densitometry, may be used to assess indirectly small airway remodeling. Investigators have used these quantitative imaging techniques in order to attempt severity grading of asthma, and to identify clusters of asthmatic patients that differ in morphologic and functional characteristics. Although standardization of image analysis procedures needs to be improved, the identification of remodeling pattern in various phenotypes of severe asthma and the ability to relate airway structures to important clinical outcomes should help target treatment more effectively. PMID:26981458

  17. KyoT2 downregulates airway remodeling in asthma.

    PubMed

    Hu, Mei; Ou-Yang, Hai-Feng; Han, Xing-Peng; Ti, Xin-Yu; Wu, Chang-Gui

    2015-01-01

    The typical pathological features of asthma are airway remodeling and airway hyperresponsiveness (AHR). KyoT2, a negative modulator of Notch signaling, has been linked to asthma in several previous studies. However, whether KyoT2 is involved in the regulation of airway remodeling or the modulation of airway resistance in asthma is unclear. In this study, we aimed to evaluate the therapeutic potential of KyoT2 in preventing asthma-associated airway remodeling and AHR. BALB/c mice were used to generate a mouse model of asthma. Additionally, the expression of Hes1 and Notch1 in airway was analyzed using Immunofluorescence examination. The asthmatic mice were intranasally administered adenovirus expressing KyoT2 and were compared to control groups. Furthermore, subepithelial fibrosis and other airway remodeling features were analyzed using hematoxylin and eosin staining, Van Gieson's staining and Masson's trichrome staining. AHR was also evaluated. This study revealed that KyoT2 downregulated the expression of Hes1, repressed airway remodeling, and alleviated AHR in asthmatic mice. It is reasonable to assume that KyoT2 downregulates airway remodeling and resistance in asthmatic mice through a Hes1-dependent mechanism. Therefore, KyoT2 is a potential clinical treatment strategy for asthma.

  18. Quantitative computed tomography imaging of airway remodeling in severe asthma.

    PubMed

    Grenier, Philippe A; Fetita, Catalin I; Brillet, Pierre-Yves

    2016-02-01

    Asthma is a heterogeneous condition and approximately 5-10% of asthmatic subjects have severe disease associated with structure changes of the airways (airway remodeling) that may develop over time or shortly after onset of disease. Quantitative computed tomography (QCT) imaging of the tracheobronchial tree and lung parenchyma has improved during the last 10 years, and has enabled investigators to study the large airway architecture in detail and assess indirectly the small airway structure. In severe asthmatics, morphologic changes in large airways, quantitatively assessed using 2D-3D airway registration and recent algorithms, are characterized by airway wall thickening, luminal narrowing and bronchial stenoses. Extent of expiratory gas trapping, quantitatively assessed using lung densitometry, may be used to assess indirectly small airway remodeling. Investigators have used these quantitative imaging techniques in order to attempt severity grading of asthma, and to identify clusters of asthmatic patients that differ in morphologic and functional characteristics. Although standardization of image analysis procedures needs to be improved, the identification of remodeling pattern in various phenotypes of severe asthma and the ability to relate airway structures to important clinical outcomes should help target treatment more effectively.

  19. Strategies and algorithms for management of the difficult airway.

    PubMed

    Heidegger, Thomas; Gerig, Hans J; Henderson, John J

    2005-12-01

    Management of the difficult airway is the most important patient safety issue in the practice of anaesthesia. Many national societies have developed algorithms and guidelines for management of the difficult airway. The key issues of this chapter are definition of terms, the advantages and disadvantages of the use of guidelines, and a comparison of different algorithms and guidelines for management of the most important clinical airway scenarios. Although there is no strong evidence of benefit for any specific strategy or algorithm for management of the difficult airway, there is strong agreement that a pre-planned strategy may lead to improved outcome.

  20. AIRWAY HYPERRESPONSIVENESS IN MICE FOLLOWING ANTIGEN AND PARTICULATE MATTER EXPOSURE IS VAGALLY MEDIATED

    EPA Science Inventory

    Sensory nerves within the airways can initiate a variety of protective reflexes. We hypothesized that insults such as exposure to antigen and particulate matter (PM) might dysregulate airway sensory nerve function, thereby contributing to enhanced airway inflammation and hyperre...

  1. 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...

  2. 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

  3. Morphological and morphometric studies of the airways of sheep with acute airway hypersensitivity to inhaled Ascaris suum.

    PubMed

    Chen, W; Alley, M R; Manktelow, B W

    1991-10-01

    The airways of 12 sheep with naturally-occurring allergic airway hypersensitivity, six of which had changes in both airway resistance and dynamic lung compliance (Group A) and six of which had changes in only dynamic lung compliance (Group B), were compared quantitatively with six non-reacting sheep (Group C) in order to examine the relation between airway hypersensitivity and various morphological features thought to be related to airway hypersensitivity. Compared to the non-reacting sheep (Group C), the hypersensitive sheep (Groups A and B) had a thinner epithelium in medium bronchi and bronchioles, fewer goblet cells in bronchioles, and greater gland area at most airway levels. The differences of the gland dimensions and the types of mucosubstance between hypersensitive and non-reacting animals were more variable. No significant differences between the three groups were noted with regard to luminal occlusion or epithelial sloughing and squamous metaplasia. Although there was a positive association between epithelial thickness and goblet cell density in the small airways, the development of allergic airway hypersensitivity in sheep may occur in the absence of major morphological changes in the airway epithelium.

  4. Severe micrognathia: indications for EXIT-to-Airway.

    PubMed

    Morris, Lee M; Lim, Foong-Yen; Elluru, Ravindhra G; Hopkin, Robert J; Jaekle, Ronald K; Polzin, William J; Crombleholme, Timothy M

    2009-01-01

    The ex utero intrapartum treatment (EXIT) procedure has become an important management option in cases of fetal airway obstruction. Select cases of severe micrognathia may be candidates for EXIT-to-Airway due to high-risk of airway obstruction at birth. Here we present three successful EXIT-to-Airway procedures for the management of congenital micrognathia in its most severe manifestations. CASE 1: A 23-year-old G3P1011 with a pregnancy complicated by severe micorgnathia, jaw index <5th percentile, as well as polyhydramnios. At 36 weeks EXIT-to-Airway was performed utilizing a bronchoscopically positioned laryngeal mask airway (LMA) during 23 min of uteroplacental support followed by tracheostomy. CASE 2: A 26-year-old G4P0120 with a pregnancy complicated by severe micrognathia, jaw index <5th percentile, and an obstructed oropharynx associated with polyhydramnios. At 37 weeks EXIT-to-Airway was performed with placement of tracheostomy. CASE 3: A 36-year-old G6P3023 with fetal magnetic resonance imaging (MRI) revealing esophageal atresia, polyhydramnios, and severe micrognathia with a jaw index <5th percentile. At 35 weeks the patient underwent EXIT-to-Airway with formal tracheostomy during 35 min of uteroplacental bypass. In the most severe cases of fetal micrognathia, EXIT-to-Airway provides time to evaluate and secure the fetal airway prior to delivery. We propose indications for EXIT-to-Airway in micrognathia to include a jaw index <5%, with indirect evidence of aerodigestive tract obstruction such as polyhydramnios, glossoptosis or an absent stomach bubble.

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

    PubMed

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

    2013-06-01

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

  6. Measurement of intraindividual airway tone heterogeneity and its importance in asthma

    PubMed Central

    Togias, Alkis

    2016-01-01

    While airways have some degree of baseline tone, the level and variability of this tone is not known. It is also unclear whether there is a difference in airway tone or in the variability of airway tone between asthmatic and healthy individuals. This study examined airway tone and intraindividual airway tone heterogeneity (variance of airway tone) in vivo in 19 individuals with asthma compared with 9 healthy adults. All participants underwent spirometry, body plethysmography, and high-resolution computed tomography at baseline and after maximum bronchodilation with albuterol. Airway tone was defined as the percent difference in airway diameter after albuterol at total lung capacity compared with baseline. The amount of airway tone in each airway varied both within and between subjects. The average airway tone did not differ significantly between the two groups (P = 0.09), but the intraindividual airway tone heterogeneity did (P = 0.016). Intraindividual airway tone heterogeneity was strongly correlated with airway tone (r = 0.78, P < 0.0001). Also, it was negatively correlated with the magnitude of the distension of the airways from functional residual capacity to total lung capacity at both baseline (r = −0.49, P = 0.03) and after maximum bronchodilation (r = −0.51, P = 0.02) in the asthma, but not the healthy group. However, we did not find any relationship between intraindividual airway tone heterogeneity and conventional lung function outcomes. Intraindividual airway tone heterogeneity appears to be an important characteristic of airway pathophysiology in asthma. PMID:27103654

  7. Baicalein Reduces Airway Injury in Allergen and IL-13 Induced Airway Inflammation

    PubMed Central

    Mabalirajan, Ulaganathan; Ahmad, Tanveer; Rehman, Rakhshinda; Leishangthem, Geeta Devi; Dinda, Amit Kumar; Agrawal, Anurag; Ghosh, Balaram; Sharma, Surendra Kumar

    2013-01-01

    Background Baicalein, a bioflavone present in the dry roots of Scutellaria baicalensis Georgi, is known to reduce eotaxin production in human fibroblasts. However, there are no reports of its anti-asthma activity or its effect on airway injury. Methodology/Principal Findings In a standard experimental asthma model, male Balb/c mice that were sensitized with ovalbumin (OVA), treated with baicalein (10 mg/kg, ip) or a vehicle control, either during (preventive use) or after OVA challenge (therapeutic use). In an alternate model, baicalein was administered to male Balb/c mice which were given either IL-4 or IL-13 intranasally. Features of asthma were determined by estimating airway hyperresponsiveness (AHR), histopathological changes and biochemical assays of key inflammatory molecules. Airway injury was determined with apoptotic assays, transmission electron microscopy and assessing key mitochondrial functions. Baicalein treatment reduced AHR and inflammation in both experimental models. TGF-β1, sub-epithelial fibrosis and goblet cell metaplasia, were also reduced. Furthermore, baicalein treatment significantly reduced 12/15-LOX activity, features of mitochondrial dysfunctions, and apoptosis of bronchial epithelia. Conclusion/Significance Our findings demonstrate that baicalein can attenuate important features of asthma, possibly through the reduction of airway injury and restoration of mitochondrial function. PMID:23646158

  8. Effects of continuous negative airway pressure-related lung deflation on upper airway collapsibility.

    PubMed

    Sériès, F; Marc, I

    1993-09-01

    Continuous negative airway pressure (CNAP) causes a decrease in lung volume, which is known to increase upper airway resistance by itself. We studied how this lung volume change could modify upper airway collapsibility with five normal awake subjects. In a first trial, pressure in a nasal mask (Pm) was progressively decreased in 3- to 5-cmH2O steps (CNAP). In a second trial, changes in lung volumes resulting from CNAP were prevented by applying simultaneously an equivalent level of negative extrathoracic pressure into a poncho-type respirator [isovolumetric CNAP (CNAPisovol)]. For each trial, we examined the relationship between the maximal inspiratory airflow of each flow-limited inspiratory cycle and the corresponding Pm by least-squares linear regression analysis and determined the critical pressure. We also determined the Pm threshold corresponding to the first Pm value below which flow limitation occurred. Flow limitation was observed in each subject with CNAP but in only two subjects with CNAPisovol. In these two subjects, the Pm threshold values were -20 and -9 cmH2O with CNAP and -39 and -16 cmH2O with CNAPisovol, respectively. Critical pressures for the same two subjects were -161 and -96 cmH2O with CNAP and -202 and -197 cmH2O with CNAPisovol, respectively. We conclude that CNAP-induced decreases in lung volume increase upper airway collapsibility.

  9. 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.

  10. New insights into upper airway innate immunity

    PubMed Central

    Hariri, Benjamin M.

    2016-01-01

    Background: Protecting the upper airway from microbial infection is an important function of the immune system. Proper detection of these pathogens is paramount for sinonasal epithelial cells to be able to prepare a defensive response. Toll-like receptors and, more recently, bitter taste receptors and sweet taste receptors have been implicated as sensors able to detect the presence of these pathogens and certain compounds that they secrete. Activation of these receptors also triggers innate immune responses to prevent or counteract infection, including mucociliary clearance and the production and secretion of antimicrobial compounds (e.g., defensins). Objective: To provide an overview of the current knowledge of the role of innate immunity in the upper airway, the mechanisms by which it is carried out, and its clinical relevance. Methods: A literature review of the existing knowledge of the role of innate immunity in the human sinonasal cavity was performed. Results: Clinical and basic science studies have shown that the physical epithelial cell barrier, mucociliary clearance, and antimicrobial compound secretion play pivotal innate immune roles in defending the sinonasal cavity from infection. Clinical findings have also linked dysfunction of these defense mechanisms with diseases, such as chronic rhinosinusitis and cystic fibrosis. Recent discoveries have elucidated the significance of bitter and sweet taste receptors in modulating immune responses in the upper airway. Conclusion: Numerous innate immune mechanisms seem to work in a concerted fashion to keep the sinonasal cavity free of infection. Understanding sinonasal innate immune function and dysfunction in health and disease has important implications for patients with respiratory ailments, such as chronic rhinosinusitis and cystic fibrosis. PMID:27657896

  11. MOEBIUS SYNDROME: CHALLENGES OF AIRWAY MANAGEMENT.

    PubMed

    Budić, Ivana; Šurdilović, Dušan; Slavković, Anđelka; Marjanović, Vesna; Stević, Marija; Simić, Dušica

    2016-03-01

    Moebius syndrome is a rare nonprogressive congenital neurological disorder with a wide range of severity and variability of symptoms. This diversity is a consequence of dysfunction of different cranial nerves (most often facial and abducens nerves), accompanying orofacial abnormalities, musculoskeletal malformations, congenital cardiac diseases, as well as specific associations of Moebius and other syndromes. The authors present anesthesia and airway management during the multiple tooth extraction surgery in a 10-year-old girl with Moebius syndrome associated with Poland and trigeminal trophic syndromes.

  12. 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

  13. A 'Good' muscle in a 'Bad' environment: the importance of airway smooth muscle force adaptation to airway hyperresponsiveness.

    PubMed

    Bossé, Ynuk; Chapman, David G; Paré, Peter D; King, Gregory G; Salome, Cheryl M

    2011-12-15

    Asthma is characterized by airway inflammation, with a consequent increase in spasmogens, and exaggerated airway narrowing in response to stimuli, termed airway hyperresponsiveness (AHR). The nature of any relationship between inflammation and AHR is less clear. Recent ex vivo data has suggested a novel mechanism by which inflammation may lead to AHR, in which increased basal ASM-tone, due to the presence of spasmogens in the airways, may "strengthen" the ASM and ultimately lead to exaggerated airway narrowing. This phenomenon was termed "force adaptation" [Bossé, Y., Chin, L.Y., Paré, P.D., Seow, C.Y., 2009. Adaptation of airway smooth muscle to basal tone: relevance to airway hyperresponsiveness. Am. J. Respir. Cell Mol. Biol. 40, 13-18]. However, it is unknown whether the magnitude of the effect of force adaptation ex vivo could contribute to exaggerated airway narrowing in vivo. Our aim was to utilize a computational model of ASM shortening in order to quantify the potential effect of force adaptation on airway narrowing when all other mechanical factors were kept constant. The shortening in the model is dictated by a balance between physiological loads and ASM force-generating capacity at different lengths. The results suggest that the magnitude of the effect of force adaptation on ASM shortening would lead to substantially more airway narrowing during bronchial challenge at any given airway generation. We speculate that the increased basal ASM-tone in asthma, due to the presence of inflammation-derived spasmogens, produces an increase in the force-generating capacity of ASM, predisposing to AHR during subsequent challenge.

  14. Numerical analysis of respiratory flow patterns within human upper airway

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Liu, Yingxi; Sun, Xiuzhen; Yu, Shen; Gao, Fei

    2009-12-01

    A computational fluid dynamics (CFD) approach is used to study the respiratory airflow dynamics within a human upper airway. The airway model which consists of the airway from nasal cavity, pharynx, larynx and trachea to triple bifurcation is built based on the CT images of a healthy volunteer and the Weibel model. The flow characteristics of the whole upper airway are quantitatively described at any time level of respiratory cycle. Simulation results of respiratory flow show good agreement with the clinical measures, experimental and computational results in the literature. The air mainly passes through the floor of the nasal cavity in the common, middle and inferior nasal meatus. The higher airway resistance and wall shear stresses are distributed on the posterior nasal valve. Although the airways of pharynx, larynx and bronchi experience low shear stresses, it is notable that relatively high shear stresses are distributed on the wall of epiglottis and bronchial bifurcations. Besides, two-dimensional fluid-structure interaction models of normal and abnormal airways are built to discuss the flow-induced deformation in various anatomy models. The result shows that the wall deformation in normal airway is relatively small.

  15. External airway splint to treat tracheomalacia following laryngotracheal reconstruction.

    PubMed

    Hsueh, Wayne D; Smith, Lee P

    2017-03-01

    This observation reports the use of an external airway splint to treat tracheomalacia in a pediatric patient. The patient underwent a double stage laryngotracheal reconstruction however was unable to be decannulated due to severe tracheomalacia. Our purpose is to further support the use of external splinting in the treatment of tracheomalacia in a unique case involving isolated nighttime airway obstruction following laryngotracheal reconstruction.

  16. High-resolution airway morphometry from polyurethane casts

    NASA Astrophysics Data System (ADS)

    Neufeld, Gordon R.; Vargas, John; Hoford, John D.; Craft, Jeanne; Shroff, Sunil; McRae, Karen M.

    1995-05-01

    An airway cast was made and imbedded in a solid polyurethane block of a contrasting color. The block was sequentially milled and photographed. The sequential photographs were scanned to create an image database which was analyzed on VIDA; a multidimensional image analysis software package. The technique shows promise as a semi-automated process for generating a high resolution morphometric database from airway casts.

  17. Repair of damaged supraglottic airway devices: A novel method

    PubMed Central

    2010-01-01

    Damage of laryngeal mask airway and other supraglottic airway devices has always been a matter of concern. Although manufacturer recommends maximum 40 uses of LMA (and its congeners) but damage before 40 uses needs to be evaluated. We hereby, describe a novel method of repair of supraglottic devices when damage occurs at mask inflation line or pilot balloon valve assembly. PMID:20565731

  18. Nitrogen Dioxide Exposure and Airway Responsiveness in Individuals with Asthma

    EPA Science Inventory

    Controlled human exposure studies evaluating the effect of inhaled NO2 on the inherent responsiveness of the airways to challenge by bronchoconstricting agents have had mixed results. In general, existing meta-analyses show statistically significant effects of NO2 on the airway r...

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

    PubMed

    Salami, Olawale; Marsland, Benjamin J

    2015-01-01

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

  20. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    DTIC Science & Technology

    2012-10-01

    blind design was used to compare between the effects of pretreatments with ipratropium bromide and placebo aerosols on the airway responses to HA... ipratropium completely prevented the WA- induced bronchoconstriction in asthmatics. In conclusion, bronchoconstriction induced by increasing airway...patients was completely prevented by pretreatment with ipratropium aerosol, indicating an involvement of cholinergic reflex. Accompanying the

  1. FSTL1 PROMOTES ASTHMATIC AIRWAY REMODELING BY INDUCING ONCOSTATIN M

    PubMed Central

    Miller, Marina; Beppu, Andrew; Rosenthal, Peter; Pham, Alexa; Das, Sudipta; Karta, Maya; Song, Dae Jin; Vuong, Christine; Doherty, Taylor; Croft, Michael; Zuraw, Bruce; Zhang, Xu; Gao, Xiang; Aceves, Seema; Chouiali, Fazila; Hamid, Qutayba; Broide, David H.

    2016-01-01

    Chronic asthma is associated with airway remodeling and decline in lung function. Here we show that follistatin like 1 (Fstl1), a mediator not previously associated with asthma is highly expressed by macrophages in the lungs of severe human asthmatics. Chronic allergen challenged Lys-Cretg/Fstl1Δ/Δ mice in whom Fstl1 is inactivated in macrophages/myeloid cells had significantly reduced airway remodeling and reduced levels of oncostatin M (OSM) a cytokine previously not known to be regulated by Fstl1. The importance of the Fstl1 induction of OSM to airway remodeling was demonstrated in murine studies in which administration of Fstl1 induced airway remodeling and increased OSM, while administration of an anti-OSM antibody blocked the effect of Fstl1 on inducing airway remodeling, eosinophilic airway inflammation, and airway hyperresponsiveness all cardinal features of asthma. Overall, these studies demonstrate that the Fstl1/oncostatin M pathway may be a novel pathway to inhibit airway remodeling in severe human asthma. PMID:26355153

  2. Mechanosensitive ATP Release Maintains Proper Mucus Hydration of Airways

    PubMed Central

    Button, Brian; Okada, Seiko F.; Frederick, Charles Brandon; Thelin, William R.; Boucher, Richard C.

    2013-01-01

    The clearance of mucus from the airways protects the lungs from inhaled noxious and infectious materials. Proper hydration of the mucus layer enables efficient mucus clearance through beating of cilia on airway epithelial cells, and reduced clearance of excessively concentrated mucus occurs in patients with chronic obstructive pulmonary disease and cystic fibrosis. Key steps in the mucus transport process are airway epithelia sensing and responding to changes in mucus hydration. We reported that extracellular adenosine triphosphate (ATP) and adenosine were important luminal auto-crine and paracrine signals that regulated the hydration of the surface of human airway epithelial cultures through their action on apical membrane purinoceptors. Mucus hydration in human airway epithelial cultures was sensed by an interaction between cilia and the overlying mucus layer: Changes in mechanical strain, proportional to mucus hydration, regulated ATP release rates, adjusting fluid secretion to optimize mucus layer hydration. This system provided a feedback mechanism by which airways maintained mucus hydration in an optimum range for cilia propulsion. Understanding how airway epithelia can sense and respond to changes in mucus properties helps us to understand how the mucus clearance system protects the airways in health and how it fails in lung diseases such as cystic fibrosis. PMID:23757023

  3. Mechanosensitive ATP release maintains proper mucus hydration of airways.

    PubMed

    Button, Brian; Okada, Seiko F; Frederick, Charles Brandon; Thelin, William R; Boucher, Richard C

    2013-06-11

    The clearance of mucus from the airways protects the lungs from inhaled noxious and infectious materials. Proper hydration of the mucus layer enables efficient mucus clearance through beating of cilia on airway epithelial cells, and reduced clearance of excessively concentrated mucus occurs in patients with chronic obstructive pulmonary disease and cystic fibrosis. Key steps in the mucus transport process are airway epithelia sensing and responding to changes in mucus hydration. We reported that extracellular adenosine triphosphate (ATP) and adenosine were important luminal autocrine and paracrine signals that regulated the hydration of the surface of human airway epithelial cultures through their action on apical membrane purinoceptors. Mucus hydration in human airway epithelial cultures was sensed by an interaction between cilia and the overlying mucus layer: Changes in mechanical strain, proportional to mucus hydration, regulated ATP release rates, adjusting fluid secretion to optimize mucus layer hydration. This system provided a feedback mechanism by which airways maintained mucus hydration in an optimum range for cilia propulsion. Understanding how airway epithelia can sense and respond to changes in mucus properties helps us to understand how the mucus clearance system protects the airways in health and how it fails in lung diseases such as cystic fibrosis.

  4. Computed tomography of nonanesthetized cats with upper airway obstruction.

    PubMed

    Stadler, Krystina; O'Brien, Robert

    2013-01-01

    Upper airway obstruction is a potentially life-threatening problem in cats and for which a noninvasive, sensitive method rapid diagnosis is needed. The purposes of this prospective study were to describe a computed tomography (CT) technique for nonanesthetized cats with upper airway obstruction, CT characteristics of obstructive diseases, and comparisons between CT findings and findings from other diagnostic tests. Ten cats with clinical signs of upper airway obstruction were recruited for the study. Four cats with no clinical signs of upper airway obstruction were recruited as controls. All cats underwent computed tomography imaging without sedation or anesthesia, using a 16-slice helical CT scanner and a previously described transparent positional device. Three-dimensional (3D) internal volume rendering was performed on all CT image sets and 3D external volume rendering was also performed on cats with evidence of mass lesions. Confirmation of upper airway obstruction was based on visual laryngeal examination, endoscopy, fine-needle aspirate, biopsy, or necropsy. Seven cats were diagnosed with intramural upper airway masses, two with laryngotracheitis, and one with laryngeal paralysis. The CT and 3D volume-rendered images identified lesions consistent with upper airway disease in all cats. In cats with mass lesions, CT accurately identified the mass and location. Findings from this study supported the use of CT imaging as an effective technique for diagnosing upper airway obstruction in nonanesthetized cats.

  5. Corticosteroids and cromolyn sodium as modulators of airway inflammation.

    PubMed

    McFadden, E R

    1988-07-01

    Heightened airway reactivity is a cardinal feature of asthma and correlates with many clinical features of the illness, such as the acute response to bronchodilator drugs, the magnitude of diurnal fluctuations in lung function, and the amount of therapy required to control symptoms. Data have accumulated indicating that a reduction in airway reactivity can decrease asthma morbidity, and many advocate treating asthmatic patients prophylactically to prevent acute exacerbations from developing, rather than responding to them after they have occurred. This approach is particularly effective if it is used when the airways are being exposed to stimuli to which they are sensitive. A number of drugs have been purported to reduce airway reactivity, but the most convincing evidence supports the effects of cromolyn and inhaled and oral steroids. Although each type of drug has its own advantages and disadvantages and different modes of action, the common denominator is believed to be a reduction in the state of airway inflammation.

  6. The difficult airway: mechanisms for effective dissemination of critical information.

    PubMed

    Mark, L J; Beattie, C; Ferrell, C L; Trempy, G; Dorman, T; Schauble, J F

    1992-01-01

    The perioperative management and dissemination of critical information regarding a patient with an unexpected difficult intubation, including successful application of a difficult airway algorithm (Figure 1), are described. Documentation and dissemination of critical information include entry of patient data into an in-hospital computerized Difficult Airway/Intubation Registry, simultaneous application of a highly visible Difficult Airway/Intubation Patient Wrist Band (coded for access to computer registry), summary reports distributed to health care providers, and enrollment of the patient in the Medic Alert Foundation International's newly established category difficult airway/intubation for 24-hour access. We postulate that the widespread use of the procedures described in this report may reduce the contribution of unexpected difficult airway/intubation to anesthetic morbidity and mortality.

  7. GPCRs and arrestins in airways: implications for asthma

    PubMed Central

    Penn, Raymond B.; Bond, Richard A.; Walker, Julia K. L.

    2015-01-01

    The obstructive lung disease asthma is treated by drugs that target, either directly or indirectly, G protein-coupled receptors (GPCRs). GPCRs coupled to Gq are the primary mediators of airway smooth muscle (ASM) contraction and increased airway resistance, whereas the Gs-coupled beta-2-adrenoceptor (β2AR) promotes pro-relaxant signaling in and relaxation of ASM resulting in greater airway patency and reversal of life-threatening bronchoconstriction. In additions, GPCR-mediated functions in other cell types, including airway epithelium and hematopoietic cells, are involved in control of lung inflammation that causes most asthma. The capacity of arrestins to regulate GPCR signaling, via either control of GPCR desensitization/resensitization, or via G protein-independent signaling, renders arrestins an intriguing therapeutic target for asthma and other obstructive lung diseases. This review will focus on the potential role of arrestins in those GPCR-mediated airway cell functions that are dysregulated in asthma. PMID:24292841

  8. Airway obstruction among Latino poultry processing workers in North Carolina.

    PubMed

    Mirabelli, Maria C; Chatterjee, Arjun B; Mora, Dana C; Arcury, Thomas A; Blocker, Jill N; Chen, Haiying; Grzywacz, Joseph G; Marín, Antonio J; Schulz, Mark R; Quandt, Sara A

    2015-01-01

    This analysis was conducted to evaluate the prevalence of airway obstruction among Latino poultry processing workers. Data were collected from 279 poultry processing workers and 222 other manual laborers via spirometry and interviewer-administered questionnaires. Participants employed in poultry processing reported the activities they perform at work. Participants with forced expiratory volume in 1 second (FEV1) or FEV1/forced expiratory volume (FVC) below the lower limits of normal were categorized as having airway obstruction. Airway obstruction was identified in 13% of poultry processing workers and 12% of the comparison population. Among poultry processing workers, the highest prevalence of airway obstruction (21%) occurred among workers deboning chickens (prevalence ratio: 1.75; 95% confidence interval: 0.97, 3.15). These findings identify variations in the prevalence of airway obstruction across categories of work activities.

  9. The Effect of Omega-3 Fatty Acids on Bronchial Hyperresponsiveness, Sputum Eosinophilia, and Mast Cell Mediators in Asthma

    PubMed Central

    Bood, Johan; Alkhabaz, Ahmad; Balgoma, David; Otis, Joceline; Delin, Ingrid; Dahlén, Barbro; Wheelock, Craig E.; Nair, Parameswaran; Dahlén, Sven-Erik; O’Byrne, Paul M.

    2015-01-01

    BACKGROUND: Omega-3 fatty acid supplements have been reported to inhibit exercise-induced bronchoconstriction (EIB). It has not been determined whether omega-3 supplements inhibit airway sensitivity to inhaled mannitol, a test for bronchial hyperresponsiveness (BHR) and model for EIB in people with mild to moderate asthma. METHODS: In a double-blind, crossover trial, subjects with asthma who had BHR to inhaled mannitol (n = 23; 14 men; mean age, 28 years; one-half taking regular inhaled corticosteroids) were randomized to omega-3 supplements (4.0 g/d eicosapentaenoic acid and 2.0 g/d docosahexaenoic acid) or matching placebo for 3 weeks separated by a 3-week washout. The primary outcome was the provoking dose of mannitol (mg) to cause a 15% fall in FEV1 (PD15). Secondary outcomes were sputum eosinophil count, spirometry, Asthma Control Questionnaire (ACQ) score, serum triacylglyceride level, and lipid mediator profile in urine and serum. RESULTS: PD15 (geometric mean, 95% CI) to mannitol following supplementation with omega-3s (78 mg, 51-119 mg) was not different from placebo (88 mg, 56-139 mg, P = .5). There were no changes in sputum eosinophils (mean ± SD) in a subgroup of 11 subjects (omega-3, 8.4% ± 8.2%; placebo, 7.8% ± 11.8%; P = .9). At the end of each treatment period, there were no differences in FEV1 % predicted (omega-3, 85% ± 13%; placebo, 84% ± 11%; P = .9) or ACQ score (omega-3, 1.1% ± 0.5%; placebo, 1.1% ± 0.5%; P = .9) (n = 23). Omega-3s caused significant lowering of blood triglyceride levels and expected shifts in serum fatty acids and eicosanoid metabolites, confirming adherence to the supplements; however, no changes were observed in urinary mast cell mediators. CONCLUSIONS: Three weeks of omega-3 supplements does not improve BHR to mannitol, decrease sputum eosinophil counts, or inhibit urinary excretion of mast cell mediators in people with mild to moderate asthma, indicating that dietary omega-3 supplementation is not useful in the

  10. Eosinophils generate brominating oxidants in allergen-induced asthma

    PubMed Central

    Wu, Weijia; Samoszuk, Michael K.; Comhair, Suzy A.A.; Thomassen, Mary Jane; Farver, Carol F.; Dweik, Raed A.; Kavuru, Mani S.; Erzurum, Serpil C.; Hazen, Stanley L.

    2000-01-01

    Eosinophils promote tissue injury and contribute to the pathogenesis of allergen-triggered diseases like asthma, but the chemical basis of damage to eosinophil targets is unknown. We now demonstrate that eosinophil activation in vivo results in oxidative damage of proteins through bromination of tyrosine residues, a heretofore unrecognized pathway for covalent modification of biologic targets in human tissues. Mass spectrometric studies demonstrated that 3-bromotyrosine serves as a specific “molecular fingerprint” for proteins modified through the eosinophil peroxidase-H2O2 system in the presence of plasma levels of halides. We applied a localized allergen challenge to model the effects of eosinophils and brominating oxidants in human lung injury. Endobronchial biopsy specimens from allergen-challenged lung segments of asthmatic, but not healthy control, subjects demonstrated significant enrichments in eosinophils and eosinophil peroxidase. Baseline levels of 3-bromotyrosine in bronchoalveolar lavage (BAL) proteins from mildly allergic asthmatic individuals were modestly but not statistically significantly elevated over those in control subjects. After exposure to segmental allergen challenge, lung segments of asthmatics, but not healthy control subjects, exhibited a >10-fold increase in BAL 3-bromotyrosine content, but only two- to threefold increases in 3-chlorotyrosine, a specific oxidation product formed by neutrophil- and monocyte-derived myeloperoxidase. These results identify reactive brominating species produced by eosinophils as a distinct class of oxidants formed in vivo. They also reveal eosinophil peroxidase as a potential therapeutic target for allergen-triggered inflammatory tissue injury in humans. PMID:10811853

  11. Changes in airway permeability and responsiveness after exposure to ozone. [Sheep

    SciTech Connect

    Abraham, W.M.; Delehunt, J.C.; Yerger, L.; Marchette, B.; Oliver, W. Jr.

    1984-06-01

    The relationship between airway responsiveness and the permeability of histamine through the airways in conscious sheep after exposure to ozone (O/sub 3/ was examined). Airway responsiveness was assessed by measuring the change from baseline in mean pulmonary flow resistance following a controlled 2-min inhalation challenge with 1% histamine, containing 200 ..mu..Ci/ml of (/sup 3/H)histamine. The rate of appearance of the (/sup 3/H)histamine in the plasma during inhalation challenge was used to estimate airway permeability. To perturb the airways, conscious sheep were exposed to either 0.5 or 1.0 ppm O/sub 3/ for 2 hr via an endotracheal tube. Airway responsiveness and airway permeability were measured prior to and 1 day after exposure. In six sheep exposed to 0.5 ppm O/sub 3/, increased airway responsiveness and airway permeability were obseved 1 day after exposure. Four of seven sheep exposed to 1.0 ppm O/sub 3/ had enhanced airway responsiveness and airway permeability, while the remaining three sheep showed corresponding decreases in airway responsiveness and airway permeability. Since the O/sub 3/-induced directional changes in airway responsiveness paralleled the directional changes in airway permeability in both the positive and negative directions, it was concluded that changes in airway responsiveness to inhaled histamine following exposure to O/sub 3/ may be related to concomitant changes in airway permeability to this agent.

  12. Rhinovirus infections in the upper airway.

    PubMed

    Winther, Birgit

    2011-03-01

    The majority of cold and flulike illnesses are caused by human rhinoviruses (HRVs). Improved detection of HRV has shown that HRVs are also associated with more serious illness, such as exacerbation of asthma, wheezing illnesses in children, chronic obstructive pulmonary disease, cardiopulmonary disease, and fatal pneumonia in immune-compromised patients. HRV is a major cause of acute viral respiratory tract infections in hospitalized children and is among the leading causes of childhood mortality worldwide. Detection of the HRV genome by reverse transcriptase-polymerase chain reaction and genomic sequencing has brought to light a new clade, HRV-C, to the already recognized HRV-A and HRV-B clades. The clinical complications related to all rhinovirus infections include acute otitis media, acute sinusitis, and acute bronchitis. The enormous public health implications from those diseases far overshadow those of the common cold. This article provides an overview of the pathogenesis of rhinovirus infection in the upper airways. Most research has been done in young healthy adults with self-limiting experimental and natural rhinovirus infections, and this may set the stage for understanding rhinovirus infections in the ear, sinus, and lower airways.

  13. Deposition of charged particles on lung airways.

    PubMed

    Cohen, B S; Xiong, J Q; Fang, C P; Li, W

    1998-05-01

    The effect of a single electric charge on the efficiency with which ultrafine particles deposit in human airways has been investigated. When inhaled short-lived radon progeny are attached to electrically neutral particles their deposition efficiency is controlled by diffusion. But most ambient particles carry one, or a few, charges. We measured and compared the deposition (DE) of singly charged, charge-neutralized, and zero-charge 20-nm and 125-nm particles in hollow-cast models of human airways. These particle sizes were selected because they are about where modal peaks occur for the activity of the short-lived radon progeny in indoor air. For singly charged 20-nm particles deposition (+/- standard error) in the casts was 3.4 +/- 0.3 times that for charge neutralized aerosols and 5.3 +/- 0.3 times the amount deposited for zero-charged particles. Corresponding ratios for the 125-nm particles were 2.3 +/- 0.3 and 6.2 +/- 0.7. Since most ambient particles are charged this effect must be considered when models are used to predict dose from inhaled ultrafine particles.

  14. Delivery of Alpha-1 Antitrypsin to Airways.

    PubMed

    Griese, Matthias; Scheuch, Gerhard

    2016-08-01

    Treatment with exogenous alpha-1 antitrypsin (AAT), a potent serine protease inhibitor, was developed originally for chronic obstructive pulmonary disease associated with AAT deficiency; however, other lung conditions involving neutrophilic inflammation and proteolytic tissue injury related to neutrophil elastase and other serine proteases may also be considered for AAT therapy. These conditions include bronchiectasis caused by primary ciliary dyskinesia, cystic fibrosis, and other diseases associated with an increased free elastase activity in the airways. Inhaled AAT may be a viable option to counteract proteolytic tissue damage. This form of treatment requires efficient drug delivery to the targeted pulmonary compartment. Aerosol technology meeting this requirement is currently available and offers an alternative therapeutic approach to systemic AAT administration. To date, early studies in humans have shown biochemical efficacy and have established the safety of inhaled AAT. However, to bring aerosol AAT therapy to patients, large phase 3 protocols in carefully selected patient populations (i.e., subgroups of patients with AAT deficiency, cystic fibrosis, or other lung diseases with bronchiectasis) will be needed with clinical end points in addition to the measurement of proteolytic activity in the airway. The outcomes likely will have to include lung function, lung structure assessed by computed tomography imaging, disease exacerbations, health status, and mortality.

  15. The cystic fibrosis lower airways microbial metagenome

    PubMed Central

    Moran Losada, Patricia; Chouvarine, Philippe; Dorda, Marie; Hedtfeld, Silke; Mielke, Samira; Schulz, Angela; Wiehlmann, Lutz

    2016-01-01

    Chronic airway infections determine most morbidity in people with cystic fibrosis (CF). Herein, we present unbiased quantitative data about the frequency and abundance of DNA viruses, archaea, bacteria, moulds and fungi in CF lower airways. Induced sputa were collected on several occasions from children, adolescents and adults with CF. Deep sputum metagenome sequencing identified, on average, approximately 10 DNA viruses or fungi and several hundred bacterial taxa. The metagenome of a CF patient was typically found to be made up of an individual signature of multiple, lowly abundant species superimposed by few disease-associated pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, as major components. The host-associated signatures ranged from inconspicuous polymicrobial communities in healthy subjects to low-complexity microbiomes dominated by the typical CF pathogens in patients with advanced lung disease. The DNA virus community in CF lungs mainly consisted of phages and occasionally of human pathogens, such as adeno- and herpesviruses. The S. aureus and P. aeruginosa populations were composed of one major and numerous minor clone types. The rare clones constitute a low copy genetic resource that could rapidly expand as a response to habitat alterations, such as antimicrobial chemotherapy or invasion of novel microbes. PMID:27730195

  16. The cystic fibrosis lower airways microbial metagenome.

    PubMed

    Moran Losada, Patricia; Chouvarine, Philippe; Dorda, Marie; Hedtfeld, Silke; Mielke, Samira; Schulz, Angela; Wiehlmann, Lutz; Tümmler, Burkhard

    2016-04-01

    Chronic airway infections determine most morbidity in people with cystic fibrosis (CF). Herein, we present unbiased quantitative data about the frequency and abundance of DNA viruses, archaea, bacteria, moulds and fungi in CF lower airways. Induced sputa were collected on several occasions from children, adolescents and adults with CF. Deep sputum metagenome sequencing identified, on average, approximately 10 DNA viruses or fungi and several hundred bacterial taxa. The metagenome of a CF patient was typically found to be made up of an individual signature of multiple, lowly abundant species superimposed by few disease-associated pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, as major components. The host-associated signatures ranged from inconspicuous polymicrobial communities in healthy subjects to low-complexity microbiomes dominated by the typical CF pathogens in patients with advanced lung disease. The DNA virus community in CF lungs mainly consisted of phages and occasionally of human pathogens, such as adeno- and herpesviruses. The S. aureus and P. aeruginosa populations were composed of one major and numerous minor clone types. The rare clones constitute a low copy genetic resource that could rapidly expand as a response to habitat alterations, such as antimicrobial chemotherapy or invasion of novel microbes.

  17. Regional aerosol deposition in human upper airways

    SciTech Connect

    Swift, D.L.

    1990-11-01

    During the current reporting period experimental studies of aerosol deposition in replicate NOPL airways have carried out. A replicate model of a 4 week old infant nasal passage was constructed from MR scans. The model completes the age range from newborn'' to 4 years, there now being one child model for 4 different ages. Deposition studies have been performed with unattached radon progeny aerosols in collaboration with ITRI, Albuquerque, NM and NRPB, Chilton, UK. Overall measurements have been performed in adult and child nasal airways indicating that the child nasal passage was slightly more efficient than the adult in removing 1 nm particles at corresponding flow rates. A similar weak dependence on flow rate was observed. Local deposition studies in an adult nasal model indicated predominant deposition in the anterior region during inspiratory flow, but measurable deposition was found throughout the model. The deposition pattern during expiration was reverse, greater deposition being observed in the posterior region. Local deposition studies of attached progeny aerosol size (100--200 nm) were performed in adult and child nasal models using technigas'' and a gamma scintillation camera. Similar to the unattached size, deposition occurred throughout the models, but was greater in the anterior region.

  18. Airway responsiveness to psychological processes in asthma and health

    PubMed Central

    Ritz, Thomas

    2012-01-01

    Psychosocial factors have been found to impact airway pathophysiology in respiratory disease with considerable consistency. Influences on airway mechanics have been studied particularly well. The goal of this article is to review the literature on airway responses to psychological stimulation, discuss potential pathways of influence, and present a well-established emotion-induction paradigm to study airway obstruction elicited by unpleasant stimuli. Observational studies have found systematic associations between lung function and daily mood changes. The laboratory-based paradigm of bronchoconstrictive suggestion has been used successfully to elicit airway obstruction in a substantial proportion of asthmatic individuals. Other studies have demonstrated modulation of airway responses to standard airway challenges with exercise, allergens, or pharmacological agents by psychological factors. Standardized emotion-induction techniques have consistently shown airway constriction during unpleasant stimulation, with surgery, blood, and injury stimuli being particularly powerful. Findings with various forms of stress induction have been more mixed. A number of methodological factors may account for variability across studies, such as choice of measurement technique, temporal association between stimulation and measurement, and the specific quality and intensity of the stimulus material, in particular the extent of implied action-orientation. Research has also begun to elucidate physiological processes associated with psychologically induced airway responses, with vagal excitation and ventilatory influences being the most likely candidate pathways, whereas the role of specific central nervous system pathways and inflammatory processes has been less studied. The technique of emotion-induction using films has the potential to become a standardized challenge paradigm for the further exploration of airway hyperresponsiveness mediated by central nervous system processes. PMID

  19. What does airway resistance tell us about lung function?

    PubMed

    Kaminsky, David A

    2012-01-01

    Spirometry is considered the primary method to detect the air flow limitation associated with obstructive lung disease. However, air flow limitation is the end-result of many factors that contribute to obstructive lung disease. One of these factors is increased airway resistance. Airway resistance is traditionally measured by relating air flow and driving pressure using body plethysmography, thus deriving airway resistance (R(aw)), specific airway resistance (sR(aw)), and specific airway conductance (sG(aw)). Other methods to measure airway resistance include the forced oscillation technique (FOT), which allows calculation of respiratory system resistance (R(RS)) and reactance (X(RS)), and the interrupter technique, which allows calculation of interrupter resistance (R(int)). An advantage of these other methods is that they may be easier to perform than spirometry, making them particularly suited to patients who cannot perform spirometry, such as young children, patients with neuromuscular disorders, or patients on mechanical ventilation. Since spirometry also requires a deep inhalation, which can alter airway resistance, these alternative methods may provide more sensitive measures of airway resistance. Furthermore, the FOT provides unique information about lung mechanics that is not available from analysis using spirometry, body plethysmography, or the interrupter technique. However, it is unclear whether any of these measures of airway resistance contribute clinically important information to the traditional measures derived from spirometry (FEV(1), FVC, and FEV(1)/FVC). The purpose of this paper is to review the physiology and methodology of these measures of airway resistance, and then focus on their clinical utility in relation to each other and to spirometry.

  20. Nonlinear Compliance Modulates Dynamic Bronchoconstriction in a Multiscale Airway Model

    PubMed Central

    Hiorns, Jonathan E.; Jensen, Oliver E.; Brook, Bindi S.

    2014-01-01

    The role of breathing and deep inspirations (DI) in modulating airway hyperresponsiveness remains poorly understood. In particular, DIs are potent bronchodilators of constricted airways in nonasthmatic subjects but not in asthmatic subjects. Additionally, length fluctuations (mimicking DIs) have been shown to reduce mean contractile force when applied to airway smooth muscle (ASM) cells and tissue strips. However, these observations are not recapitulated on application of transmural pressure (PTM) oscillations (that mimic tidal breathing and DIs) in isolated intact airways. To shed light on this paradox, we have developed a biomechanical model of the intact airway, accounting for strain-stiffening due to collagen recruitment (a large component of the extracellular matrix (ECM)), and dynamic actomyosin-driven force generation by ASM cells. In agreement with intact airway studies, our model shows that PTM fluctuations at particular mean transmural pressures can lead to only limited bronchodilation. However, our model predicts that moving the airway to a more compliant point on the static pressure-radius relationship (which may involve reducing mean PTM), before applying pressure fluctuations, can generate greater bronchodilation. This difference arises from competition between passive strain-stiffening of ECM and force generation by ASM yielding a highly nonlinear relationship between effective airway stiffness and PTM, which is modified by the presence of contractile agonist. Effectively, the airway at its most compliant may allow for greater strain to be transmitted to subcellular contractile machinery. The model predictions lead us to hypothesize that the maximum possible bronchodilation of an airway depends on its static compliance at the PTM about which the fluctuations are applied. We suggest the design of additional experimental protocols to test this hypothesis. PMID:25517167

  1. Emergency surgical airway in life-threatening acute airway emergencies--why are we so reluctant to do it?

    PubMed

    Greenland, K B; Acott, C; Segal, R; Goulding, G; Riley, R H; Merry, A F

    2011-07-01

    'Can't intubate, can't oxygenate' scenarios are rare but are often poorly managed, with potentially disastrous consequences. In our opinion, all doctors should be able to create a surgical airway if necessary. More practically, at least all anaesthetists should have this ability. There should be a change in culture to one that encourages and facilitates the performance of a life-saving emergency surgical airway when required. In this regard, an understanding of the human factors that influence the decision to perform an emergency surgical airway is as important as technical skill. Standardisation of difficult airway equipment in areas where anaesthesia is performed is a step toward ensuring that an emergency surgical airway will be performed appropriately Information on the incidence and clinical management of 'can't intubate, can't oxygenate' scenarios should be compiled through various sources, including national coronial inquest databases and anaesthetic critical incident reporting systems. A systematic approach to teaching and maintaining human factors in airway crisis management and emergency surgical airway skills to anaesthetic trainees and specialists should be developed: in our opinion participation should be mandatory. Importantly, the view that performing an emergency surgical airway is an admission of anaesthetist failure should be strongly countered.

  2. Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.

    PubMed Central

    Tang, W; Geba, G P; Zheng, T; Ray, P; Homer, R J; Kuhn, C; Flavell, R A; Elias, J A

    1996-01-01

    Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to respiratory viruses, cytokines, and histamine. To further define its potential effector functions, the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the resulting transgene mice were characterized. In contrast to transgene (-) littermates, the airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory foci contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased amounts of types III and I collagen, increased numbers of alpha smooth muscle actin and desmin-containing cells and a spectrum of stromal elements including fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also demonstrated that 2-mo-old transgene (+) mice had increased airways resistance and non-specific airways hyperresponsiveness to methacholine when compared with their transgene (-) littermates. These studies demonstrate that the targeted expression of IL-11 in the mouse airway causes a B and T cell-predominant inflammatory response, airway remodeling with increased types III and I collagen, the local accumulation of fibroblasts, myofibroblasts, and myocytes, and obstructive physiologic dysregulation. IL-11 may play an important role in the inflammatory and fibrotic responses in viral and/or nonviral human airway disorders. PMID:8981933

  3. DEVELOPMENT OF THE SMALL AIRWAYS AND ALVEOLI FROM CHILDHOOD TO ADULT LUNG MEASURED BY AEROSOL-DERIVED AIRWAY MORPHOMETRY

    EPA Science Inventory

    Understanding the human development of pulmonary airspaces is important for calculating the dose from exposure to inhaled materials as a function of age. We have measured, in vivo, the airspace caliber of the small airways and alveoli by aerosol-derived airway morphometry (ADAM) ...

  4. Carinal and tubular airway particle concentrations in the large airways of non-smokers in the general population: evidence for high particle concentration at airway carinas.

    PubMed Central

    Churg, A; Vedal, S

    1996-01-01

    OBJECTIVE: To evaluate the extent to which human airway carinas accumulate ambient atmospheric particles, a newly developed technique was used to micro-dissect and analyse particle concentration in tubular segments and carinas of the large airways of 10 necropsy lungs from non-smokers from the general population of Vancouver. METHODS: Ratios of the particle concentrations on the carinas to the tubular segment immediately preceding it were measured with analytical electron microscopy for the mainstem bronchus, upper and lower lobe bronchi, and four different segmental or subsegmental bronchi--that is, Weibel generations 1 to about 5. A total of 119 carinal-tubular pairs was evaluated. RESULTS: Over all cases, both carinal and tubular particle concentrations increased with increasing airway generation; the median ratio of carinal to tubular particle concentration was 9:1 and did not show any trend with airway generation. The ratio was > 5 in 71% of carinal-tubular pairs, > 10 in 42% of pairs, > 20 in 31% of pairs, and > 100 in 9% of pairs. Some subjects showed a notable tendency to high ratios, with many ratios > 100, and other subjects had a tendency toward low ratios. The predominant mineral species in both carinas and tubular airway segments was crystalline silica and the relative proportion was similar in both sites; however, mean particle diameter was consistently less in the carinal tissues. CONCLUSIONS: These findings suggest that the ratio of carinal to tubular retained particles in the large airways in non-smokers is higher than might be supposed from data generated in airway casts, and that there is considerable variation in this ratio between subjects. This finding is of potential interest in models of carcinogen, toxin, and dose of fibrogenic agent to the large airways as it suggests high and sometimes extreme concentrations of toxic particles at carinas, and thus reinforces the notion that carinas may be sites of initiation of disease. PMID:8983467

  5. The Tulip GT® airway versus the facemask and Guedel airway: a randomised, controlled, cross-over study by Basic Life Support-trained airway providers in anaesthetised patients.

    PubMed

    Shaikh, A; Robinson, P N; Hasan, M

    2016-03-01

    We performed a randomised, controlled, cross-over study of lung ventilation by Basic Life Support-trained providers using either the Tulip GT® airway or a facemask with a Guedel airway in 60 anaesthetised patients. Successful ventilation was achieved if the provider produced an end-tidal CO2 > 3.5 kPa and a tidal volume > 250 ml in two of the first three breaths, within 60 sec and within two attempts. Fifty-seven (95%) providers achieved successful ventilation using the Tulip GT compared with 35 (58%) using the facemask (p < 0.0001). Comparing the Tulip GT and facemask, the mean (SD) end-tidal CO2 was 5.0 (0.7) kPa vs 2.5 (1.5) kPa, tidal volume was 494 (175) ml vs 286 (186) ml and peak inspiratory pressure was 18.3 (3.4) cmH2 O vs 13.6 (7) cmH2 O respectively (all p < 0.0001). Forty-seven (78%) users favoured the Tulip GT airway. These results are similar to a previous manikin study using the same protocol, suggesting a close correlation between human and manikin studies for this airway device. We conclude that the Tulip GT should be considered as an adjunct to airway management both within and outside hospitals when ventilation is being undertaken by Basic Life Support-trained airway providers.

  6. Lack of seasonal variation in the incidence of eosinophilic oesophagitis in adolescent and adult non-PPI-responsive oesophageal eosinophilia midwestern US populations

    PubMed Central

    Frederickson, Nicholas W; Bayman, Levent; Valestin, Jessica; Redd, Matthew; Lee, Ye-Jin; Soubra, Mahmoud

    2014-01-01

    Background Eosinophilic oesophagitis (EoO) has been associated with allergic disorders as well as aeroallergens. The current literature has shown a possible association between seasonal variation, mainly in the spring, and the incidence of EoO. However, this data was based on small population studies that did not exclude proton-pump inhibitor (PPI)-responsive oesophageal eosinophilia (PPI-ROE) in their cohort. Aim The aim of this study was to determine if there is a seasonal variation associated with the diagnosis of EoO in patients that had been treated with high-dose PPI prior to diagnosis. Methods Oesophageal biopsies were obtained from a cohort of patients who presented with symptoms of dysphagia, odynophagia, and heartburn during a 10-year period. Symptomatic patients who had biopsies from the mid and distal oesophagus with ≥20 eosinophils per high-power field (hpf) while on high-dose PPI treatment for at least 5 weeks were diagnosed as having EoO. The monthly and seasonal incidences were determined (winter, January–March; spring, April–June; summer, July–September; Autumn, October–December). Results A total of 20,718 patients were identified and their records evaluated. From this cohort, 193 (0.93%) symptomatic patients had biopsy-proven oesophageal eosinophilia (≥20 eosinophils/hpf) and no seasonal variation was seen in this group. However, only 57 (0.28%) had been adequately treated with PPI prior to diagnosis (i.e. non-PPI-ROE biopsy-proven EoO; ≥20 eosinophils/hpf: 39 males, 18 females; age 29.5 years). The most common medical history components included asthma (12.3%) and food allergies (3.5%), and the most common presenting symptoms included dysphagia (50.9%) and heartburn (26.3%). The monthly and seasonal incidences in our cohort were with no apparent trend (p = 0.713 and 0.703, respectively). Conclusions The incidence of EoO was consistent across all 12 months as well as during the four seasons. Our data does not support a seasonal

  7. ["Eosinophilia-myalgia" syndrome due to L-tryptophan containing products. Cooperative evaluation of French Regional Centers of Pharmacovigilance. Analysis of 24 cases].

    PubMed

    Castot, A; Bidault, I; Bournerias, I; Carlier, P; Efthymiou, M L

    1991-01-01

    By November 17, 1989, the MMWR published the 154 first reports of a syndrome consisting of myalgia and eosinophilia (EMS), occurring with the consumption of L-tryptophan containing products (L-TrpCp) and which might represent a new clinical entity. To standardize reporting over the country, the CDC of Atlanta developed the following case definition: 1) a peripheral blood total eosinophil count of more than 1 x 10(9) cells per liter 2) generalized myalgia sufficiently severe to affect a patient's ability to pursue daily activities 3) the exclusion of infections or neoplastic conditions. The FDA then, announced its intention to seek a nationwide recall of all tryptophan containing products, followed by other european countries (UK, Germany, France). In France, a first decree (January 4th 1990) completed by a decree on May 11th confirms this decision for one year. This measure did not concern the medicinal products or some dietary supplements for newborn or young children. Since December 11th, 1989, 24 cases have been reported to the Regional Adverse Drug Reaction Monitoring Centres in France. These cases share the same features as the cases notified previously in the USA: overrepresentation of females, no relationship with the time and the daily intake, clinical similarities to the Shulman syndrome, and unknown prognosis. Now, more than one year after the onset of this illness, it seems that discontinuation of the ingestion of L-TrpCp can resolve or improve the symptoms in most cases, but sometimes the syndrome can persist. The causal relationship between the ingestion of L-TrpCp and this syndrome has been established. Whatever the mechanism for the development of EMS among tryptophan users remains unclear, as well as the role of eosinophilia and the factors for fibroblast proliferation. The epidemic emergence of this syndrome in July 89 raises the possibility of the contamination of tryptophan during the manufacturing process. To confirm this hypothesis, the same

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

    PubMed Central

    Turner, P J; Foreman, J C

    1999-01-01

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

  9. Early airway infection, inflammation, and lung function in cystic fibrosis

    PubMed Central

    Nixon, G; Armstrong, D; Carzino, R; Carlin, J; Olinsky, A; Robertson, C; Grimwood, K

    2002-01-01

    Aims: To determine the relation between lower airway infection and inflammation, respiratory symptoms, and lung function in infants and young children with cystic fibrosis (CF). Methods: A prospective study of children with CF aged younger than 3 years, diagnosed by a newborn screening programme. All were clinically stable and had testing as outpatients. Subjects underwent bronchial lavage (BL) and lung function testing by the raised volume rapid thoracoabdominal compression technique under general anaesthesia. BL fluid was cultured and analysed for neutrophil count, interleukin 8, and neutrophil elastase. Lung function was assessed by forced expiratory volume in 0.5, 0.75, and 1 second. Results: Thirty six children with CF were tested on 54 occasions. Lower airway infection shown by BL was associated with a 10% reduction in FEV0.5 compared with subjects without infection. No relation was identified between airway inflammation and lung function. Daily moist cough within the week before testing was reported on 20/54 occasions, but in only seven (35%) was infection detected. Independent of either infection status or airway inflammation, those with daily cough had lower lung function than those without respiratory symptoms at the time of BL (mean adjusted FEV0.5 195 ml and 236 ml respectively). Conclusions: In young children with CF, both respiratory symptoms and airway infection have independent, additive effects on lung function, unrelated to airway inflammation. Further studies are needed to understand the mechanisms of airway obstruction in these young patients. PMID:12244003

  10. Three-dimensional reconstruction of upper airways from MDCT

    NASA Astrophysics Data System (ADS)

    Perchet, Diane; Fetita, Catalin; Preteux, Francoise

    2005-03-01

    Under the framework of clinical respiratory investigation, providing accurate modalities for morpho-functional analysis is essential for diagnosis improvement, surgical planning and follow-up. This paper focuses on the upper airways investigation and develops an automated approach for 3D mesh reconstruction from MDCT acquisitions. In order to overcome the difficulties related to the complex morphology of the upper airways and to the image gray level heterogeneity of the airway lumens and thin bony septa, the proposed 3D reconstruction methodology combines 2D segmentation and 3D surface regularization approaches. The segmentation algorithm relies on mathematical morphology theory and provides airway lumen robust discrimination from the surrounding tissues, while preserving the connectivity relationship between the different anatomical structures. The 3D regularization step uses an energy-based modeling in order to achieve a smooth and well-fitted 3D surface of the upper airways. An accurate 3D mesh representation of the reconstructed airways makes it possible to develop specific clinical applications such as virtual endoscopy, surgical planning and computer assisted intervention. In addition, building up patient-specific 3D models of upper airways is highly valuable for the study and design of inhaled medication delivery via computational fluid dynamics (CFD) simulations.

  11. FAMM Flap in Reconstructing Postsurgical Nasopharyngeal Airway Stenosis

    PubMed Central

    Nangole, Ferdinand Wanjala; Khainga, Stanley Ominde

    2014-01-01

    Introduction. Postsurgical nasopharyngeal airway stenosis can be a challenge to manage. The stenosis could be as a result of any surgical procedure in the nasopharyngeal region that heals extensive scarring and fibrosis. Objective. To evaluate patients with nasopharyngeal stenosis managed with FAMM flap. Study Design. Prospective study of patients with nasopharyngeal stenosis at the Kenyatta National Hospital between 2010 and 2013 managed with FAMM flap. Materials and Methods. Patients with severe nasopharyngeal airway stenosis were reviewed and managed with FAMM flaps at the Kenyatta National Hospital. Postoperatively they were assessed for symptomatic improvement in respiratory distress, patency of the nasopharyngeal airway, and donor site morbidity. Results. A total of 8 patients were managed by the authors in a duration of 4 years with nasopharyngeal stenosis. Five patients were managed with unilateral FAMM flaps in a two-staged surgical procedure. Four patients had complete relieve of the airway obstruction with a patent airway created. One patient had a patent airway created though with only mild improvement in airway obstruction. Conclusion. FAMM flap provides an alternative in the management of postsurgical severe nasopharyngeal stenosis. It is a reliable flap that is easy to raise and could provide adequate epithelium for the stenosed pharynx. PMID:25328699

  12. The usefulness of biomarkers of airway inflammation in managing asthma.

    PubMed

    Patil, Sarita U; Long, Aidan A

    2010-01-01

    The goal of managing asthma is to maintain disease control. Current approaches to assessment of control do not include measurement of airway inflammation. This study was designed to assess the usefulness of biomarkers of airway inflammation in guiding asthma management decisions. A literature review was performed. Bronchial biopsy is a direct measure of airway inflammation but not practical for routine use. Enumeration of sputum eosinophils is very useful in guiding changes in controller medication to decrease asthma exacerbations, whereas measurement of exhaled nitric oxide has not proven to be useful in this regard. Serial measurement of airway hyperreactivity as a guide to asthma management yields inconclusive results. Use of indirect stimuli for bronchial challenge offers both practical and theoretical advantages in the assessment of airway hyperreactivity. Data on the analysis of exhaled breath condensate have not yet been studied adequately in guiding management decisions. Enumeration of sputum cell counts appears to be the most useful biomarker of airway inflammation in guiding asthma management decisions. Combined approaches using simple methods of measuring airway hyperreactivity and obtaining sputum samples hold promise for the future, particularly if rapid analysis of cellular products in sputum can be developed.

  13. Coupled cellular therapy and magnetic targeting for airway regeneration.

    PubMed

    Ordidge, Katherine L; Gregori, Maria; Kalber, Tammy L; Lythgoe, Mark F; Janes, Sam M; Giangreco, Adam

    2014-06-01

    Airway diseases including COPD (chronic obstructive pulmonary disease), cystic fibrosis and lung cancer are leading causes of worldwide morbidity and mortality, with annual healthcare costs of billions of pounds. True regeneration of damaged airways offers the possibility of restoring lung function and protecting against airway transformation. Recently, advances in tissue engineering have allowed the development of cadaveric and biosynthetic airway grafts. Although these have produced encouraging results, the ability to achieve long-term functional airway regeneration remains a major challenge. To promote regeneration, exogenously delivered stem and progenitor cells are being trialled as cellular therapies. Unfortunately, current evidence suggests that only small numbers of exogenously delivered stem cells engraft within lungs, thereby limiting their utility for airway repair. In other organ systems, magnetic targeting has shown promise for improving long-term robust cell engraftment. This technique involves in vitro cell expansion, magnetic actuation and magnetically guided cell engraftment to sites of tissue damage. In the present paper, we discuss the utility of coupling stem cell-mediated cellular therapy with magnetic targeting for improving airway regeneration.

  14. Mitochondrial Transplantation Attenuates Airway Hyperresponsiveness by Inhibition of Cholinergic Hyperactivity

    PubMed Central

    Su, Yuan; Zhu, Liping; Yu, Xiangyuan; Cai, Lei; Lu, Yankai; Zhang, Jiwei; Li, Tongfei; Li, Jiansha; Xia, Jingyan; Xu, Feng; Hu, Qinghua

    2016-01-01

    Increased cholinergic activity has been highlighted in the pathogenesis of airway hyperresponsiveness, and alternations of mitochondrial structure and function appear to be involved in many lung diseases including airway hyperresponsiveness. It is crucial to clarify the cause-effect association between mitochondrial dysfunction and cholinergic hyperactivity in the pathogenesis of airway hyperresponsiveness. Male SD rats and cultured airway epithelial cells were exposed to cigarette smoke plus lipopolysaccharide administration; mitochondria isolated from airway epithelium were delivered into epithelial cells in vitro and in vivo. Both the cigarette smoke plus lipopolysaccharide-induced cholinergic hyperactivity in vitro and the airway hyperresponsiveness to acetylcholine in vivo were reversed by the transplantation of exogenous mitochondria. The rescue effects of exogenous mitochondria were imitated by the elimination of excessive reactive oxygen species or blockage of muscarinic M3 receptor, but inhibited by M receptor enhancer. Mitochondrial transplantation effectively attenuates cigarette smoke plus lipopolysaccharide-stimulated airway hyperresponsiveness through the inhibition of ROS-enhanced epithelial cholinergic hyperactivity. PMID:27279915

  15. 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

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

    PubMed

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

    2015-01-01

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

  17. Inhibition of airway surface fluid absorption by cholinergic stimulation

    PubMed Central

    Joo, Nam Soo; Krouse, Mauri E.; Choi, Jae Young; Cho, Hyung-Ju; Wine, Jeffrey J.

    2016-01-01

    In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated absorption. The conjoint action accelerates clearance, and the increased transport of mucus out of the airways restores ASL depth while cleansing the airways. We were intrigued by early reports of cholinergic inhibition of absorption by airways in some species. To reinvestigate this phenomenon, we studied inward short-circuit currents (Isc) in tracheal mucosa from human, sheep, pig, ferret, and rabbit and in two types of cultured cells. Basal Isc was inhibited 20–70% by the ENaC inhibitor, benzamil. Long-lasting inhibition of ENaC-dependent Isc was also produced by basolateral carbachol in all preparations except rabbit and the H441 cell line. Atropine inhibition produced a slow recovery or prevented inhibition if added before carbachol. The mechanism for inhibition was not determined and is most likely multi-factorial. However, its physiological significance is expected to be increased mucus clearance rates in cholinergically stimulated airways. PMID:26846701

  18. Protein tyrosine phosphatase SHP2 regulates TGF-β1 production in airway epithelia and asthmatic airway remodeling in mice

    PubMed Central

    Qin, X.-J.; Zhang, G.-S.; Zhang, X.; Qiu, Z.-W.; Wang, P.-L.; Li, Y.-W.; Li, W.; Xie, Q.-M.; Ke, Y.-H.; Lee, J. J.; Shen, H.-H.

    2014-01-01

    Background Transforming growth factor (TGF)-β1 produced in airway epithelia has been suggested as a contributor to the airway remodeling observed in asthma patients. The protein tyrosine phosphatase SHP2 is a demonstrable modulator of TGF-β1 production and thus a potential regulator of airway remodeling. Objectives To define the signal event by which SHP2 regulates asthmatic responses in airway epithelial cells by using a mouse model of experimental OVA-induced airway remodeling. Methods The airways of Shp2flox/flox mice were infected with recombinant adenovirus vectors expressing a Cre recombinase–green fluorescence protein (GFP) fusion protein as part of allergen provocation studies using mice sensitized with ovalbumin (OVA) and repeatedly challenged with OVA. Several endpoint pathologies were assessed, including airway hyper-responsiveness (AHR), lung inflammatory score, peribronchial collagen deposition, and α-smooth muscle actin (SMA) hyperplasia. In vitro studies using airway epithelial cells (BEAS-2B) were used to investigate the role of SHP2 in the regulation of pulmonary remodeling events, including the expression of collagen, α-SMA, and TGF-β1. Results Chronic OVA challenges in wild-type mice resulted in airway remodeling and lung dysfunction (e.g., increased inflammatory scores, collagen deposition (fibrosis), smooth muscle hyperplasia, and a significant increase in AHR). These endpoint pathology metrics were each significantly attenuated by conditional shp2 gene knockdown in airway epithelia. In vitro studies using BEAS-2B cells also demonstrated that the level of TGF-β1 production by these cells correlated with the extent of shp2 gene expression. Conclusions SHP2 activities in airway epithelial cells appear to modulate TGF-β1 production and, in turn, regulate allergic airway remodeling following allergen provocation. Clinical Implications Our findings identify SHP2 as a previously underappreciated contributor to the airway remodeling and lung

  19. 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.

  20. Association between lung function and airway wall density

    NASA Astrophysics Data System (ADS)

    Leader, J. Ken; Zheng, Bin; Fuhrman, Carl R.; Tedrow, John; Park, Sang C.; Tan, Jun; Pu, Jiantao; Drescher, John M.; Gur, David; Sciurba, Frank C.

    2009-02-01

    Computed tomography (CT) examination is often used to quantify the relation between lung function and airway remodeling in chronic obstructive pulmonary disease (COPD). In this preliminary study, we examined the association between lung function and airway wall computed attenuation ("density") in 200 COPD screening subjects. Percent predicted FVC (FVC%), percent predicted FEV1 (FEV1%), and the ratio of FEV1 to FVC as a percentage (FEV1/FVC%) were measured post-bronchodilator. The apical bronchus of the right upper lobe was manually selected from CT examinations for evaluation. Total airway area, lumen area, wall area, lumen perimeter and wall area as fraction of the total airway area were computed. Mean HU (meanHU) and maximum HU (maxHU) values were computed across pixels assigned membership in the wall and with a HU value greater than -550. The Pearson correlation coefficients (PCC) between FVC%, FEV1%, and FEV1/FVC% and meanHU were -0.221 (p = 0.002), -0.175 (p = 0.014), and -0.110 (p = 0.123), respectively. The PCCs for maxHU were only significant for FVC%. The correlations between lung function and the airway morphometry parameters were slightly stronger compared to airway wall density. MeanHU was significantly correlated with wall area (PCC = 0.720), airway area (0.498) and wall area percent (0.611). This preliminary work demonstrates that airway wall density is associated with lung function. Although the correlations in our study were weaker than a recent study, airway wall density initially appears to be an important parameter in quantitative CT analysis of COPD.

  1. Transcriptional Regionalization of the Fruit Fly’s Airway Epithelium

    PubMed Central

    Faisal, Muhammad N.; Hoffmann, Julia; El-Kholy, Samar; Kallsen, Kimberley; Wagner, Christina; Bruchhaus, Iris; Fink, Christine; Roeder, Thomas

    2014-01-01

    Although airway epithelia are primarily devoted to gas exchange, they have to fulfil a number of different tasks including organ maintenance and the epithelial immune response to fight airborne pathogens. These different tasks are at least partially accomplished by specialized cell types in the epithelium. In addition, a proximal to distal gradient mirroring the transition from airflow conduction to real gas exchange, is also operative. We analysed the airway system of larval Drosophila melanogaster with respect to region-specific expression in the proximal to distal axis. The larval airway system is made of epithelial cells only. We found differential expression between major trunks of the airways and more distal ones comprising primary, secondary and terminal ones. A more detailed analysis was performed using DNA-microarray analysis to identify cohorts of genes that are either predominantly expressed in the dorsal trunks or in the primary/secondary/terminal branches of the airways. Among these differentially expressed genes are especially those involved in signal transduction. Wnt-signalling associated genes for example are predominantly found in secondary/terminal airways. In addition, some G-protein coupled receptors are differentially expressed between both regions of the airways, exemplified by those activated by octopamine or tyramine, the invertebrate counterparts of epinephrine and norepinephrine. Whereas the OAMB is predominantly found in terminal airway regions, the oct3βR has higher expression levels in dorsal trunks. In addition, we observed a significant association of both, genes predominantly expressed in dorsal trunks or in primary to terminal branches branches with those regulated by hypoxia. Taken together, this observed differential expression is indicative for a proximal to distal transcriptional regionalization presumably reflecting functional differences in these parts of the fly’s airway system. PMID:25020150

  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. Angiogenesis and airway reactivity in asthmatic Brown Norway rats.

    PubMed

    Wagner, Elizabeth M; Jenkins, John; Schmieder, Anne; Eldridge, Lindsey; Zhang, Qiong; Moldobaeva, Aigul; Zhang, Huiying; Allen, John S; Yang, Xiaoxia; Mitzner, Wayne; Keupp, Jochen; Caruthers, Shelton D; Wickline, Samuel A; Lanza, Gregory M

    2015-01-01

    Expanded and aberrant bronchial vascularity, a prominent feature of the chronic asthmatic airway, might explain persistent airway wall edema and sustained leukocyte recruitment. Since it is well established that there are causal relationships between exposure to house dust mite (HDM) and the development of asthma, determining the effects of HDM in rats, mammals with a bronchial vasculature similar to humans, provides an opportunity to study the effects of bronchial angiogenesis on airway function directly. We studied rats exposed bi-weekly to HDM (Der p 1; 50 μg/challenge by intranasal aspiration, 1, 2, 3 weeks) and measured the time course of appearance of increased blood vessels within the airway wall. Results demonstrated that within 3 weeks of HDM exposure, the number of vessels counted within airway walls of bronchial airways (0.5-3 mm perimeter) increased significantly. These vascular changes were accompanied by increased airway responsiveness to methacholine. A shorter exposure regimen (2 weeks of bi-weekly exposure) was insufficient to cause a significant increase in functional vessels or reactivity. Yet, 19F/1H MR imaging at 3T following αvβ3-targeted perfluorocarbon nanoparticle infusion revealed a significant increase in 19F signal in rat airways after 2 weeks of bi-weekly HDM, suggesting earlier activation of the process of neovascularization. Although many antigen-induced mouse models exist, mice lack a bronchial vasculature and consequently lack the requisite human parallels to study bronchial edema. Overall, our results provide an important new model to study the impact of bronchial angiogenesis on chronic inflammation and airways hyperreactivity.

  4. Upper airway segmentation and measurement in MRI using fuzzy connectedness

    NASA Astrophysics Data System (ADS)

    Liu, Jianguo; Udupa, Jayaram K.; Odhner, Dewey; McDonough, Joe M.; Arens, Raanan

    2002-04-01

    The purpose of this work is to build a computerized system for the delineation of upper airway structures via MRI and to evaluate its effectiveness for routine clinical use in aiding diagnosis of upper airway disorders in children. We use two MRI protocols, axial T1 and T2, to gather information about different aspects of the airway and its surrounding soft tissue structures including adenoid, tonsils, tongue and soft palate. These images are processed and segmented to compute the architectural parameters of the airway such as its surface description, volume, central (medial) line, and cross-sectional areas at planes orthogonal to the central line. We have built a software package based on 3DVIEWNIX and running on a 450 MHz Pentium PC under Linux system (and on a Sun workstation under Unix) for the various operations of visualization, segmentation, registration, prefiltering, interpolation, standardization, and quantitative analysis of the airway. The system has been tested utilizing 40 patient studies. For every study, the system segmented and displayed a smooth 3D rendition of the airway, its central line and a plot of the cross-sectional area of the airway orthogonal to the central line as a function of the distance from one end of the central line. The tests indicate 97% precision and accuracy for segmentation. The mean time taken per study is about 4 minutes for the airway. This includes operator interaction time and processing time. This method provides a robust and fast means of assessing the airway size, shape, and places of restriction, as well as providing a structural data set suitable for use in modeling studies of airflow and mechanics.

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

    PubMed Central

    Blankman, Elizabeth; Jensen, Christopher C.; Krishnan, Ramaswamy; James, Alan L.; Elliot, John G.; Green, Francis H.; Liu, Jeffrey C.; Seow, Chun Y.; Park, Jin-Ah; Beckerle, Mary C.; Paré, Peter D.; Fredberg, Jeffrey J.; Smith, Mark A.

    2017-01-01

    Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI) whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM) cells to stretch, but underlying molecular mechanisms–and their failure in asthma–remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma. PMID:28278518

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

    PubMed

    Rosner, Sonia R; Pascoe, Christopher D; Blankman, Elizabeth; Jensen, Christopher C; Krishnan, Ramaswamy; James, Alan L; Elliot, John G; Green, Francis H; Liu, Jeffrey C; Seow, Chun Y; Park, Jin-Ah; Beckerle, Mary C; Paré, Peter D; Fredberg, Jeffrey J; Smith, Mark A

    2017-01-01

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

  7. Airway management evolution - in a search for an ideal extraglottic airway device.

    PubMed

    Michálek, Pavel; Miller, Donald M

    2014-01-01

    Extraglottic airway devices (EADs) are commonly used equipment for airway maintenance during elective procedures under general anaesthesia. They may be used also in other indications such as conduit for tracheal intubation or rescue airway device in prehospital medicine. Current classifications of the EADs lack systematic approach and therefore classification according to the sealing sites and sealing mechanisms is suggested in this review article. Modern EADs are disposable, latex-free devices made of plastic materials most commonly from polyvinylchloride (PVC). The bowl of uncuffed sealers is manufactured from different materials such as thermoplastic elastomers or ethylene-vinyl-acetate co-polymer. EADs create various physical forces exerted on the adjacent tissues which may contribute to different sealing characteristic of particular device or to variable incidence of postoperative complications. Desired features of an ideal EAD involve easy insertion, high insertion success rate even by inexperienced users, protection against aspiration of gastric contents and low incidence of postoperative complications such as sore throat, hoarseness, cough or swallowing difficulties.

  8. Non-malignant central airway obstruction.

    PubMed

    Barros Casas, David; Fernández-Bussy, Sebastian; Folch, Erik; Flandes Aldeyturriaga, Javier; Majid, Adnan

    2014-08-01

    The most common causes of non-malignant central airway obstruction are post-intubation and post-tracheostomytracheal stenosis, followed by the presence of foreign bodies, benign endobronchial tumours and tracheobronchomalacia. Other causes, such as infectious processes or systemic diseases, are less frequent. Despite the existence of numerous classification systems, a consensus has not been reached on the use of any one of them in particular. A better understanding of the pathophysiology of this entity has allowed us to improve diagnosis and treatment. For the correct diagnosis of nonspecific clinical symptoms, pulmonary function tests, radiological studies and, more importantly, bronchoscopy must be performed. Treatment must be multidisciplinary and tailored to each patient, and will require surgery or endoscopic intervention using thermoablative and mechanical techniques.

  9. Liquid and surfactant delivery into pulmonary airways

    PubMed Central

    Halpern, David; Fujioka, Hideki; Takayama, Shuichi; Grotberg, James B.

    2008-01-01

    We describe the mechanisms by which liquids and surfactants can be delivered into the pulmonary airways. These are instilled and transported throughout the lung in clinical therapies such as surfactant replacement therapy, partial liquid ventilation and drug delivery. The success of these treatments is contingent on the liquid distribution and the delivery to targeted regions of the lung. The targeting of a liquid plug can be influenced by a variety of factors such as the physical properties of the liquid, the interfacial activity, the gravitational orientation, instillation method and propagation speed. We provide a review of experimental and theoretical studies that examine these effects in single tubes or channels, in tubes with single bifurcations and in the whole lung. PMID:18585985

  10. Airway Reflux, Cough and Respiratory Disease

    PubMed Central

    Molyneux, Ian D.; Morice, Alyn H.

    2011-01-01

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

  11. Airway Management in a Patient with Wolf-Hirschhorn Syndrome

    PubMed Central

    Udani, Andrea G.

    2016-01-01

    We present a case of a 3-month-old female with Wolf-Hirschhorn syndrome (WHS) undergoing general anesthesia for laparoscopic gastrostomy tube placement with a focus on airway management. WHS is a rare 4p microdeletion syndrome resulting in multiple congenital abnormalities, including craniofacial deformities. Microcephaly, micrognathia, and glossoptosis are common features in WHS patients and risk factors for a pediatric airway that is potentially difficult to intubate. We discuss anesthesia strategies for airway preparation and management in a WHS patient requiring general anesthesia with endotracheal intubation. PMID:27752382

  12. Airways microbiota: Hidden Trojan horses in asbestos exposed individuals?

    PubMed

    Magouliotis, Dimitrios E; Tasiopoulou, Vasiliki S; Molyvdas, Paschalis-Adam; Gourgoulianis, Konstantinos I; Hatzoglou, Chrissi; Zarogiannis, Sotirios G

    2014-11-01

    Malignant pleura mesothelioma (MPM) is a rare type of cancer with devastating prognosis, which develops in the pleural cavity from transformed mesothelium. MPM has been directly associated with asbestos exposure however there are aspects of the pathophysiology involved in the translocation of asbestos fibers in the pleura that remain unclear. Here, we propose and discuss that certain proteins secreted by airways symbiotic microbiota create membrane pores to the airway epithelial cells, through which asbestos fibers can penetrate the lung parenchyma