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Sample records for vitro airways hyperreactivity

  1. Inherent and antigen-induced airway hyperreactivity in NC mice

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    Tetsuto Kobayashi

    1999-01-01

    Full Text Available In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those strains in vivo. NC mice again showed comparable airway reactivity to that seen in A/J mice and a significantly greater reactivity than that seen in BALB/c and C57BL/6 mice. To investigate the effects of airway inflammation on airway reactivity to acetylcholine in vivo, NC and BALB/c mice were sensitized to and challenged with antigen. Sensitization to and challenge with antigen induced accumulation of inflammatory cells, especially eosinophils, in lung and increased airway reactivity in NC and BALB/c mice. These results indicate that NC mice exhibit inherent and antigen-induced airway hyperreactivity. Therefore, NC mice are a suitable strain to use in investigating the mechanisms underlying airway hyperreactivity and such studies will provide beneficial information for understanding the pathophysiology of asthma.

  2. Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization

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    Rossi, Antonietta; Caiazzo, Elisabetta; Bilancia, Rossella; Riemma, Maria A.; Pagano, Ester; Cicala, Carla; Ialenti, Armando; Zjawiony, Jordan K.; Izzo, Angelo A.; Capasso, Raffaele; Roviezzo, Fiorentina

    2017-01-01

    Salvinorin A, a neoclerodane diterpene isolated from Salvia divinorum, exerts a number of pharmacological actions which are not solely limited to the central nervous system. Recently it has been demonstrated that Salvinorin A inhibits acute inflammatory response affecting leukotriene (LT) production. Since LTs are potent lipid mediators implicated in allergic diseases, we evaluated the effect of Salvinorin A on allergic inflammation and on airways following sensitization in the mouse. Mice were sensitized with s.c. injection of ovalbumin (OVA) on days 1 and 8. Sensitized mice received on days 9 and 12 on the shaved dorsal surface air administration to induce the development of the air-pouches. On day 15 animals were challenged by injection of OVA into the air-pouch. Salvinorin A, administered (10 mg/kg) before each allergen exposure, significantly reduced OVA-induced LT increase in the air pouch. This effect was coupled to a reduction in cell recruitment and Th2 cytokine production. In another set of experiments, mice were sensitized with OVA and both bronchial reactivity and pulmonary inflammation were assessed. Salvinorin A abrogated bronchial hyperreactivity and interleukin (IL)-13 production, without effect on pulmonary inflammation. Indeed cell infiltration and peribronchial edema were still present following diterpenoid treatment. Similarly, pulmonary IL-4 and plasmatic IgE levels were not modulated. Conversely, Salvinorin A significantly reduced LTC4 production in the lung of sensitized mice. Finally mast cell activity was evaluated by means of toluidine blue staining. Data obtained evidenced that Salvinorin A significantly inhibited mast cell degranulation in the lung. Our study demonstrates that Salvinorin A inhibits airway hyperreactivity induced by sensitization by inhibition of LT production and mast cell degranulation. In conclusion Salvinorin A could represent a promising candidate for drug development in allergic diseases such as asthma. PMID

  3. Insect Bite Hypersensitivity in Horses is Associated with Airway Hyperreactivity.

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    Lanz, S; Brunner, A; Graubner, C; Marti, E; Gerber, V

    2017-11-01

    Genetic and epidemiologic evidence suggests that in horses, as in other species, different manifestations of hypersensitivity may occur together. Horses affected with insect bite hypersensitivity (IBH) show airway hyperreactivity (AH) to inhaled histamine, even in the absence of overt clinical signs of equine asthma (EA). Twenty-two healthy controls (group C), 24 horses suffering from IBH alone (group IBH), and 23 horses suffering from IBH and EA (group IBH/EA). The clinical histories were assessed using 2 standardized questionnaires, the Horse Owner Assessed Respiratory Signs Index (HOARSI), and IBH scoring. Horses were classified as EA-affected if their HOARSI was >1 and as IBH-affected if IBH score was >0. Confounding disorders were excluded by clinical examination. The arterial partial pressure of oxygen (PaO 2 ) was measured and flowmetric plethysmography used to assess airway reactivity to increasing doses of inhaled histamine. The median histamine provocation concentration (PC) when ∆ flow values increased by 35% (PC35) was significantly higher in group C (5.94 [1.11-26.33] mg/mL) compared to group IBH (2.95 [0.23-10.13] mg/mL) and group IBH/EA (2.03 [0.43-10.94] mg/mL; P < 0.01). The PC50 and PC75 showed very similar differences between groups. Furthermore, PaO 2 was significantly lower in group IBH (84 ± 8 mmHg) and group IBH/EA (78 ± 11 mmHg) compared to group C (89 ± 6 mmHg; P < 0.01). IBH is associated with AH and decreased PaO 2 , even in the absence of overt respiratory clinical signs. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  4. Newly divided eosinophils limit ozone-induced airway hyperreactivity in nonsensitized guinea pigs.

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    Wicher, Sarah A; Jacoby, David B; Fryer, Allison D

    2017-06-01

    Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory cells were harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day after ozone, mature eosinophils dominate the inflammatory response and potentiate vagally induced bronchoconstriction. However, by 3 days, newly divided eosinophils have reached the lungs, where they inhibit ozone-induced airway hyperreactivity because depleting them with antibody to IL-5 or a TNF-α antagonist worsened vagally induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs 3 days later failed to occur. Thus mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs, where 3 days later, newly divided eosinophils attenuate vagally mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNF-α antagonist or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus interventions targeting eosinophils, although beneficial in atopic individuals, may delay resolution of airway hyperreactivity in nonatopic individuals. Copyright

  5. Effects of Flavin7 on allergen induced hyperreactivity of airways

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    Franova S

    2009-12-01

    Full Text Available Abstract Some studies have suggested that the polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effects of 21 days of the flavonoid Flavin7 administration on experimentally induced airway inflammation in ovalbumin-sensitized guinea pigs. We assessed tracheal smooth muscle reactivity by an in vitro muscle-strip method; changes in airway resistance by an in vivo plethysmographic method; histological picture of tracheal tissue; and the levels of interleukin 4 (IL-4, and interleukin 5 (IL-5 in bronchoalveolar lavage fluid (BALF. Histological investigation of tracheal tissue and the concentrations of the inflammatory cytokines IL-4 and IL-5 in BALF were used as indices of airway inflammation. Administration of Flavin7 caused a significant decrease of specific airway resistance after histamine nebulization and a decline in tracheal smooth muscle contraction amplitude in response to bronchoconstricting mediators. Flavin7 minimized the degree of inflammation estimated on the basis of eosinophil calculation and IL-4 and IL-5 concentrations. In conclusion, administration of Flavin7 showed bronchodilating and anti-inflammatory effects on allergen-induced airway inflammation.

  6. IL-17RA Signaling in Airway Inflammation and Bronchial Hyperreactivity in Allergic Asthma.

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    Willis, Cynthia R; Siegel, Lori; Leith, Anh; Mohn, Deanna; Escobar, Sabine; Wannberg, Sharon; Misura, Kira; Rickel, Erika; Rottman, James B; Comeau, Michael R; Sullivan, John K; Metz, Daniela P; Tocker, Joel; Budelsky, Alison L

    2015-12-01

    Asthma is a heterogeneous disease characterized by airway inflammation and hyperreactivity. IL-17 receptor A (IL-17RA) is a shared receptor subunit required for activity of IL-17 family cytokines, including IL-17A and IL-25. IL-17A and IL-25 induce different proinflammatory responses, and concentrations are elevated in subjects with asthma. However, the individual contributions of IL-17A and IL-25 to disease pathogenesis are unclear. We explored proinflammatory activities of the IL-17 pathway in models of pulmonary inflammation and assessed its effects on contractility of human bronchial airway smooth muscle. In two mouse models, IL-17RA, IL-17RB, or IL-25 blockade reduced airway inflammation and airway hyperreactivity. Individually, IL-17A and IL-25 enhanced contractility of human bronchial smooth muscle induced by methacholine or carbachol. IL-17A had more pronounced effects on methacholine-induced contractility in bronchial rings from donors with asthma compared with donors without asthma. Blocking the IL-17 pathway via IL-17RA may be a useful therapy for some patients with asthma by reducing pulmonary inflammation and airway hyperreactivity.

  7. Long-term nicotine exposure dampens LPS-induced nerve-mediated airway hyperreactivity in murine airways.

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    Xu, Yuan; Cardell, Lars-Olaf

    2017-09-01

    Nicotine is a major component of cigarette smoke. It causes addiction and is used clinically to aid smoke cessation. The aim of the present study is to investigate the effect of nicotine on lipopolysaccharide (LPS)-induced airway hyperreactivity (AHR) and to explore the potential involvement of neuronal mechanisms behind nicotine's effects in murine models in vivo and in vitro. BALB/c mice were exposed to nicotine in vivo via subcutaneous Alzet osmotic minipumps containing nicotine tartate salt solution (24 mg·kg-1·day-1) for 28 days. LPS (0.1 mg/ml, 20 µl) was administered intranasally for 3 consecutive days during the end of this period. Lung functions were measured with flexiVent. For the in vitro experiments, mice tracheae were organcultured with either nicotine (10 μM) or vehicle (DMSO, 0.1%) for 4 days. Contractile responses of the tracheal segments were measured in myographs following electric field stimulation (EFS; increasing frequencies of 0.2 to 12.8 Hz) before and after incubation with 10 µg/ml LPS for 1 h. Results showed that LPS induced AHR to methacholine in vivo and increased contractile responses to EFS in vitro. Interestingly, long-term nicotine exposure markedly dampened this LPS-induced AHR both in vitro and in vivo. Tetrodotoxin (TTX) inhibited LPS-induced AHR but did not further inhibit nicotine-suppressed AHR in vivo. In conclusion, long-term nicotine exposure dampened LPS-induced AHR. The effect of nicotine was mimicked by TTX, suggesting the involvement of neuronal mechanisms. This information might be used for evaluating the long-term effects of nicotine and further exploring of how tobacco products interact with bacterial airway infections. Copyright © 2017 the American Physiological Society.

  8. Effectiveness of levodropropizine against cigarette smoke-induced airway hyperreactivity: possible mechanism.

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    Daffonchio, L; Hernandez, A; Melillo, G; Clavenna, G; Omini, C

    1993-04-01

    We verified the possible effect of the new antitussive drug levodropropizine on airway hyperreactivity and lung inflammation induced by cigarette smoke exposure in anaesthetized guinea-pigs. Levodropropizine, administered by aerosol at 25 mg/ml for 30 s completely prevented smoke induced airway hyperreactivity. The protective effect was early in onset (3 min) and lasted up to 30 min. The same dose of codeine, administered in the form of an aerosol, decreased the increase in airway responsiveness induced by smoke inhalation slightly but not significantly. In parallel with the functional results, levodropropizine also inhibited the recruitment of inflammatory cells triggered by smoke exposure within the airway lumen. When levodropropizine was administered i.v. to anaesthetized guinea-pigs, it reduced the bronchocontractile effect of capsaicin dose-dependently, whereas it was without effect against substance P-induced bronchoconstriction. These data demonstrate the ability of levodropropizine to counteract the hyperreactive phenomenon and the associated inflammatory event induced by cigarette smoke exposure, an effect which might depend on its capacity to modulate the activation of the peptidergic system.

  9. Curcumin attenuates airway hyperreactivity induced by ischemia-reperfusion of the pancreas in rats.

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    Chen, K H; Chao, D; Liu, C F; Chen, C F; Wang, D

    2010-04-01

    Ischemia-reperfusion (I/R) of the rat pancreas induces acute pancreatitis with a systemic inflammatory response. Activated inflammatory cells are sequestered in the lung, and the consequent respiratory burst may increase airway reactivity. In this study, we characterized the effect of the antioxidant curcumin on airway hyperreactivity induced by pancreatic I/R. Ischemia of the pancreas was induced by clamping the gastroduodenal and the splenic artery for 2 hours followed by reperfusion for 6 hours. The pulmonary function data of Penh, a measurement of airway resistance, were used to show the airway responses to a methacholine challenge. The blood concentration of oxygen radicals, nitric oxide, and tumor necrosis factor-alpha (TNFalpha) were measured after pancreatic I/R. mRNA expressions of inducible nitric oxide synthase (iNOS) and TNFalpha in lung tissues were measured after pancreatic I/R. Pretreatment with curcumin (20 mg/kg) was administered by intraperitoneal injection 2 hours before pancreatic I/R. The protocol resulted in significant elevations of the blood concentrations of amylase, hydroxyl radical, nitric oxide, TNFalpha, and white cells among the I/R group. iNOS and TNFalpha mRNA expressions also significantly increased in lung tissues. Pulmonary function data showed that pancreatic I/R induced significant increases in responses to methacholine challenge: Penh increased significantly in the I/R group when compared with the sham group. Pretreatment with curcumin significantly attenuated the inflammatory, oxidative, and nitrosative responses and lung tissue iNOS and TNFalpha expressions. Curcumin also attenuated airway reactivity to methacholine challenge. I/R of the pancreas induced systemic inflammatory responses with respiratory burst, nitrosative stress, and hyperresponses in the airways. Curcumin, which has antioxidant and anti-inflammatory effects, significantly attenuated the inflammatory responses and airway hyperreactivity induced by pancreatic I

  10. Post-Exposure Antioxidant Treatment in Rats Decreases Airway Hyperplasia and Hyperreactivity Due to Chlorine Inhalation

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    Bracher, Andreas; Doran, Stephen F.; Squadrito, Giuseppe L.; Fernandez, Solana; Postlethwait, Edward M.; Bowen, Larry; Matalon, Sadis

    2012-01-01

    We assessed the safety and efficacy of combined intravenous and aerosolized antioxidant administration to attenuate chlorine gas–induced airway alterations when administered after exposure. Adult male Sprague-Dawley rats were exposed to air or 400 parts per million (ppm) chlorine (a concentration likely to be encountered in the vicinity of industrial accidents) in environmental chambers for 30 minutes, and returned to room air, and they then received a single intravenous injection of ascorbic acid and deferoxamine or saline. At 1 hour and 15 hours after chlorine exposure, the rats were treated with aerosolized ascorbate and deferoxamine or vehicle. Lung antioxidant profiles, plasma ascorbate concentrations, airway morphology, and airway reactivity were evaluated at 24 hours and 7 days after chlorine exposure. At 24 hours after exposure, chlorine-exposed rats had significantly lower pulmonary ascorbate and reduced glutathione concentrations. Treatment with antioxidants restored depleted ascorbate in lungs and plasma. At 7 days after exposure, in chlorine-exposed, vehicle-treated rats, the thickness of the proximal airways was 60% greater than in control rats, with twice the amount of mucosubstances. Airway resistance in response to methacholine challenge was also significantly elevated. Combined treatment with intravenous and aerosolized antioxidants restored airway morphology, the amount of airway mucosubstances, and airway reactivity to control levels by 7 days after chlorine exposure. Our results demonstrate for the first time, to the best of our knowledge, that severe injury to major airways in rats exposed to chlorine, as characterized by epithelial hyperplasia, mucus accumulation, and airway hyperreactivity, can be reversed in a safe and efficacious manner by the post-exposure administration of ascorbate and deferoxamine. PMID:22162906

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

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

    1998-01-01

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

  12. Dexamethasone reduces tachykinin but not ACh airway hyperreactivity after O[sub 3

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    Murlas, C.G.; Lang, Z.; Chodimella, V. (Rush Univ., Chicago, IL (United States))

    1993-01-01

    We investigated whether dexamethasone pretreatment affected the acute increase in airway reactivity produced by high-level ozone exposure. Reactivity to intravenous IV substance P (SP), IV acetylcholine (ACh), or aerosolized capsaicin (CAP) before and 1 hr after ozone exposure (3 ppm for 2 hr) was determined by measuring specific airway resistance in anesthetized, spontaneously breathing guinea pigs, half of whom had been pretreated for 2 days pre-ozone with dexamethasone (2 mg/kg intramuscularly [IM] daily). The amount of IV SP, IV ACh, or inhaled capsaicin necessary to increase baseline specific airway resistance by 100% (ED200ACh or ED200SP) or 35% (ED135CAP) was determined by interpolation from dose-response curves. Compared to their pre-ozone status on the day of exposure, we found that dexamethasone-pretreated animals manifested significantly less of an increase in airway reactivity postozone to IV SP or inhaled CAP than did untreated animals. Changes in logEDs of the pretreated group were 0.18 +/- 0.03 (mean +/- SE) for SP and 2.20 +/- 0.11 for CAP compared to 0.27 +/- 0.04 and 3.38 +/- 0.34, respectively, for the untreated groups post-ozone (p < 0.05 and n = 4 for each). In contrast, dexamethasone pretreatment had no effect on IV ACh reactivity postozone: changes in logED200ACh were 0.27 +/- 0.08 and 0.28 +/- 0.04 for the pretreated and untreated groups, respectively (n = 4). In animals pretreated with captopril to block possible dexamethasone stimulation of angiotensin-converting enzyme synthesis that could influence tachykinin reactivity, we found that the corticosteroid effect on post-ozone SP reactivity was as marked as that seen in animals without captopril (n = 4). These reactivity studies were consistent with the possibility that dexamethasone may ameliorate ozone-induced, tachykinin hyperreactivity by stimulating airway neutral endopeptidase (NEP).

  13. Poly(ADP-ribose) polymerase inhibition with HYDAMTIQ reduces allergen-induced asthma-like reaction, bronchial hyper-reactivity and airway remodelling.

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    Lucarini, Laura; Pini, Alessandro; Gerace, Elisabetta; Pellicciari, Roberto; Masini, Emanuela; Moroni, Flavio

    2014-03-01

    Activation of poly(ADP-ribose) polymerases (PARPs) is considered a key event in the molecular and cellular processes leading from acute asthma attacks to bronchial hyper-reactivity, leucocyte recruitment, chronic inflammation, airway remodelling and lung damage. The present investigation has been carried out to investigate the action of hydroxyl-dimethylaminomethyl-thieno[2,3-c]isoquinolin-5(4H)-one (HYDAMTIQ), a new potent PARP inhibitor, in the process leading from asthma-like events to airway damage. Ovalbumin-sensitized guinea pigs exposed two times to allergen inhalation were treated for 8 days with vehicle or HYDAMTIQ. Asthma-like signs, bronchial hyper-reactivity to methacholine, cytokine production, histamine release from mast cells, airway remodelling, collagen deposition and lung damage were evaluated. Repeated HYDAMTIQ administration (1-10 mg/kg/day i.p.) reduced lung PARP activity, delayed the appearance and reduced the severity of allergen-induced cough and dyspnoea and dampened the increased bronchial responses to methacholine. HYDAMTIQ-treated animals presented reduced bronchial or alveolar abnormalities, lower number of eosinophils and other leucocytes in the lung and decreased smooth muscle or goblet cell hyperplasia. The treatment also reduced lung oxidative stress markers, such as malondialdehyde or 8-hydroxy-2'-deoxyguanosine and the lung content of pro-inflammatory cytokines (TNF-α, interleukin (IL)-1β, IL-5, IL-6 and IL-18). Finally, mast cells isolated from the peritoneal or pleural cavities of sensitized, HYDAMTIQ-treated animals had a reduced ability to release histamine when exposed to ovalbumin in vitro. Our findings support the proposal that PARP inhibitors could have a therapeutic potential to reduce chronic lung inflammation, airway damage and remodelling in severe unresponsive asthmatic patients. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and

  14. Up-Regulation of Endothelin Receptors Induced by Cigarette Smoke — Involvement of MAPK in Vascular and Airway Hyper-Reactivity

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    Yaping Zhang

    2010-01-01

    Full Text Available Cigarette smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway hyper-reactivity plays an important role in the pathogenesis of cardiovascular and airway diseases. Recent studies have demonstrated that endothelin receptor up-regulation mediates vascular and airway hyper-reactivity in response to endothelin-1 (ET-1, endothelin receptor agonist in cardiovascular and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated endothelin receptors by cigarette smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (spasm and adverse proliferation (remodeling of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette smoke exposure that induces activation of intracellular mitogen-activated protein kinase (MAPK and subsequently results in the up-regulation of endothelin receptors in the vasculature and airways, which mediates vascular and airway hyper-reactivity, one of the important pathogenic characteristics of cardiovascular and airway diseases. Understanding the molecular mechanisms of how cigarette smoke causes up-regulation of endothelin receptors in the vasculature and airways may provide new strategies for the treatment of cigarette smoke—associated cardiovascular and lung diseases.

  15. Physical Therapy Treatment of Impaired Chest Mobility in Patients with Airway Sensory Hyperreactivity.

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    Johansson, Ewa-Lena; Ternestén-Hasseus, Ewa; Olsén, Monika Fagevik; Millqvist, Eva

    2017-04-01

    In sensory hyperreactivity (SHR), patients have symptoms from the airways and the chest induced by environmental irritants like scenting products and cigarette smoke. They are characterized by increased cough reaction to inhaled capsaicin compared with healthy controls. Lung function tests are normal, and asthma medications have no or little effect. In a recent published article, patients with SHR were found to have impaired chest mobility and increased pain sensitivity. The purpose of this study was to evaluate if a physiotherapeutic intervention can increase chest mobility in SHR, influence these patients' symptoms and reduce capsaicin cough sensitivity. Forty-one SHR patients were initially randomized in to groups, one for training and one for symptom registration in this controlled training study. It consisted of a daily training programme containing simple movements to increase the flexibility of the chest, a breathing exercise and a relaxation session as well as symptom registration. Chest expansion was measured with a measuring tape and thoracic and abdominal movement with light sensors. Pain sensitivity was assessed using pressure algometry and a standardized capsaicin inhalation threshold provocation-evaluated cough sensitivity. Twenty seven patients were left for analyses after 12 weeks and 26 patients after 24 weeks. Chest mobility and upper thoracic respiratory movements improved (p < 0.01), feeling of chest pressure and the capsaicin cough sensitivity decreased (p < 0.01). The patients also showed of significantly lowered pain pressure thresholds measured with algometry, compared with healthy controls (p < 0.001). Improvement of chest mobility after physiotherapeutic intervention indicates that these patients may have acquired a dysfunctional breathing pattern. The regular use of a training programme and structural breathing instructions can be used to improve chest mobility, chest symptoms and capsaicin cough sensitivity in patients

  16. Airway Remodeling and Hyperreactivity in a Model of Bronchopulmonary Dysplasia and Their Modulation by IL-1 Receptor Antagonist.

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    Royce, Simon G; Nold, Marcel F; Bui, Christine; Donovan, Chantal; Lam, Maggie; Lamanna, Emma; Rudloff, Ina; Bourke, Jane E; Nold-Petry, Claudia A

    2016-12-01

    Bronchopulmonary dysplasia (BPD) is a chronic disease of extreme prematurity that has serious long-term consequences including increased asthma risk. We earlier identified IL-1 receptor antagonist (IL-1Ra) as a potent inhibitor of murine BPD induced by combining perinatal inflammation (intraperitoneal LPS to pregnant dams) and exposure of pups to hyperoxia (fraction of inspired oxygen = 0.65). In this study, we determined whether airway remodeling and hyperresponsiveness similar to asthma are evident in this model, and whether IL-1Ra is protective. During 28-day exposure to air or hyperoxia, pups received vehicle or 10 mg/kg IL-1Ra by daily subcutaneous injection. Lungs were then prepared for histology and morphometry of alveoli and airways, or for real-time PCR, or inflated with agarose to prepare precision-cut lung slices to visualize ex vivo intrapulmonary airway contraction and relaxation by phase-contrast microscopy. In pups reared under normoxic conditions, IL-1Ra treatment did not affect alveolar or airway structure or airway responses. Pups reared in hyperoxia developed a severe BPD-like lung disease, with fewer, larger alveoli, increased subepithelial collagen, and increased expression of α-smooth muscle actin and cyclin D1. After hyperoxia, methacholine elicited contraction with similar potency but with an increased maximum reduction in lumen area (air, 44%; hyperoxia, 89%), whereas dilator responses to salbutamol were maintained. IL-1Ra treatment prevented hyperoxia-induced alveolar disruption and airway fibrosis but, surprisingly, not the increase in methacholine-induced airway contraction. The current study is the first to demonstrate ex vivo airway hyperreactivity caused by systemic maternal inflammation and postnatal hyperoxia, and it reveals further preclinical mechanistic insights into IL-1Ra as a treatment targeting key pathophysiological features of BPD.

  17. Upper airway inflammation exacerbates bronchial hyperreactivity in mouse models of rhinosinusitis and allergic asthma.

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    Liang, Kai-Li; Jiang, Rong-San; Wang, Ren-Ching; Koo, Malcolm; Chen, Shyh-Chang; Huang, Wan-Chun; Yeh, Yueh-Chiao

    2013-07-01

    Recent studies have suggested that upper airway inflammation has a strong impact on lower airway diseases. The purpose of this study was to assess whether nasal inflammation could exacerbate allergic asthma in a mouse model. Mice were assigned to 4 groups: control (Cont), either rhinosinusitis (R) or allergic asthma (A) alone, and both rhinosinusitis and allergic asthma (R&A). Mice underwent induction of nasal inflammation (R and R&A) or sham surgery (Cont and A) on day 1. Mice in the A and R&A groups were sensitized to ovalbumin on days 1, 7, and 14, followed by aerosol challenge on days 18 to 20, whereas in the Cont and R groups only saline was administered. All mice were assessed for airway hyperresponsiveness (AHR) and were euthanized on day 21. The sera, bronchoalveolar lavage fluids (BALFs), and nasal and lung tissues were collected for further analyses. Histology findings confirmed upper and lower airway inflammation in experimental mice. Significantly increased AHR and total serum immunoglobulin E (IgE) were observed in the R&A group when compared with those of the Cont, R, and A groups. Responses to IgG2a induction were also found in sera and BALFs from mice with rhinosinusitis (R and R&A). Higher levels of interleukin 4 (IL-4) and IL-13, and increased eosinophilic inflammation were detected in BALFs and lung tissues from the experimental groups when compared with those from the Cont group. Our results confirm that upper airway inflammation could exacerbate allergic asthma, and provide support to the concept of "one airway, one disease. © 2013 ARS-AAOA, LLC.

  18. The association between reflux esophagitis and airway hyper-reactivity in patients with gastro-esophageal reflux

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    Ashraf Karbasi

    2013-01-01

    Full Text Available Background: The association of gastro-esophageal reflux (GER with a wide variety of pulmonary disorders was recognized. We aimed to evaluate the effect of GER-induced esophagitis on airway hyper-reactivity (AHR in patients and the response to treatment. Materials and Methods: In this cohort study, 30 patients attending the gastrointestinal clinic of a university hospital with acid reflux symptoms were included. All patients were evaluated endoscopically and divided into case group with esophagitis and control group without any evidence of esophagitis. Spirometry and methacholine test were done in all patients before and after treatment of GER with pantoprazole 40 mg daily for six months. Results: There was a significant difference in the rate of positive methacholine test between the cases (40% and the controls (6.7% prior to anti-acid therapy (P < 0.0001. After six months of treatment, the frequency of positive methacholine test diminished from 40 to 13.3% in the case group (P < 0.05 but did not change in the controls (P = 0.15. Conclusion: The presence of esophagitis due to GER would increase the AHR and treatment with pantoperazole would decrease AHR in patients with proved esophagitis and no previous history of asthma after six months.

  19. MAPK/NF-κB-dependent upregulation of kinin receptors mediates airway hyperreactivity

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    Zhang, Yaping; Cardell, Lars-Olaf; Edvinsson, Lars

    2013-01-01

    to the development of AHR is limited. Activation of intracellular mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) and their related signal pathways including protein kinase C (PKC), phosphoinositide 3-kinase (PI3K) and protein kinase A (PKA) signaling pathways may result in airway kinin...

  20. Air pollution, bronchial hyperreactivity and airway disease in children; Luftverschmutzung, bronchiale Hyperreagibilitaet und Atemwegserkrankungen bei Kindern

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    Forster, J. [Freiburg Univ. (Germany). Universitaets-Kinderklinik; Hendel-Kramer, A. [Freiburg Univ. (Germany). Universitaets-Kinderklinik; Karmaus, W. [Freiburg Univ. (Germany). Universitaets-Kinderklinik; Kuehr, J. [Freiburg Univ. (Germany). Universitaets-Kinderklinik; Moseler, M. [Freiburg Univ. (Germany). Universitaets-Kinderklinik; Urbanek, R. [Freiburg Univ. (Germany). Universitaets-Kinderklinik; Weiss, K. [Freiburg Univ. (Germany). Universitaets-Kinderklinik

    1992-11-01

    In the study population the lifetime prevalence of asthma (4,97% of n = 704) and point prevalence of bronchial hyperreactivity (26.7% of n = 558: positive bronchial challenge test with 400 {mu}g carbachol) could be attributed partially to the use of single-room heatings. The finding was confirmed by a nested case-control-study. Outdoor NO{sub 2} and related particle pollution, both found to be relatively low compared to other German towns, were not associated with the prevalence of asthma or bronchial hyperreactivity. The Incidence of asthmatic symptoms during the study period (22 months) was associated with an NO{sub 2} exposure of more than 40 {mu}g/m{sup 3} (average outdoor concentration in fall/winter). In individuals with asthmatic symptoms (n = 106) forced expiratory volume (FEV{sub 1}/VC{sub IN}) was reduced in a dose dependent manner, if the average exposure exceeded 40 {mu}g/m{sup 3}. Conclusion: Individuals with asthmatic symptoms are prone to detrimental effects of NO{sub 2} air pollution exceeding 40 {mu}g/m{sup 3} (average outdoor concentration in fall/winter). In so far the current outdoor air pollution gives cause for concern, thus we recommend further effort in order to reduce NO{sub 2} and related pollutants. On an individual basis, in children with asthma (and with asthma in the family) the parents should be advised not to use single-room heatings. (orig./MG) [Deutsch] Mit Hilfe statistischer Erklaerungsmodelle wurde im ersten Studien-Querschnitt (N = 704) die Lebenszeitpraevalenz von Asthma bronchiale und die bronchiale Hyperreagibilitaet untersucht. Die Lebenszeit-Praevalenz von Asthma bronchiale betrug 4.97% (n = 35). Als ein signifikanter Risikofaktor fuer Asthma wurde die Verwendung einer Einzelraumheizung identifiziert. Zugleich trat bei 558 mit 400 {mu}g Carbachol provozierten Probanden in 26.6% eine bronchiale Hyperreagibilitaet auf. Die in der Untersuchungsregion probandennah gemessene relativ niedrigen Aussenluft-Immissionen von NO{sub 2

  1. Petasites extract Ze 339 (PET) inhibits allergen-induced Th2 responses, airway inflammation and airway hyperreactivity in mice.

    Science.gov (United States)

    Brattström, A; Schapowal, A; Maillet, I; Schnyder, B; Ryffel, B; Moser, R

    2010-05-01

    The herbal Petasites hybridus (butterbur) extract (Ze 339, PET) is known to have leukotriene inhibiting properties, and therefore might inhibit allergic diseases. The effect of PET was investigated in ovalbumin (OVA) immunized BALB/c mice given intranasally together with antigen challenge in the murine model of allergic airway disease (asthma) with the analysis of the inflammatory and immune parameters in the lung. PET given with the antigen challenge inhibited the allergic response. PET inhibited airway hyperresponsiveness (AHR) and eosinophil recruitment into the bronchoalveolar lavage (BAL) fluid upon allergen challenge, but had no effect in the saline control mice. Eosinophil recruitment was further assessed in the lung by eosinophil peroxidase (EPO) activity at a concentration of 100 microg PET. Microscopic investigations revealed less inflammation, eosinophil recruitment and mucus hyperproduction in the lung with 100 microg PET. Diminution of AHR and inflammation was associated with reduced IL-4, IL-5 and RANTES production in the BAL fluid with 30 microg PET, while OVA specific IgE and eotaxin serum levels remained unchanged. PET, which has been reported to inhibit leukotriene activity, reduced allergic airway inflammation and AHR by inhibiting the production of the Th2 cytokines IL-4 and IL-5, and RANTES. Copyright (c) 2009 John Wiley & Sons, Ltd.

  2. [Airway hyperreactivity in patients with allergic and non-allergic rhinitis].

    Science.gov (United States)

    González Hernández, Jessica; Gómez Vera, Javier; Orea Solano, Modesto; Flores Sandoval, Graciela; Ríos Nava, Roberto; de la Torre, Fernando

    2003-01-01

    Epidemiologically there is an association between allergic rhinitis and asthma due to a common inflammatory process. Asthma can affect 40% of the patients with rhinitis and 80% of asthmatics present rhinitis. The relationship between the two diseases is explained by the term of "a united airway". Some patients with allergic rhinitis have nonspecific bronchial hyper-responsiveness, specially during the exacerbation stage. These patients have a unique physiologic characteristic that differs from the asthmatic and healthy subjects developing bronchoconstriction not related to clinical bronchospasm, therefore, allergic rhinitis is considered a risk factor for the asthma development. To determine if there is bronchial hyper-responsiveness in patients with allergic and not allergic rhinitis, by correlating with the eosinophilia in nasal mucosa. We studied a total of 32 patients with an age range from 18 to 38 years, of both sexes (11 men and 17 women) of the Hospital Regional Lic. Adolfo Lopez Mateos, ISSSTE. They were submitted to clinical history, laboratory studies (blood count cell, serum IgE levels, eosinophils of nasal mucosa), roentgenograms (paranasal sinus and esophagus-gastroduodenal series) and allergy skin tests with 32 allergens. It was taken biopsy of nasal mucosa for the search of eosinophils and it was carried out bronchial challenge with distilled water. Twenty-eight patients concluded the study, they were divided in two groups: a group of 15 patients with diagnosis of allergic rhinitis and another group of 13 patients with diagnosis of non allergic rhinitis. Fifty-six spirometry studies were performed and only 4 patients (26.6%) with diagnosis of allergic rhinitis presented fall of the FEV1 in the bronchial challenge in comparison with the group of non allergic rhinitis in which there were no changes in the FEV1 later to the bronchial challenge. This difference was statistically significant (-4.3 and 0.15, respectively with a p < 0.0370, CI 95

  3. Effect of anti-IL-5 and IL-5 on airway hyperreactivity and eosinophils in guinea pigs

    NARCIS (Netherlands)

    Oosterhout, A.J.M.; Ladenius, A.R.C.; Savelkoul, H.F.J.; Ark, van I.; Delsman, K.C.; Nijkamp, F.P.

    1993-01-01

    Chronic ovalbumin challenge of sensitized guinea pigs induces bronchoalveolar lavage (BAL) eosinophilia, neutrophilia, and tracheal hyperreactivity. In the present study, the influence of monoclonal antibody to murine interleukin-5 (anti-IL-5) on these phenomena is examined. In ovalbumin-sensitized

  4. Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction.

    Science.gov (United States)

    Rigas, Diamanda; Lewis, Gavin; Aron, Jennifer L; Wang, Bowen; Banie, Homayon; Sankaranarayanan, Ishwarya; Galle-Treger, Lauriane; Maazi, Hadi; Lo, Richard; Freeman, Gordon J; Sharpe, Arlene H; Soroosh, Pejman; Akbari, Omid

    2017-05-01

    Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function. ILC2s and Treg cells were evaluated by using in vitro suppression assays, cell-contact assays, and gene expression panels. Also, human ILC2s and Treg cells were adoptively transferred into NOD SCID γC-deficient mice, which were given isotype or anti-inducible T-cell costimulator ligand (ICOSL) antibodies and then challenged with IL-33 and assessed for airway hyperreactivity. We show that induced Treg cells, but not natural Treg cells, effectively suppress the production of the ILC2-driven proinflammatory cytokines IL-5 and IL-13 both in vitro and in vivo. Mechanistically, our data reveal the necessity of inducible T-cell costimulator (ICOS)-ICOS ligand cell contact for Treg cell-mediated ILC2 suppression alongside the suppressive cytokines TGF-β and IL-10. Using a translational approach, we then demonstrate that human induced Treg cells suppress syngeneic human ILC2s through ICOSL to control airway inflammation in a humanized ILC2 mouse model. These findings suggest that peripheral expansion of induced Treg cells can serve as a promising therapeutic target against ILC2-dependent asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  6. Involvement of tachykinin NK1 receptor in the development of allergen-induced airway hyperreactivity and airway inflammation in conscious, unrestrained guinea pigs

    NARCIS (Netherlands)

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

    It has been suggested that tachykinin NK1 receptor-mediated neurogenic inflammation, characterized by microvascular leakage, mucus secretion, and infiltration and activation of inflammatory cells in the airways, may be involved in allergic asthma. Therefore, in a guinea pig model of allergic asthma,

  7. Evaluation of Effect of Taxus baccata Leaves Extract on Bronchoconstriction and Bronchial Hyperreactivity in Experimental Animals

    Science.gov (United States)

    Patel, PK; Patel, KV; Gandhi, TR

    2011-01-01

    The present investigation was undertaken to evaluate the bronchodilating effect and bronchial hyperreactivity of alcoholic extract of Taxus baccata Linn. (AET) leaves in experimental animals. Bronchodilator activity of AET was studied on the histamine and acetylcholine aerosol induced bronchospasm in guinea pigs and bronchial hyperreactivity was studied on bronchoalveolar lavage fluid (BALF) in the egg albumin sensitized guinea pigs and by histopathological studies. In vitro mast cell stabilizing activity was studied using compound 48/80 as a degranulating agent. Treatment with AET (200 and 400 mg/kg, p.o., for 7 days) showed significant protection against histamine and acetylcholine aerosol induced bronchospasm in guinea pigs. Significant decrease in the total leukocyte and differential leukocyte count in the BALF of the egg albumin sensitized guinea pigs was observed by administration of AET (200 and 400 mg/kg, p.o., for 15 days). AET dose dependently protected the mast cell disruption induced by compound 48/80. These results suggest that AET not only has bronchodilating activity but also decreases bronchial hyperreactivity by decreasing the infiltration of inflammatory cells in the airway and inhibiting the release of histamine like mediators from the mast cell by stabilizing it. PMID:21607053

  8. Inhibition of p21 activated kinase (PAK reduces airway responsiveness in vivo and in vitro in murine and human airways.

    Directory of Open Access Journals (Sweden)

    Wyn C Hoover

    Full Text Available The p21-activated protein kinases (Paks have been implicated in the regulation of smooth muscle contractility, but the physiologic effects of Pak activation on airway reactivity in vivo are unknown. A mouse model with a genetic deletion of Pak1 (Pak1(-/- was used to determine the role of Pak in the response of the airways in vivo to challenge with inhaled or intravenous acetylcholine (ACh. Pulmonary resistance was measured in anesthetized mechanically ventilated Pak1(-/- and wild type mice. Pak1(-/- mice exhibited lower airway reactivity to ACh compared with wild type mice. Tracheal segments dissected from Pak1(-/- mice and studied in vitro also exhibited reduced responsiveness to ACh compared with tracheas from wild type mice. Morphometric assessment and pulmonary function analysis revealed no differences in the structure of the airways or lung parenchyma, suggesting that that the reduced airway responsiveness did not result from structural abnormalities in the lungs or airways due to Pak1 deletion. Inhalation of the small molecule synthetic Pak1 inhibitor, IPA3, also significantly reduced in vivo airway responsiveness to ACh and 5-hydroxytryptamine (5-Ht in wild type mice. IPA3 inhibited the contractility of isolated human bronchial tissues to ACh, confirming that this inhibitor is also effective in human airway smooth muscle tissue. The results demonstrate that Pak is a critical component of the contractile activation process in airway smooth muscle, and suggest that Pak inhibition could provide a novel strategy for reducing airway hyperresponsiveness.

  9. [Hyper-reactive malarial splenomegaly].

    Science.gov (United States)

    Maazoun, F; Deschamps, O; Barros-Kogel, E; Ngwem, E; Fauchet, N; Buffet, P; Froissart, A

    2015-11-01

    Hyper-reactive malarial splenomegaly is a rare and severe form of chronic malaria. This condition is a common cause of splenomegaly in endemic areas. The pathophysiology of hyper-reactive malarial splenomegaly involves an intense immune reaction (predominantly B cell-driven) to repeated/chronic infections with Plasmodium sp. The diagnosis may be difficult, due to a poorly specific clinical presentation (splenomegaly, fatigue, cytopenias), a long delay between residence in a malaria-endemic area and onset of symptoms, and a frequent absence of parasites on conventional thin and thick blood smears. A strongly contributive laboratory parameter is the presence of high levels of total immunoglobulin M. When the diagnostic of hyper-reactive malarial splenomegaly is considered, search for anti-Plasmodium antibodies and Plasmodium nucleic acids (genus and species) by PCR is useful. Diagnosis of hyper-reactive malarial splenomegaly relies on the simultaneous presence of epidemiological, clinical, biological and follow-up findings. Regression of both splenomegaly and hypersplenism following antimalarial therapy allows the differential diagnosis with splenic lymphoma, a common complication of hyper-reactive malarial splenomegaly. Although rare in Western countries, hyper-reactive malarial splenomegaly deserves increased medical awareness to reduce the incidence of incorrect diagnosis, to prevent progression to splenic lymphoma and to avoid splenectomy. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  10. Popcorn flavoring effects on reactivity of rat airways in vivo and in vitro.

    Science.gov (United States)

    Zaccone, Eric J; Thompson, Janet A; Ponnoth, Dovenia S; Cumpston, Amy M; Goldsmith, W Travis; Jackson, Mark C; Kashon, Michael L; Frazer, David G; Hubbs, Ann F; Shimko, Michael J; Fedan, Jeffrey S

    2013-01-01

    "Popcorn workers' lung" is an obstructive pulmonary disease produced by inhalation of volatile artificial butter flavorings. In rats, inhalation of diacetyl, a major component of butter flavoring, and inhalation of a diacetyl substitute, 2,3-pentanedione, produce similar damage to airway epithelium. The effects of diacetyl and 2,3-pentanedione and mixtures of diacetyl, acetic acid, and acetoin, all components of butter flavoring, on pulmonary function and airway reactivity to methacholine (MCh) were investigated. Lung resistance (RL) and dynamic compliance (Cdyn) were negligibly changed 18 h after a 6-h inhalation exposure to diacetyl or 2,3-pentanedione (100-360 ppm). Reactivity to MCh was not markedly changed after diacetyl, but was modestly decreased after 2,3-pentanedione inhalation. Inhaled diacetyl exerted essentially no effect on reactivity to mucosally applied MCh, but 2,3-pentanedione (320 and 360 ppm) increased reactivity to MCh in the isolated, perfused trachea preparation (IPT). In IPT, diacetyl and 2,3-pentanedione (≥3 mM) applied to the serosal and mucosal surfaces of intact and epithelium-denuded tracheas initiated transient contractions followed by relaxations. Inhaled acetoin (150 ppm) exerted no effect on pulmonary function and airway reactivity in vivo; acetic acid (27 ppm) produced hyperreactivity to MCh; and exposure to diacetyl + acetoin + acetic acid (250 + 150 + 27 ppm) led to a diacetyl-like reduction in reactivity. Data suggest that the effects of 2,3-pentanedione on airway reactivity are greater than those of diacetyl, and that flavorings are airway smooth muscle relaxants and constrictors, thus indicating a complex mechanism.

  11. Serum cytokine levels, cigarette smoking and airway responsiveness among pregnant women

    NARCIS (Netherlands)

    Tsunoda, M; Litonjua, AA; Kuniak, MP; Weiss, ST; Satoh, T; Guevarra, L; Tollerud, DJ

    Background. Five to twenty percent of healthy, nonasthmatic individuals exhibit airway hyperreactivity. Because cytokines are important intermediates in airway responses, we investigated the relationship between serum cytokines and airway responsiveness in a well-characterized population of pregnant

  12. Deterioration of epithelium mediated mechanisms in diabetic-antigen sensitized airways of guinea pigs.

    Science.gov (United States)

    Bano, Saidullah; Swati, Omanwar; Kambadur, Muralidhar; Mohammad, Fahim

    2016-01-01

    The onset of diabetes causes disruption of respiratory epithelial mediators. The present study investigates whether diabetes modifies the epithelium mediated bronchial responses in hyper-reactive airway smooth muscle (ASM) primarily through nitric oxide (NO), cyclooxygenase (COX), and epithelium derived hyperpolarizing factor (EpDHF) pathways. Experimental model of guinea pigs having hyper-reactive airways with or without diabetes were developed. The responses of tracheal rings to cumulative concentrations of acetylcholine (ACh) and isoproterenol (IP) in the presence and absence of epithelium and before and after incubation with NO, K+ATP and COX inhibitors, N-(ω)-Nitro-L-arginine methyl ester (L-NAME; 100 μM), glybenclamide (10 μM) and indomethacin (100 μM) were assessed. In diabetic guinea pigs with hyper-reactive airways, a decrease in ACh induced bronchoconstriction was observed after epithelium removal and after incubation with L-NAME/indomethacin, suggesting damage to NO/COX pathways. Hyper-reactivity did not alter the response of trachea to ACh but affected the response to IP which was further reduced in hyper-reactive animals with diabetes. The ASM response to IP after glybenclamide treatment did not alter in hyper-reactive guinea pigs and diabetic guinea pigs with hyper-reactive airways, suggesting damage to the EpDHF pathway. Treatment with indomethacin reduced IP response in the hyper-reactive model, and did not produce any change in diabetic model with hyper-reactive airways, indicating further disruption of the COX pathway. EpDHF pathway is damaged in hyper-reactive guinea pigs and in diabetic guinea pigs with hyper-reactive airways. Diabetes further aggravates the NO and COX mediated pathways in diabetic guinea pigs with hyper-reactive airways.

  13. The Development and Validation of an In Vitro Airway Model to Assess Realistic Airway Deposition and Drug Permeation Behavior of Orally Inhaled Products Across Synthetic Membranes.

    Science.gov (United States)

    Huynh, Bao K; Traini, Daniela; Farkas, Dale R; Longest, P Worth; Hindle, Michael; Young, Paul M

    2017-09-07

    Current in vitro approaches to assess lung deposition, dissolution, and cellular transport behavior of orally inhaled products (OIPs) have relied on compendial impactors to collect drug particles that are likely to deposit in the airway; however, the main drawback with this approach is that these impactors do not reflect the airway and may not necessarily represent drug deposition behavior in vivo. The aim of this article is to describe the development and method validation of a novel hybrid in vitro approach to assess drug deposition and permeation behavior in a more representative airway model. The medium-sized Virginia Commonwealth University (VCU) mouth-throat (MT) and tracheal-bronchial (TB) realistic upper airway models were used in this study as representative models of the upper airway. The TB model was modified to accommodate two Snapwell® inserts above the first TB airway bifurcation region to collect deposited nebulized ciprofloxacin-hydrochloride (CIP-HCL) droplets as a model drug aerosol system. Permeation characteristics of deposited nebulized CIP-HCL droplets were assessed across different synthetic membranes using the Snapwell test system. The Snapwell test system demonstrated reproducible and discriminatory drug permeation profiles for already dissolved and nebulized CIP-HCL droplets through a range of synthetic permeable membranes under different test conditions. The rate and extent of drug permeation depended on the permeable membrane material used, presence of a stirrer in the receptor compartment, and, most importantly, the drug collection method. This novel hybrid in vitro approach, which incorporates a modified version of a realistic upper airway model, coupled with the Snapwell test system holds great potential to evaluate postairway deposition characteristics, such as drug permeation and particle dissolution behavior of OIPs. Future studies will expand this approach using a cell culture-based setup instead of synthetic membranes, within a

  14. In Vitro Microfluidic Models of Mucus-Like Obstructions in Small Airways

    Science.gov (United States)

    Mulligan, Molly K.; Grotberg, James B.; Sznitman, Josué

    2012-11-01

    Liquid plugs can form in the lungs as a result of a host of different diseases, including cystic fibrosis and chronic obstructive pulmonary disease. The existence of such fluid obstructions have been found as far down in the bronchiole tree as the sixteenth generation, where bronchiole openings have diameters on the order of a hundred to a few hundred microns. Understanding the propagation of liquid plugs within the bifurcating branches of bronchiole airways is important because their presence in the lungs, and their rupture and break-up, can cause injury to the epithelial cells lining the airway walls as a result of high wall shear stresses. In particular, liquid plug rupture and break-up frequently occurs at airway bifurcations. Until present, however, experimental studies of liquid plugs have generally been restricted to Newtonian fluids that do not reflect the actual pseudoplastic properties of lung mucus. The present work attempts to uncover the propagation, rupture and break-up of mucus-like liquid plugs in the lower generations of the airway tree using microfluidic models. Our approach allows the dynamics of mucus-like plug break-up to be studied in real-time, in a one-to-one in vitro model, as a function of mucus rheology and bronchial tree geometry.

  15. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro

    OpenAIRE

    Benam, Kambez H; Villenave, Remi; Lucchesi, Carolina; Varone, Antonio; Hubeau, Cedric; Lee, Hyun-Hee; Alves, Stephen E; Salmon, Michael; Ferrante, Thomas Charles; Weaver, James C.; Bahinski, Anthony; Hamilton, Geraldine A; Ingber, Donald Elliot

    2015-01-01

    Here we describe development of a human ‘lung small airway-on-a-chip’ containing a differentiated, mucociliary, bronchiolar epithelium and an underlying microvascular endothelium that experiences fluid flow, which enables analysis of organ-level lung pathophysiology in vitro. Exposure of the epithelium to IL-13 reconstitutes the goblet cell hyperplasia, cytokine hypersecretion and decreased ciliary function of asthmatics. Small airway chips lined by epithelial cells from chronic obstructive p...

  16. The effects of exogenous lipid on THP-1 cells: an in vitro model of airway aspiration?

    Directory of Open Access Journals (Sweden)

    Yvette A. Hayman

    2017-03-01

    Full Text Available Chronic inflammatory diseases of the airways are associated with gastro-oesophageal reflux (GOR and aspiration events. The observation of lipid-laden macrophages (LLMs within the airway may indicate aspiration secondary to GOR. The proposed mechanism, that lipid droplets from undigested or partially digested food are aspirated leading to accumulation in scavenging macrophages, led us to hypothesise that an activated population of LLMs could interact with other immune cells to induce bronchial inflammation. To test this, we generated an in vitro model using differentiated THP-1 cells, which were treated with a high-fat liquid feed. Here, we show that THP-1 cells can take up lipid from the high-fat feed independent of actin polymerisation or CD36-dependent phagocytosis. These cells did not exhibit M1 or M2 polarisation. Gene array analysis confirmed over 8000 genes were upregulated by at least twofold following high fat exposure, and IL-8 was the most upregulated gene. Pathway analysis revealed upregulation of genes known to be involved in chronic obstructive pulmonary disease (COPD pathophysiology. We suggest that aspiration and macrophage phagocytosis may be important mechanisms in the aetiology of diseases such as COPD and cystic fibrosis that are characterised by high levels of IL-8 within the airways.

  17. Mucociliary clearance defects in a murine in vitro model of pneumococcal airway infection.

    Science.gov (United States)

    Fliegauf, Manfred; Sonnen, Andreas F-P; Kremer, Bernhard; Henneke, Philipp

    2013-01-01

    Mucociliary airway clearance is an innate defense mechanism that protects the lung from harmful effects of inhaled pathogens. In order to escape mechanical clearance, airway pathogens including Streptococcus pneumoniae (pneumococcus) are thought to inactivate mucociliary clearance by mechanisms such as slowing of ciliary beating and lytic damage of epithelial cells. Pore-forming toxins like pneumolysin, may be instrumental in these processes. In a murine in vitro airway infection model using tracheal epithelial cells grown in air-liquid interface cultures, we investigated the functional consequences on the ciliated respiratory epithelium when the first contact with pneumococci is established. High-speed video microscopy and live-cell imaging showed that the apical infection with both wildtype and pneumolysin-deficient pneumococci caused insufficient fluid flow along the epithelial surface and loss of efficient clearance, whereas ciliary beat frequency remained within the normal range. Three-dimensional confocal microscopy demonstrated that pneumococci caused specific morphologic aberrations of two key elements in the F-actin cytoskeleton: the junctional F-actin at the apical cortex of the lateral cell borders and the apical F-actin, localized within the planes of the apical cell sides at the ciliary bases. The lesions affected the columnar shape of the polarized respiratory epithelial cells. In addition, the planar architecture of the entire ciliated respiratory epithelium was irregularly distorted. Our observations indicate that the mechanical supports essential for both effective cilia strokes and stability of the epithelial barrier were weakened. We provide a new model, where--in pneumococcal infection--persistent ciliary beating generates turbulent fluid flow at non-planar distorted epithelial surface areas, which enables pneumococci to resist mechanical cilia-mediated clearance.

  18. Mucociliary clearance defects in a murine in vitro model of pneumococcal airway infection.

    Directory of Open Access Journals (Sweden)

    Manfred Fliegauf

    Full Text Available Mucociliary airway clearance is an innate defense mechanism that protects the lung from harmful effects of inhaled pathogens. In order to escape mechanical clearance, airway pathogens including Streptococcus pneumoniae (pneumococcus are thought to inactivate mucociliary clearance by mechanisms such as slowing of ciliary beating and lytic damage of epithelial cells. Pore-forming toxins like pneumolysin, may be instrumental in these processes. In a murine in vitro airway infection model using tracheal epithelial cells grown in air-liquid interface cultures, we investigated the functional consequences on the ciliated respiratory epithelium when the first contact with pneumococci is established. High-speed video microscopy and live-cell imaging showed that the apical infection with both wildtype and pneumolysin-deficient pneumococci caused insufficient fluid flow along the epithelial surface and loss of efficient clearance, whereas ciliary beat frequency remained within the normal range. Three-dimensional confocal microscopy demonstrated that pneumococci caused specific morphologic aberrations of two key elements in the F-actin cytoskeleton: the junctional F-actin at the apical cortex of the lateral cell borders and the apical F-actin, localized within the planes of the apical cell sides at the ciliary bases. The lesions affected the columnar shape of the polarized respiratory epithelial cells. In addition, the planar architecture of the entire ciliated respiratory epithelium was irregularly distorted. Our observations indicate that the mechanical supports essential for both effective cilia strokes and stability of the epithelial barrier were weakened. We provide a new model, where--in pneumococcal infection--persistent ciliary beating generates turbulent fluid flow at non-planar distorted epithelial surface areas, which enables pneumococci to resist mechanical cilia-mediated clearance.

  19. Transduction efficiencies of novel AAV vectors in mouse airway epithelium in vivo and human ciliated airway epithelium in vitro.

    Science.gov (United States)

    Limberis, Maria P; Vandenberghe, Luk H; Zhang, Liqun; Pickles, Raymond J; Wilson, James M

    2009-02-01

    We have characterized the ability of adeno-associated virus (AAV) serotypes 1-9 in addition to nineteen novel vectors isolated from various tissues, to transduce mouse and human ciliated airway epithelium (HAE). Vectors expressing alpha-1-antitrypsin (AAT) and beta-galactosidase were co-instilled into the mouse lung. Of all the vectors tested rh.64R1, AAV5 and AAV6 were the most efficient. The high transduction observed in mouse was reproduced in HAE cell cultures for both rh.64R1 and AAV6 but not for AAV5. Since AAV6 was the most efficient vector in mouse and HAE we also tested the transduction efficiencies of the AAV6 singleton vectors (i.e., AAV6 variants with targeted mutations) in these models. Of these, AAV6.2 transduced mouse airway epithelium and HAE with greater efficiency than all other AAV vectors tested. We demonstrated that AAV6.2 exhibits improved transduction efficiency compared to previously reported AAVs in mouse airways and in culture models of human airway epithelium and that this vector requires further development for preclinical and clinical testing.

  20. Airway hyperresponsiveness in asthma : lessons from in vitro model systems and animal models

    NARCIS (Netherlands)

    Meurs, H.; Gosens, R.; Zaagsma, J.

    Airway hyperresponsiveness (AHR) is a hallmark clinical symptom of asthma. At least two components of AHR have been identified: 1) baseline AHR, which is persistent and presumably caused by airway remodelling due to chronic recurrent airway inflammation; and 2) acute and variable AHR, which is

  1. Primary Paediatric Bronchial Airway Epithelial Cell in Vitro Responses to Environmental Exposures

    Directory of Open Access Journals (Sweden)

    Neil McInnes

    2016-03-01

    Full Text Available The bronchial airway epithelial cell (BAEC is the site for initial encounters between inhaled environmental factors and the lower respiratory system. Our hypothesis was that release of pro inflammatory interleukins (IL-6 and IL-8 from primary BAEC cultured from children will be increased after in vitro exposure to common environmental factors. Primary BAEC were obtained from children undergoing clinically indicated routine general anaesthetic procedures. Cells were exposed to three different concentrations of lipopolysaccharide (LPS or house dust mite allergen (HDM or particulates extracted from side stream cigarette smoke (SSCS. BAEC were obtained from 24 children (mean age 7.0 years and exposed to stimuli. Compared with the negative control, there was an increase in IL-6 and IL-8 release after exposure to HDM (p ≤ 0.001 for both comparisons. There was reduced IL-6 after higher compared to lower SSCS exposure (p = 0.023. There was no change in BAEC release of IL-6 or IL-8 after LPS exposure. BAEC from children are able to recognise and respond in vitro with enhanced pro inflammatory mediator secretion to some inhaled exposures.

  2. Distribution of Major Basic Protein on Human Airway following In Vitro Eosinophil Incubation

    Directory of Open Access Journals (Sweden)

    Ailing Xue

    2010-01-01

    Full Text Available Major basic protein (MBP released from activated eosinophils may influence airway hyperresponsiveness (AHR by either direct effects on airway myocytes or by an indirect effect. In this study, human bronchi, freshly isolated human eosinophils, or MBP purified from human eosinophil granules were incubated for studying eosinophil infiltration and MBP localization. Eosinophils immediately adhered to intact human airway as well as to cultured human airway myocytes and epithelium. Following incubation 18–24 h, eosinophils migrated into the airway media, including the smooth muscle layer, but had no specific recruitment to airway neurons. Eosinophils released significant amounts of MBP within the airway media, including areas comprising the smooth muscle layer. Most deposits of MBP were focally discrete and restricted by immunologic detection to a maximum volume of ∼300 μm3 about the eosinophil. Native MBP applied exogenously was immediately deposited on the surface of the airway, but required at least 1 h to become detected within the media of the airway wall. Tissue MBP infiltration and deposition increased in a time- and concentration-dependent manner. Taken together, these findings suggest that eosinophil-derived cationic proteins may alter airway hyperresponsiveness (AHR in vivo by an effect that is not limited to the bronchial epithelium.

  3. Airway barrier dysfunction induced by exposure to carbon nanotubes in vitro: which role for fiber length?

    Science.gov (United States)

    Rotoli, B M; Bussolati, O; Barilli, A; Zanello, P P; Bianchi, M G; Magrini, A; Pietroiusti, A; Bergamaschi, A; Bergamaschi, E

    2009-06-01

    Although carbon nanotubes (CNTs) are increasingly used, their biological effects are only incompletely characterized. However, experimental evidence suggests that the intratracheal instillation of CNTs causes the formation of interstitial granulomas and progressive pulmonary fibrosis in rodents. Using human epithelial Calu-3 cells as a model of airway epithelium in vitro, we have recently reported that the exposure to commercial multi-walled CNTs (MWCNTs) causes a progressive decrease of the transepithelial electrical resistance (TEER), pointing to a CNT-dependent impairment of the epithelial barrier function. To characterize better this behavior, we compared the effects of two types of MWCNTs and single-walled CNTs (SWCNTs) of different lengths on the TEER of Calu-3 monolayers. All the materials were used at a dose of 100 microg/mL corresponding to an exposure of 73 microg/cm(2) of cell monolayer. Only the longer MWCNTs and SWCNTs cause a significant decrease in TEER. To elucidate the mechanism underlying the changes in barrier function, the expression of the junction proteins occludin and ZO-1 has been also assessed. No significant decrease in the mRNA for either protein is detectable after the exposure to any type of CNTs. It is concluded that the impairment of barrier function in Calu-3 monolayers is a peculiar effect of CNTs endowed with clear cut fiber properties and is not referable to marked changes in the expression of junction proteins.

  4. The Raf-1 inhibitor GW5074 and dexamethasone suppress sidestream smoke-induced airway hyperresponsiveness in mice

    OpenAIRE

    Lei, Ying; Cao, Yong-Xiao; Xu, Cang-Bao; Zhang, Yaping

    2008-01-01

    Abstract Background Sidestream smoke is closely associated with airway inflammation and hyperreactivity. The present study was designed to investigate if the Raf-1 inhibitor GW5074 and the anti-inflammatory drug dexamethasone suppress airway hyperreactivity in a mouse model of sidestream smoke exposure. Methods Mice were repeatedly exposed to smoke from four cigarettes each day for four weeks. After the first week of the smoke exposure, the mice received either dexamethasone intraperitoneally...

  5. Effect of obesity on bronchial hyperreactivity among Latino children.

    Science.gov (United States)

    Del Rio-Navarro, Blanca E; Blandon-Vijil, Virginia; Escalante-Domínguez, Alberto J; Berber, Arturo; Castro-Rodriguez, Jose A

    2013-12-01

    The association between obesity and bronchial hyperreactivity (BHR) in children has not been fully demonstrated in cross-sectional or longitudinal studies, and no study has specifically addressed Latino children. A cross-sectional study of 450 children (10-18 years) from public schools was conducted in Mexico city. Among this group, 260 met the study criteria (no chronic respiratory illnesses, including asthma and rhinitis; no acute respiratory infections; and no tobacco-exposure or endocrine or body dysmorphic disorders), and 229 performed reproducible pulmonary function and methacholine challenge tests and were fully analyzed. According to BMI percentiles, 40 were normal weight, 116 were obese, and 73 morbidly obese. Children in the morbidly obese group had significantly higher % FVC than those in the normal-weight group, and obese children had higher % PEF those in the morbidly obese and normal-weight groups. In the BHR methacholine challenge test, baseline FEV1 values among obese children were significantly lower than in the morbidly obese group. Using adjusted percentages for FEV1 , values were significantly lower among obese compared to morbidly obese children at metacholine concentrations of 0.25, 1, and 4 mg/ml. The proportion of positive BHR (PC20  ≤ 16 mg/ml) was higher in these two groups compared to normal-weight children (28.4%, 17.8%, and 12.5%, respectively), although differences were not significant. Our findings show that obesity by itself is not a sufficient condition to alter airway responsiveness to methacholine in a group of adolescents. © 2013 Wiley Periodicals, Inc.

  6. Growth and characterization of different human rhinovirus C types in three-dimensional human airway epithelia reconstituted in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Tapparel, Caroline, E-mail: Caroline.Tapparel@hcuge.ch [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland); Sobo, Komla [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland); Constant, Samuel; Huang, Song [Epithelix sárl, 14 Chemin des Aulx, 1228 Plan les Ouates, Geneva (Switzerland); Van Belle, Sandra; Kaiser, Laurent [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland)

    2013-11-15

    New molecular diagnostic tools have recently allowed the discovery of human rhinovirus species C (HRV-C) that may be overrepresented in children with lower respiratory tract complications. Unlike HRV-A and HRV-B, HRV-C cannot be propagated in conventional immortalized cell lines and their biological properties have been difficult to study. Recent studies have described the successful amplification of HRV-C15, HRV-C11, and HRV-C41 in sinus mucosal organ cultures and in fully differentiated human airway epithelial cells. Consistent with these studies, we report that a panel of clinical HRV-C specimens including HRV-C2, HRV-C7, HRV-C12, HRV-C15, and HRV-C29 types were all capable of mediating productive infection in reconstituted 3D human primary upper airway epithelial tissues and that the virions enter and exit preferentially through the apical surface. Similar to HRV-A and HRV-B, our data support the acid sensitivity of HRV-C. We observed also that the optimum temperature requirement during HRV-C growth may be type-dependent. - Highlights: • A 3D human upper airway epithelia reconstituted in vitro supports HRV-C growth. • HRV-Cs enter and exit preferentially at the apical side of this ALI culture system. • HRV-Cs are acid sensitive. • Temperature sensitivity may be type-dependent for HRV-Cs.

  7. Models to study airway smooth muscle contraction in vivo, ex vivo and in vitro : Implications in understanding asthma

    NARCIS (Netherlands)

    Wright, David; Sharma, Pawan; Ryu, Min-Hyung; Risse, Paul-Andre; Ngo, Melanie; Maarsingh, Harm; Koziol-White, Cynthia; Jha, Aruni; Halayko, Andrew J.; West, Adrian R.

    Asthma is a chronic obstructive airway disease characterised by airway hyperresponsiveness (AHR) and airway wall remodelling. The effector of airway narrowing is the contraction of airway smooth muscle (ASM), yet the question of whether an inherent or acquired dysfunction in ASM contractile function

  8. Cleavage of the SARS coronavirus spike glycoprotein by airway proteases enhances virus entry into human bronchial epithelial cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yiu-Wing Kam

    Full Text Available BACKGROUND: Entry of enveloped viruses into host cells requires the activation of viral envelope glycoproteins through cleavage by either intracellular or extracellular proteases. In order to gain insight into the molecular basis of protease cleavage and its impact on the efficiency of viral entry, we investigated the susceptibility of a recombinant native full-length S-protein trimer (triSpike of the severe acute respiratory syndrome coronavirus (SARS-CoV to cleavage by various airway proteases. METHODOLOGY/PRINCIPAL FINDINGS: PURIFIED TRISPIKE PROTEINS WERE READILY CLEAVED IN VITRO BY THREE DIFFERENT AIRWAY PROTEASES: trypsin, plasmin and TMPRSS11a. High Performance Liquid Chromatography (HPLC and amino acid sequencing analyses identified two arginine residues (R667 and R797 as potential protease cleavage site(s. The effect of protease-dependent enhancement of SARS-CoV infection was demonstrated with ACE2 expressing human bronchial epithelial cells 16HBE. Airway proteases regulate the infectivity of SARS-CoV in a fashion dependent on previous receptor binding. The role of arginine residues was further shown with mutant constructs (R667A, R797A or R797AR667A. Mutation of R667 or R797 did not affect the expression of S-protein but resulted in a differential efficacy of pseudotyping into SARS-CoVpp. The R667A SARS-CoVpp mutant exhibited a lack of virus entry enhancement following protease treatment. CONCLUSIONS/SIGNIFICANCE: These results suggest that SARS S-protein is susceptible to airway protease cleavage and, furthermore, that protease mediated enhancement of virus entry depends on specific conformation of SARS S-protein upon ACE2 binding. These data have direct implications for the cell entry mechanism of SARS-CoV along the respiratory system and, furthermore expand the possibility of identifying potential therapeutic agents against SARS-CoV.

  9. Next generation in vitro systems for biofilm studies - a cystic fibrosis patient airway perspective

    DEFF Research Database (Denmark)

    Weiss Nielsen, Martin

    Bacterial infections have a large impact on the health of the general public, however individuals with cystic fibrosis (CF) are immensely susceptible to acquire pulmonary infections with environmental bacteria, viruses and fungal species. Ultimately pulmonary infections are the major cause......, while the ongoing immune response gradually leads to pulmonary deterioration. Physiologically different oxygen environments are present in the different compartments of the CF airways and this has a profound impact on bacterial growth and the effect of chemotherapeutics to eradicate the bacteria...... was to develop an accurate tool for growing biofilms that can mimic the cystic fibrosis airways, emulating one of the most important characteristics of the human airways, the oxygen environments. Microfluidic approaches that allow biofilm formation under controllable oxygen concentrations, and furthermore enable...

  10. FOXJ1 Prevents Cilia Growth Inhibition by Cigarette Smoke in Human Airway Epithelium In Vitro

    Science.gov (United States)

    Brekman, Angelika; Walters, Matthew S.; Tilley, Ann E.

    2014-01-01

    Airway epithelium ciliated cells play a central role in clearing the lung of inhaled pathogens and xenobiotics, and cilia length and coordinated beating are important for airway clearance. Based on in vivo studies showing that the airway epithelium of healthy smokers has shorter cilia than that of healthy nonsmokers, we investigated the mechanisms involved in cigarette smoke–mediated inhibition of ciliogenesis by assessing normal human airway basal cell differentiation in air–liquid interface (ALI) cultures in the presence of nontoxic concentrations of cigarette smoke extract (CSE). Measurements of cilia length from Day 28 ALI cultures demonstrated that CSE exposure was associated with shorter cilia (P cilia length observed in vivo. This phenotype correlated with a broad CSE-mediated suppression of genes involved in cilia-related transcriptional regulation, intraflagellar transport, cilia motility, structural integrity, and basal body development but not of control genes or epithelial barrier integrity. The CSE-mediated inhibition of cilia growth could be prevented by lentivirus-mediated overexpression of FOXJ1, the major cilia-related transcription factor, which led to partial reversal of expression of cilia-related genes suppressed by CSE. Together, the data suggest that components of cigarette smoke are responsible for a broad suppression of genes involved in cilia growth, but, by stimulating ciliogenesis with the transcription factor FOXJ1, it may be possible to maintain close to normal cilia length despite the stress of cigarette smoking. PMID:24828273

  11. Rhinovirus infection induces expression of airway remodelling factors in vitro and in vivo

    NARCIS (Netherlands)

    Kuo, Curtis; Lim, Sam; King, Nicholas J C; Bartlett, Nathan W; Walton, Ross P; Zhu, Jie; Glanville, Nicholas; Aniscenko, Julia; Johnston, Sebastian L; Burgess, Janette K; Black, Judith L; Oliver, Brian G

    BACKGROUND AND OBJECTIVE: A hallmark of asthma is airway remodelling, which includes increased deposition of extracellular matrix (ECM) protein. Viral infections may promote the development of asthma and are the most common causes of asthma exacerbations. We evaluated whether rhinovirus (RV)

  12. β-adrenoceptor responsiveness in non-allergic and allergic airways. An in-vitro approach.

    NARCIS (Netherlands)

    Amsterdam, Ronald Gijsbertus Maria van

    1991-01-01

    In this thesis, the main objective was to learn in more detail about the factors governing β-adrenoceptor function in non-allergic and allergic airways obstruction. We made use of isolated tissues restricting to some extend the myriad interactive processes involved. ... Zie: Summary

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

    Directory of Open Access Journals (Sweden)

    Brian W. P. Seymour

    2003-01-01

    Full Text Available 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.

  14. Cardiovascular Hyperreactivity and its Association with Cardiovascular Risk Factors

    Directory of Open Access Journals (Sweden)

    Milagros Lisset León Regal

    2015-12-01

    Full Text Available Background: several studies show a relationship between cardiovascular hyperreactivity and cardiovascular risk factors. However, finding new evidence to corroborate. Objective: to determine the association between cardiovascular reactivity and cardiovascular risk factors in normotensive individuals. Methods: a cross-sectional, correlational study was conducted in a universe composed of the population aged 15 to 74 years in the urban area of Cienfuegos municipality. The sample included 644 people studied in 2010. The variables analyzed were: sex, skin color, age, height, weight, body mass index, waist circumference, triglycerides, cholesterol, HDL cholesterol and fasting blood glucose. Chi-square and prevalence ratio with a 95 % confidence interval were calculated. Results: the prevalence of cardiovascular hyperreactivity was 42.3 %. A prevalence ratio of 51.3 % in men and 36.8 % in women was observed and it exceeded 65 % in individuals older than 64 years. It increased with age. Highest percentage of hyperreactivity was found in obese and overweight individuals. Triglyceride levels associated with cardiovascular hyperreactivity were also significant. Conclusions: there is an association between cardiovascular hyperreactivity and cardiovascular risk factors such as obesity, hypertriglyceridemia and hypercholesterolemia in normotensive individuals, a situation still observed in non-obese individuals.

  15. Analysis of NLRP3 in the Development of Allergic Airway Disease in Mice1

    OpenAIRE

    Allen, Irving C.; Jania, Corey M.; Wilson, Justin E.; Tekeppe, Erin M.; Hua, Xiaoyang; Brickey, Willie J.; Kwan, Mildred; Koller, Beverly H.; Tilley, Stephen L.; Ting, Jenny P.-Y.

    2012-01-01

    The contribution of NLRP3, a member of the nucleotide-binding domain leucine-rich repeat containing (NLR) family, in the development of allergic airway disease is currently controversial. Here, we used multiple allergic asthma models to examine the physiologic role of NLRP3. We found no significant differences in airway eosinophilia, histopathology, mucus production and airway hyperreactivity between wild type and Nlrp3-/- mice in either acute (alum-dependent) or chronic (alum-independent) OV...

  16. S-Nitrosoglutathione Attenuates Airway Hyperresponsiveness in Murine Bronchopulmonary Dysplasia.

    Science.gov (United States)

    Raffay, Thomas M; Dylag, Andrew M; Di Fiore, Juliann M; Smith, Laura A; Einisman, Helly J; Li, Yuejin; Lakner, Mitchell M; Khalil, Ahmad M; MacFarlane, Peter M; Martin, Richard J; Gaston, Benjamin

    2016-10-01

    Bronchopulmonary dysplasia (BPD) is characterized by lifelong obstructive lung disease and profound, refractory bronchospasm. It is observed among survivors of premature birth who have been treated with prolonged supplemental oxygen. Therapeutic options are limited. Using a neonatal mouse model of BPD, we show that hyperoxia increases activity and expression of a mediator of endogenous bronchoconstriction, S-nitrosoglutathione (GSNO) reductase. MicroRNA-342-3p, predicted in silico and shown in this study in vitro to suppress expression of GSNO reductase, was decreased in hyperoxia-exposed pups. Both pretreatment with aerosolized GSNO and inhibition of GSNO reductase attenuated airway hyperresponsiveness in vivo among juvenile and adult mice exposed to neonatal hyperoxia. Our data suggest that neonatal hyperoxia exposure causes detrimental effects on airway hyperreactivity through microRNA-342-3p-mediated upregulation of GSNO reductase expression. Furthermore, our data demonstrate that this adverse effect can be overcome by supplementing its substrate, GSNO, or by inhibiting the enzyme itself. Rates of BPD have not improved over the past two decades; nor have new therapies been developed. GSNO-based therapies are a novel treatment of the respiratory problems that patients with BPD experience. Copyright © 2016 by The Author(s).

  17. In vitro assessment of human airway toxicity from major aldehydes in automotive emissions

    Energy Technology Data Exchange (ETDEWEB)

    Grafstroem, R.C. [Karolinska Inst., Stockholm (Sweden). Inst. of Environmental Medicine

    1997-09-01

    Automotive exhausts can significantly contribute to the levels of reactive aldehydes, including formaldehyde, acetaldehyde and acrolein, in urban air. The use of alcohols as an alternative fuel for gasoline or diesel may further increase these emissions. Since it is unclear if aldehyde inhalation may induce pathological states, including cancer, in human airways, the toxic properties of the above-mentioned aldehydes were studied in cultured target cell types. Each aldehyde modified vital cellular functions in a dose-dependent manner, and invariably inhibited growth and induced abnormal terminal differentiation. Decreases of cellular thiols and increases of intracellular Ca{sup 2+} were observed, and moreover, variable types and amounts of short-lived or persistent genetic damage were induced. The concentrations required for specified levels of a particular type of injury varied up to 10000-fold among the aldehydes. Overall, distinctive patterns of cytopathological activity were observed, which differed both qualitatively and quantitatively among the aldehydes. Finally, aldehydes inhibited DNA repair processes and increased cytotoxicity and mutagenesis in synergy with other known toxicants, indicating that aldehydes may also enhance damage by other constituents in automotive exhausts. In summary, the aldehydes, notably {sup m}u{sup M}-mM formaldehyde, caused pathological effects and induced mechanisms that relate to acute toxicity and cancer development in airway epithelial cells. Since `no-effect` levels may not exist for carcinogenic agents, the overall results support a need for elimination of aldehydes in automotive exhausts. 41 refs

  18. Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

    Directory of Open Access Journals (Sweden)

    Seidel Petra

    2012-10-01

    Full Text Available Abstract Background Activated mast cells are present within airway smooth muscle (ASM bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide, long-acting β2-agonists (salmeterol, formoterol and thiazolidinediones (ciglitazone, rosiglitazone on CXCL10 production by ASM cells (ASMC from people with and without asthma were investigated in vitro. Methods Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher’s post-hoc test. Results Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix. The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Conclusions Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

  19. Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies.

    Science.gov (United States)

    Seidel, Petra; Alkhouri, Hatem; Lalor, Daniel J; Burgess, Janette K; Armour, Carol L; Hughes, J Margaret

    2012-10-04

    Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro. Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher's post-hoc test. Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix). The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1 nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM) inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

  20. Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats.

    Science.gov (United States)

    Chitano, P; Rado, V; Di Stefano, A; Papi, A; Boniotti, A; Zancuoghi, G; Boschetto, P; Romano, M; Salmona, M; Ciaccia, A; Fabbri, L M; Mapp, C E

    1996-06-01

    In a previous study on bronchoalveolar lavage fluid from rats exposed in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that there is an influx of macrophages into the airways. The present study investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue inflammation and morphology; (b) airway microvascular leakage; (c) in vitro contractile response of main bronchi. Lung tissue was studied by light microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of 20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle responsiveness was evaluated by concentration-responses curves to acetylcholine (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12-28 V) to electrical field stimulation. Histology showed an increased total inflammation at the level of respiratory bronchioles and alveoli. No influx of inflammatory cells was found in the main bronchi. A loss of cilia in the epithelium of small airways and ectasia of alveolar capillaries was also found. By contrast, no alterations to microvascular permeability or modification of bronchial smooth muscle responsiveness was found. Subchronic exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does not cause any persistent alteration to microvascular permeability or bronchial smooth muscle responsiveness in rats.

  1. Constitutive overexpression of muscarinic receptors leads to vagal hyperreactivity.

    Directory of Open Access Journals (Sweden)

    Angelo Livolsi

    Full Text Available BACKGROUND: Alterations in muscarinic receptor expression and acetylcholinesterase (AchE activity have been observed in tissues from Sudden Infant Death Syndrome (SIDS. Vagal overactivity has been proposed as a possible cause of SIDS as well as of vasovagal syncopes. The aim of the present study was to seek whether muscarinic receptor overexpression may be the underlying mechanism of vagal hyperreactivity. Rabbits with marked vagal pauses following injection of phenylephrine were selected and crossed to obtain a vagal hyperreactive strain. The density of cardiac muscarinic receptors and acetylcholinesterase (AchE gene expression were assessed. Blood markers of the observed cardiac abnormalities were also sought. METHODOLOGY/PRINCIPAL FINDINGS: Cardiac muscarinic M(2 and M(3 receptors were overexpressed in hyperreactive rabbits compared to control animals (2.3-fold and 2.5-fold, respectively and the severity of the phenylephrine-induced bradycardia was correlated with their densities. A similar overexpression of M(2 receptors was observed in peripheral mononuclear white blood cells, suggesting that cardiac M(2 receptor expression can be inferred with high confidence from measurements in blood cells. Sequencing of the coding fragment of the M(2 receptor gene revealed a single nucleotide mutation in 83% of hyperreactive animals, possibly contributing for the transcript overexpression. Significant increases in AchE expression and activity were also assessed (AchE mRNA amplification ratio of 3.6 versus normal rabbits. This phenomenon might represent a compensatory consequence of muscarinic receptors overexpression. Alterations in M(2 receptor and AchE expression occurred between the 5th and the 7th week of age, a critical period also characterized by a higher mortality rate of hyperreactive rabbits (52% in H rabbits versus 13% in normal rabbits and preceeded the appearance of functional disorders. CONCLUSIONS/SIGNIFICANCE: The results suggest that

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

    NARCIS (Netherlands)

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

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

  3. Clinical Marker of Platelet Hyperreactivity in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Jin Hwa Kim

    2013-12-01

    Full Text Available Atherothrombotic complications are important causes of morbidity and mortality in diabetic patients. Diabetes has been considered to be a prothrombotic status. Several factors contribute to the prothrombotic condition, such as increasing coagulation, impaired fibrinolysis, endothelial dysfunction, and platelet hyperreactivity. Among the factors that contribute to the prothrombotic status in diabetes, altered platelet function plays a crucial role. Although understanding platelet function abnormalities in diabetes still remains as a challenge, more attention should be focused on platelet function for effective management and the prediction of atherothrombotic events in diabetic patients. This review will provide an overview on the current status of knowledge of platelet function abnormalities and clinical marker of platelet hyperreactivity in patients with diabetes.

  4. Winter ambient training conditions are associated with increased bronchial hyperreactivity and with shifts in serum innate immunity proteins in young competitive speed skaters.

    Science.gov (United States)

    Kurowski, Marcin; Jurczyk, Janusz; Moskwa, Sylwia; Jarzębska, Marzanna; Krysztofiak, Hubert; Kowalski, Marek L

    2018-01-01

    Regular training modulates airway inflammation and modifies susceptibility to respiratory infections. The impact of exercise and ambient conditions on airway hyperreactivity and innate immunity has not been well studied. We aimed to assess exercise-related symptoms, lung function, airway hyperresponsiveness and innate immunity proteins in relation to meteorological conditions and exercise load in competitive athletes. Thirty-six speed skaters were assessed during winter (WTP) and summer (STP) periods. The control group comprised 22 non-exercising subjects. An allergy questionnaire for athletes (AQUA) and IPAQ (International Physical Activity Questionnaire) were used to assess symptoms and exercise. Meteorological parameters were acquired from World Meteorological Organization resources. Serum innate immunity proteins were measured by ELISA. Exercise-associated respiratory symptoms were reported by 79.4% of skaters. Despite similar exercise load and lung parameters during both periods, positive methacholine challenge was more frequent during winter ( p = 0.04). Heat shock protein HSPA1 and IL-1RA were significantly decreased during STP compared to WTP and controls. During WTP, IL-1RA was elevated in skaters reporting exercise-induced symptoms ( p = 0.007). sCD14 was elevated in athletes versus controls in both periods ( p training conditions, but not training load, influence bronchial hyperreactivity and the innate immune response in competitive athletes assessed during winter. The protective effect of regular exercise against respiratory infections is associated with a shift in serum innate immunity proteins.

  5. Airway responses to aerosolized methacholine and citric acid in ponies with recurrent airway obstruction (heaves).

    Science.gov (United States)

    Armstrong, P J; Derksen, F J; Slocombe, R F; Robinson, N E

    1986-03-01

    We measured lung function and airway reactivity in response to methacholine and citric acid administered by aerosol in 2 groups of ponies (principal and control). Principal ponies had a history of heaves, a disease characterized by recurrent airway obstruction. Control ponies had no history of respiratory disease. Both principal and control ponies were paired (principal and control), and measurements were made when principal ponies were in clinical remission (Period A), following barn exposure when principal ponies had acute airway obstruction (Period B), and 1 and 2 wk after they were returned to pasture (Periods C and D). Differences between groups were primarily found at Period B. Barn housing (Period B) decreased dynamic compliance (Cdyn) and increased pulmonary resistance (RL) of principal but not of control ponies. When compared with control ponies at Period B, principal ponies demonstrated airway hyperreactivity. The dose of methacholine required to reduce Cdyn to 65% of baseline (ED65Cdyn) was lower, the change in RL induced by an aerosol of 0.1 mg/ml methacholine (delta RL 0.1) was higher, and the percent change in Cdyn in response to an aerosol of 0.1 mg/ml methacholine (delta %Cdyn 0.1) was larger in principal than in control ponies. A 10-min inhalation of 10% citric acid aerosol did not cause changes in Cdyn in either group of ponies. Control ponies did not increase RL in response to citric acid, whereas at Period B, RL of principal ponies increased following citric acid. We conclude that ponies in clinical remission from heaves are not hyperreactive to aerosols of methacholine or citric acid. Hyperreactivity only exists during acute exacerbations of airway obstruction.

  6. Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Zhou, Yue

    2016-09-01

    Rodents are routinely used in inhalation toxicology tests as human surrogates. However, in vitro dosimetry tests in rodent casts are still scarce due to small rodent airways and in vitro tests to quantify sub-regional dosimetry are still impractical. We hypothesized that for inertial particles whose deposition is dominated by airflow convection (Reynolds number) and particle inertia (Stokes number), the deposition should be similar among airway replicas of different scales if their Reynolds and Stokes numbers are kept the same. In this study, we aimed to (1) numerically test the hypothesis in three airway geometries: a USP induction port, a human nose model, and a Sprague-Dawley rat nose model, and (2) find the range of applicability of this hypothesis. Five variants of the USP and human nose models and three variants of the rat nose model were tested. Inhalation rates and particle sizes were scaled to match the Reynolds number and Stokes numbers. A low-Reynolds-number k–ω model was used to resolve the airflow and a Lagrangian tracking algorithm was used to simulate the particle transport and deposition. Statistical analysis of predicted doses was conducted using ANOVA. For normal inhalation rates and particle dia- meters ranging from 0.5 to 24 mm, the deposition differences between the life-size and scaled models are insignificant for all airway geometries considered (i.e., human nose, USP, and rat nose). Furthermore, the deposition patterns and exit particle profiles also look similar among scaled models. However, deposition rates and patterns start to deviate if inhalation rates are too low, or particle sizes are too large. For the rat nose, the threshold velocity was found to be 0.71 m/s and the threshold Froude number to be 50. Results of this study provide a theoretical foundation for sub-regional in vitro dosimetry tests in small animals and for interpretation of data from inter-species or intra-species with varying body sizes.

  7. Salmeterol attenuates chemotactic responses in rhinovirus-induced exacerbation of allergic airways disease by modulating protein phosphatase 2A.

    Science.gov (United States)

    Hatchwell, Luke; Girkin, Jason; Dun, Matthew D; Morten, Matthew; Verrills, Nicole; Toop, Hamish D; Morris, Jonathan C; Johnston, Sebastian L; Foster, Paul S; Collison, Adam; Mattes, Joerg

    2014-06-01

    β-Agonists are used for relief and control of asthma symptoms by reversing bronchoconstriction. They might also have anti-inflammatory properties, but the underpinning mechanisms remain poorly understood. Recently, a direct interaction between formoterol and protein phosphatase 2A (PP2A) has been described in vitro. We sought to elucidate the molecular mechanisms by which β-agonists exert anti-inflammatory effects in allergen-driven and rhinovirus 1B-exacerbated allergic airways disease (AAD). Mice were sensitized and then challenged with house dust mite to induce AAD while receiving treatment with salmeterol, formoterol, or salbutamol. Mice were also infected with rhinovirus 1B to exacerbate lung inflammation and therapeutically administered salmeterol, dexamethasone, or the PP2A-activating drug (S)-2-amino-4-(4-[heptyloxy]phenyl)-2-methylbutan-1-ol (AAL[S]). Systemic or intranasal administration of salmeterol protected against the development of allergen- and rhinovirus-induced airway hyperreactivity and decreased eosinophil recruitment to the lungs as effectively as dexamethasone. Formoterol and salbutamol also showed anti-inflammatory properties. Salmeterol, but not dexamethasone, increased PP2A activity, which reduced CCL11, CCL20, and CXCL2 expression and reduced levels of phosphorylated extracellular signal-regulated kinase 1 and active nuclear factor κB subunits in the lungs. The anti-inflammatory effect of salmeterol was blocked by targeting the catalytic subunit of PP2A with small RNA interference. Conversely, increasing PP2A activity with AAL(S) abolished rhinovirus-induced airway hyperreactivity, eosinophil influx, and CCL11, CCL20, and CXCL2 expression. Salmeterol also directly activated immunoprecipitated PP2A in vitro isolated from human airway epithelial cells. Salmeterol exerts anti-inflammatory effects by increasing PP2A activity in AAD and rhinovirus-induced lung inflammation, which might potentially account for some of its clinical benefits

  8. Fragile X mice develop sensory hyperreactivity to auditory stimuli.

    Science.gov (United States)

    Chen, L; Toth, M

    2001-01-01

    Fragile X syndrome is the most prevalent cause of mental retardation. It is usually caused by the transcriptional inactivation of the FMR-1 gene. Although the cognitive defect is the most recognized symptom of fragile X syndrome, patients also show behavioral problems such as hyperarousal, hyperactivity, autism, aggression, anxiety and increased sensitivity to sensory stimuli. Here we investigated whether fragile X mice (fmr-1 gene knockout mice) exhibit abnormal sensitivity to sensory stimuli. First, hyperreactivity of fragile X mice to auditory stimulus was indicated in the prepulse inhibition paradigm. A moderately intense prepulse tone, that suppresses startle response to a strong auditory stimulus, elicited a significantly stronger effect in fragile X than in control mice. Second, sensory hyperreactivity of fragile X mice was demonstrated by a high seizure susceptibility to auditory stimulation. Selective induction of c-Fos, an early-immediate gene product, indicated that seizures involve auditory brainstem and thalamic nuclei. Audiogenic seizures were not due to a general increase in brain excitability because three different chemical convulsants (kainic acid, bicuculline and pentylenetetrazole) elicited similar effects in fragile X and wild-type mice. These data are consistent with the increased responsiveness of fragile X patients to auditory stimuli. The auditory hypersensitivity suggests an abnormal processing in the auditory system of fragile X mice, which could provide a useful model to study the molecular and cellular changes underlying fragile X syndrome.

  9. Pivotal Role of MUC1 Glycosylation by Cigarette Smoke in Modulating Disruption of Airway Adherens Junctions In Vitro

    OpenAIRE

    Zhang, Lili; Gallup, Marianne; Zlock, Lorna; Chen, Yu Ting Feeling; Finkbeiner, Walter E.; McNamara, Nancy A.

    2014-01-01

    Cigarette smoke increases the risk of lung cancer by 20-fold and accounts for 87% of lung cancer deaths. In the normal airway, heavily O-glycosylated mucin-1 (MUC1) and adherens junctions (AJs) establish a structural barrier that protects the airway from infectious, inflammatory and noxious stimuli. Smoke disrupts cell-cell adhesion via its damaging effects on the AJ protein, epithelial cadherin (E-cad). Loss of E-cad is a major hallmark of epithelial-mesenchymal transition (EMT) and has been...

  10. In vitro surfactant and perfluorocarbon aerosol deposition in a neonatal physical model of the upper conducting airways.

    Directory of Open Access Journals (Sweden)

    Estibalitz Goikoetxea

    Full Text Available OBJECTIVE: Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways. METHODS: The main characteristics of the surfactant and PFC aerosols produced by a nebulization system, including the distal air pressure and air flow rate, liquid flow rate and mass median aerodynamic diameter (MMAD, were measured at different driving pressures (4-7 bar. Then, a three-dimensional model of the upper conducting airways of a neonate was manufactured by rapid prototyping and a deposition study was conducted. RESULTS: The nebulization system produced relatively large amounts of aerosol ranging between 0.3±0.0 ml/min for surfactant at a driving pressure of 4 bar, and 2.0±0.1 ml/min for distilled water (H2Od at 6 bar, with MMADs between 2.61±0.1 µm for PFD at 7 bar and 10.18±0.4 µm for FC-75 at 6 bar. The deposition study showed that for surfactant and H2Od aerosols, the highest percentage of the aerosolized mass (∼65% was collected beyond the third generation of branching in the airway model. The use of this delivery system in combination with continuous positive airway pressure set at 5 cmH2O only increased total airway pressure by 1.59 cmH2O at the highest driving pressure (7 bar. CONCLUSION: This aerosol generating system has the potential to deliver relatively large amounts of surfactant and PFC beyond the third generation of branching in a neonatal airway model with minimal alteration of pre-set respiratory support.

  11. In Vitro Surfactant and Perfluorocarbon Aerosol Deposition in a Neonatal Physical Model of the Upper Conducting Airways

    Science.gov (United States)

    Goikoetxea, Estibalitz; Murgia, Xabier; Serna-Grande, Pablo; Valls-i-Soler, Adolf; Rey-Santano, Carmen; Rivas, Alejandro; Antón, Raúl; Basterretxea, Francisco J.; Miñambres, Lorena; Méndez, Estíbaliz; Lopez-Arraiza, Alberto; Larrabe-Barrena, Juan Luis; Gomez-Solaetxe, Miguel Angel

    2014-01-01

    Objective Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways. Methods The main characteristics of the surfactant and PFC aerosols produced by a nebulization system, including the distal air pressure and air flow rate, liquid flow rate and mass median aerodynamic diameter (MMAD), were measured at different driving pressures (4–7 bar). Then, a three-dimensional model of the upper conducting airways of a neonate was manufactured by rapid prototyping and a deposition study was conducted. Results The nebulization system produced relatively large amounts of aerosol ranging between 0.3±0.0 ml/min for surfactant at a driving pressure of 4 bar, and 2.0±0.1 ml/min for distilled water (H2Od) at 6 bar, with MMADs between 2.61±0.1 µm for PFD at 7 bar and 10.18±0.4 µm for FC-75 at 6 bar. The deposition study showed that for surfactant and H2Od aerosols, the highest percentage of the aerosolized mass (∼65%) was collected beyond the third generation of branching in the airway model. The use of this delivery system in combination with continuous positive airway pressure set at 5 cmH2O only increased total airway pressure by 1.59 cmH2O at the highest driving pressure (7 bar). Conclusion This aerosol generating system has the potential to deliver relatively large amounts of surfactant and PFC beyond the third generation of branching in a neonatal airway model with minimal alteration of pre-set respiratory support. PMID:25211475

  12. Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol.

    Science.gov (United States)

    Neilson, Louise; Mankus, Courtney; Thorne, David; Jackson, George; DeBay, Jason; Meredith, Clive

    2015-10-01

    Development of physiologically relevant test methods to analyse potential irritant effects to the respiratory tract caused by e-cigarette aerosols is required. This paper reports the method development and optimisation of an acute in vitro MTT cytotoxicity assay using human 3D reconstructed airway tissues and an aerosol exposure system. The EpiAirway™ tissue is a highly differentiated in vitro human airway culture derived from primary human tracheal/bronchial epithelial cells grown at the air-liquid interface, which can be exposed to aerosols generated by the VITROCELL® smoking robot. Method development was supported by understanding the compatibility of these tissues within the VITROCELL® system, in terms of airflow (L/min), vacuum rate (mL/min) and exposure time. Dosimetry tools (QCM) were used to measure deposited mass, to confirm the provision of e-cigarette aerosol to the tissues. EpiAirway™ tissues were exposed to cigarette smoke and aerosol generated from two commercial e-cigarettes for up to 6 h. Cigarette smoke reduced cell viability in a time dependent manner to 12% at 6 h. E-cigarette aerosol showed no such decrease in cell viability and displayed similar results to that of the untreated air controls. Applicability of the EpiAirway™ model and exposure system was demonstrated, showing little cytotoxicity from e-cigarette aerosol and different aerosol formulations when compared directly with reference cigarette smoke, over the same exposure time. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells

    Science.gov (United States)

    Katawa, Gnatoulma; Layland, Laura E.; Debrah, Alex Y.; von Horn, Charlotte; Batsa, Linda; Kwarteng, Alexander; Arriens, Sandra; W. Taylor, David; Specht, Sabine; Hoerauf, Achim; Adjobimey, Tomabu

    2015-01-01

    Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytometry, filarial-specific cytokine responses and PCR arrays, we compared the immune cell profiles, including Th subsets, in individuals presenting the two polar forms of infection and endemic normals (EN). In addition to elevated frequencies of memory CD4+ T cells, individuals with HO showed accentuated Th17 and Th2 profiles but decreased CD4+CD25hiFoxp3+ regulatory T cells. These profiles included increased IL-17A+, IL-4+, RORC2+ and GATA3+CD4+ T cell populations. Flow cytometry data was further confirmed using a PCR array since Th17-related genes (IL-17 family members, IL-6, IL-1β and IL-22) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. In addition, stronger Onchocerca volvulus-specific Th2 responses, especially IL-13, were observed in vitro in hyperreactive individuals when compared to GEO or EN groups. This study provides initial evidence that elevated frequencies of Th17 and Th2 cells form part of the immune network instigating the development of severe onchocerciasis. PMID:25569210

  14. Morphological and functional properties of the conducting human airways investigated by in vivo CT and in vitro MRI.

    Science.gov (United States)

    Van de Moortele, Tristan; Wendt, Christine H; Coletti, Filippo

    2017-11-02

    The accurate representation of the human airway anatomy is crucial for understanding and modeling the structure-function relationship in both healthy and diseased lungs. The present knowledge in this area is based on morphometric studies of excised lung casts, partially complemented by in vivo studies in which computed tomography (CT) was used on a small number of subjects. In the present study, we analyze CT scans of a cohort of healthy subjects and obtain comprehensive morphometric information down to the seventh generation of bronchial branching, including airway diameter, length, branching angle, and rotation angle. While some of the geometrical parameters (such as the child-to-parent branch diameter ratio) are found to be in line with accepted values, for others (such as the branch length-to-diameter ratio) our findings challenge the common assumptions. We also evaluate several metrics of self-similarity, including the fractal dimension of the airway tree. Additionally, we use phase-contrast magnetic resonance imaging (MRI) to obtain the volumetric flow field in the 3D printed airway model of one of the subjects during steady inhalation. This is used to relate structural and functional parameters and, in particular, to close the power-law relationship between branch flow rate and diameter. The diameter exponent is found to be significantly lower than in the usually assumed Poiseuille regime, which we attribute to the strong secondary (i.e. transverse) velocity component. The strength of the secondary velocity with respect to the axial component exceeds the levels found in idealized airway models, and persists within the first seven generations. Copyright © 2017, Journal of Applied Physiology.

  15. Role of oxidative stress on platelet hyperreactivity during aging.

    Science.gov (United States)

    Fuentes, Eduardo; Palomo, Iván

    2016-03-01

    Thrombotic events are common causes of morbidity and mortality in the elderly. Age-accelerated vascular injury is commonly considered to result from increased oxidative stress. There is abundant evidence that oxidative stress regulate several components of thrombotic processes, including platelet activation. Thus oxidative stress can trigger platelet hyperreactivity by decreasing nitric oxide bioavailability. Therefore oxidative stress measurement may help in the early identification of asymptomatic subjects at risk of thrombosis. In addition, oxidative stress inhibitors and platelet-derived nitric oxide may represent a novel anti-aggregation/-activation approach. In this article the relative contribution of oxidative stress and platelet activation in aging is explored. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Prevention of bronchial hyperreactivity in a rat model of precapillary pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Beghetti Maurice

    2011-04-01

    Full Text Available Abstract Background The development of bronchial hyperreactivity (BHR subsequent to precapillary pulmonary hypertension (PHT was prevented by acting on the major signalling pathways (endothelin, nitric oxide, vasoactive intestine peptide (VIP and prostacyclin involved in the control of the pulmonary vascular and bronchial tones. Methods Five groups of rats underwent surgery to prepare an aorta-caval shunt (ACS to induce sustained precapillary PHT for 4 weeks. During this period, no treatment was applied in one group (ACS controls, while the other groups were pretreated with VIP, iloprost, tezosentan via an intraperitoneally implemented osmotic pump, or by orally administered sildenafil. An additional group underwent sham surgery. Four weeks later, the lung responsiveness to increasing doses of an intravenous infusion of methacholine (2, 4, 8 12 and 24 μg/kg/min was determined by using the forced oscillation technique to assess the airway resistance (Raw. Results BHR developed in the untreated rats, as reflected by a significant decrease in ED50, the equivalent dose of methacholine required to cause a 50% increase in Raw. All drugs tested prevented the development of BHR, iloprost being the most effective in reducing both the systolic pulmonary arterial pressure (Ppa; 28%, p = 0.035 and BHR (ED50 = 9.9 ± 1.7 vs. 43 ± 11 μg/kg in ACS control and iloprost-treated rats, respectively, p = 0.008. Significant correlations were found between the levels of Ppa and ED50 (R = -0.59, p = 0.016, indicating that mechanical interdependence is primarily responsible for the development of BHR. Conclusions The efficiency of such treatment demonstrates that re-establishment of the balance of constrictor/dilator mediators via various signalling pathways involved in PHT is of potential benefit for the avoidance of the development of BHR.

  17. Ozone increases airway hyperreactivity and mucus hyperproduction in mice previously exposed to allergen

    DEFF Research Database (Denmark)

    Larsen, Søren T; Matsubara, Shigeki; McConville, Glen

    2010-01-01

    Acute exacerbations of asthma represent a common clinical problem with major economic impact. Air pollutants including ozone have been shown to contribute to asthma exacerbation, but the mechanisms underlying ozone-induced asthma exacerbation are only partially understood. The present study aimed...... with goblet-cell metaplasia. Even the lowest concentration of ozone tested, 100 ppb, which may be exceeded in urban environments and in the workplace, resulted in a significant increase in AHR, most prominent 24 h after exposure in the OVA-exposed mice....

  18. Assays for in vitro monitoring of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cell migration.

    Science.gov (United States)

    Goncharova, Elena A; Goncharov, Dmitry A; Krymskaya, Vera P

    2006-01-01

    Migration of human pulmonary vascular smooth muscle (VSM) cells contributes to vascular remodeling in pulmonary arterial hypertension and atherosclerosis. Evidence also indicates that, in part, migration of airway smooth muscle (ASM) cells may contribute to airway remodeling associated with asthma. Here we describe migration of VSM and ASM cells in vitro using Transwell or Boyden chamber assays. Because dissecting signaling mechanisms regulating cell migration requires molecular approaches, our protocol also describes how to assess migration of transfected VSM and ASM cells. Transwell or Boyden chamber assays can be completed in approximately 8 h and include plating of serum-deprived VSM or ASM cell suspension on membrane precoated with collagen, migration of cells toward chemotactic gradient and visual (Transwell) or digital (Boyden chamber) analysis of membrane. Although the Transwell assay is easy, the Boyden chamber assay requires hands-on experience; however, both assays are reliable cell-based approaches providing valuable information on how chemotactic and inflammatory factors modulate VSM and ASM migration.

  19. Use of continuous positive airway pressure reduces airway reactivity in adults with asthma.

    Science.gov (United States)

    Busk, Michael; Busk, Nancy; Puntenney, Paula; Hutchins, Janet; Yu, Zhangsheng; Gunst, Susan J; Tepper, Robert S

    2013-02-01

    Asthma is characterised by airway hyperreactivity, which is primarily treated with β-adrenergic bronchodilators and anti-inflammatory agents. However, mechanical strain during breathing is an important modulator of airway responsiveness and we have previously demonstrated in animal models that continuous positive airway pressure (CPAP) resulted in lower in vivo airway reactivity. We now evaluated whether using nocturnal CPAP decreased airway reactivity in clinically-stable adults with asthma. Adults with stable asthma and normal spirometry used nocturnal CPAP (8-10 cmH(2)O) or sham treatment (0-2 cmH(2)O) for 7 days. Spirometry and bronchial challenges were obtained before and after treatment. The primary outcome was the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC(20)). The CPAP group (n=16) had a significant decrease in airway reactivity (change in (Δ)logPC(20) 0.406, p<0.0017) while the sham group (n=9) had no significant change in airway reactivity (ΔlogPC(20) 0.003, p=0.9850). There was a significant difference in the change in airway reactivity for the CPAP versus the sham group (ΔlogPC(20) 0.41, p<0.043). Our findings indicate that chronic mechanical strain of the lungs produced using nocturnal CPAP for 7 days reduced airway reactivity in clinically stable asthmatics. Future studies of longer duration are required to determine whether CPAP can also decrease asthma symptoms and/or medication usage.

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

    Science.gov (United States)

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

    2017-02-01

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

  1. Human autoantibody to defensin: disease association with hyperreactive onchocerciasis (sowda).

    Science.gov (United States)

    Gallin, M Y; Jacobi, A B; Büttner, D W; Schönberger, O; Marti, T; Erttmann, K D

    1995-07-01

    Chronic hyperreactive onchodermatitis (sowda) is a severe form of onchocerciasis observed in a subset of individuals infected with the filarial nematode Onchocerca volvulus. SDS-PAGE and immunoblot analyses of O. volvulus adult worm extracts were used to characterize the antigens of the marked antibody response of sowda patients. One 2.5-kD antigen was recognized by sera from all 35(100%) sowda patients that were studied. In comparison, only 7 of 44 (16%) patients with generalized onchocerciasis and 11 of 21 (52%) of exposed individuals with no microfilariae in skin snips and no signs of disease showed reactivity to this antigen. Microfilaricidal treatment of sowda patients with improvement of the clinical status was associated with a decrease or disappearance of antibodies to the 2.5-kD antigen. Amino acid sequencing of the antigen indicated identity to human defensins 1-3 of neutrophils. Defensin was demonstrated by immunohistochemical staining in onchocercal nodules on the surface of adult filariae and in the surrounding tissue. A similar staining pattern was observed for other proteins present in neutrophils such as myeloperoxidase, elastase, and the L-1 protein complex (MRP 8/MRP 14), indicating that neutrophils, macrophages, and their proteins predominate in the environment adjacent to the worms. These results demonstrate an association between the presence of autoantibodies to defensins and an infectious disease of known etiology. The association with a particular form of onchocerciasis, sowda, suggests a link between formation of autoantibodies to defensin and enhanced immune reactivity towards the parasite.

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

    Directory of Open Access Journals (Sweden)

    Silvia Schnyder-Candrian

    2012-01-01

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

  3. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy ... to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear ...

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

    Directory of Open Access Journals (Sweden)

    Ana Agua-Doce

    Full Text Available 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.

  5. Atopy, cytokine production, and airway reactivity as predictors of pre-school asthma and airway responsiveness.

    Science.gov (United States)

    Sarria, Edgar E; Mattiello, Rita; Yao, Weiguo; Chakr, Valentina; Tiller, Christina J; Kisling, Jeffrey; Tabbey, Rebeka; Yu, Zhangsheng; Kaplan, Mark H; Tepper, Robert S

    2014-02-01

    Childhood asthma is often characterized by recurrent wheezing, airway hyper-reactivity, atopy, and altered immune characteristics; however, our understanding of the development of these relationships from early in life remains unclear. The aim of our study was to evaluate whether atopy, cytokine production by peripheral blood mononuclear cells (PBMCs), and airway responsiveness, assessed in infants and toddlers, are associated with asthma and airway responsiveness at 4-years of age. Infants with eczema (N = 116), enrolled prior to wheezing, were assessed at entry (mean age of 10.7 months), at 1-year follow-up (N = 112), and at 4-years of age (N = 94). Total serum IgE, specific IgE to allergens, and cytokines produced by stimulated PBMCs, were assessed at entry and 1-year follow-up. Spirometry was obtained at all 3-visits, while airway reactivity to methacholine was assessed at entry and 1-year follow-up, and bronchodilator (BD) responsiveness, as well as current asthma was assessed at 4-years of age. We found that pre-school children with asthma had lower spirometry and a greater BD-response. Serum IgE, particularly to egg and/or milk, and altered cytokine production by PBMCs at entry to the study were associated with asthma, lower spirometry, and greater airway responsiveness at 4-years of age. In addition, we found that airway responsiveness, as well as spirometry, tracked from infancy to 4-years of age. While spirometry and airway responsiveness track longitudinally from early in life, atopy and cytokine production by PBMCs are associated not only with an increased risk of pre-school asthma, but also lower spirometry and increased airway responsiveness. © 2013 Wiley Periodicals, Inc.

  6. Effect of nintedanib on airway inflammation and remodeling in a murine chronic asthma model.

    Science.gov (United States)

    Lee, Hwa Young; Hur, Jung; Kim, In Kyoung; Kang, Ji Young; Yoon, Hyoung Kyu; Lee, Sook Young; Kwon, Soon Suk; Kim, Young Kyoon; Rhee, Chin Kook

    Nintedanib is a multi-tyrosine kinase receptor inhibitor recently approved for treatment of idiopathic pulmonary fibrosis. Although angiogenesis is a key process involved in airway structural changes in patients with bronchial asthma, the effect of nintedanib targeting the angiokinase pathway on airway inflammation and remodeling has not been evaluated. We used a 3-month ovalbumin (OVA) challenge mouse model of airway remodeling. Nintedanib was orally administrated during the challenge period, and the effects were examined based on the percentage of airway inflammatory cells, airway hyper-reactivity (AHR), peribronchial goblet cell hyperplasia, total lung collagen and smooth muscle area. The expression of growth factor receptors was analyzed in mice lung tissues. The OVA challenged group showed a significant increase in airway eosinophilic inflammation, elevated Th2 cytokines, AHR, and airway remodeling compared to those in the control group. The airway remodeling process, as evaluated by goblet cell hyperplasia, total lung collagen level, and airway smooth muscle area, was suppressed by nintedanib compared to that by OVA. Nintedanib effectively suppressed the phosphorylation of vascular endothelial growth factor/ platelet derived growth factor subunit2/fibroblast growth factor3 receptors in the mice lung. Nintedanib effectively ameliorated airway inflammation and remodeling in an OVA-induced chronic asthma model. These results suggest that nintedanib could be a new treatment agent targeting airway remodeling in patients with severe asthma.

  7. Avian Influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways

    National Research Council Canada - National Science Library

    Scull, Margaret A; Gillim-Ross, Laura; Santos, Celia; Roberts, Kim L; Bordonali, Elena; Subbarao, Kanta; Barclay, Wendy S; Pickles, Raymond J

    2009-01-01

    .... Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37 degrees C...

  8. 3D Reconstruction of the Human Airway Mucosa In Vitro as an Experimental Model to Study NTHi Infections

    Science.gov (United States)

    Marrazzo, Pasquale; Maccari, Silvia; Taddei, Annarita; Bevan, Luke; Telford, John; Soriani, Marco; Pezzicoli, Alfredo

    2016-01-01

    We have established an in vitro 3D system which recapitulates the human tracheo-bronchial mucosa comprehensive of the pseudostratified epithelium and the underlying stromal tissue. In particular, we reported that the mature model, entirely constituted of primary cells of human origin, develops key markers proper of the native tissue such as the mucociliary differentiation of the epithelial sheet and the formation of the basement membrane. The infection of the pseudo-tissue with a strain of NonTypeable Haemophilus influenzae results in bacteria association and crossing of the mucus layer leading to an apparent targeting of the stromal space where they release large amounts of vesicles and form macro-structures. In summary, we propose our in vitro model as a reliable and potentially customizable system to study mid/long term host-pathogen processes. PMID:27101006

  9. 3D Reconstruction of the Human Airway Mucosa In Vitro as an Experimental Model to Study NTHi Infections.

    Directory of Open Access Journals (Sweden)

    Pasquale Marrazzo

    Full Text Available We have established an in vitro 3D system which recapitulates the human tracheo-bronchial mucosa comprehensive of the pseudostratified epithelium and the underlying stromal tissue. In particular, we reported that the mature model, entirely constituted of primary cells of human origin, develops key markers proper of the native tissue such as the mucociliary differentiation of the epithelial sheet and the formation of the basement membrane. The infection of the pseudo-tissue with a strain of NonTypeable Haemophilus influenzae results in bacteria association and crossing of the mucus layer leading to an apparent targeting of the stromal space where they release large amounts of vesicles and form macro-structures. In summary, we propose our in vitro model as a reliable and potentially customizable system to study mid/long term host-pathogen processes.

  10. Effect of Dexamethasone and Fluticasone on Airway Hyperresponsiveness in Horses With Inflammatory Airway Disease.

    Science.gov (United States)

    Léguillette, R; Tohver, T; Bond, S L; Nicol, J A; McDonald, K J

    2017-07-01

    Airway hyperresponsiveness (AWHR), expressed as hypersensitivity (PC 75 R L ) or hyperreactivity (slope of the histamine dose-response curve), is a feature of inflammatory airway disease (IAD) or mild equine asthma in horses. Glucocorticoids are used empirically to treat IAD. To determine whether dexamethasone (DEX) (0.05 mg/kg IM q24h) and inhaled fluticasone (FLUT) (3,000 μg q12h) administered by inhalation are effective in decreasing AWHR, lung inflammation, and clinical signs in horses with IAD. A randomized crossover study design was used. Eight horses with IAD were assigned to a treatment group with either DEX or FLUT. Measured outcomes included lung mechanics during bronchoprovocative challenges, bronchoalveolar lavage fluid (BALF) cytology, and scoring of clinical signs during exercise. Dexamethasone and FLUT abolished the increase in R L by 75% at any histamine bronchoprovocative dose in all horses after the first week of treatment. However, after 2 weeks of FLUT treatment, 1 horse redeveloped hypersensitivity. There was a significant decrease in the number of lymphocytes after treatment with both DEX and FLUT (P = .039 for both) but no significant differences in other BALF cell types or total cell counts (P > .05). There was no difference in the scoring of the clinical signs during each treatment and washout period (P > .05). Both DEX and FLUT treatments significantly inhibit airway hypersensitivity and hyperreactivity in horses with IAD. There are no significant effects on the clinical signs or the number of inflammatory cells (except lymphocytes) in BALF. The treatments have no residual effect 3 weeks after discontinuation. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  11. Molecular genetic and biochemical responses in human airway epithelial cell cultures exposed to titanium nanoparticles in vitro.

    Science.gov (United States)

    Aydın, Elanur; Türkez, Hasan; Hacımüftüoğlu, Fazıl; Tatar, Abdulgani; Geyikoğlu, Fatime

    2017-07-01

    Titanium nanoparticles (NPs) have very wide application areas such as paint, cosmetics, pharmaceuticals, and biomedical applications. And, to translate these nanomaterials to the clinic and industrial domains, their safety needs to be verified, particularly in terms of genotoxicity and cytotoxicity. Therefore, in this study, we aimed to investigate of cytotoxicity and changes in gene expression profiles influenced by commonly titanium (as titanium carbide, titanium carbo-nitride, titanium (II) oxide, titanium (III) oxide, titanium (IV) oxide, titanium nitride, titanium silicon oxide) NPs in human alveolar epithelial (HPAEpiC) and pharynx (HPPC) cell lines in vitro since inhalation is an important pathway for exposure to these NPs. HPAEpiC and HPPC cells were treated with titanium (0-100 µg/mL), NPs for 24 and 48 h, and then cytotoxicity was detected by, [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT), uptake of neutral red (NR) and lactate dehydrogenase (LDH) release assays, while genotoxicity was also analyzed by cDNA array - RT-PCR assay. According to the results of MTT, NR and LDH assays, all tested NPs induced cytotoxicity on both HPAEpiC and HPPC cells in a time- and dose-dependent manner. Determining and analyzing the gene expression profiles of HPAEpiC and HPPC cells, titanium NPs showed more changes in genes related to DNA damage or repair, oxidative stress, and apoptosis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2056-2064, 2017. © 2017 Wiley Periodicals, Inc.

  12. Platelet hyperreactivity and prognosis in survivors of myocardial infarction

    NARCIS (Netherlands)

    Trip, M. D.; Cats, V. M.; van Capelle, F. J.; Vreeken, J.

    1990-01-01

    We tested the hypothesis that an increase in spontaneous aggregability of platelets in vitro predicts mortality and coronary events in patients who have survived a recent myocardial infarction. A cohort of 149 survivors of infarction entered our study three months after the index infarction and was

  13. Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways: e1000424

    National Research Council Canada - National Science Library

    Margaret A Scull; Laura Gillim-Ross; Celia Santos; Kim L Roberts; Elena Bordonali; Kanta Subbarao; Wendy S Barclay; Raymond J Pickles

    2009-01-01

    .... Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37°C...

  14. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Team Your cystic fibrosis care team includes a group of CF health care professionals who partner with ... Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy ...

  15. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. ... or caregiver. Older kids and adults can choose ACTs that they can do on their own. Share ...

  16. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy to ...

  17. Airway Clearance Techniques (ACTs)

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    Full Text Available ... CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ... for fitting ACTs into daily life Airway Clearance Techniques | Webcast To learn more about how you can ...

  18. Predicting airway hyperreactivity to mannitol using exhaled nitric oxide in an unselected sample of adolescents and young adults

    DEFF Research Database (Denmark)

    Sverrild, A; Malinovschi, A; Porsbjerg, C

    2013-01-01

    the diagnostic accuracy of FeNO using absolute and normalized values to predict the presence of AHR to inhaled mannitol in an unselected population. Levels of FeNO and AHR to inhaled, dry-powder mannitol was measured in 180 unselected, steroid-naïve, non-smoking adolescents and young adults. The area under...... and specific tool for predicting the response to inhaled mannitol in an unselected sample of non-smoking, steroid-naïve subjects, and a low FeNO indicates that extra diagnostic work-up using inhaled mannitol will add very little extra information....

  19. Assays for in vitro monitoring of proliferation of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cells.

    Science.gov (United States)

    Goncharova, Elena A; Lim, Poay; Goncharov, Dmitry A; Eszterhas, Andrew; Panettieri, Reynold A; Krymskaya, Vera P

    2006-01-01

    Vascular and airway remodeling, which are characterized by airway smooth muscle (ASM) and pulmonary arterial vascular smooth muscle (VSM) proliferation, contribute to the pathology of asthma, pulmonary hypertension, restenosis and atherosclerosis. To evaluate the proliferation of VSM and ASM cells in response to mitogens, we perform a [3H]thymidine incorporation assay. The proliferation protocol takes approximately 48 h and includes stimulating cells synchronized in G0/G1 phase of the cell cycle with agonists, labeling cells with [3H]thymidine and examining levels of [3H]thymidine incorporation by scintillation counting. Although using radiolabeled [3H]thymidine incorporation is a limitation, the greatest benefit of the assay is providing reliable and statistically significant data.

  20. Attenuated metoclopramide-induced vascular hyperreactivity to cold stress in athletic subjects.

    Science.gov (United States)

    Blanco, M; Gómez, J; Blanco, G; Negrín, C; Velasco, M

    1998-11-01

    We have previously reported a metoclopramide-induced vascular hyperreactivity to the cold pressor test (CPT) in normotensive and hypertensive subjects. The present study was designed to determine whether the state of physical training influences the cardiovascular responses to the CPT in normotensive subjects under metoclopramide (MTC) treatment. In 20 untrained subjects and 32 athletes (football players and runners), the blood pressure and heart rate responses to the CPT were studied after a 30-minute infusion of MTC (7.5 microg/kg per minute) and two placebo periods, before and after MTC, with 5% glucose solution. Under placebo conditions, the CPT produced significant increases of systolic blood pressure (SBP) in the untrained subjects and the runners, but not in the football players (17.2, 17.8, and 6.5 mm Hg for untrained subjects, runners, and football players, respectively). The runners responded with a lesser increase in diastolic blood pressure (DBP) during the CPT than did the others (15.8, 17.9, and 18.2 mm Hg for runners, untrained subjects, and football players, respectively). In the presence of MTC, the CPT induced a larger increase in blood pressure (SBP/DBP) in the untrained subjects (21.4/24.1 mm Hg) than in the football players (10/18.7 mm Hg) and runners (18.7/13.9 mm Hg). MTC diminished the hyperreactivity responses to the CPT in the trained subjects (41 and 56% for football players and runners, respectively). Our conclusions are as follows: (1) Vascular responses to cold stress are attenuated in athletic subjects compared with untrained subjects. (2) The metoclopramide-induced vascular hyperreactivity, formerly reported for normotensive and hypertensive subjects, seems to be absent in trained subjects. (3) It is suggested that a probable dopaminergic system adaptation occurs during exercise.

  1. Nephropathy in type 1 diabetes is associated with increased circulating activated platelets and platelet hyperreactivity

    DEFF Research Database (Denmark)

    Tarnow, Inge; Michelson, Alan D.; Barnard, Marc R.

    2009-01-01

    -diabetic controls (P = 0.0075). There were no differences between groups in activated GPIIb/IIIa or in response to TRAP at any end-point. More patients with nephropathy received aspirin (71.4%) compared to normoalbuminuric patients (27.4%) (P ..., is associated with circulating activated platelets and platelet hyperreactivity to ADP, despite the confounding variable of more nephropathy patients receiving aspirin. This platelet activation is likely to contribute to the known increased risk of cardiovascular events in patients with diabetic nephropathy...

  2. Differential susceptibility of inbred mouse strains to chlorine-induced airway fibrosis

    Science.gov (United States)

    Mo, Yiqun; Chen, Jing; Schlueter, Connie F.

    2013-01-01

    Chlorine is a reactive gas that is considered a chemical threat agent. Humans who develop acute lung injury from chlorine inhalation typically recover normal lung function; however, a subset can experience chronic airway disease. To examine pathological changes following chlorine-induced lung injury, mice were exposed to a single high dose of chlorine, and repair of the lung was analyzed at multiple times after exposure. In FVB/NJ mice, chlorine inhalation caused pronounced fibrosis of larger airways that developed by day 7 after exposure and was associated with airway hyperreactivity. In contrast, A/J mice had little or no airway fibrosis and had normal lung function at day 7. Unexposed FVB/NJ mice had less keratin 5 staining (basal cell marker) than A/J mice in large intrapulmonary airways where epithelial repair was poor and fibrosis developed after chlorine exposure. FVB/NJ mice had large areas devoid of epithelium on day 1 after exposure leading to fibroproliferative lesions on days 4 and 7. A/J mice had airways covered by squamous keratin 5-stained cells on day 1 that transitioned to a highly proliferative reparative epithelium by day 4 followed by the reappearance of ciliated and Clara cells by day 7. The data suggest that lack of basal cells in the large intrapulmonary airways and failure to effect epithelial repair at these sites are factors contributing to the development of airway fibrosis in FVB/NJ mice. The observed differences in susceptibility to chlorine-induced airway disease provide a model in which mechanisms and treatment of airway fibrosis can be investigated. PMID:23171502

  3. Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation.

    Science.gov (United States)

    Musah, Sadiatu; Schlueter, Connie F; Humphrey, David M; Powell, Karen S; Roberts, Andrew M; Hoyle, Gary W

    2017-01-15

    Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24h after exposure to 800ppm chlorine for 4min to study acute effects or up to 7days after exposure to 400ppm for 8min to study longer term effects. Acute effects observed 6 or 24h after inhalation of 800ppm chlorine for 4min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400ppm chlorine for 8min, rabbits exhibited mild hypoxemia, increased area of pressure-volume loops, and airway hyperreactivity. Lung histology 7days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice

    DEFF Research Database (Denmark)

    Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin

    2012-01-01

    Apolipoprotein E (apoE) is an endogenous negative regulator of airway hyperreactivity (AHR) and mucous cell metaplasia in experimental models of house dust mite (HDM)-induced airway disease. The gene encoding human apoE is polymorphic, with three common alleles (e2, e3, and e4) reflecting single...... amino acid substitutions at amino acids 112 and 158. The objective of this study was to assess whether the human apoE alleles modify airway responses to repeated nasal HDM challenges. Mice expressing the human apoE e2 (huApoE2), e3 (huApoE3), or e4 (huApoE4) alleles received nasal HDM challenges......, and airway responses were compared with mice expressing the endogenous murine apoE gene (muApoE). huApoE3 mice displayed significant reductions in AHR, mucous cell metaplasia, and airway inflammation compared with muApoE mice. The attenuated severity of airway inflammation in huApoE3 mice was associated...

  5. Primary in vitro culture of porcine tracheal epithelial cells in an air-liquid interface as a model to study airway epithelium and Aspergillus fumigatus interactions.

    Science.gov (United States)

    Khoufache, Khaled; Cabaret, Odile; Farrugia, Cécile; Rivollet, Danièle; Alliot, Annie; Allaire, Eric; Cordonnier, Catherine; Bretagne, Stéphane; Botterel, Françoise

    2010-12-01

    Since the airway epithelium is the first tissue encountered by airborne fungal spores, specific models are needed to study this interaction. We developed such a model using primary porcine tracheal epithelial cells (PTEC) as a possible alternative to the use of primary human cells. PTEC were obtained from pigs and were cultivated in an air-liquid interface. Fluorescent brightener was employed to quantify the internalization of Aspergillus fumigatus conidia. Potential differences (Vt) and transepithelial resistances (Rt) after challenge with the mycotoxin, verruculogen, were studied. Primers for porcine inflammatory mediator genes IL-8, TNF-alpha, and GM-CSF were designed for a quantitative real-time PCR procedure to study cellular responses to challenges with A. fumigatus conidia. TEM showed the differentiation of ciliated cells and the PTEC ability to internalize conidia. The internalization rate was 21.9 ± 1.4% after 8 h of incubation. Verruculogen (10(-6) M) significantly increased Vt without having an effect on the Rt. Exposure of PTEC to live A. fumigatus conidia for 24 h induced a 10- to 40-fold increase in the mRNA levels of inflammatory mediator genes. PTEC behave similarly to human cells and are therefore a suitable alternative to human cells for studying interaction between airway epithelium and A. fumigatus.

  6. The Presence of Migraines and Its Association with Sensory Hyperreactivity and Anxiety Symptomatology in Children with Autism Spectrum Disorder

    Science.gov (United States)

    Sullivan, Jillian C.; Miller, Lucy J.; Nielsen, Darcy M.; Schoen, Sarah A.

    2014-01-01

    Migraine headaches are associated with sensory hyperreactivity and anxiety in the general population, but it is unknown whether this is also the case in autism spectrum disorders. This pilot study asked parents of 81 children (aged 7-17 years) with autism spectrum disorders to report their child's migraine occurrence, sensory hyperreactivity…

  7. Low-grade parasitaemias and cold agglutinins in patients with hyper-reactive malarious splenomegaly and acute haemolysis

    NARCIS (Netherlands)

    Torres, R.J.; Villegas, L; Perez, D. H. Campora; Flores-Suarez, L.F.; Torres V, M A; Campos, M

    A cluster of 16 cases of hyper-reactive malarious splenomegaly (HMS) with severe, acute haemolysis, from an isolated, Venezuelan, Yanomami population, was prospectively investigated. Nine (69%) of the 13 HMS sera investigated but only one (7%) of 14 control sera (P < 0.005) contained elevated titres

  8. Reduced platelet hyperreactivity and platelet-monocyte aggregation in HIV-infected individuals receiving a raltegravir-based regimen

    NARCIS (Netherlands)

    Tunjungputri, R.N.; Ven, A.J. van der; Schonsberg, A.; Mathan, T.S.M.; Koopmans, P.P.; Roest, M.; Fijnheer, R.; Groot, P.G. de; Mast, Q. de

    2014-01-01

    OBJECTIVE: Platelets are key cells in atherosclerosis and acute cardiovascular events. Platelet hyperreactivity and increased platelet-monocyte aggregation (PMA) are found in HIV-infected patients and may contribute to the excess cardiovascular risk. The integrase inhibitor raltegravir (RAL) has

  9. Airway Clearance Techniques (ACTs)

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    Full Text Available ... of treatment options. Airway Clearance Active Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of ... Pulmonary Exacerbations Clinical Care Guidelines SCREENING & TREATING DEPRESSION & ANXIETY GUIDELINES Clinician Resources As a clinician, you’re ...

  10. Emergency airway puncture

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003017.htm Emergency airway puncture To use the sharing features on this page, please enable JavaScript. Emergency airway puncture is the placement of a hollow ...

  11. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Consider Regarding a Lung Transplant Medications Antibiotics Bronchodilators Mucus Thinners Nebulizer Care at Home Vascular Access Devices ... them use percussion (clapping) or vibration to loosen mucus from airway walls. See how different airway clearance ...

  12. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Make a Charitable Gift Our Corporate Supporters Workplace Engagement DONATE YOUR PROPERTY eCards for a Cure About ... airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

  13. Glucose depletion in the airway surface liquid is essential for sterility of the airways.

    Directory of Open Access Journals (Sweden)

    Alejandro A Pezzulo

    2011-01-01

    Full Text Available Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface liquid (ASL and is normally sterile despite constant exposure to bacteria. The balance between bacterial growth and killing in the airway determines the outcome of exposure to inhaled or aspirated bacteria: infection or sterility. We hypothesized that restriction of carbon sources--including glucose--in the ASL is required for sterility of the lungs. We found that airway epithelia deplete glucose from the ASL via a novel mechanism involving polarized expression of GLUT-1 and GLUT-10, intracellular glucose phosphorylation, and low relative paracellular glucose permeability in well-differentiated cultures of human airway epithelia and in segments of airway epithelia excised from human tracheas. Moreover, we found that increased glucose concentration in the ASL augments growth of P. aeruginosa in vitro and in the lungs of hyperglycemic ob/ob and db/db mice in vivo. In contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a P. aeruginosa mutant that is unable to utilize glucose as a carbon source. Our data suggest that depletion of glucose in the airway epithelial surface is a novel mechanism for innate immunity. This mechanism is important for sterility of the airways and has implications in hyperglycemia and conditions that result in disruption of the epithelial barrier in the lung.

  14. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger

    2013-01-01

    Rationale – Chronic Obstructive Pulmonary Disease (COPD) is a combination of chronic bronchitis and emphysema, which both may lead to airway obstruction. Under normal circumstances, airway dimensions vary as a function of inspiration level. We aim to study the influence of COPD and emphysema......-20% (mild), 20%-30% (moderate) or >30% (severe). Spirometry was performed annually and participants were divided into severity groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Data were analysed in a mixed effects regression model with log(airway lumen diameter...... and emphysema, respectively. Conclusions – Airway distensibility decreases significantly with increasing severity of both GOLD status and emphysema, indicating that in COPD the dynamic change in airway calibre during respiration is compromised. Chronic bronchitis and emphysema appear to be interacting...

  15. Effects of in vitro exposure to hay dust on the gene expression of chemokines and cell-surface receptors in primary bronchial epithelial cell cultures established from horses with chronic recurrent airway obstruction.

    Science.gov (United States)

    Ainsworth, Dorothy M; Matychak, Marybeth; Reyner, Claudia L; Erb, Hollis N; Young, Jean C

    2009-03-01

    To examine effects of in vitro exposure to solutions of hay dust, lipopolysaccharide (LPS), or beta-glucan on chemokine and cell-surface receptor (CSR) gene expression in primary bronchial epithelial cell cultures (BECCs) established from healthy horses and horses with recurrent airway obstruction (RAO). BECCs established from bronchial biopsy specimens of 6 RAO-affected horses and 6 healthy horses. 5-day-old BECCs were treated with PBS solution, hay dust solutions, LPS, or beta-glucan for 6 or 24 hours. Gene expression of interleukin (IL)-8, chemokine (C-X-C motif) ligand 2 (CXCL2), IL-1beta, toll-like receptor 2, toll-like receptor 4, IL-1 receptor 1, and glyceraldehyde 3-phosphate dehydrogenase was measured with a kinetic PCR assay. Treatment with PBS solution for 6 or 24 hours was not associated with a significant difference in chemokine or CSR expression between BECCs from either group of horses. In all BECCs, treatment with hay dust or LPS for 6 hours increased IL-8, CXCL2, and IL-1beta gene expression > 3-fold; at 24 hours, only IL-1beta expression was upregulated by > 3-fold. In all BECCs, CSR gene expression was not increased following any treatment. With the exception of a 3.7-fold upregulation of CXCL2 in BECCs from RAO-affected horses (following 6-hour hay dust treatment), no differences in chemokine or CSR gene expression were detected between the 2 groups. At 24 hours, CXCL2 gene expression in all BECCs was downregulated. Epithelial CXCL2 upregulation in response to hay dust particulates may incite early airway neutrophilia in horses with RAO.

  16. Neurotrophins in allergic airway dysfunction: what the mouse model is teaching us.

    Science.gov (United States)

    Lommatzsch, Marek; Braun, Armin; Renz, Harald

    2003-05-01

    Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are potent mediators of neuronal plasticity in the adult. There is increasing evidence that they regulate a variety of immune functions as well. Thus, neurotrophins are candidate molecules for neuroimmune interactions in allergic bronchial asthma, where elevated neurotrophin levels have been reported. In a mouse model of allergic airway inflammation we have identified macrophages and lymphocytes as additional cellular sources of NGF and BDNF in the inflamed lung. There was an unusual time course of BDNF in bronchoalveolar lavage fluid. BDNF levels peaked 1 week after the last allergen challenge, and did not correlate with the time course of the inflammatory response. In a series of experiments using blocking anti-NGF and anti-BDNF antibodies, we have shown that NGF specifically enhances inflammation and the allergic early-phase response. In contrast, BDNF influenced chronic airway obstruction and local neuronal hyperreactivity without affecting inflammation. Using transgenic mice overexpressing NGF in the airway epithelium, we have confirmed the data obtained from anti-NGF experiments. Allergen-challenged NGF overexpressors displayed a markedly augmented airway inflammation, early-phase response, and sensory irritation compared to wild-type mice. Studies with p75-NTR (-/-) knockout mice showed that these NGF effects are at least in part mediated by the low-affinity neurotrophin receptor. Thus, our experiments suggest that NGF and BDNF have a profound, but differential impact on allergic airway dysfunction.

  17. Analysis of NLRP3 in the Development of Allergic Airway Disease in Mice1

    Science.gov (United States)

    Allen, Irving C.; Jania, Corey M.; Wilson, Justin E.; Tekeppe, Erin M.; Hua, Xiaoyang; Brickey, Willie J.; Kwan, Mildred; Koller, Beverly H.; Tilley, Stephen L.; Ting, Jenny P.-Y.

    2012-01-01

    The contribution of NLRP3, a member of the nucleotide-binding domain leucine-rich repeat containing (NLR) family, in the development of allergic airway disease is currently controversial. Here, we used multiple allergic asthma models to examine the physiologic role of NLRP3. We found no significant differences in airway eosinophilia, histopathology, mucus production and airway hyperreactivity between wild type and Nlrp3-/- mice in either acute (alum-dependent) or chronic (alum-independent) OVA models. In addition to the OVA model, we also did not detect a role for NLRP3 in the development of allergic airway disease induced by either acute or chronic house dust mite (HDM) antigen exposure. While we did not observe significant phenotypic differences in any of the models tested, we did observe a significant reduction of IL-13 and IL-33 in Nlrp3-/- mice compared to wild type controls in the chronic OVA model without added alum. In all of the allergic airway disease models, the levels of the NLRP3 inflammasome associated cytokines IL-1β and IL-18 in the lung were below the level of detection. In sum, this report surveyed four different allergic asthma models and found a modest and selected role for NLRP3 in the alum-free OVA model. However this difference did not greatly alter the clinical outcome of the disease. This suggests that the role of NLRP3 in allergic asthma has to be re-evaluated. PMID:22323538

  18. Toxicity assessment of aggregated/agglomerated cerium oxide nanoparticles in an in vitro 3D airway model: The influence of mucociliary clearance

    NARCIS (Netherlands)

    Kuper, C.F.; Gröllers-Mulderij, M.; Maarschalkerweerd, T.; Meulendijks, N.M.M.; Reus, A.; Acker, F. van; Zondervan-van den Beuken, E.K.; Wouters, M.E.L.; Bijlsma, S.; Kooter, I.M.

    2014-01-01

    We investigated the toxicity of aggregated nanoparticles of cerium oxide (CeO2) using an in vitro 3D human bronchial epithelial model that included a mucociliary apparatus (MucilAir™). CeO2 was dispersed in saline and applied to the apical surface of the model. CeO2 did not induce distinct effects

  19. Development of an in vitro model assay system for the evaluation of the effects of toxic chemicals on human airways. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, J.L.; Filbert, M.G.

    1994-03-01

    The ability of the anticholinesterase agent soman to contract human bronchi was examined. Soman (1-2 uM) had variable effects on human bronchi that had not been stimulated with an electric field stimulator (EFS). In bronchi continuously stimulated by EFS (0.5 Hz, 1 ms, 12 V), soman produced contractions in all tissues examined (12 preparations from 9 humans). In tissues stimulated by EFS, the beta-adrenoreceptor agonist isoproterenol produced relaxations that were greater in magnitude than the contractions produced by soman. The duration of the isoproterenol induced relaxations was variable. Of 12 preparations studied, 3 showed no reversal of the relaxation within 120 min, 6 showed a slow reversal with a reversal time of 106 + or - 6 min and 3 showed rapid reversal with a 50% reversal time of 14 min. In the latter group the duration of the relaxation produced by isoproterenol was doubled (28 + or - 2 min) by the M2 muscarinic receptor antagonist AFDX 116 (10 uM). These results show that the isolated human bronchus is a useful model for studying the effects of toxic chemical agents such as soman on the airways. The data obtained with isoproterenol suggest that beta-2 agonists may be useful adjuncts for treating the effects of anticholinesterase agents.

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

    Science.gov (United States)

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

    2007-12-31

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

  1. Early hyperreactive malarial splenomegaly and risk factors for evolution into the full-blown syndrome: a single-centre, retrospective, longitudinal study

    OpenAIRE

    Bisoffi, Zeno; Leoni, Stefania; Buonfrate, Dora; Lodesani, Claudia; Eseme, Franklin Esoka; Monteiro, Geraldo Badona; Marocco, Stefania; Guerriero, Massimo

    2015-01-01

    Background The hyperreactive malarial splenomegaly (HMS) represents a chronic, potentially fatal complication of malaria. Case definition includes: gross splenomegaly, high level of anti-malarial antibody and IgM, response to long-term anti-malarial prophylaxis. In this study, a large series of patients not fully meeting the case definition was tentatively classified as early hyperreactive malarial splenomegaly (e-HMS). The main research questions was: does ?e-HMS? tend to evolve to the full-...

  2. Experimental food allergy to peanut enhances the immune response to house dust mite in the airways of mice.

    Science.gov (United States)

    Utsch, L; Logiantara, A; van Ree, R; van Rijt, L S

    2017-01-01

    Food allergy has been associated with an increased risk for the development of allergic asthma. Asthma is a risk factor for the development of an anaphylactic response to food allergens. An immunological interplay between sensitization to different allergens in different compartments of the body might be involved. To evaluate the immunological interplay between intragastrical peanut (PE) sensitization and respiratory sensitization to house dust mite (HDM) allergens. BALB/c mice were intragastrically sensitized to peanut or sham-sensitized and challenged systemically to PE. Between sensitization and challenge, mice were intranasally exposed to HDM extract or PBS, as a control. The response to HDM (eosinophil recruitment, cytokine response, HDM-specific immunoglobulins and airway hyper-reactivity) and to PE (cytokine response, mast cells in gut, mMCP-1 in serum and body temperature) was assessed. A preceding PE sensitization increased HDM-induced production of IL-4, IL-5, IL-13 and IFNγ in lung-draining lymph nodes and total IgE levels in HDM-sensitized mice. However, recruitment of inflammatory cells to the airways or airway hyper-reactivity was not aggravated in PE/HDM double-sensitized mice. Alternatively, HDM-induced airway inflammation did not significantly affect the immune response or the anaphylactic response to a systemic challenge with peanut. Our data show that a preceding peanut sensitization boosted IgE- and HDM-specific Th2 response in the airways in mice. It contributes to the understanding of the underlying immunological mechanism of polysensitization which often occurs in allergic individuals over time. © 2016 John Wiley & Sons Ltd.

  3. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger

    2013-01-01

    Rationale – Chronic Obstructive Pulmonary Disease (COPD) is a combination of chronic bronchitis and emphysema, which both may lead to airway obstruction. Under normal circumstances, airway dimensions vary as a function of inspiration level. We aim to study the influence of COPD and emphysema......-dose CT for a period of 5 years (table 1). Images were reconstructed both with high contrast resolution (3 mm, kernel C) for emphysema analysis and with high spatial resolution (1 mm, kernel D) for airway analysis. Images were analysed by in-house developed software designed to segment lungs and localize...... the interior and exterior airway wall surface in three dimensions, and branches were matched in consecutive scans by image registration. Emphysema was defined as attenuation Emphysema limits were set at

  4. Chemotherapy for malignancy induces a remission in asthma symptoms and airway inflammation but not airway hyperresponsiveness.

    Science.gov (United States)

    Jones, P D; Henry, R L; Gibson, P G; Hankin, R; Carty, K

    1998-07-01

    Inflammation with infiltrations of eosinophils and mast cells into the walls of airways is considered to increase airway hyperresponsiveness (AHR), which in turn characterizes asthma. We present a child with AHR in whom the clinical course of asthma was related to eosinophilic bronchitis. Our patient was admitted at age 6 months with bronchiolitis and at age 4 years with asthma. Inhaled corticosteroids were begun at age 7 years. At age 8 he developed a meningeal sarcoma. While on chemotherapy, his asthma symptoms resolved and he no longer required prophylactic asthma treatment. After 14 months off all chemotherapy, he again had mild episodic asthma. While receiving chemotherapy for malignancy, he had an admission with a coagulase negative staphylococcal bacteremia. During sputum induction with 4.5% saline, he developed cough, wheeze, and a 20% reduction in peak expiratory flow (220 to 180 L/min) that reversed after treatment with salbutamol. The sputum cell count was 1.7 x 10(6)/ml with 1.1 x 10(6) being neutrophils. Two weeks later and prior to the induction of the second sputum, a 21% increase in FEV1 was recorded after bronchodilator inhalation (82% to 99% of predicted). The second sputum contained 2.7 x 10(6)/ml cells with 1.6 x 10(6)/ml neutrophils. Neither eosinophils nor mast cells were identified in the sputum. A third sputum obtained 14 months after the cessation of chemotherapy showed a sputum cell count of 16 x 10(6)/ml, with 11.6 x 10(6) neutrophils and 0.4 x 10(6) eosinophils; no mast cells were detected. A reversible 15% reduction in FEV1 was detected on hypertonic saline challenge testing. This boy had persistent airway hyperreactivity and reversible airways obstruction on three occasions during and following chemotherapy. When he developed asthma symptoms, his sputum contained neutrophils and eosinophils; while on chemotherapy his sputum did not contain eosinophils and he was symptom-free and off all asthma therapy. One can speculate that

  5. Engineering Airway Epithelium

    Directory of Open Access Journals (Sweden)

    John P. Soleas

    2012-01-01

    Full Text Available Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990. In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium.

  6. [Platelet hyperreactivity and antiaggregatory properties of nootropic drugs under conditions of alloxan-induced diabetes in rats].

    Science.gov (United States)

    Zhiliuk, V I; Levykh, A É; Mamchur, V I

    2012-01-01

    The effects of nootropic drugs (noopept, pentoxifylline, piracetam, pramiracetam, Ginkgo biloba extract, entrop, cerebrocurin and citicoline) on platelet aggregation in rats with experimental diabetes have been studied. It is established that all these drugs exhibit an inhibitory action of various degrees against platelet hyperreactivity under conditions of chronic hyperglycemia. The maximum universality of the antiaggregatory action is characteristic of pramiracetam, entrop and Ginkgo biloba extract.

  7. Human airway smooth muscle

    OpenAIRE

    Jongste, Johan

    1987-01-01

    textabstractThe function of airway smooth muscle in normal subjects is not evident. Possible physiological roles include maintenance of optimal regional ventilation/perfusion ratios, reduction of anatomic dead space, stabilisation of cartilaginous bronchi, defense against impurities and, less likely, squeezing mucus out of mucous glands and pulling open the alveoli next to the airways1 . Any role of airway smooth muscle is necessarily limited, because an important degree of contraction will l...

  8. Suppression of Th17-polarized airway inflammation by rapamycin.

    Science.gov (United States)

    Joean, Oana; Hueber, Anja; Feller, Felix; Jirmo, Adan Chari; Lochner, Matthias; Dittrich, Anna-Maria; Albrecht, Melanie

    2017-11-10

    Because Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation. Consecutively, we assessed the efficacy of methylprednisolone, roflumilast, azithromycin, AM80 and rapamycin against acute or chronic Th17-dependent airway inflammation. Quantifiers for Th17-associated inflammation comprised: bronchoalveolar lavage (BAL) differential cell counts, allergen-specific cytokine and immunoglobulin secretion, as well as flow cytometric phenotyping of pulmonary inflammatory cells. Only rapamycin proved effective against acute Th17-dependent airway inflammation, accompanied by increased plasmacytoid dendritic cells (pDCs) and reduced neutrophils as well as reduced CXCL-1 levels in BAL. Chronic Th17-dependent airway inflammation was unaltered by rapamycin treatment. None of the other agents showed efficacy in our models. Our results demonstrate that Th17-dependent airway inflammation is difficult to treat with known agents. However, we identify rapamycin as an agent with inhibitory potential against acute Th17-polarized airway inflammation.

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

    Science.gov (United States)

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

    2014-10-01

    only in female offspring. Prenatal progesterone supplementation ameliorates airway hyperreactivity in prenatally stressed murine offspring.

  10. Emotional hyperreactivity in response to childhood abuse by primary caregivers in patients with borderline personality disorder.

    Science.gov (United States)

    Lobbestael, Jill; Arntz, Arnoud

    2015-09-01

    One of the core postulated features of borderline personality disorder (BPD) is extreme emotional reactivity to a wide array of evocative stimuli. Findings from previous experimental research however are mixed, and some theories suggest specificity of hyper emotional responses, as being related to abuse, rejection and abandonment only. The current experiment examines the specificity of emotional hyperreactivity in BPD. The impact of four film clips (BPD-specific: childhood abuse by primary caregivers; BPD-nonspecific: peer bullying; positive; and neutral) on self-reported emotional affect was assessed in three female groups; BPD-patients (n = 24), cluster C personality disorder patients (n = 17) and non-patient controls (n = 23). Results showed that compared to the neutral film clip, BPD-patients reacted with more overall negative affect following the childhood abuse clip, and with more anger following the peer bullying clip than the two other groups. The current study was restricted to assessment of the impact of evocative stimuli on self-reported emotions, and the order in which the film clips were presented to the participants was fixed. Results suggest that BPD-patients only react generally excessively emotional to stimuli related to childhood abuse by primary caregivers, and with excessive anger to peer-bullying stimuli. These findings are thus not in line with the core idea of general emotional hyperreactvity in BPD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. [Possibility of achieving and maintaining asthma control in patients with bronchial cold hyperreactivity].

    Science.gov (United States)

    Kolosov, V P; Pirogov, A B; Perel'man, Iu M; Mal'tseva, T A; Prikhod'ko, A G

    2014-01-01

    To evaluate the clinical efficiency of tactics to widen the scope of monotherapy with inhaled glucocorticosteroids (IGCS) in asthmatic patients with bronchial cold hyperreactivity (BCHR) during winter to achieve control of the disease in real clinical practice. An open-label longitudinal study was conducted in a cold period in 106 asthmatics divided into 2 groups: 1) those with BCHR and 2) those with unchanged bronchial reactivity to a cold stimulus. The study involved monitoring the symptoms by the asthma control test, peak expiratory flow rate (PEFR), and spirometry results before and after cold bronchoprovocation testing; assessment of the pattern of bronchial inflammation from the ratios of induced sputum (IS) cell populations; and estimation of the number of asthma exacerbations and emergency care recourses. Group 1 used a stepwise increase of the scope of basic therapy with beclomethasone dipropionate 1000 microg/day until asthma control was achieved, which was followed by the therapy with the stable dose. Group 2 received monotherapy with beclomethasone dipropionate as the stable dosage of asthma control achievement in patients with BCHR. A stepwise increase in the scope of IGCS monotherapy in asthmatic patients with BCHR during winter can yield the results of disease control and the incidence of exacerbations, which are similar to those seen in asthmatics with no signs of BCHR (53 and 49%, respectively).

  12. Effects of outdoor and indoor air pollution on lung function, bronchial hyperreactivity, mucociliary, risk of pulmonary disease and course of disease. Auswirkung der Luftverunreinigung auf spirometrische Messgroessen, bronchiale Hyperreagibilitaet, Krankheitsrisiko und Krankheitsverlauf

    Energy Technology Data Exchange (ETDEWEB)

    Eltschka, R.; Herceg, R.; Matthys, H. (Freiburg Univ. (Germany, F.R.). Medizinische Universitaetsklinik)

    1989-04-01

    Our research project has been launched to gain new insights into etiopathogenesis of bronchial hyperreactivity in asthma and chronic bronchitis, by taking into account the effects of indoor and outdoor pollution on the respiratory system. We managed to find participants of 3 defined risk groups (123 hyperreactive patients, 40 with a history of asthma and 30 normal subjects). In patients with hyperreactivity without clinical symptoms of asthma we found a reduced mucociliary clearance (mc). With our long term project we want to investigate whether or not patients with a reduced mc with or without bronchial hyperreactivity undergo a different risk inhaling noxes and to which degree mc will be of prognostic value. (orig.).

  13. Obstetric airway management

    African Journals Online (AJOL)

    high rate of general anaesthesia (30% of emergency, and 8% of elective, Caesarean sections), readily available senior cover ... better training and preparation, earlier identification of the difficult airway, and potentially increased regional .... in high-volume theatres. References. 1. Preston R, Jee R. Obstetric airway ...

  14. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... toddlers will need help from a parent or caregiver. Older kids and adults can choose ACTs that they can do on their ... (clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

  15. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger

    2013-01-01

    on the airway distensibility, defined as the ratio of relative change in lumen diameter to the relative change in total lung volume (TLV) divided by predicted total lung capacity (pTLC) . Methods – We included 1900 participants from the Danish Lung Cancer Screening Trial (DLCST); all randomized to annual low......-dose CT for a period of 5 years (table 1). Images were reconstructed both with high contrast resolution (3 mm, kernel C) for emphysema analysis and with high spatial resolution (1 mm, kernel D) for airway analysis. Images were analysed by in-house developed software designed to segment lungs and localize......-20% (mild), 20%-30% (moderate) or >30% (severe). Spirometry was performed annually and participants were divided into severity groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Data were analysed in a mixed effects regression model with log(airway lumen diameter...

  16. Cellular effects in an in vitro human 3D cellular airway model and A549/BEAS-2B in vitro cell cuultures following air exposure to cerium oxide particles at an air-liquid interface

    NARCIS (Netherlands)

    Kooter, I.M.; Grollers-Mulderij, M.; Steenhof, M.; Duistermaat, E.; Acker, F.A.A. van; Staal, Y.C.M.; Tromp, P.C.; Schoen, E.D.; Kuiper, C.F.; Someren, E.P. van

    2016-01-01

    There is a need for representative in vitro models to assess the effects of airborne particles on lung health. The ob-jective of this study was to assess the cellular effects of cerium oxide (Ce02) particles exposed via an air—liquid interface in three relevant cell models in parallel. BEAS-2B,

  17. Epidemiology of pollution-induced airway disease in Japan

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-12-31

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

  18. Airway smooth muscle cells : regulators of airway inflammation

    NARCIS (Netherlands)

    Zuyderduyn, Suzanne

    2007-01-01

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

  19. PPARγ as a Potential Target to Treat Airway Mucus Hypersecretion in Chronic Airway Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Yongchun Shen

    2012-01-01

    Full Text Available Airway mucus hypersecretion (AMH is a key pathophysiological feature of chronic airway inflammatory diseases such as bronchial asthma, cystic fibrosis, and chronic obstructive pulmonary disease. AMH contributes to the pathogenesis of chronic airway inflammatory diseases, and it is associated with reduced lung function and high rates of hospitalization and mortality. It has been suggested that AMH should be a target in the treatment of chronic airway inflammatory diseases. Recent evidence suggests that a key regulator of airway inflammation, hyperresponsiveness, and remodeling is peroxisome proliferator-activated receptor gamma (PPARγ, a ligand-activated transcription factor that regulates adipocyte differentiation and lipid metabolism. PPARγ is expressed in structural, immune, and inflammatory cells in the lung. PPARγ is involved in mucin production, and PPARγ agonists can inhibit mucin synthesis both in vitro and in vivo. These findings suggest that PPARγ is a novel target in the treatment of AMH and that further work on this transcription factor may lead to new therapies for chronic airway inflammatory diseases.

  20. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger

    2013-01-01

    on the airway distensibility, defined as the ratio of relative change in lumen diameter to the relative change in total lung volume (TLV) divided by predicted total lung capacity (pTLC) . Methods – We included 1900 participants from the Danish Lung Cancer Screening Trial (DLCST); all randomized to annual low...

  1. Surfactant in airway disease.

    Science.gov (United States)

    Enhorning, Goran

    2008-04-01

    Beta(2)-adrenergic agonists cause a release of pulmonary surfactant into lung airways. The surfactant phospholipids maintain the patency of the conducting airways, but this function is inhibited by plasma proteins entering an inflamed airway. The physical behavior of the surfactant can be studied with a pulsating bubble surfactometer and a capillary surfactometer. Calf lung surfactant extract was found to be inhibited by plasma proteins and by a lowering of temperature. Severe breathing difficulties and malfunctioning surfactant developed in BALB/c mice inhaling ozone or infected with respiratory syncytial virus, mainly as a result of proteins invading the airways. Patients with asthma were challenged with allergens in an area of one lung. BAL fluid (BALF) from such an area contained a surfactant that functioned poorly (ie, an inability to maintain airway openness) compared with BALF from the other lung or from the lungs of healthy volunteers. When proteins in the BALF were removed, surfactant performance clearly improved. Eosinophils, so prominent in asthmatic patients, synthesize the enzyme lysophospholipase, which, together with the enzyme phospholipase A(2), catalyzes the hydrolysis of the main component of the surfactant, phosphatidylcholine. Such hydrolysis incapacitates the ability of the surfactant to maintain airway patency. The treatment of asthma with beta(2)-adrenergic agonists and steroids will have a valuable effect on the surfactant system. It will cause a release of fresh surfactant into terminal airways. Surfactant can also be nebulized and inhaled, which has been shown to be an effective treatment.

  2. Temporal Monitoring of Differentiated Human Airway Epithelial Cells Using Microfluidics.

    Directory of Open Access Journals (Sweden)

    Cornelia Blume

    Full Text Available The airway epithelium is exposed to a variety of harmful agents during breathing and appropriate cellular responses are essential to maintain tissue homeostasis. Recent evidence has highlighted the contribution of epithelial barrier dysfunction in the development of many chronic respiratory diseases. Despite intense research efforts, the responses of the airway barrier to environmental agents are not fully understood, mainly due to lack of suitable in vitro models that recapitulate the complex in vivo situation accurately. Using an interdisciplinary approach, we describe a novel dynamic 3D in vitro model of the airway epithelium, incorporating fully differentiated primary human airway epithelial cells at the air-liquid interface and a basolateral microfluidic supply of nutrients simulating the interstitial flow observed in vivo. Through combination of the microfluidic culture system with an automated fraction collector the kinetics of cellular responses by the airway epithelium to environmental agents can be analysed at the early phases for the first time and with much higher sensitivity compared to common static in vitro models. Following exposure of primary differentiated epithelial cells to pollen we show that CXCL8/IL-8 release is detectable within the first 2h and peaks at 4-6h under microfluidic conditions, a response which was not observed in conventional static culture conditions. Such a microfluidic culture model is likely to have utility for high resolution temporal profiling of toxicological and pharmacological responses of the airway epithelial barrier, as well as for studies of disease mechanisms.

  3. Popcorn worker's lung: in vitro exposure to diacetyl, an ingredient in microwave popcorn butter flavoring, increases reactivity to methacholine.

    Science.gov (United States)

    Fedan, J S; Dowdy, J A; Fedan, K B; Hubbs, A F

    2006-08-15

    Workers who inhale microwave popcorn butter flavorings experience decrements in lung function and can develop clinical bronchiolitis obliterans, i.e., "popcorn worker's lung" (Kreiss, K., Gomaa, A., Kullman, G., Fedan, K., Simoes, E.J., Enright, P.L., 2002. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N. Engl. J. Med. 347, 330-338.). In a rat inhalation model, vapors of an artificial butter flavoring damaged the epithelium of the upper and lower airways (Hubbs, A.F., Battelli, L.A., Goldsmith, W.T., Porter, D.W., Frazer, D., Friend, S., Schwegler-Berry, D., Mercer, R.R., Reynolds, J.S., Grote, A., Castranova, V., Kullman, G., Fedan, J.S., Dowdy, J., Jones, W.G., 2002. Necrosis of nasal and airway epithelium in rats inhaling vapors of artificial butter flavoring. Toxicol. Appl. Pharmacol. 185, 128-135.). Diacetyl, a butter flavoring component, is a major volatile ketone in the popcorn-processing workplace. We investigated the effects of diacetyl on epithelium of guinea pig isolated airway preparations and the effects of diacetyl in vitro on reactivity to bronchoactive agents. In the isolated, perfused trachea preparation, diacetyl added to the intraluminal (mucosal) bath elicited responses that began with contraction (threshold ca. 3 mM) and ended with relaxation. After a 4-h incubation with intraluminal diacetyl (3 mM), contractions to extraluminal (serosal) methacholine (MCh) were slightly increased; however, sensitivity to intraluminally (mucosally) applied MCh was increased by 10-fold. Relaxation responses of MCh (3 x 10(-7) M)-contracted tracheas to extraluminally applied terbutaline and intraluminally applied 120 mM KCl, to evoke epithelium-derived relaxing factor release, were unaffected by diacetyl. Exposure of the tracheal epithelium in Ussing chambers to diacetyl decreased transepithelial potential difference and resistance. These findings suggest that diacetyl exposure compromised epithelial barrier function, leading to

  4. Airway Clearance Techniques (ACTs)

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    Full Text Available ... decisions about your health care. CF Genetics: The Basics CF Mutations Video Series CFTR2 Personalized Medicine Types ... of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy Coughing and ...

  5. Airway Clearance Techniques (ACTs)

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    Full Text Available ... and Resources Bioinformatics Tools for CF CFTR Antibodies Distribution Program CFTR Assays CFFT Biorepository CFTR Chemical Compound ... huffing . Many of them use percussion (clapping) or vibration to loosen mucus from airway walls. See how ...

  6. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Guidelines Bone Disease in CF Clinical Care Guidelines Cystic Fibrosis-Related Diabetes Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway ...

  7. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care ... attack bacteria. Choose What's Best for You Your respiratory therapist or another member of your CF care ...

  8. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Medications Antibiotics Bronchodilators Mucus Thinners Nebulizer Care at Home Vascular Access Devices: PICCs and Ports Partnerships for ... Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance ...

  9. Emergency airway puncture - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100113.htm Emergency airway puncture - series—Normal anatomy To use the ... 2016 Updated by: Jacob L. Heller, MD, MHA, Emergency Medicine, Virginia Mason Medical Center, Seattle, WA. Also ...

  10. Airway Clearance Techniques (ACTs)

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    Full Text Available ... a Family Parenting as an Adult With CF Treatments & Therapies People with cystic fibrosis are living longer ... to specialized CF care and a range of treatment options. Airway Clearance Active Cycle of Breathing Technique ...

  11. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Clinician Career Development Awards Clinician Training Awards Mutation Analysis Program Network News Network News: NACFC 2017 Network ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

  12. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Advocacy Achievements Advocacy News Briefings, Testimonies, and Regulatory Comments Congressional Cystic Fibrosis Caucus Our Policy Agenda Policy ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

  13. Airway Clearance Techniques (ACTs)

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    Full Text Available ... GI Care Guidelines Antioxidants Clinical Care Guidelines Enteral Tube Feeding Clinical Care Guidelines Nutrition in Children and ... clear your airways. Most are easy to do. Infants and toddlers will need help from a parent ...

  14. Human airway smooth muscle

    NARCIS (Netherlands)

    J.C. de Jongste (Johan)

    1987-01-01

    textabstractThe function of airway smooth muscle in normal subjects is not evident. Possible physiological roles include maintenance of optimal regional ventilation/perfusion ratios, reduction of anatomic dead space, stabilisation of cartilaginous bronchi, defense against impurities and, less

  15. Airway Clearance Techniques (ACTs)

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    Full Text Available ... people with cystic fibrosis so that they make smart decisions about CF-related research, treatment, and access ... Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance ...

  16. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Medications Antibiotics Bronchodilators Mucus Thinners Nebulizer Care at Home Vascular Access Devices PICCs and Ports Partnerships for ... Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance ...

  17. Airway Clearance Techniques (ACTs)

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    Full Text Available ... in CF Clinical Care Guidelines Cystic Fibrosis-Related Diabetes Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care Guidelines Chronic Medications to Maintain Lung Health Clinical Care Guidelines ...

  18. Airway Clearance Techniques (ACTs)

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    Full Text Available ... a Family Parenting as an Adult With CF Treatments & Therapies People with cystic fibrosis are living longer and ... to specialized CF care and a range of treatment options. Airway Clearance Active Cycle of Breathing Technique ( ...

  19. Airway Clearance Techniques (ACTs)

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    Full Text Available ... in CF Clinical Care Guidelines Cystic Fibrosis-Related Diabetes Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care Guidelines Chronic Medications to Maintain Lung ...

  20. Airway Clearance Techniques (ACTs)

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    Full Text Available ... huffing . Many of them use percussion (clapping) or vibration to loosen mucus from airway walls. See how ... 20814 301-951-4422 800-344-4823 (toll free) We will not rest until we find a ...

  1. Blockage of upper airway

    Science.gov (United States)

    ... obstruction - acute upper Images Throat anatomy Choking Respiratory system References Cukor J, Manno M. Pediatric respiratory emergencies: upper airway obstruction and infections. In: Marx J, ed. Rosen's Emergency Medicine: Concepts and Clinical Practice . 8th ed. Philadelphia, PA: Elsevier ...

  2. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... many challenges, including medical, social, and financial. By learning more about how you can manage your disease every day, you can ... Clearance Active Cycle of Breathing Technique (ACBT) Airway Clearance Techniques ( ...

  3. A study of two generic health-related quality of life questionnaires--Nottingham Health Profile and Short-Form 36 Health Survey--and of coping in patients with sensory hyperreactivity.

    Science.gov (United States)

    Kristofferzon, Marja-Leena; Ternesten-Hasséus, Ewa

    2013-10-29

    Sensory hyperreactivity (SHR) is one explanation for airway symptoms induced by chemicals and scents. Little is known about health-related quality of life (HRQOL) and coping, in this group of patients. A study was done in patients with SHR to (1) compare the Nottingham Health Profile (NHP) and the Short-Form 36 Health Survey (SF-36) in regard to their suitability, validity, reliability, and acceptability; (2) evaluate how the patients cope with the illness; (3) assess whether there are differences between women and men with respect to HRQOL and coping; and (4) assess whether there are differences between patients and normative data with respect to HRQOL and coping. A total of 115 patients (91 women) with SHR were asked to answer five questionnaires: a study-specific questionnaire, the Chemical Sensitivity Scale for Sensory Hyperreactivity (CSS-SHR), the NHP, the SF-36, and the Jalowiec Coping Scale-60. Eighty-three patients (72%; 70 women) completed all questionnaires. The SF-36 scores were less skewed and more homogeneously distributed and showed fewer floor and ceiling effects than the NHP scores. The SF-36 was also discriminated better between patients with high and low CSS-SHR scores. The reliability standard for both questionnaires was satisfactory. There were no gender differences in HRQOL. Patients with SHR had significantly lower HRQOL scores than the normative data in comparable domains of the NHP and the SF-36: emotional reactions/mental health, energy/vitality, physical mobility/functioning, and pain/bodily pain. In social isolation/functioning, the results were different; the NHP scores were similar to the normative data and the SF-36 scores were lower. The most commonly used coping styles were optimistic, self-reliant, and confrontational. Women used optimistic coping more than men. Compared with the normative group, patients with SHR used confrontational and optimistic coping more and emotive coping less. The current findings showed that both the NHP

  4. Phenotypic Responses of Differentiated Asthmatic Human Airway Epithelial Cultures to Rhinovirus

    OpenAIRE

    Jianwu Bai; Smock, Steven L.; Jackson, George R.; MacIsaac, Kenzie D.; Yongsheng Huang; Courtney Mankus; Jonathan Oldach; Brian Roberts; Yu-Lu Ma; Klappenbach, Joel A.; Crackower, Michael A.; Alves, Stephen E.; Patrick J. Hayden

    2015-01-01

    Objectives Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model. Methods Air-liquid interface (ALI) human airway epithelial...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-01-01

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

  6. Following up infant bronchiolitis patients provided new evidence for and against the united airway disease hypothesis.

    Science.gov (United States)

    Lauhkonen, Eero; Koponen, Petri; Nuolivirta, Kirsi; Helminen, Merja; Paassilta, Marita; Toikka, Jyri; Korppi, Matti

    2016-11-01

    The united airway disease (UAD) hypothesis suggests that allergic rhinitis and asthma develop together. We evaluated the evidence for and against the UAD hypothesis at five to seven years of age after hospitalisation for bronchiolitis at less than six months. This study used prospective follow-up data for 102 children hospitalised for bronchiolitis under the age of six months. We included the presence of previous and current asthma, prolonged rhinitis and skin prick tests (SPT) to common inhaled allergens and lung function by impulse oscillometry (IOS) at five to seven years of age. Bronchial hyper-reactivity (BHR) was assessed using the exercise challenge test and bronchodilation test. Current asthma, but not previous transient asthma, was associated with prolonged rhinitis and a positive SPT. BHR, which reflected reactive airways, but not lung function, was associated with respiratory allergy, namely the combination of current asthma, prolonged rhinitis and a positive SPT. This post-bronchiolitis follow-up study suggested an association between respiratory allergy and reactive airways at five to seven years of age, which supported the UAD hypothesis. However, previous transient asthma and a reduction in lung function reduction did not support the hypothesis. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  7. Lentivirus vector-mediated gene transfer to the developing bronchiolar airway epithelium in the fetal lamb.

    Science.gov (United States)

    Yu, Ze-Yan; McKay, Karen; van Asperen, Peter; Zheng, Maolin; Fleming, Jane; Ginn, Samantha L; Kizana, Eddy; Latham, Margot; Feneley, Michael P; Kirkland, Peter D; Rowe, Peter B; Lumbers, Eugenie R; Alexander, Ian E

    2007-06-01

    Development of effective and durable gene therapy for treatment of the respiratory manifestations of cystic fibrosis remains a formidable challenge. Obstacles include difficulty in achieving efficient gene transfer to mature airway epithelium and the need to stably transduce self-renewing epithelial progenitor cells in order to avoid loss of transgene expression through epithelial turnover. Targeting the developing airway epithelium during fetal life offers the prospect of circumventing these challenges. In the current study we investigated vesicular stomatitis virus glycoprotein (VSVg)-pseudotyped HIV-1-derived lentivirus vector-mediated gene transfer to the airway epithelium of mid-gestation fetal lambs, both in vitro and in vivo. In the in vitro studies epithelial sheet explants and lung organ culture were used to examine transduction of the proximal and more distal airway epithelium, respectively. For the in vivo studies, vector was delivered directly into the proximal airway. We found that even during the early pseudoglandular and canalicular phases of lung development, occurring through mid-gestation, the proximal bronchial airway epithelium was relatively mature and highly resistant to lentivirus-mediated transduction. In contrast, the more distal bronchiolar airway epithelium was relatively permissive for transduction although the absolute levels achieved remained low. This result is promising as the bronchiolar airway epithelium is a major site of pathology in the cystic fibrosis airway, and much higher levels of transduction are likely to be achieved by developing strategies that increase the amount of vector reaching the more distal airway after intratracheal delivery.

  8. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan, E-mail: yuan.xu@ki.se; Cardell, Lars-Olaf

    2014-02-15

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    BACKGROUND AND OBJECTIVE: Asthma-related morbidity is greater in older compared with younger asthmatics. Airway closure is also greater in older asthmatics, an observation that may be explained by differences in airway inflammation. We hypothesized that in older adult patients with asthma......, neutrophil airway inflammation increases airway closure during bronchoconstriction, while eosinophil airway inflammation increases airway hyperresponsiveness (AHR). METHODS: Asthmatic subjects (n = 26), aged ≥55 years (68% female), were studied, and AHR to 4.5% saline challenge was measured by the response......-dose ratio (%fall in forced expiratory volume in 1 s (FEV1 )/mg saline). Airway closure was assessed during bronchoconstriction percent change in forced vital capacity (FVC)/percent change in FEV1 (i.e. Closing Index). Airway inflammation was assessed by induced sputum and exhaled nitric oxide (eNO). RESULTS...

  10. Wogonin Induces Eosinophil Apoptosis and Attenuates Allergic Airway Inflammation

    Science.gov (United States)

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

    2015-01-01

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

  11. Analysis of the proteome of human airway epithelial secretions

    Directory of Open Access Journals (Sweden)

    Park Yongsung

    2011-01-01

    Full Text Available Abstract Background Airway surface liquid, often referred to as mucus, is a thin layer of fluid covering the luminal surface that plays an important defensive role against foreign particles and chemicals entering the lungs. Airway mucus contains various macromolecules, the most abundant being mucin glycoproteins, which contribute to its defensive function. Airway epithelial cells cultured in vitro secrete mucins and nonmucin proteins from their apical surface that mimics mucus production in vivo. The current study was undertaken to identify the polypeptide constituents of human airway epithelial cell secretions to gain a better understanding of the protein composition of respiratory mucus. Results Fifty-five proteins were identified in the high molecular weight fraction of apical secretions collected from in vitro cultures of well-differentiated primary human airway epithelial cells and isolated under physiological conditions. Among these were MUC1, MUC4, MUC5B, and MUC16 mucins. By proteomic analysis, the nonmucin proteins could be classified as inflammatory, anti-inflammatory, anti-oxidative, and/or anti-microbial. Conclusions Because the majority of the nonmucin proteins possess molecular weights less than that selected for analysis, it is theoretically possible that they may associate with the high molecular weight and negatively charged mucins to form a highly ordered structural organization that is likely to be important for maintaining the proper defensive function of airway mucus.

  12. Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling

    NARCIS (Netherlands)

    Gosens, Reinout; Bos, I.S.; Zaagsma, Hans; Meurs, Herman

    2005-01-01

    Rationale: Recent findings have demonstrated that muscarinic M-3 receptor stimulation enhances airway smooth muscle proliferation to peptide growth factors in vitro. Because both peptide growth factor expression and acetylcholine release are known to be augmented in allergic airway inflammation, it

  13. Insulin-Induced Laminin Expression Promotes a Hypercontractile Airway Smooth Muscle Phenotype

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Schaafsma, Dedmer; Tran, Thai; Zaagsma, Johan; Meurs, Herman

    2009-01-01

    Airway smooth muscle (ASM) plays a key role in the development of airway hyperresponsiveness and remodeling in asthma, which may involve maturation of ASM cells to a hypercontractile phenotype. In vitro studies have indicated that long-term exposure of bovine tracheal smooth muscle (BTSM) to insulin

  14. Increased Airway Reactivity and Hyperinsulinemia in Obese Mice Are Linked by ERK Signaling in Brain Stem Cholinergic Neurons

    Directory of Open Access Journals (Sweden)

    Luiz O.S. Leiria

    2015-05-01

    Full Text Available Obesity is a major risk factor for asthma, which is characterized by airway hyperreactivity (AHR. In obesity-associated asthma, AHR may be regulated by non-TH2 mechanisms. We hypothesized that airway reactivity is regulated by insulin in the CNS, and that the high levels of insulin associated with obesity contribute to AHR. We found that intracerebroventricular (ICV-injected insulin increases airway reactivity in wild-type, but not in vesicle acetylcholine transporter knockdown (VAChT KDHOM−/−, mice. Either neutralization of central insulin or inhibition of extracellular signal-regulated kinases (ERK normalized airway reactivity in hyperinsulinemic obese mice. These effects were mediated by insulin in cholinergic nerves located at the dorsal motor nucleus of the vagus (DMV and nucleus ambiguus (NA, which convey parasympathetic outflow to the lungs. We propose that increased insulin-induced activation of ERK in parasympathetic pre-ganglionic nerves contributes to AHR in obese mice, suggesting a drug-treatable link between obesity and asthma.

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

    NARCIS (Netherlands)

    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.; Buh, 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.; Sarabia, A. M. Cepeda; 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.; Wagner, A. Fink; Fletcher, M.; Fokkens, W. J.; Fonseca, J.; Franco, A.; Frith, P.; Furber, A.; Gaga, M.; Garces, J.; Garcia-Aymerich, J.; Gamkrelidze, A.; Gonzales-Diaz, S.; Gouzi, F.; Guzman, 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.; Carlsen, K. C. Lodrup; Louis, R.; MacNee, W.; Mair, A.; Majer, I.; Manning, P.; Keenoy, E. de Manuel; Masjedi, M. R.; Meten, E.; Melo-Gomes, E.; Menzies-Gow, A.; Mercier, G.; Mercier, J.; Michel, J. P.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Molimard, M.; Mamas, 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.; Pontal, F. Radier; 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.; Schunemann, 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.

    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

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

    NARCIS (Netherlands)

    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.

    2014-01-01

    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

  17. Airway structural components drive airway smooth muscle remodeling in asthma

    NARCIS (Netherlands)

    Dekkers, Bart G J; Maarsingh, Harm; Meurs, Herman; Gosens, Reinoud

    2009-01-01

    Chronic asthma is an inflammatory airways disease characterized by pathological changes in the airway smooth muscle (ASM) bundle that contribute to airway obstruction and hyperresponsiveness. Remodeling of the ASM is associated with an increased smooth muscle mass, involving components of cellular

  18. The laminin beta 1-competing peptide YIGSR induces a hypercontractile, hypoproliferative airway smooth muscle phenotype in an animal model of allergic asthma

    NARCIS (Netherlands)

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

    2010-01-01

    Background: Fibroproliferative airway remodelling, including increased airway smooth muscle (ASM) mass and contractility, contributes to airway hyperresponsiveness in asthma. In vitro studies have shown that maturation of ASM cells to a (hyper)contractile phenotype is dependent on laminin, which can

  19. Long-term exposure of adults to outdoor air pollution is associated with increased airway obstruction and higher prevalence of bronchial hyperresponsiveness

    Energy Technology Data Exchange (ETDEWEB)

    Jammres, Y.; Delpierre, S.; Burnet, H. [Univ. de la Mediterranee, Marseilles (France); Delvolgo, M.J.; Humbert-Tena, C. [Hopital Nord et, Marseilles (France). Lab. des Explorations Fonctionnelles

    1998-11-01

    The authors studied the association between long-term exposure to outdoor air pollution and the severity of obstructive pulmonary disease and prevalence of bronchial hyperreactivity to {beta}2 agonists in two groups of adult patients who were of similar ages and who had similar smoking habits. The subjects lived in downtown districts or in the outer suburbs of Marseilles, the neighborhood that contained air samplers. The regions were similar with respect to sulfur dioxide levels, but levels of nitric oxides and particulate matter were higher in the downtown area than the suburbs. The authors assessed airway obstruction, as determined by a decrease in forced expiratory volume in 1 s, mean forced expiratory flow measured between 25% and 75% of vital capacity, and an elevated value of central airway resistance. The authors tested the changes in these variables induced by inhalation of a {beta}2 agonist. Baseline lung function was altered more significantly in both male and female patients who lived in downtown Marseilles than in those who resided in the suburbs, and the differences persisted regardless of the season during which the study occurred. Prevalence of bronchial hyperreactivity and symptoms of asthma were higher in the downtown than suburban male subjects. The results of this study suggest that an association exists between actual environmental exposure to outdoor air pollution and respiratory effects in sensitive adults represented by patients with chronic obstructive pulmonary disease or asthma.

  20. Effectiveness of Earmuffs and Noise-cancelling Headphones for Coping with Hyper-reactivity to Auditory Stimuli in Children with Autism Spectrum Disorder: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Nobuhiko Ikuta

    2016-12-01

    Conclusion: This study demonstrated the effectiveness of standard earmuffs and NC headphones in helping children with ASD to cope with problem behaviours related to hyper-reactivity to auditory stimuli, therefore, children with ASD could use earmuffs to help to deal with unpleasant sensory auditory stimuli.

  1. Incidence of unanticipated difficult airway using an objective airway score versus a standard clinical airway assessment

    DEFF Research Database (Denmark)

    Nørskov, Anders Kehlet; Rosenstock, Charlotte Valentin; Wetterslev, Jørn

    2013-01-01

    Pre-operative airway assessment in Denmark is based on a non-specific clinical assessment. Systematic, evidence-based and consistent airway assessment may reduce the incidence of unanticipated difficult airway management. By assessing multiple predictors for difficult airway management......, the predictive value of the assessment increases. The Simplified Airway Risk Index (SARI) is a multivariate risk score for predicting difficult intubation.This study aims to compare the use of the SARI with a non-specified clinical airway assessment on predicting difficult intubation. Further, to compare......-specific assessment. Data from patients' pre-operative airway assessment are registered in the Danish Anaesthesia Database. Objective scores for intubation and mask ventilation grade the severity of airway managements. The accuracy of predicting difficult intubation and mask ventilation is measured for each group...

  2. Distinct PKA and Epac compartmentalization in airway function and plasticity

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Racke, Kurt; Schmidt, Martina

    Asthma and chronic obstructive pulmonary disease (COPD) are obstructive lung diseases characterized by airway obstruction, airway inflammation and airway remodelling. Next to inflammatory cells and airway epithelial cells, airway mesenchymal cells, including airway smooth muscle cells and

  3. Inhibitory effects of a standardized extract of Justicia pectoralis in an experimental rat model of airway hyper-responsiveness.

    Science.gov (United States)

    Moura, Carlos T M; Batista-Lima, Francisco J; Brito, Teresinha S; Silva, Alfredo A V; Ferreira, Luan C; Roque, Cássia R; Aragão, Karoline S; Havt, Alexandre; Fonseca, Francisco N; Leal, Luzia K A M; Magalhães, Pedro J C

    2017-06-01

    Justicia pectoralis is a plant useful for the treatment of respiratory diseases. Here, we studied the antiasthmatic properties of a standardized extract of J. pectoralis (Jp). Ovalbumin (OVA)-sensitized rats were actively challenged with saline or OVA to study airway hyper-responsiveness after oral treatment with saline or Jp. The ability of Jp to inhibit hyper-reactivity was evaluated in isolated trachea mounted in isolated organ bath chamber. Using KCl or carbachol as contractile agents, tracheal rings of OVA-challenged rats contracted with higher magnitude than trachea of rats challenged with saline. Such hyper-responsive phenotype of OVA-challenged tissues decreased with Jp administration. In Ca + -free medium, Jp or its major constituent coumarin inhibited preferentially the contractions induced by Ca 2+ addition in tissues of OVA-challenged rats stimulated with KCl or acetylcholine. In tissues depleted of their internal Ca + stores in the presence of thapsigargin, Jp inhibited the contraction induced by capacitative Ca 2+ entry. By gavage, Jp abolished the increase caused by challenge with OVA on the levels of IL-1β and TNF-α in the bronchoalveolar fluid and also impaired the changes in gene expression of canonical transient receptor proteins. Jp has antiasthmatic properties in an experimental model that reproduces tracheal hyper-reactivity. © 2017 Royal Pharmaceutical Society.

  4. Obstetric airway management

    African Journals Online (AJOL)

    The use of video laryngoscopy in obstetric theatres must be explored and consideration given to it being placed permanently in high-volume theatres. References. 1. Preston R, Jee R. Obstetric airway management. Int Anesthesiol Clin. 2014;52(2):1-28. 2. Boutonnet M, Faitot V, Katz A, et al. Mallampati class changes during.

  5. The HIV Airway

    African Journals Online (AJOL)

    Adele

    been reported to result in airway obstruction. Conditions not limited to immunocomromised states such as epiglottitis, retropharyngeal abcesses, mediastinal masses and. Ludwig's angina are seen, with increased severity, in HIV in- fected individuals. Knowledge of a patients' HIV status may alert one to potential.

  6. Total airway reconstruction.

    Science.gov (United States)

    Connor, Matthew P; Barrera, Jose E; Eller, Robert; McCusker, Scott; O'Connor, Peter

    2013-02-01

    We present a case of obstructive sleep apnea (OSA) that required multilevel surgical correction of the airway and literature review and discuss the role supraglottic laryngeal collapse can have in OSA. A 34-year-old man presented to a tertiary otolaryngology clinic for treatment of OSA. He previously had nasal and palate surgeries and a Repose tongue suspension. His residual apnea hypopnea index (AHI) was 67. He had a dysphonia associated with a true vocal cord paralysis following resection of a benign neck mass in childhood. He also complained of inspiratory stridor with exercise and intolerance to continuous positive airway pressure. Physical examination revealed craniofacial hypoplasia, full base of tongue, and residual nasal airway obstruction. On laryngoscopy, the paretic aryepiglottic fold arytenoid complex prolapsed into the laryngeal inlet with each breath. This was more pronounced with greater respiratory effort. Surgical correction required a series of operations including awake tracheostomy, supraglottoplasty, midline glossectomy, genial tubercle advancement, maxillomandibular advancement, and reconstructive rhinoplasty. His final AHI was 1.9. Our patient's supraglottic laryngeal collapse constituted an area of obstruction not typically evaluated in OSA surgery. In conjunction with treating nasal, palatal, and hypopharyngeal subsites, our patient's supraglottoplasty represented a key component of his success. This case illustrates the need to evaluate the entire upper airway in a complicated case of OSA. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  7. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... NACFC Carolyn and C. Richard Mattingly Leadership in Mental Health Care Award Mary M. Kontos Award NACFC Reflections ... help your infant or child manage their lung health, watch parents of children with CF and a respiratory therapist talk about the different techniques they use for airway ... Autogenic Drainage Positive Expiratory Pressure High-Frequency Chest ...

  8. Airway management and morbid obesity

    DEFF Research Database (Denmark)

    Kristensen, Michael S

    2010-01-01

    airway and the function of the lungs (decreased residual capacity and aggravated ventilation perfusion mismatch) worse than in lean patients. Proper planning and preparation of airway management is essential, including elevation of the patient's upper body, head and neck. Preoxygenation is mandatory...... solely on whether morbid obesity is present or not. It is important to ensure sufficient depth of anaesthesia before initiating manipulation of the airway because inadequate anaesthesia depth predisposes to aspiration if airway management becomes difficult. The intubating laryngeal mask airway is more...

  9. Bronchial hyperreactivity in non-atopic children with asthma and reflux: effect of anti-reflux treatment.

    Science.gov (United States)

    Khoshoo, Vikram; Mohnot, Sopan; Haydel, Robert; Saturno, Emilio; Edell, Dean; Kobernick, Aaron

    2009-11-01

    The prevalence of bronchial hyperreactivity (BHR) or the effect of anti-reflux treatment on BHR in children with asthma and gastroesophageal reflux disease (GERD) is not known. Thirty non-atopic children with persistent asthma were studied. Extended esophageal pH monitoring was used to diagnose GERD and methacholine challenge test (MCT) was used as a marker of BHR and performed before and 2 years after anti-GERD treatment. Of the 21 patients positive for GERD (group A), 15 had positive MCT suggesting BHR. Of the 9 patients negative for GERD (group B), 5 had positive MCT. On repeat testing 2 years later, 11/15 group A patients and 3/5 group B patients tested negative for BHR. Group A patients were receiving fewer asthma medications and experienced fewer exacerbations than Group B patients. BHR is prevalent in children with asthma and GERD and improves with anti-GERD treatment.

  10. Respiratory syncytial virus infection and bronchial hyperreactivity in children up to two years of age in correlation with atopy.

    Science.gov (United States)

    Relić, Tijana; Ilić, Nevenka; Kostić, Gordana; Jovanović, Dara; Tambur, Zoran; Lazarević, Ivana

    2016-01-01

    Bronchiolitis in early childhood caused by respiratory syncytial virus (RSV) is considered to be important risk factor of the recurrent wheezing and asthma development. The aim of this study was to examine the frequency of RSV infection and atopy in children up to two years of age and to determine their correlation with bronchial hyperreactivity. The study included 175 children aged 5-24 months. The presence of RSV infection was identified by serum levels of IgA and IgG determined by ELISA. Bronchial hyperreactivity (BHR) has been defined as the existence of chronic bronchial disease and/or three or more previous suspected diagnosis of acute bronchial disease. Atopy was confirmed by detection of the specific serum IgE using quantitative multitest Phadiatop infant (cut off 0.35 kUA/L). The children with atopy were more frequently infected with RSV (43.3%) than those without atopy (22.8%; p = 0.02). The higher frequency of RSV infection was found in children with BHR in comparison with those without it but only in the group who also had atopy (77.8% vs. 28.6%, p = 0.018). In the female children, BHR and RSV infection were associated in 62.5% of cases, regardless the atopy. In the male children with atopy, RSV infection was associated with BHR in 83.3% of the cases, while in those without atopy, RSV infection with BHR was found in only 17.4% of the cases. Children up to two years of age with atopy are more frequently infected with RSV (43.3%) than nonatopic children. Every third child with atopy develops BHR and 77.8% of them also have RSV infection. Atopic children are at higher risk for development of BHR when infected with RSV also.

  11. Bronchial thermoplasty and the role of airway smooth muscle: are we on the right direction?

    Directory of Open Access Journals (Sweden)

    Menzella F

    2017-09-01

    Full Text Available Francesco Menzella,1 Mirco Lusuardi,2 Carla Galeone,1 Nicola Facciolongo1 1Department of Medical Specialties, Pneumology Unit, IRCCS – Arcispedale Santa Maria Nuova, Reggio Emilia, 2Unit of Respiratory Rehabilitation, AUSL Reggio Emilia, S Sebastiano Hospital, Correggio, Italy Abstract: Asthma is characterized by inflammation of the airways that includes eosinophils, basal membrane thickening, epithelial sloughing, vascular changes, smooth muscle hypertrophy and hyperplasia, and mucous gland hyperplasia. Recently, there have been studies on the role of hypersensitivity and inflammation in asthma, but the role of bronchial smooth muscle remains unclear. Bronchial thermoplasty is an endoscopic procedure that is approved by the US Food and Drug Administration (FDA for the treatment of severe refractory asthma, based on the local delivery of radio frequency at 65°C to the airways, with the aim of controlling bronchospasm through a reduction of airway smooth muscle (ASM. Several recent studies have shown significant improvement in clinical outcomes of bronchial thermoplasty for asthma, including symptom control, reduction in exacerbation and hospitalization rates, improved quality of life, and reduction in number of working days or school days lost due to asthma. Data from these recent studies have shown reduction in ASM following bronchial thermoplasty and changes in inflammation patterns. It has also been argued that bronchial thermoplasty may have modulating effects on neuroendocrine epithelial cells, bronchial nerve endings, TRPV1 nerve receptors, and type-C unmyelinated fibers in the bronchial mucosa. This may involve interrupting the central and local reflexes responsible for the activation of bronchospasm in the presence of bronchial hyperreactivity. Several questions remain regarding the use of bronchial thermoplasty, mechanism of action, selection of appropriate patients, and long-term effects. In this review, the role of ASM in the

  12. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

  13. Superimposed pressure oscillations: An alternative to treat airway hyperresponsiveness in an acute sensitized airways mouse model.

    Science.gov (United States)

    Jo-Avila, M J; Al-Jumaily, A M

    2017-04-01

    The main driving mechanism during an asthma attack is the hyper-constrictions of airway smooth muscle (ASM), which reduces the airway lumen and makes normal breathing difficult. In spite of some noticeable side effects, bronchodilator drugs such as salbutamol are used to alleviate these symptoms by inducing temporary relaxation of the contracted ASM. In vitro studies have shown that mechanical oscillation can induce relaxation in isolated contracted ASM obtained from healthy subjects but not from asthmatics. To date, little is known about in vivo ASM behaviours, in particular in asthmatic subjects. This in vivo study aims at determining the effect of various superimposed pressure oscillation (SIPO) patterns (different to those occurring during normal breathing) on sensitized airways during an ACh challenge (mimicking an asthmatic attack) and comparing it with the effect of a widely studied broncho-relaxant drug, Isoproterenol (ISO). The study shows that superimposed pressure oscillation in the range of 5-15Hz induces approximately 50% relaxation on pre-constricted sensitized airways in vivo; however, this behaviour was not observed at 20Hz. Our finding suggests that mechanical oscillation, particularly SIPO, may act as a bronchodilator and achieve ASM relaxation. Copyright © 2016. Published by Elsevier B.V.

  14. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  15. Perturbed airway closure

    Science.gov (United States)

    Grotberg, James B.; Halpern, David

    1998-11-01

    The small airways of the lungs are lined with a thin viscous film. A surface-tension driven instability at the air-liquid interface may induce the formation of a liquid bridge blocking airflow if there is sufficient fluid within the film. As a result of the pressures generated within the non-uniform film, the airway wall may also collapse. These instabilities often occur in premature neonates who do not produce sufficient quantities of surfactant. Often, they are placed in ventilators to diminish the risk of airway closure. Two fundamental parameters are the frequency of the ventilation and the tidal volume of the delivered gas. In the current study, we consider the effect of an oscillatory shear stress impinged by the air on a thin film coating a single compliant tube. Nonlinear evolution equations are derived for the film thickness and the wall position. Numerical solutions show that the oscillatory shear stress can saturate the growth of a disturbance at the air-liquid interface. For a given film thickness, there is a critical frequency, dependent on wall parameters, above which closure does not occur when forced by oscillatory shear but will close when unforced.

  16. Prior Bordetella pertussis infection modulates allergen priming and the severity of airway pathology in a murine model of allergic asthma.

    Science.gov (United States)

    Ennis, D P; Cassidy, J P; Mahon, B P

    2004-09-01

    It has been proposed that T helper (Th)2-driven immune deviation in early life can be countered by Th1 inducing childhood infections and that such counter-regulation can protect against allergic asthma. To test whether Th1-inducing infection with Bordetella pertussis protects against allergic asthma using well-characterized murine models. Groups of mice were sensitized to ovalbumin (OVA) in the presence or absence of B. pertussis, a well-characterized Th1 inducing respiratory infection. Immunological, pathological and physiological parameters were measured to assess the impact of infection on immune deviation and airway function. We demonstrate that OVA sensitization does not affect the development of B. pertussis-specific immune responses dominated by IgG2a and IFN-gamma and does not impair Th1-mediated clearance of airway infection. In contrast, B. pertussis infection at the time of sensitization modulated the response to OVA and significantly reduced total serum and OVA-specific IgE. The pattern of cytokine responses, in particular OVA-specific IL-5 responses in the spleen was also modulated. However, B. pertussis did not cause global suppression as IL-10 and IL-13 levels were enhanced in OVA-stimulated spleen cell cultures and in lavage fluid from infected co-sensitized mice. Histopathological examination revealed that B. pertussis infection prior to OVA sensitization resulted in increased inflammation of bronchiolar walls with accompanying hyperplasia and mucous metaplasia of lining epithelia. These pathological changes were accompanied by increased bronchial hyper-reactivity to methacholine exposure. Contrary to the above premise, a Th1 response induced by a common childhood infection does not protect against bronchial hyper-reactivity, but rather exacerbates the allergic asthmatic response, despite modulation of immune mediators.

  17. AAV-6 mediated efficient transduction of mouse lower airways

    OpenAIRE

    Li, Wuping; Zhang, Liqun; Wu, Zhijian; Pickles, Raymond J.; Samulski, R. Jude

    2011-01-01

    AAV1 and AAV6 are two closely related AAV serotypes. In the present study, we found AAV6 was more efficient in transducing mouse lower airway epithelia in vitro and in vivo than AAV1. To further explore the mechanism of this difference, we found that significantly more AAV1 bound to mouse airway epithelia than AAV6, yet transduction by AAV6 was far superior. Lectin competition assays demonstrated that both AAV1 and AAV6 similarly utilize α-2, 3-, and to a lesser extend α-2, 6- linked sialic a...

  18. Anticholinergic treatment in airways diseases.

    LENUS (Irish Health Repository)

    Flynn, Robert A

    2009-10-01

    The prevalence of chronic airways diseases such as chronic obstructive pulmonary disease and asthma is increasing. They lead to symptoms such as a cough and shortness of breath, partially through bronchoconstriction. Inhaled anticholinergics are one of a number of treatments designed to treat bronchoconstriction in airways disease. Both short-acting and long-acting agents are now available and this review highlights their efficacy and adverse event profile in chronic airways diseases.

  19. Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices.

    Directory of Open Access Journals (Sweden)

    Tjitske A Oenema

    Full Text Available Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β1 augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A or TGF-β receptor kinase (SB431542 prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl mimicked the effects of methacholine. Collectively, bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling.

  20. Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-alpha in rats

    Directory of Open Access Journals (Sweden)

    Arruda Marcio Jose Cristiano de

    2006-01-01

    Full Text Available INTRODUCTION: Intestinal or hepatic ischemia/reperfusion induces acute lung injury in animal models of multiple organ failure. Tumor necrosis factor (TNF- alpha is involved in the underlying inflammatory mechanism of acute respiratory distress syndrome. Although the inflammatory cascade leading to acute respiratory distress syndrome has been extensively investigated, the mechanical components of acute respiratory distress syndrome are not fully understood. Our hypothesis is that splanchnic ischemia/reperfusion increases airway reactivity and serum TNF-alpha levels. OBJECTIVE: To assess bronchial smooth muscle reactivity under methacholine stimulation, and to measure serum TNF-alpha levels following intestinal and/or hepatic ischemia/reperfusion in rats. METHOD: Rats were subjected to 45 minutes of intestinal ischemia, or 20 minutes of hepatic ischemia, or to both (double ischemia, or sham procedures (control, followed by 120 minutes of reperfusion. The animals were then sacrificed, and the bronchial response to increasing methacholine molar concentrations (10-7 to 3 x 10-4 was evaluated in an ex-vivo bronchial muscle preparation. Serum TNF-alpha was determined by the L929-cell bioassay. RESULTS: Bronchial response (g/100 mg tissue showed increased reactivity to increasing methacholine concentrations in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. Similarly, serum TNF-alpha (pg/mL concentration was increased in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. CONCLUSION: Intestinal ischemia, either isolated or associated with hepatic ischemia, increased bronchial smooth muscle reactivity, suggesting a possible role for bronchial constriction in respiratory dysfunction following splanchnic ischemia/reperfusion. This increase occurred in concomitance with serum TNF-alpha increase, but whether the increase in TNF-alpha caused this bronchial contractility remains

  1. The Laryngeal Mask Airway (LMA) as an alternative to airway ...

    African Journals Online (AJOL)

    Background: To evaluate the possibility of airway management using a laryngeal mask airway (LMA) during dental procedures on mentally retarded (MR) patients and patients with genetic diseases. Design: A prospective pilot study. Setting: University Hospital. Methods: A pilot study was designed to induce general ...

  2. Airways Disease: Phenotyping Heterogeneity Using Measures of Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Siddiqui Salman

    2007-06-01

    Full Text Available Despite asthma and chronic obstructive pulmonary disease being widely regarded as heterogeneous diseases, a consensus for an accurate system of classification has not been agreed. Recent studies have suggested that the recognition of subphenotypes of airway disease based on the pattern of airway inflammation may be particularly useful in increasing our understanding of the disease. The use of non-invasive markers of airway inflammation has suggested the presence of four distinct phenotypes: eosinophilic, neutrophilic, mixed inflammatory and paucigranulocytic asthma. Recent studies suggest that these subgroups may differ in their etiology, immunopathology and response to treatment. Importantly, novel treatment approaches targeted at specific patterns of airway inflammation are emerging, making an appreciation of subphenotypes particularly relevant. New developments in phenotyping inflammation and other facets of airway disease mean that we are entering an era where careful phenotyping will lead to targeted therapy.

  3. A mechanical design principle for tissue structure and function in the airway tree.

    Directory of Open Access Journals (Sweden)

    Adam S LaPrad

    Full Text Available With every breath, the dynamically changing mechanical pressures must work in unison with the cells and soft tissue structures of the lung to permit air to efficiently traverse the airway tree and undergo gas exchange in the alveoli. The influence of mechanics on cell and tissue function is becoming apparent, raising the question: how does the airway tree co-exist within its mechanical environment to maintain normal cell function throughout its branching structure of diminishing dimensions? We introduce a new mechanical design principle for the conducting airway tree in which mechanotransduction at the level of cells is driven to orchestrate airway wall structural changes that can best maintain a preferred mechanical microenvironment. To support this principle, we report in vitro radius-transmural pressure relations for a range of airway radii obtained from healthy bovine lungs and model the data using a strain energy function together with a thick-walled cylinder description. From this framework, we estimate circumferential stresses and incremental Young's moduli throughout the airway tree. Our results indicate that the conducting airways consistently operate within a preferred mechanical homeostatic state, termed mechanical homeostasis, that is characterized by a narrow range of circumferential stresses and Young's moduli. This mechanical homeostatic state is maintained for all airways throughout the tree via airway wall dimensional and mechanical relationships. As a consequence, cells within the airway walls throughout the airway tree experience similar oscillatory strains during breathing that are much smaller than previously thought. Finally, we discuss the potential implications of how the maintenance of mechanical homeostasis, while facilitating healthy tissue-level alterations necessary for maturation, may lead to airway wall structural changes capable of chronic asthma.

  4. Anaesthesia and subglottic airway obstruction

    African Journals Online (AJOL)

    2009-07-14

    Jul 14, 2009 ... Keywords: shared airway; jet ventilation; TIVA/TCI; laser excision; monitoring. Abstract. In this article, we describe the anaesthetic management and laser excision of a subglottic tumour that caused upper airway obstruction. Stridor was the presenting feature. A good history and careful assessment will ...

  5. Airway management and morbid obesity.

    Science.gov (United States)

    Kristensen, Michael S

    2010-11-01

    Morbidly obese patients present with excess fatty tissue externally on the breast, neck, thoracic wall and abdomen and internally in the mouth, pharynx and abdomen. This excess tissue tends to make access (intubation, tracheostomy) to and patency (during sedation or mask ventilation) of the upper airway and the function of the lungs (decreased residual capacity and aggravated ventilation perfusion mismatch) worse than in lean patients. Proper planning and preparation of airway management is essential, including elevation of the patient's upper body, head and neck. Preoxygenation is mandatory in morbidly obese patients and should be followed by actions to counteract atelectasis formation. The decision as to weather to use a rapid sequence induction, an awake intubation or a standard induction with hypnotics should depend on the thorough airway examination and comorbidity and should not be based solely on whether morbid obesity is present or not. It is important to ensure sufficient depth of anaesthesia before initiating manipulation of the airway because inadequate anaesthesia depth predisposes to aspiration if airway management becomes difficult. The intubating laryngeal mask airway is more efficient in the morbidly obese patients than in lean patients and serves as a rescue device for both failed ventilation and failed intubation. In the 24 h following anaesthesia, morbidly obese patients experience frequent oxygen desaturation periods that can be counteracted by continuous positive airway pressure, noninvasive ventilation and physiotherapy.

  6. CGRP induction in cystic fibrosis airways alters the submucosal gland progenitor cell niche in mice.

    Science.gov (United States)

    Xie, Weiliang; Fisher, John T; Lynch, Thomas J; Luo, Meihui; Evans, Turan I A; Neff, Traci L; Zhou, Weihong; Zhang, Yulong; Ou, Yi; Bunnett, Nigel W; Russo, Andrew F; Goodheart, Michael J; Parekh, Kalpaj R; Liu, Xiaoming; Engelhardt, John F

    2011-08-01

    In cystic fibrosis (CF), a lack of functional CF transmembrane conductance regulator (CFTR) chloride channels causes defective secretion by submucosal glands (SMGs), leading to persistent bacterial infection that damages airways and necessitates tissue repair. SMGs are also important niches for slow-cycling progenitor cells (SCPCs) in the proximal airways, which may be involved in disease-related airway repair. Here, we report that calcitonin gene-related peptide (CGRP) activates CFTR-dependent SMG secretions and that this signaling pathway is hyperactivated in CF human, pig, ferret, and mouse SMGs. Since CGRP-expressing neuroendocrine cells reside in bronchiolar SCPC niches, we hypothesized that the glandular SCPC niche may be dysfunctional in CF. Consistent with this hypothesis, CFTR-deficient mice failed to maintain glandular SCPCs following airway injury. In wild-type mice, CGRP levels increased following airway injury and functioned as an injury-induced mitogen that stimulated SMG progenitor cell proliferation in vivo and altered the proliferative potential of airway progenitors in vitro. Components of the receptor for CGRP (RAMP1 and CLR) were expressed in a very small subset of SCPCs, suggesting that CGRP indirectly stimulates SCPC proliferation in a non-cell-autonomous manner. These findings demonstrate that CGRP-dependent pathways for CFTR activation are abnormally upregulated in CF SMGs and that this sustained mitogenic signal alters properties of the SMG progenitor cell niche in CF airways. This discovery may have important implications for injury/repair mechanisms in the CF airway.

  7. Airway management and morbid obesity

    DEFF Research Database (Denmark)

    Kristensen, Michael S

    2010-01-01

    Morbidly obese patients present with excess fatty tissue externally on the breast, neck, thoracic wall and abdomen and internally in the mouth, pharynx and abdomen. This excess tissue tends to make access (intubation, tracheostomy) to and patency (during sedation or mask ventilation) of the upper...... in morbidly obese patients and should be followed by actions to counteract atelectasis formation. The decision as to weather to use a rapid sequence induction, an awake intubation or a standard induction with hypnotics should depend on the thorough airway examination and comorbidity and should not be based...... solely on whether morbid obesity is present or not. It is important to ensure sufficient depth of anaesthesia before initiating manipulation of the airway because inadequate anaesthesia depth predisposes to aspiration if airway management becomes difficult. The intubating laryngeal mask airway is more...

  8. Hyperreactivity of Blood Leukocytes in Patients with NAFLD to Ex Vivo Lipopolysaccharide Treatment Is Modulated by Metformin and Phosphatidylcholine but Not by Alpha Ketoglutarate.

    Science.gov (United States)

    Zwolak, Agnieszka; Szuster-Ciesielska, Agnieszka; Daniluk, Jadwiga; Słabczyńska, Olga; Kandefer-Szerszeń, Martyna

    2015-01-01

    Toll-like receptor 4 and proinflammatory cytokines play a central role in the progression of nonalcoholic fatty liver disease. We investigated IL-1, IL-6 and TNFα production and toll-like receptor 4 in both--obese and lean patients with non-alcoholic fatty liver disease who met different sets of metabolic syndrome criteria and linked the results with the disease burden. 95 subjects were divided into four groups depending on the following criteria: presence or absence of metabolic syndrome and/or non-alcoholic fatty liver disease, glucose tolerance (prediabetes or normoglycemia) and BMI value (obese or lean). We determined the levels of IL-1β, IL-6, TNFα, and monocyte toll-like receptor 4 expression in fresh blood as well as in blood cultures treated with lipopolysaccharide with or without metformin, alphaketoglutarate or phosphatidylcholine supplementation. The blood leukocytes of patients with non-alcoholic fatty liver disease are hypersensitive to lipopolysaccharide treatment and produce elevated levels of pro-inflammatory cytokines in response to ex vivo treatment with lipopolysaccharide. Moreover, they overexpress toll-like receptor-4. Hyperreactivity was typical mainly for obese patients with non-alcoholic fatty liver disease together with metabolic syndrome and decreased with the severity of disease. Metformin was the most effective in attenuation of hyperreactivity in all groups of patients with non-alcoholic fatty liver disease, but in obese patients the effectiveness of metformin was weaker than in lean. The reduction of cytokine level by metformin was accompanied by the decrease in toll-like receptor-4 expression. phosphatidylcholine also attenuated hyperreactivity to lipopolysaccharide but mainly in obese patients. Alpha ketoglutarate did not modulate cytokines' level and toll-like receptor 4 expression in non-alcoholic fatty liver disease patients. Metformin and phosphatidylcholine attenuated lipopolysaccharide induced toll-like receptor 4

  9. Airway Inflammation and Structural Changes in Airway Hyper-Responsiveness and Asthma: An Overview

    Directory of Open Access Journals (Sweden)

    Louis-Philippe Boulet

    1998-01-01

    Full Text Available Asthma treatment has moved from bronchodilator therapy to an emphasis on anti-inflammatory therapy. Airway inflammation is believed to induce airway hyper-responsiveness (AHR through the release of mediators that increase the airway response to agonists. However, the exact contribution of airway inflammation in the physiology of airway hyper-responsiveness remains undefined. Structural modifications in airways resulting from inflammation may contribute to the development and persistence of AHR and the development of asthma. This paper reviews some of the main components of airway inflammation and structural changes in asthma, and discusses how these processes may interact to modify airway function and induce respiratory symptoms.

  10. Vessel-guided airway tree segmentation

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; Sporring, Jon; Ashraf, Haseem

    2010-01-01

    method is evaluated on 250 low dose computed tomography images from a lung cancer screening trial. Our experiments showed that applying the region growing algorithm on the airway appearance model produces more complete airway segmentations, leading to on average 20% longer trees, and 50% less leakage......This paper presents a method for airway tree segmentation that uses a combination of a trained airway appearance model, vessel and airway orientation information, and region growing. We propose a voxel classification approach for the appearance model, which uses a classifier that is trained...... to differentiate between airway and non-airway voxels. This is in contrast to previous works that use either intensity alone or hand crafted models of airway appearance. We show that the appearance model can be trained with a set of easily acquired, incomplete, airway tree segmentations. A vessel orientation...

  11. Upper airway resistance syndrome.

    Science.gov (United States)

    Montserrat, J M; Badia, J R

    1999-03-01

    This article reviews the clinical picture, diagnosis and management of the upper airway resistance syndrome (UARS). Presently, there is not enough data on key points like the frequency of UARS and the morbidity associated with this condition. Furthermore, the existence of LIARS as an independent sleep disorder and its relation with snoring and obstructive events is in debate. The diagnosis of UARS is still a controversial issue. The technical limitations of the classic approach to monitor airflow with thermistors and inductance plethysmography, as well as the lack of a precise definition of hypopnea, may have led to a misinterpretation of UARS as an independent diagnosis from the sleep apnea/hypopnea syndrome. The diagnosis of this syndrome can be missed using a conventional polysomnographic setting unless appropriate techniques are applied. The use of an esophageal balloon to monitor inspiratory effort is currently the gold standard. However, other sensitive methods such as the use of a pneumotachograph and, more recently, nasal cannula/pressure transducer systems or on-line monitoring of respiratory impedance with the forced oscillation technique may provide other interesting possibilities. Recognition and characterization of this subgroup of patients within sleep breathing disorders is important because they are symptomatic and may benefit from treatment. Management options to treat UARS comprise all those currently available for sleep apnea/hypopnea syndrome (SAHS). However, the subset of patients classically identified as LIARS that exhibit skeletal craneo-facial abnormalities might possibly obtain further benefit from maxillofacial surgery.

  12. Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation.

    Science.gov (United States)

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

    2016-06-01

    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.

  13. AAV-6 mediated efficient transduction of mouse lower airways.

    Science.gov (United States)

    Li, Wuping; Zhang, Liqun; Wu, Zhijian; Pickles, Raymond J; Samulski, R Jude

    2011-09-01

    AAV1 and AAV6 are two closely related AAV serotypes. In the present study, we found AAV6 was more efficient in transducing mouse lower airway epithelia in vitro and in vivo than AAV1. To further explore the mechanism of this difference, we found that significantly more AAV1 bound to mouse airway epithelia than AAV6, yet transduction by AAV6 was far superior. Lectin competition assays demonstrated that both AAV1 and AAV6 similarly utilize α-2, 3-, and to a lesser extend α-2, 6- linked sialic acids as the receptors for transduction. Furthermore, the rates of AAV endocytosis could not account for the transduction differences of AAV1 and AAV6. Finally, it was revealed that AAV6 was less susceptible to ubiquitin/proteasome-mediated blocks than AAV1 when transducing mouse airway epithelia. Thus compared with AAV1, AAV6 has a unique ability to escape proteasome-mediated degradation, which is likely responsible for its higher transduction efficiency in mouse airway epithelium. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. PPARγ Ligands Regulate Noncontractile and Contractile Functions of Airway Smooth Muscle: Implications for Asthma Therapy

    Directory of Open Access Journals (Sweden)

    Chantal Donovan

    2012-01-01

    Full Text Available In asthma, the increase in airway smooth muscle (ASM can contribute to inflammation, airway wall remodeling and airway hyperresponsiveness (AHR. Targetting peroxisome proliferator-activated receptor γ (PPARγ, a receptor upregulated in ASM in asthmatic airways, may provide a novel approach to regulate these contributions. This review summarises experimental evidence that PPARγ ligands, such as rosiglitazone (RGZ and pioglitazone (PGZ, inhibit proliferation and inflammatory cytokine production from ASM in vitro. In addition, inhaled administration of these ligands reduces inflammatory cell infiltration and airway remodelling in mouse models of allergen-induced airways disease. PPARγ ligands can also regulate ASM contractility, with acute treatment eliciting relaxation of mouse trachea in vitro through a PPARγ-independent mechanism. Chronic treatment can protect against the loss of bronchodilator sensitivity to β2-adrenoceptor agonists and inhibit the development of AHR associated with exposure to nicotine in utero or following allergen challenge. Of particular interest, a small clinical trial has shown that oral RGZ treatment improves lung function in smokers with asthma, a group that is generally unresponsive to conventional steroid treatment. These combined findings support further investigation of the potential for PPARγ agonists to target the noncontractile and contractile functions of ASM to improve outcomes for patients with poorly controlled asthma.

  15. Electrical field stimulation causes oxidation of exogenous histamine in Krebs-Henseleit buffer: A potential source of error in studies of isolated airways

    NARCIS (Netherlands)

    A.R. Hulsmann (Anthon); R.H. Raatgeep (Rolien); I.M. Garrelds (Ingrid); A.W. van Toorenenbergen (Albert); J.C. de Jongste (Johan)

    1993-01-01

    textabstractElectric field stimulation (EFS) relaxes human histamine-precontracted airways in vitro. This relaxation is only partly neurally mediated. Nonneural relaxation has been also shown in blood vessels and is due to the generation of oxygen radicals by EFS. In isolated airways the origin of

  16. Environmentally persistent free radicals induce airway hyperresponsiveness in neonatal rat lungs

    Directory of Open Access Journals (Sweden)

    Lominiki Slawo

    2011-03-01

    Full Text Available Abstract Background Increased asthma risk/exacerbation in children and infants is associated with exposure to elevated levels of ultrafine particulate matter (PM. The presence of a newly realized class of pollutants, environmentally persistent free radicals (EPFRs, in PM from combustion sources suggests a potentially unrecognized risk factor for the development and/or exacerbation of asthma. Methods Neonatal rats (7-days of age were exposed to EPFR-containing combustion generated ultrafine particles (CGUFP, non-EPFR containing CGUFP, or air for 20 minutes per day for one week. Pulmonary function was assessed in exposed rats and age matched controls. Lavage fluid was isolated and assayed for cellularity and cytokines and in vivo indicators of oxidative stress. Pulmonary histopathology and characterization of differential protein expression in lung homogenates was also performed. Results Neonates exposed to EPFR-containing CGUFP developed significant pulmonary inflammation, and airway hyperreactivity. This correlated with increased levels of oxidative stress in the lungs. Using differential two-dimensional electrophoresis, we identified 16 differentially expressed proteins between control and CGUFP exposed groups. In the rats exposed to EPFR-containing CGUFP; peroxiredoxin-6, cofilin1, and annexin A8 were upregulated. Conclusions Exposure of neonates to EPFR-containing CGUFP induced pulmonary oxidative stress and lung dysfunction. This correlated with alterations in the expression of various proteins associated with the response to oxidative stress and the regulation of glucocorticoid receptor translocation in T lymphocytes.

  17. Increased cyclooxygenase-2-derived prostanoids contributes to the hyperreactivity to noradrenaline in mesenteric resistance arteries from offspring of diabetic rats.

    Science.gov (United States)

    Ramos-Alves, Fernanda E; de Queiroz, Diego B; Santos-Rocha, Juliana; Duarte, Gloria P; Xavier, Fabiano E

    2012-01-01

    This study analyzed the effect of in utero exposure to maternal diabetes on contraction to noradrenaline in mesenteric resistance arteries (MRA) from adult offspring, focusing on the role of cyclooxygenase (COX)-derived prostanoids. Diabetes in the maternal rat was induced by a single injection of streptozotocin (50 mg/kg body weight) on day 7 of pregnancy. Contraction to noradrenaline was analyzed in isolated MRA from offspring of diabetic (O-DR) and non-diabetic (O-CR) rats at 3, 6 and 12 months of age. Release of thromboxane A(2) (TxA(2)) and prostaglandins E(2) (PGE(2)) and F(2α) (PGF(2α)), was measured by specific enzyme immunoassay kits. O-DR developed hypertension from 6 months of age compared with O-CR. Arteries from O-DR were hyperactive to noradrenaline only at 6 and 12 months of age. Endothelial removal abolished this hyperreactivity to noradrenaline between O-CR and O-DR. Preincubation with either the COX-1/2 (indomethacin) or COX-2 inhibitor (NS-398) decreased noradrenaline contraction only in 6- and 12-month-old O-DR, while it remained unmodified by COX-1 inhibitor SC-560. In vessels from 6-month-old O-DR, a similar reduction in the contraction to noradrenaline produced by NS-398 was observed when TP and EP receptors were blocked (SQ29548+AH6809). In 12-month-old O-DR, this effect was only achieved when TP, EP and FP were blocked (SQ29548+AH6809+AL8810). Noradrenaline-stimulated TxB(2) and PGE(2) release was higher in 6- and 12-month-old O-DR, whereas PGF(2α) was increased only in 12-month-old O-DR. Our results demonstrated that in utero exposure to maternal hyperglycaemia in rats increases the participation of COX-2-derived prostanoids on contraction to noradrenaline, which might help to explain the greater response to this agonist in MRA from 6- and 12-month-old offspring. As increased contractile response in resistance vessels may contribute to hypertension, our results suggest a role for these COX-2-derived prostanoids in elevating vascular

  18. Air pollution, bronchial hyperreactivity and bronchial pulmonary disorders in children and adults. Luftverschmutzung, bronchiale Hyperreagibilitaet und Atemwegserkrankungen bei Kindern und Erwachsenen

    Energy Technology Data Exchange (ETDEWEB)

    Kuehr, J.; Hendel-Kramer, A.; Hader, S.; Urbanek, R. (Freiburg Univ. (Germany, F.R.). Universitaets-Kinderklinik); Karmaus, W. (Wissenschaftszentrum Berlin fuer Sozialforschung gGmbH (WZB) (Germany, F.R.)); Steinitz, H. (Staatliches Gesundheitsamt, Freiburg im Breisgau (Germany, F.R.)); Stephan, V. (National Institutes of Health, Bethesda, MD (USA))

    1989-04-01

    Bronchial hyperreactivity (BH) is a common feature of bronchial asthma. A sample of 560 school children of 2 different climate areas in the South-West of Germany was analyzed by standardized questionnaire, residential factors, passive smoking and skin prick testing (SPT) with 10 common aeoroallergens. BH was investigated by a standardized carbachol inhalation procedure (CIP) in cumulative manner. Pollutants (NO{sub 2}, particulate combustion products) in the outdoor air near the childrens residences were measured in the same winter season. The mode of heating and the ventilation manners (VM) in houses were characterized as parameters for indoor climate. In 149 children (26.6%) a BH in the CIP appeared. For multiple logistic regression analysis the best model to explain the existence of BH was fitted. In this final model the relative risk was significantly increased (odds ratio 2.39, 95%-confidence interval 1.19-4.77) by use of stoves within the dwelling burnt with gas, coal or oil. As confounding variable sensitization in SPT and passive smoking appeared significant. Outdoor air pollution and VM were not of significant relative risk. Therefore the indoor climate in residences which are heated by stoves within the rooms burnt with gas, coal or oil must be considered as a potential risk factor for bronchial hyperreactivity in childhood. (orig./MG).

  19. Pulmonary surfactant in the airway physiology: a direct relaxing effect on the smooth muscle.

    Science.gov (United States)

    Calkovska, A; Uhliarova, B; Joskova, M; Franova, S; Kolomaznik, M; Calkovsky, V; Smolarova, S

    2015-04-01

    Beside alveoli, surface active material plays an important role in the airway physiology. In the upper airways it primarily serves in local defense. Lower airway surfactant stabilizes peripheral airways, provides the transport and defense, has barrier and anti-edematous functions, and possesses direct relaxant effect on the smooth muscle. We tested in vitro the effect of two surfactant preparations Curosurf® and Alveofact® on the precontracted smooth muscle of intra- and extra-pulmonary airways. Relaxation was more pronounced for lung tissue strip containing bronchial smooth muscle as the primary site of surfactant effect. The study does not confirm the participation of ATP-dependent potassium channels and cAMP-regulated epithelial chloride channels known as CFTR chloride channels, or nitric oxide involvement in contractile response of smooth muscle to surfactant.By controlling wall thickness and airway diameter, pulmonary surfactant is an important component of airway physiology. Thus, surfactant dysfunction may be included in pathophysiology of asthma, COPD, or other diseases with bronchial obstruction. Copyright © 2015. Published by Elsevier B.V.

  20. United airway disease: current perspectives

    Directory of Open Access Journals (Sweden)

    Giavina-Bianchi P

    2016-05-01

    Full Text Available Pedro Giavina-Bianchi,* Marcelo Vivolo Aun,* Priscila Takejima, Jorge Kalil, Rosana Câmara Agondi Clinical Immunology and Allergy Division, Faculty of Medicine, University of São Paulo, São Paulo, Brazil*These authors contributed equally to this work. Abstract: 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. Keywords: ARIA, united airway disease, rhinitis, asthma, allergy, atopy, immediate hypersensitivity reaction, guideline

  1. Airway smooth muscle excitation-contraction coupling and airway hyperresponsiveness.

    Science.gov (United States)

    Hirota, Simon; Helli, Peter B; Catalli, Adriana; Chew, Allyson; Janssen, Luke J

    2005-01-01

    The primary complaints from patients with asthma pertain to function of airway smooth muscle (ASM) function including shortness of breath, wheezing, and coughing. Thus, it is imperative to better understand the mechanisms underlying excitation-contraction coupling in ASM. Here, we review the various signaling pathways underlying contraction in ASM, and then examine how these are altered in asthma and airway hyperresponsiveness (a hallmark feature of asthma). Throughout, we highlight how studies of vascular smooth muscle have helped or hindered progress in understanding ASM physiology and pathophysiology.

  2. Postoperative Airway Obstruction by a Bone Fragment

    Directory of Open Access Journals (Sweden)

    Patrick Schober

    2017-01-01

    Full Text Available Postoperative airway obstructions are potentially life-threatening complications. These obstructions may be classified as functional (sagging tongue, laryngospasm, or bronchospasm, pathoanatomical (airway swelling or hematoma within the airways, or foreign body-related. Various cases of airway obstruction by foreign bodies have previously been reported, for example, by broken teeth or damaged airway instruments. Here we present the exceptional case of a postoperative airway obstruction due to a large fragment of the patient’s maxillary bone, left accidentally in situ after transoral surgical tumor resection. Concerning this type of airway obstruction, we discuss possible causes, diagnosis, and treatment options. Although it is an exceptional case after surgery, clinicians should be aware of this potentially life-threatening complication. In summary, this case demonstrates that the differential diagnosis of postoperative airway obstructions should include foreign bodies derived from surgery, including tissue and bone fragments.

  3. Autocrine regulation of asthmatic airway inflammation: role of airway smooth muscle

    NARCIS (Netherlands)

    S. McKay (Sue); H.S. Sharma (Hari)

    2002-01-01

    textabstractChronic airway inflammation is one of the main features of asthma. Release of mediators from infiltrating inflammatory cells in the airway mucosa has been proposed to contribute directly or indirectly to changes in airway structure and function. The airway smooth

  4. Comparing the Laryngeal Mask Airway, Cobra Perilaryngeal Airway and Face Mask in Children Airway Management.

    Science.gov (United States)

    Tekin, Beyza; Hatipoğlu, Zehra; Türktan, Mediha; Özcengiz, Dilek

    2016-04-01

    We compared the effects of the laryngeal mask airway (LMA), face mask and Cobra perilaryngeal airway (PLA) in the airway management of spontaneously breathing paediatric patients undergoing elective inguinal surgery. In this study, 90 cases of 1-14-year-old children undergoing elective inguinal surgery were scheduled. The patients were randomly divided into three groups. Anaesthesia was provided with sevoflurane and 50%-50% nitrous oxide and oxygen. After providing an adequate depth of anaesthesia, supraglottic airway devices were inserted in the group I and II patients. The duration and number of insertion, haemodynamic parameters, plateau and peak inspiratory pressure and positive end-expiratory pressure of the patients were recorded preoperatively, after induction and at 5, 10, 15 and 30 min peroperatively. There were no statistical differences between the groups in terms of haemodynamic parameters (p>0.05). In group II, instrumentation success was higher and instrumentation time was shorter than group II. The positive end-expiratory pressure and plateau and peak inspiratory pressure values were statistically lower in group II (pairway safety and to avoid possible complications, LMA and Cobra PLA could be alternatives to face mask and that the Cobra PLA provided lower airway pressure and had a faster and more easy placement than LMA.

  5. Airway management in Ludwig's angina.

    Science.gov (United States)

    Neff, S P; Merry, A F; Anderson, B

    1999-12-01

    A 37-year-old 91 kg man presented with features of Ludwig's angina. Anaesthesia for incision and drainage of his submandibular abscess was undertaken by two specialist anaesthetists with an otorhinolaryngological surgeon prepared for immediate tracheostomy. After preoxygenation, gas induction with sevoflurane in oxygen was followed by a gush of pus into the oral cavity and laryngospam causing acute upper airway obstruction. This resolved with 25 mg of suxamethonium and an endotracheal tube was passed into the trachea with difficulty. Options for management of the difficult airway in Ludwig's angina are discussed.

  6. Anti-Cytotoxic and Anti-Inflammatory Effects of the Macrolide Antibiotic Roxithromycin in Sulfur Mustard-Exposed Human Airway Epithelial Cells

    National Research Council Canada - National Science Library

    Gao1, Radharaman Ray2, Yan Xiao3, Peter E. Barker3 and Prab, Xiugong

    2006-01-01

    .... In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE...

  7. Outcomes following prehospital airway management in severe ...

    African Journals Online (AJOL)

    Outcomes following prehospital airway management in severe traumatic brain injury. ... Patients were categorised by their method of airway management: rapid sequence intubation (RSI), sedation-assisted intubation, failed intubation, basic airway management, and intubated without drugs. Good outcomes were defined by ...

  8. Emergency surgical airway management in Denmark

    DEFF Research Database (Denmark)

    Rosenstock, C V; Nørskov, A K; Wetterslev, J

    2016-01-01

    BACKGROUND: The emergency surgical airway (ESA) is the final option in difficult airway management. We identified ESA procedures registered in the Danish Anaesthesia Database (DAD) and described the performed airway management. METHODS: We extracted a cohort of 452 461 adult patients undergoing...

  9. The Laryngeal Mask Airway (LMA) as an alternative to airway ...

    African Journals Online (AJOL)

    Adele

    The altered anatomy of the upper airways ... problems with tracheal intubation.2 Nasotracheal intubation may cause bleeding and contamination of the tube with the nasal cavity content. Post-intubation pain in the throat may. P Michalek. 1 ... All patients were examined preoperatively, and were given oral pretreatment using ...

  10. Functional phenotype of airway myocytes from asthmatic airways

    NARCIS (Netherlands)

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

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

  11. Comparison of airway responses in sheep of different age in precision-cut lung slices (PCLS.

    Directory of Open Access Journals (Sweden)

    Verena A Lambermont

    Full Text Available Animal models should display important characteristics of the human disease. Sheep have been considered particularly useful to study allergic airway responses to common natural antigens causing human asthma. A rationale of this study was to establish a model of ovine precision-cut lung slices (PCLS for the in vitro measurement of airway responses in newborn and adult animals. We hypothesized that differences in airway reactivity in sheep are present at different ages.Lambs were delivered spontaneously at term (147d and adult sheep lived till 18 months. Viability of PCLS was confirmed by the MTT-test. To study airway provocations cumulative concentration-response curves were performed with different allergic response mediators and biogenic amines. In addition, electric field stimulation, passive sensitization with house dust mite (HDM and mast cells staining were evaluated.PCLS from sheep were viable for at least three days. PCLS of newborn and adult sheep responded equally strong to methacholine and endothelin-1. The responses to serotonin, leukotriene D4 and U46619 differed with age. No airway contraction was evoked by histamine, except after cimetidine pretreatment. In response to EFS, airways in PCLS from adult and newborn sheep strongly contracted and these contractions were atropine sensitive. Passive sensitization with HDM evoked a weak early allergic response in PCLS from adult and newborn sheep, which notably was prolonged in airways from adult sheep. Only few mast cells were found in the lungs of non-sensitized sheep at both ages.PCLS from sheep lungs represent a useful tool to study pharmacological airway responses for at least three days. Sheep seem well suited to study mechanisms of cholinergic airway contraction. The notable differences between newborn and adult sheep demonstrate the importance of age in such studies.

  12. Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Guang-Ni; Yang, Kai; Xu, Zu-Peng; Zhu, Liang; Hou, Li-Na; Qi, Hong; Chen, Hong-Zhuan, E-mail: hongzhuan_chen@hotmail.com; Cui, Yong-Yao, E-mail: yongyaocui@yahoo.com.cn

    2012-07-01

    Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclin D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation. -- Highlights: ► CSE induces tracheal cell proliferation, hyper-contractility and α-SMA expression. ► Anisodamine reverses CSE-induced tracheal hyper-contractility and cell proliferation. ► ERK, PI3K, and NF-κB pathways and cyclin D1 contribute to the reversal effect.

  13. Is surgical airway necessary for airway management in deep neck infections and Ludwig angina?

    Science.gov (United States)

    Wolfe, Mary M; Davis, James W; Parks, Steven N

    2011-02-01

    Deep neck infections are potentially life-threatening conditions because of airway compromise. Management requires early recognition, antibiotics, surgical drainage, and effective airway control. The Surgical Education and Self-Assessment Program 12 states that awake tracheostomy is the treatment of choice for these patients. With advanced airway control techniques such as retrograde intubation, GlideScope, and fiberoptic intubation, surgical airway is not required. A retrospective analysis of all deep neck abscesses treated from December 1999 to July 2006 was performed. All patients who underwent urgent or emergent surgery for Ludwig angina and submental, submandibular, sublingual, and parapharyngeal abscesses (Current Procedural Terminology codes 41015, 41016, 41017, 42320, and 42725) were included in our review. Charts were studied for age, presence of true Ludwig angina, presence of airway compromise, airway management, morbidity/mortality, and the requirement for surgical airway. Of 29 patients, 6 (20%) had symptoms consistent with true Ludwig angina. Nineteen (65.5%) had evidence of airway compromise. Eight (42%) of these 19 patients required advanced airway control techniques. No patient required a surgical airway, and no mortality resulted from airway compromise. Advance airway control techniques were required more often in patients with airway compromise (P Ludwig angina and deep neck abscesses requires good clinical judgment. Patients with deep neck infections and symptoms of airway compromise may be safely managed with advanced airway control techniques. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Mannitol versus hypertonic saline: Safety and efficacy of mannitol and hypertonic saline in sputum induction and bronchial hyperreactivity assessment.

    Science.gov (United States)

    Alvarez-Puebla, M J; Olaguibel, J M; Almudevar, E; Echegoyen, A A; Vela, C; de Esteban, B

    2015-08-01

    Eosinophilic asthma phenotype predicts good response to corticosteroids and associates to asthmatic exacerbations. Sputum induction by hypertonic saline (HS) inhalation is technically demanding. Bronchial hyperresponsiveness (BHR) to osmotic agents indirectly mirrors active airway inflammation. We compared the safety and ability of HS and mannitol to induce sputum and measure BHR. We evaluated the stability of inflammatory phenotypes. We studied 35 non-smoking asthmatics randomized to undergo HS and mannitol challenges on 2 days 1 week apart. Sputum was sampled for cell analysis and phenotyped as eosinophilic (≥3% eosinophils) and non-eosinophilic (mannitol and nine of them also had BHR to HS. Drops in forced expiratory volume in 1 s were higher from HS challenge than from mannitol challenge. Adequate sputum samples were obtained from 80% subjects (68% mannitol and 71% HS). Eosinophils and macrophages from both challenges correlated. Neutrophils were higher in sputum from HS. Ninety percent samples were equally phenotyped with HS and mannitol. Fractional exhaled nitric oxide, sputum eosinophils and BHR correlated in both challenges. HS and mannitol showed similar capacity to produce valuable sputum samples. BHR to both osmotic stimuli partially resembled airway eosinophilic inflammation but mannitol was more sensitive than HS to assess BHR. Eosinophilic phenotype remained stable in most patients with both stimuli. © The Author(s) 2015.

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

    Directory of Open Access Journals (Sweden)

    Park Chang-Soo

    2006-02-01

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

  16. Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model.

    Directory of Open Access Journals (Sweden)

    Konrad Urbanek

    Full Text Available The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce.To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model.GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro.Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties.Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide system activation and tissue

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

    Directory of Open Access Journals (Sweden)

    Karryn T Grafton

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

  18. allergy, asthma airway and anaphylaxis

    African Journals Online (AJOL)

    The perioperative preparation of children presenting for surgery aims to identify medical problems that might influence the outcome and to institute management strategies to reduce those risks. Respiratory and airway complications remain the most significant cause of morbidity and mortality in modern paediatric ...

  19. Analysis of airways in computed tomography

    DEFF Research Database (Denmark)

    Petersen, Jens

    Chronic Obstructive Pulmonary Disease (COPD) is major cause of death and disability world-wide. It affects lung function through destruction of lung tissue known as emphysema and inflammation of airways, leading to thickened airway walls and narrowed airway lumen. Computed Tomography (CT) imaging...... have become the standard with which to assess emphysema extent but airway abnormalities have so far been more challenging to quantify. Automated methods for analysis are indispensable as the visible airway tree in a CT scan can include several hundreds of individual branches. However, automation...

  20. Airway Disease and Management in Bronchopulmonary Dysplasia.

    Science.gov (United States)

    Amin, Raouf S; Rutter, Michael J

    2015-12-01

    This article presents an overview of the diagnosis and management of airway problems encountered in infants with severe bronchopulmonary dysplasia (BPD). Respiratory failure in premature infants develops as a result of parenchymal and airway diseases. The survival of increasingly premature infants and the ventilatory support required by premature lungs may result in airway disease. The management of respiratory failure depends on whether it is primarily caused by parenchymal versus airway diseases. Continuous airway pressure early in the neonatal period has favorably changed the incidence of BPD. This article discusses the indications, timing, and guidelines for care of tracheotomy. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Hyperreactivity of Blood Leukocytes in Patients with NAFLD to Ex Vivo Lipopolysaccharide Treatment Is Modulated by Metformin and Phosphatidylcholine but Not by Alpha Ketoglutarate.

    Directory of Open Access Journals (Sweden)

    Agnieszka Zwolak

    Full Text Available Toll-like receptor 4 and proinflammatory cytokines play a central role in the progression of nonalcoholic fatty liver disease. We investigated IL-1, IL-6 and TNFα production and toll-like receptor 4 in both--obese and lean patients with non-alcoholic fatty liver disease who met different sets of metabolic syndrome criteria and linked the results with the disease burden.95 subjects were divided into four groups depending on the following criteria: presence or absence of metabolic syndrome and/or non-alcoholic fatty liver disease, glucose tolerance (prediabetes or normoglycemia and BMI value (obese or lean. We determined the levels of IL-1β, IL-6, TNFα, and monocyte toll-like receptor 4 expression in fresh blood as well as in blood cultures treated with lipopolysaccharide with or without metformin, alphaketoglutarate or phosphatidylcholine supplementation.The blood leukocytes of patients with non-alcoholic fatty liver disease are hypersensitive to lipopolysaccharide treatment and produce elevated levels of pro-inflammatory cytokines in response to ex vivo treatment with lipopolysaccharide. Moreover, they overexpress toll-like receptor-4. Hyperreactivity was typical mainly for obese patients with non-alcoholic fatty liver disease together with metabolic syndrome and decreased with the severity of disease. Metformin was the most effective in attenuation of hyperreactivity in all groups of patients with non-alcoholic fatty liver disease, but in obese patients the effectiveness of metformin was weaker than in lean. The reduction of cytokine level by metformin was accompanied by the decrease in toll-like receptor-4 expression. phosphatidylcholine also attenuated hyperreactivity to lipopolysaccharide but mainly in obese patients. Alpha ketoglutarate did not modulate cytokines' level and toll-like receptor 4 expression in non-alcoholic fatty liver disease patients.Metformin and phosphatidylcholine attenuated lipopolysaccharide induced toll

  2. Avian Influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways.

    Directory of Open Access Journals (Sweden)

    Margaret A Scull

    2009-05-01

    Full Text Available Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE, we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37 degrees C, avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal airways (32 degrees C. These data support the hypothesis that avian influenza viruses, ordinarily adapted to the temperature of the avian enteric tract (40 degrees C, rarely infect humans, in part due to differences in host airway regional temperatures. Previously, a critical residue at position 627 in the avian influenza virus polymerase subunit, PB2, was identified as conferring temperature-dependency in mammalian cells. Here, we use reverse genetics to show that avianization of residue 627 attenuates a human virus, but does not account for the different infection between 32 degrees C and 37 degrees C. To determine the mechanism of temperature restriction of avian influenza viruses in HAE at 32 degrees C, we generated recombinant human influenza viruses in either the A/Victoria/3/75 (H3N2 or A/PR/8/34 (H1N1 genetic background that contained avian or avian-like glycoproteins. Two of these viruses, A/Victoria/3/75 with L226Q and S228G mutations in hemagglutinin (HA and neuraminidase (NA from A/Chick/Italy/1347/99 and A/PR/8/34 containing the H7 and N1 from A/Chick/Italy/1347/99, exhibited temperature restriction approaching that of wholly avian influenza viruses. These data suggest that influenza viruses bearing avian or avian-like surface glycoproteins have a reduced capacity to establish productive infection at the temperature of the human proximal airways. This temperature restriction may limit zoonotic transmission of avian influenza viruses and

  3. Airway malacia in children with achondroplasia.

    Science.gov (United States)

    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. © 2013 Wiley Periodicals, Inc.

  4. Ultrasonography in the management of the airway

    DEFF Research Database (Denmark)

    Kristensen, M S

    2011-01-01

    In this study, it is described how to use ultrasonography (US) for real-time imaging of the airway from the mouth, over pharynx, larynx, and trachea to the peripheral alveoli, and how to use this in airway management. US has several advantages for imaging of the airway - it is safe, quick......, repeatable, portable, widely available, and it must be used dynamically for maximum benefit in airway management, in direct conjunction with the airway management, i.e. immediately before, during, and after airway interventions. US can be used for direct observation of whether the tube enters the trachea...... or the esophagus by placing the ultrasound probe transversely on the neck at the level of the suprasternal notch during intubation, thus confirming intubation without the need for ventilation or circulation. US can be applied before anesthesia induction and diagnose several conditions that affect airway management...

  5. Degrees of reality: airway anatomy of high-fidelity human patient simulators and airway trainers.

    Science.gov (United States)

    Schebesta, Karl; Hüpfl, Michael; Rössler, Bernhard; Ringl, Helmut; Müller, Michael P; Kimberger, Oliver

    2012-06-01

    Human patient simulators and airway training manikins are widely used to train airway management skills to medical professionals. Furthermore, these patient simulators are employed as standardized "patients" to evaluate airway devices. However, little is known about how realistic these patient simulators and airway-training manikins really are. This trial aimed to evaluate the upper airway anatomy of four high-fidelity patient simulators and two airway trainers in comparison with actual patients by means of radiographic measurements. The volume of the pharyngeal airspace was the primary outcome parameter. Computed tomography scans of 20 adult trauma patients without head or neck injuries were compared with computed tomography scans of four high-fidelity patient simulators and two airway trainers. By using 14 predefined distances, two cross-sectional areas and three volume parameters of the upper airway, the manikins' similarity to a human patient was assessed. The pharyngeal airspace of all manikins differed significantly from the patients' pharyngeal airspace. The HPS Human Patient Simulator (METI®, Sarasota, FL) was the most realistic high-fidelity patient simulator (6/19 [32%] of all parameters were within the 95% CI of human airway measurements). The airway anatomy of four high-fidelity patient simulators and two airway trainers does not reflect the upper airway anatomy of actual patients. This finding may impact airway training and confound comparative airway device studies.

  6. Airway Secretory microRNAome Changes during Rhinovirus Infection in Early Childhood.

    Directory of Open Access Journals (Sweden)

    Maria J Gutierrez

    Full Text Available Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome and examine the changes during rhinovirus (RV infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood.Nasal airway secretions were obtained from children (≤3 yrs. old during PCR-confirmed RV infections (n = 10 and age-matched controls (n = 10. Nasal EVs were isolated with polymer-based precipitation and global miR profiles generated using NanoString microarrays. We validated our in vivo airway secretory miR data in an in vitro airway epithelium model using apical secretions from primary human bronchial epithelial cells (HBEC differentiated at air-liquid interface (ALI. Bioinformatics tools were used to determine the unified (nasal and bronchial signature airway secretory miRNAome and changes during RV infection in children.Multiscale analysis identified four signature miRs comprising the baseline airway secretory miRNAome: hsa-miR-630, hsa-miR-302d-3p, hsa- miR-320e, hsa-miR-612. We identified hsa-miR-155 as the main change in the baseline miRNAome during RV infection in young children. We investigated the potential biological relevance of the airway secretion of hsa-mir-155 using in silico models derived from gene datasets of experimental in vivo human RV infection. These analyses confirmed that hsa-miR-155 targetome is an overrepresented pathway in the upper airways of individuals infected with RV.Comparative analysis of the airway secretory microRNAome in children indicates that RV infection is associated with airway

  7. Automatic airway-artery analysis on lung CT to quantify airway wall thickening and bronchiectasis

    DEFF Research Database (Denmark)

    Perez-Rovira, Adria; Kuo, Wieying; Petersen, Jens

    2016-01-01

    Purpose: Bronchiectasis and airway wall thickening are commonly assessed in computed tomography (CT) by comparing the airway size with the size of the accompanying artery. Thus, in order to automate the quantification of bronchiectasis and wall thickening following a similar principle......, and pairs airway branches with the accompanying artery, then quantifies airway wall thickening and bronchiectasis by measuring the wall-artery ratio (WAR) and lumen and outer wall airway-artery ratio (AAR). Measurements that do not use the artery size for normalization are also extracted, including wall......-consuming manual annotations and visual scoring methods to quantify abnormal widening and thickening of airways....

  8. Airway epithelial transcription factor NK2 homeobox 1 inhibits mucous cell metaplasia and Th2 inflammation.

    Science.gov (United States)

    Maeda, Yutaka; Chen, Gang; Xu, Yan; Haitchi, Hans Michael; Du, Lingling; Keiser, Angela R; Howarth, Peter H; Davies, Donna E; Holgate, Stephen T; Whitsett, Jeffrey A

    2011-08-15

    Airway mucous cell metaplasia and chronic inflammation are pathophysiological features that influence morbidity and mortality associated with asthma and other chronic pulmonary disorders. Elucidation of the molecular mechanisms regulating mucous metaplasia and hypersecretion provides the scientific basis for diagnostic and therapeutic opportunities to improve the care of chronic pulmonary diseases. To determine the role of the airway epithelial–specific transcription factor NK2 homeobox 1 (NKX2-1, also known as thyroid transcription factor-1 [TTF-1]) in mucous cell metaplasia and lung inflammation. Expression of NKX2-1 in airway epithelial cells from patients with asthma was analyzed. NKX2-1 +/-gene targeted or transgenic mice expressing NKX2-1 in conducting airway epithelial cells were sensitized to the aeroallergen ovalbumin. In vitro studies were used to identify mechanisms by which NKX2-1 regulates mucous cell metaplasia and inflammation. NKX2-1 was suppressed in airway epithelial cells from patients with asthma. Reduced expression of NKX2-1 in heterozygous NKX2-1 +/- gene targeted mice increased mucous metaplasia in the small airways after pulmonary sensitization to ovalbumin. Conversely, mucous cell metaplasia induced by aeroallergen was inhibited by expression of NKX2-1 in the respiratory epithelium in vivo. Genome-wide mRNA analysis of lung tissue from ovalbumin-treated mice demonstrated that NKX2-1 inhibited mRNAs associated with mucous metaplasia and Th2-regulated inflammation,including Spdef, Ccl17, and Il13. In vitro, NKX2-1 inhibited SPDEF, a critical regulator of airway mucous cell metaplasia,and the Th2 chemokine CCL26. The present data demonstrate a novel function for NKX2-1 in a gene network regulating mucous cell metaplasia and allergic inflammation in the respiratory epithelium.

  9. Microscale distribution and dynamic surface tension of pulmonary surfactant normalize the recruitment of asymmetric bifurcating airways.

    Science.gov (United States)

    Yamaguchi, Eiichiro; Nolan, Liam P; Gaver, Donald P

    2017-05-01

    We investigate the influence of bifurcation geometry, asymmetry of daughter airways, surfactant distribution, and physicochemical properties on the uniformity of airway recruitment of asymmetric bifurcating airways. To do so, we developed microfluidic idealized in vitro models of bifurcating airways, through which we can independently evaluate the impact of carina location and daughter airway width and length. We explore the uniformity of recruitment and its relationship to the dynamic surface tension of the lining fluid and relate this behavior to the hydraulic (P Hyd ) and capillary (P Cap ) pressure drops. These studies demonstrate the extraordinary importance of P Cap in stabilizing reopening, even in highly asymmetric systems. The dynamic surface tension of pulmonary surfactant is integral to this stability because it modulates P Cap in a velocity-dependent manner. Furthermore, the surfactant distribution at the propagating interface can have a very large influence on recruitment stability by focusing surfactant preferentially to specific daughter airways. This implies that modification of the surfactant distribution through novel modes of ventilation could be useful in inducing uniformly recruited lungs, aiding in gas exchange, and reducing ventilator-induced lung injury. NEW & NOTEWORTHY The dynamic surface tension of pulmonary surfactant is integral to the uniformity of asymmetric bifurcation airway recruitments because it modulates capillary pressure drop in a velocity-dependent manner. Also, the surfactant distribution at the propagating interface can have a very large influence on recruitment stability by focusing surfactant preferentially to specific daughter airways. This implies that modification of the surfactant distribution through novel modes of ventilation could be useful in inducing uniformly recruited lungs, reducing ventilator-induced lung injury. Copyright © 2017 the American Physiological Society.

  10. Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells.

    Science.gov (United States)

    Huff, Ryan D; Hsu, Alan C-Y; Nichol, Kristy S; Jones, Bernadette; Knight, Darryl A; Wark, Peter A B; Hansbro, Philip M; Hirota, Jeremy A

    2017-01-01

    The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases. We therefore examined how airway epithelial cells regulate uric acid production. Allergen and cigarette smoke mouse models were performed using house dust mite (HDM) and cigarette smoke exposure, respectively, with outcome measurements of lung uric acid levels. Primary human airway epithelial cells isolated from clinically diagnosed patients with asthma and chronic obstructive pulmonary disease (COPD) were grown in submerged cultures and compared to age-matched healthy controls for uric acid release. HBEC-6KT cells, a human airway epithelial cell line, were grown under submerged monolayer conditions for mechanistic and gene expression studies. HDM, but not cigarette smoke exposure, stimulated uric acid production in vivo and in vitro. Primary human airway epithelial cells from asthma, but not COPD patients, displayed elevated levels of extracellular uric acid in culture. In HBEC-6KT, production of uric acid was sensitive to the xanthine dehydrogenase (XDH) inhibitor, allopurinol, and the ATP Binding Cassette C4 (ABCC4) inhibitor, MK-571. Lastly, the pro-inflammatory cytokine combination of TNF-α and IFN-γ elevated extracellular uric acid levels and XDH gene expression in HBEC-6KT cells. Our results suggest that the active production of uric acid from human airway epithelial cells may be intrinsically altered in asthma and be further induced by pro-inflammatory cytokines.

  11. Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Ryan D Huff

    Full Text Available The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases. We therefore examined how airway epithelial cells regulate uric acid production.Allergen and cigarette smoke mouse models were performed using house dust mite (HDM and cigarette smoke exposure, respectively, with outcome measurements of lung uric acid levels. Primary human airway epithelial cells isolated from clinically diagnosed patients with asthma and chronic obstructive pulmonary disease (COPD were grown in submerged cultures and compared to age-matched healthy controls for uric acid release. HBEC-6KT cells, a human airway epithelial cell line, were grown under submerged monolayer conditions for mechanistic and gene expression studies.HDM, but not cigarette smoke exposure, stimulated uric acid production in vivo and in vitro. Primary human airway epithelial cells from asthma, but not COPD patients, displayed elevated levels of extracellular uric acid in culture. In HBEC-6KT, production of uric acid was sensitive to the xanthine dehydrogenase (XDH inhibitor, allopurinol, and the ATP Binding Cassette C4 (ABCC4 inhibitor, MK-571. Lastly, the pro-inflammatory cytokine combination of TNF-α and IFN-γ elevated extracellular uric acid levels and XDH gene expression in HBEC-6KT cells.Our results suggest that the active production of uric acid from human airway epithelial cells may be intrinsically altered in asthma and be further induced by pro-inflammatory cytokines.

  12. Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells

    Science.gov (United States)

    Huff, Ryan D.; Hsu, Alan C-Y.; Nichol, Kristy S.; Jones, Bernadette; Knight, Darryl A.; Wark, Peter A. B.; Hansbro, Philip M.

    2017-01-01

    Introduction The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases. We therefore examined how airway epithelial cells regulate uric acid production. Materials and methods Allergen and cigarette smoke mouse models were performed using house dust mite (HDM) and cigarette smoke exposure, respectively, with outcome measurements of lung uric acid levels. Primary human airway epithelial cells isolated from clinically diagnosed patients with asthma and chronic obstructive pulmonary disease (COPD) were grown in submerged cultures and compared to age-matched healthy controls for uric acid release. HBEC-6KT cells, a human airway epithelial cell line, were grown under submerged monolayer conditions for mechanistic and gene expression studies. Results HDM, but not cigarette smoke exposure, stimulated uric acid production in vivo and in vitro. Primary human airway epithelial cells from asthma, but not COPD patients, displayed elevated levels of extracellular uric acid in culture. In HBEC-6KT, production of uric acid was sensitive to the xanthine dehydrogenase (XDH) inhibitor, allopurinol, and the ATP Binding Cassette C4 (ABCC4) inhibitor, MK-571. Lastly, the pro-inflammatory cytokine combination of TNF-α and IFN-γ elevated extracellular uric acid levels and XDH gene expression in HBEC-6KT cells. Conclusions Our results suggest that the active production of uric acid from human airway epithelial cells may be intrinsically altered in asthma and be further induced by pro-inflammatory cytokines. PMID:28863172

  13. Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway responses

    Directory of Open Access Journals (Sweden)

    Koga Hikari

    2013-01-01

    Full Text Available Abstract Background Chronic asthma is often associated with neutrophilic infiltration in the airways. Neutrophils contain elastase, a potent secretagogue in the airways, nonetheless the role for neutrophil elastase as well as neutrophilic inflammation in allergen-induced airway responses is not well defined. In this study, we have investigated the impact of neutrophil elastase inhibition on the development of allergic airway inflammation and airway hyperresponsiveness (AHR in previously sensitized and challenged mice. Methods BALB/c mice were sensitized and challenged (primary with ovalbumin (OVA. Six weeks later, a single OVA aerosol (secondary challenge was delivered and airway inflammation and airway responses were monitored 6 and 48 hrs later. An inhibitor of neutrophil elastase was administered prior to secondary challenge. Results Mice developed a two-phase airway inflammatory response after secondary allergen challenge, one neutrophilic at 6 hr and the other eosinophilic, at 48 hr. PAR-2 expression in the lung tissues was enhanced following secondary challenge, and that PAR-2 intracellular expression on peribronchial lymph node (PBLN T cells was also increased following allergen challenge of sensitized mice. Inhibition of neutrophil elastase significantly attenuated AHR, goblet cell metaplasia, and inflammatory cell accumulation in the airways following secondary OVA challenge. Levels of IL-4, IL-5 and IL-13, and eotaxin in BAL fluid 6 hr after secondary allergen challenge were significantly suppressed by the treatment. At 48 hr, treatment with the neutrophil elastase inhibitor significantly reduced the levels of IL-13 and TGF-β1 in the BAL fluid. In parallel, in vitro IL-13 production was significantly inhibited in spleen cells from sensitized mice. Conclusion These data indicate that neutrophil elastase plays an important role in the development of allergic airway inflammation and hyperresponsiveness, and would suggest that the

  14. Genetics of complex airway disease.

    Science.gov (United States)

    Cookson, William O C; Moffatt, Miriam F

    2011-05-01

    The past 3 years have seen highly significant genetic effects identified for a wide variety of common complex diseases, including the airway disorders of asthma and chronic obstructive pulmonary disease. It appears that only a portion of the genetically mediated susceptibility to complex diseases has been identified, and there is much left to be discovered. This review briefly describes the results of the genome-wide association studies of asthma and gives an overview of the parallel and increasingly large-scale studies that are taking place with chronic obstructive pulmonary disease. The future impact is discussed of technological advances that allow increasingly large-scale gene expression studies, next-generation sequencing, and genome-wide testing for epigenetic effects. The use of genetic technology to examine the airway microbiota that interact with the mucosa in health and disease is described.

  15. Rhinoscleroma Causing Upper Airway Obstruction

    Directory of Open Access Journals (Sweden)

    Geetika Verma

    2005-01-01

    Full Text Available Rhinoscleroma is a chronic granulomatous condition of the respiratory tract, and is not uncommon in tropical regions; particularly, Mexico, Central America and the Middle East. A few cases have been reported in North America, primarily involving immigrants from endemic countries. The causative organism is Klebsiella rhinoscleromatis, a Gram-negative coccobacillus. Diagnosis is made on the basis of culture of the organism and the characteristic pathology of Mikulicz cells on light microscopy. The condition primarily affects the upper airway, and frequently presents with nasal discharge, nasal obstruction or frontal facial pain. Despite the term 'rhinoscleroma', there may be involvement of the entire respiratory tract. Although the condition is slowly progressive, its natural course portends extensive destruction. Laryngotracheal involvement occurs in approximately 15% to 80% of cases, but patients rarely present with isolated laryngotracheal disease. In the present paper, a case of rhinoscleroma presenting with symptoms of upper airway obstruction is described.

  16. Airway inflammatory and atopy-related responses in athletes

    African Journals Online (AJOL)

    may influence the respiratory system through altering airway function5, and possibly inducing airway remodelling, .... oedema which together reduce airway function, resulting in atopy-related airway symptoms.1,4 .... ual or abnormal healing process resulting in airway structural alterations.23 This remodelling process is ...

  17. Genetics of Complex Airway Disease

    OpenAIRE

    Cookson, William O. C.; Moffatt, Miriam F.

    2011-01-01

    The past 3 years have seen highly significant genetic effects identified for a wide variety of common complex diseases, including the airway disorders of asthma and chronic obstructive pulmonary disease. It appears that only a portion of the genetically mediated susceptibility to complex diseases has been identified, and there is much left to be discovered. This review briefly describes the results of the genome-wide association studies of asthma and gives an overview of the parallel and incr...

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

    Directory of Open Access Journals (Sweden)

    Abeynaike Latasha

    2010-08-01

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

  19. Airway injury during emergency transcutaneous airway access: a comparison at cricothyroid and tracheal sites.

    LENUS (Irish Health Repository)

    Salah, Nazar

    2009-12-01

    Oxygenation via the cricothyroid membrane (CTM) may be required in emergencies, but inadvertent tracheal cannulation may occur. In this study, we compared airway injury between the tracheal and CTM sites using different techniques for airway access.

  20. Extraction of airways from CT (EXACT’09)

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; Ginneken, Bram van; Reinhardt, Joseph M.

    2012-01-01

    This paper describes a framework for establishing a reference airway tree segmentation, which was used to quantitatively evaluate 15 different airway tree extraction algorithms in a standardized manner. Because of the sheer difficulty involved in manually constructing a complete reference standard...... from scratch, we propose to construct the reference using results from all algorithms that are to be evaluated. We start by subdividing each segmented airway tree into its individual branch segments. Each branch segment is then visually scored by trained observers to determine whether...... or not it is a correctly segmented part of the airway tree. Finally, the reference airway trees are constructed by taking the union of all correctly extracted branch segments. Fifteen airway tree extraction algorithms from different research groups are evaluated on a diverse set of 20 chest computed tomography (CT) scans...

  1. Redesigning an airway cart using lean methodology.

    Science.gov (United States)

    Weigel, Wade A

    2016-09-01

    Use lean methodology to create a more efficient difficult airway management equipment transport and setup. The 5S steps of sort, set in order, sweep, standardize, and sustain were used to create a redesigned airway cart. The 5S steps provided the framework to separate the needed from unneeded equipment, logical equipment placement on the cart, and a plan to maintain improvements. Simulations were utilized to compare the revised airway cart to the previous airway equipment storage. Hospital operating rooms and equipment storage rooms. Simulated difficult airway scenarios without patient involvement. Difficult airway equipment 5S process. Total pieces and cost of airway equipment before and after intervention. Walking distance and time to retrieve equipment, setup equipment, and setup defect rate during a simulation. Previously, airway equipment was stored in 4 locations which was reduced a single difficult airway cart. The total pieces of equipment stored was reduced 89% and the cost of disposable equipment inventory was reduced 81%. Simulations looking at the acquisition and setup of equipment during a difficult airway scenario revealed a 39% reduction in equipment set up time, a 77% reduction in non-valued-added set up time, and a 74% reduction in walking distance. There was no difference in set up defect rates. Application of this lean method resulted in a revised single cart with equipment pared down to only what is needed, arranged according to frequency and order of use in a difficult airway. In a simulated difficult airway, there was a reduction in non-value-added time and walking distance to retrieve the equipment. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Management of antenatally detected fetal airway obstruction.

    Science.gov (United States)

    Walker, Paul; Cassey, John; O'callaghan, Stephen

    2005-06-01

    Five cases of antenatally diagnosed fetal airway obstruction have been cared for at the John Hunter Children's Hospital, Newcastle, Australia. A multidisciplinary team manages them during the perinatal period. We present our technique at the time of delivery, which aims to afford us the greatest flexibility in managing both the mother, her child's airway, and the underlying lesion. We begin with an ex utero intrapartum technique (EXIT) and favor routine rigid bronchoscopy to secure the neonate's airway without preliminary attempts at endotracheal intubation.

  3. Multiscale Vessel-guided Airway Tree Segmentation

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; Sporring, Jon; de Bruijne, Marleen

    2009-01-01

    This paper presents a method for airway tree segmentation that uses a combination of a trained airway appearance model, vessel and airway orientation information, and region growing. The method uses a voxel classification based appearance model, which involves the use of a classifier...... is evaluated within EXACT’09 on a diverse set of CT scans. Results show a favorable combination of a relatively large portion of the tree detected correctly with very few false positives....

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

    Directory of Open Access Journals (Sweden)

    Umesh C S Yadav

    2009-08-01

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

  5. Liquid Therapy Delivery Models Using Microfluidic Airways

    Science.gov (United States)

    Mulligan, Molly K.; Grotberg, James B.; Waisman, Dan; Filoche, Marcel; Sznitman, Josué

    2013-11-01

    The propagation and break-up of viscous and surfactant-laden liquid plugs in the lungs is an active area of research in view of liquid plug installation in the lungs to treat a host of different pulmonary conditions. This includes Infant Respiratory Distress Syndrome (IRDS) the primary cause of neonatal death and disability. Until present, experimental studies of liquid plugs have generally been restricted to low-viscosity Newtonian fluids along a single bifurcation. However, these fluids reflect poorly the actual liquid medication therapies used to treat pulmonary conditions. The present work attempts to uncover the propagation, rupture and break-up of liquid plugs in the airway tree using microfluidic models spanning three or more generations of the bronchiole tree. Our approach allows the dynamics of plug propagation and break-up to be studied in real-time, in a one-to-one scale in vitro model, as a function of fluid rheology, trailing film dynamics and bronchial tree geometry. Understanding these dynamics are a first and necessary step to deliver more effectively boluses of liquid medication to the lungs while minimizing the injury caused to epithelial cells lining the lungs from the rupture of such liquid plugs.

  6. [Serum proteomic analysis of cicatricial airway stenosis].

    Science.gov (United States)

    Wang, Li-huan; Zhang, Jie; Wang, Juan; Wang, Ting; Zhang, Ying-ying; Xu, Min

    2013-07-01

    To establish serum protein fingerprint profile in patients with cicatricial airway stenosis and compared with healthy control. Serum samples of 17 cicatricial airway stenosis patients and 17 healthy persons were analyzed by SELDI-TOF-MS to select the differently expressed proteins through Biomarker Wizard software. Compared with healthy control, 49 protein biomarkers were identified. Among them, 25 proteins were up-regulated, 24 proteins were down-regulated. These proteins were confirmed by searching database. There are obvious differentially expressed proteins in patients with cicatricial airway stenosis and controls, which may related with the development of airway scar.

  7. Improvised bubble continuous positive airway pressure (BCPAP ...

    African Journals Online (AJOL)

    Improvised bubble continuous positive airway pressure (BCPAP) device at the National Hospital Abuja gives immediate improvement in respiratory rate and oxygenation in neonates with respiratory distress.

  8. Automated Lobe-Based Airway Labeling

    Directory of Open Access Journals (Sweden)

    Suicheng Gu

    2012-01-01

    Full Text Available 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.

  9. Anatomic Optical Coherence Tomography of Upper Airways

    Science.gov (United States)

    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.

  10. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    2012-01-01

    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  11. Airway contractility and remodeling : Links to asthma symptoms

    NARCIS (Netherlands)

    West, Adrian R.; Syyong, Harley T.; Siddiqui, Sana; Pascoe, Chris D.; Murphy, Thomas M.; Maarsingh, Harm; Deng, Linhong; Maksym, Geoffrey N.; Bosse, Ynuk

    Respiratory symptoms are largely caused by obstruction of the airways. In asthma, airway narrowing mediated by airway smooth muscle (ASM) contraction contributes significantly to obstruction. The spasmogens produced following exposure to environmental triggers, such as viruses or allergens, are

  12. Airway inflammation and mannitol challenge test in COPD

    NARCIS (Netherlands)

    de Nijs, Selma B.; Fens, Niki; Lutter, Rene; Dijkers, Erica; Krouwels, Frans H.; Smids-Dierdorp, Barbara S.; van Steenwijk, Reindert P.; Sterk, Peter J.

    2011-01-01

    ABSTRACT: BACKGROUND: Eosinophilic airway inflammation has successfully been used to tailor anti-inflammatory therapy in chronic obstructive pulmonary disease (COPD). Airway hyperresponsiveness (AHR) by indirect challenges is associated with airway inflammation. We hypothesized that AHR to inhaled

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

    Directory of Open Access Journals (Sweden)

    Jingbo Zhang

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

  14. Airway, responsiveness and inflammation in adolescent elite swimmers

    DEFF Research Database (Denmark)

    Pedersen, Lise; Lund, T.K.; Barnes, P.J.

    2008-01-01

    Background: Whereas increased airway hyperresponsiveness (AHR) and airway inflammation are well documented in adult elite athletes, it remains uncertain whether the same airway changes are present in adolescents involved in elite sport. Objective: To investigate airway responsiveness and airway...... at airway responsiveness as a continuous variable, the swimmers were more responsive to EVH than unselected subjects, but less responsive to metbacholine compared with subjects with asthma. We found no differences in the prevalence of respiratory symptoms between the swimmers and the unselected adolescents...

  15. Airway uric acid is a sensor of inhaled protease allergens and initiates type 2 immune responses in respiratory mucosa1

    Science.gov (United States)

    Hara, Kenichiro; Iijima, Koji; Elias, Martha K.; Seno, Satoshi; Tojima, Ichiro; Kobayashi, Takao; Kephart, Gail M.; Kurabayashi, Masahiko; Kita, Hirohito

    2014-01-01

    While type 2 immune responses to environmental antigens are thought to play pivotal roles in asthma and allergic airway diseases, the immunological mechanisms that initiate the responses are largely unknown. Many allergens have biologic activities, including enzymatic activities and abilities to engage innate pattern-recognition receptors such as TLR4. Here we report that IL-33 and thymic stromal lymphopoietin (TSLP) were produced quickly in the lungs of naïve mice exposed to cysteine proteases, such as bromelain and papain, as a model for allergens. IL-33 and TSLP sensitized naïve animals to an innocuous airway antigen OVA, which resulted in production of type 2 cytokines and IgE antibody and eosinophilic airway inflammation when mice were challenged with the same antigen. Importantly, upon exposure to proteases, uric acid (UA) was rapidly released into the airway lumen, and removal of this endogenous UA by uricase prevented type 2 immune responses. UA promoted secretion of IL-33 by airway epithelial cells in vitro, and administration of UA into the airways of naïve animals induced extracellular release of IL-33, followed by both innate and adaptive type 2 immune responses in vivo. Finally, a potent UA synthesis inhibitor, febuxostat, mitigated asthma phenotypes that were caused by repeated exposure to natural airborne allergens. These findings provide mechanistic insights into the development of type 2 immunity to airborne allergens and recognize airway UA as a key player that regulates the process in respiratory mucosa. PMID:24663677

  16. Airway branching morphogenesis in three dimensional culture

    Directory of Open Access Journals (Sweden)

    Gudjonsson Thorarinn

    2010-11-01

    Full Text Available Abstract Background Lungs develop from the fetal digestive tract where epithelium invades the vascular rich stroma in a process called branching morphogenesis. In organogenesis, endothelial cells have been shown to be important for morphogenesis and the maintenance of organ structure. The aim of this study was to recapitulate human lung morphogenesis in vitro by establishing a three dimensional (3D co-culture model where lung epithelial cells were cultured in endothelial-rich stroma. Methods We used a human bronchial epithelial cell line (VA10 recently developed in our laboratory. This cell line cell line maintains a predominant basal cell phenotype, expressing p63 and other basal markers such as cytokeratin-5 and -14. Here, we cultured VA10 with human umbilical vein endothelial cells (HUVECs, to mimic the close interaction between these cell types during lung development. Morphogenesis and differentiation was monitored by phase contrast microscopy, immunostainings and confocal imaging. Results We found that in co-culture with endothelial cells, the VA10 cells generated bronchioalveolar like structures, suggesting that lung epithelial branching is facilitated by the presence of endothelial cells. The VA10 derived epithelial structures display various complex patterns of branching and show partial alveolar type-II differentiation with pro-Surfactant-C expression. The epithelial origin of the branching VA10 colonies was confirmed by immunostaining. These bronchioalveolar-like structures were polarized with respect to integrin expression at the cell-matrix interface. The endothelial-induced branching was mediated by soluble factors. Furthermore, fibroblast growth factor receptor-2 (FGFR-2 and sprouty-2 were expressed at the growing tips of the branching structures and the branching was inhibited by the FGFR-small molecule inhibitor SU5402. Discussion In this study we show that a human lung epithelial cell line can be induced by endothelial cells to

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

    Science.gov (United States)

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

    2000-05-01

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

  18. In vitro Evaluation of Dry Powder Inhaler Devices of Corticosteroid Preparations

    Directory of Open Access Journals (Sweden)

    Gen Tamura

    2012-01-01

    Conclusions: Because in vitro differences in the aerosolization among different DPI devices containing ICS and combined drug preparations were observed, prescribers of these preparations should consider whether the patients will benefit more from the treatment of the central airways versus the peripheral airways.

  19. Nasal continuous positive airway pressure

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Lamwers, Stephanie; Tepel, Martin

    2012-01-01

    Obstructive sleep apnoea (OSA) is linked to increased cardiovascular risk. This risk can be reduced by nasal continuous positive airway pressure (nCPAP) treatment. As OSA is associated with an increase of several vasoconstrictive factors, we investigated whether nCPAP influences the digital volume...... pulse wave. We performed digital photoplethysmography during sleep at night in 94 consecutive patients who underwent polysomnography and 29 patients treated with nCPAP. Digital volume pulse waves were obtained independently of an investigator and were quantified using an algorithm for continuous...

  20. Airway management in spontaneously breathing anaesthetized children: comparison of the Laryngeal Mask Airway with the cuffed oropharyngeal airway.

    Science.gov (United States)

    Mamaya, Biruta

    2002-06-01

    The efficacy and safety of the smallest size of the cuffed oropharyngeal airway (COPA) for school age, spontaneously breathing children was investigated and compared with the Laryngeal Mask Airway (LMA). Seventy children of school age (7-16 years) were divided into two groups: the COPA (n=35) and the LMA (n=35). Induction was with propofol i.v. or halothane, nitrous oxide, oxygen and fentanyl. After depression of laryngopharyngeal reflexes, a COPA size 8 cm or an LMA was inserted. Ventilation was manually assisted until spontaneous breathing was established. For maintenance, propofol i.v. and fentanyl or halothane with nitrous oxide were used. Local anaesthesia or peripheral blocks were also used. Both extratracheal airways had a highly successful insertion rate, but more positional manoeuvres to achieve a satisfactory airway were required with the COPA, 28.6% versus LMA 2.9%. The need to change the method of airway management was higher (8.6%) in the COPA group. After induction, the need for assisted ventilation was higher in the LMA group 54.3% versus 20% in the COPA group. Airway reaction to cuff inflation was higher in the LMA group 14.3% versus COPA 5.7%. Problems during surgery were similar, except continuous chin support to establish an effective airway was more frequent (11.4%) in the COPA group. In the postoperative period, blood on the device and incidence of sore throat were detected less in the COPA group. The COPA is a good extratracheal airway that provides new possibilities for airway management in school age children with an adequate and well sealed airway, during spontaneous breathing or during short-term assisted manual ventilation.

  1. Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae.

    Science.gov (United States)

    Suri, Reetika; Periselneris, Jimstan; Lanone, Sophie; Zeidler-Erdely, Patti C; Melton, Geoffrey; Palmer, Keith T; Andujar, Pascal; Antonini, James M; Cohignac, Vanessa; Erdely, Aaron; Jose, Ricardo J; Mudway, Ian; Brown, Jeremy; Grigg, Jonathan

    2016-02-01

    Welders are at increased risk of pneumococcal pneumonia. The mechanism for this association is not known. The capacity of pneumococci to adhere to and infect lower airway cells is mediated by host-expressed platelet-activating factor receptor (PAFR). We sought to assess the effect of mild steel welding fumes (MS-WF) on PAFR-dependent pneumococcal adhesion and infection to human airway cells in vitro and on pneumococcal airway infection in a mouse model. The oxidative potential of MS-WF was assessed by their capacity to reduce antioxidants in vitro. Pneumococcal adhesion and infection of A549, BEAS-2B, and primary human bronchial airway cells were assessed by means of quantitative bacterial culture and expressed as colony-forming units (CFU). After intranasal instillation of MS-WF, mice were infected with Streptococcus pneumoniae, and bronchoalveolar lavage fluid (BALF) and lung CFU values were determined. PAFR protein levels were assessed by using immunofluorescence and immunohistochemistry, and PAFR mRNA expression was assessed by using quantitative PCR. PAFR was blocked by CV-3988, and oxidative stress was attenuated by N-acetylcysteine. MS-WF exhibited high oxidative potential. In A549 and BEAS-2B cells MS-WF increased pneumococcal adhesion and infection and PAFR protein expression. Both CV-3988 and N-acetylcysteine reduced MS-WF-stimulated pneumococcal adhesion and infection of airway cells. MS-WF increased mouse lung PAFR mRNA expression and increased BALF and lung pneumococcal CFU values. In MS-WF-exposed mice CV-3988 reduced BALF CFU values. Hypersusceptibility of welders to pneumococcal pneumonia is in part mediated by the capacity of welding fumes to increase PAFR-dependent pneumococcal adhesion and infection of lower airway cells. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  2. Human immunodeficiency virus and the airway

    African Journals Online (AJOL)

    Analee Milner

    Therefore, it is still of value to recognise and understand the pathology caused by degrees of immune compromise from HIV/AIDS. Ironically, ART may impact on the airway owing to immune reconstitution inflammatory syndrome and lipodystrophy. Keywords: AIDS, ART, airway, head and neck manifestation, HIV, human ...

  3. Recovery room nurses' knowledge regarding postoperative airway ...

    African Journals Online (AJOL)

    Background: Recovery room nurses should have the knowledge and skill to identify and manage postoperative airway emergencies in adult patients. Aim: To determine the knowledge of recovery room nurses regarding postoperative airway emergencies in adult patients in private hospitals in Northern Gauteng. Methods: A ...

  4. Early Airway Intervention for Craniofacial Anomalies.

    Science.gov (United States)

    Bohm, Lauren A; Sidman, James D; Roby, Brianne

    2016-11-01

    This article reviews the presentation of children with craniofacial anomalies by the most common sites of airway obstruction. Major craniofacial anomalies may be categorized into those with midface hypoplasia, mandible hypoplasia, combined midface and mandible hypoplasia, and midline deformities. Algorithms of airway interventions are provided to guide the initial management of these complex patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Airway Management in Severe Combat Maxillofacial Trauma.

    Science.gov (United States)

    Keller, Matthew W; Han, Peggy P; Galarneau, Michael R; Brigger, Matthew T

    2015-10-01

    Airway stabilization is critical in combat maxillofacial injury as normal anatomical landmarks can be obscured. The study objective was to characterize the epidemiology of airway management in maxillofacial trauma. Retrospective database analysis. Military treatment facilities in Iraq and Afghanistan and stateside tertiary care centers. In total, 1345 military personnel with combat-related maxillofacial injuries sustained March 2004 to August 2010 were identified from the Expeditionary Medical Encounter Database using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. Descriptive statistics, including basic demographics, injury severity, associated injuries, and airway interventions, were collected. A logistic regression was performed to determine factors associated with the need for tracheostomy. A total of 239 severe maxillofacial injuries were identified. The most common mechanism of injury was improvised explosive devices (66%), followed by gunshot wounds (8%), mortars (5%), and landmines (4%). Of the subjects, 51.4% required intubation on their initial presentation. Of tracheostomies, 30.4% were performed on initial presentation. Of those who underwent bronchoscopy, 65.2% had airway inhalation injury. There was a significant relationship between the presence of head and neck burn and association with airway inhalation injury (P maxillofacial fracture and the need for tracheostomy (P = .0001). There is a high incidence of airway injury in combat maxillofacial trauma, which may be underestimated. Airway management in this population requires a high degree of suspicion and low threshold for airway stabilization. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

  6. Airway and Extracellular Matrix Mechanics in COPD

    NARCIS (Netherlands)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-12

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

  8. Failure of erythromycin to eliminate airway colonization with ureaplasma urealyticum in very low birth weight infants

    Directory of Open Access Journals (Sweden)

    Kruger Thomas E

    2003-09-01

    Full Text Available Abstract Background Airway colonization of mechanically ventilated very low birth weight infants (birth weight Ureaplasma urealyticum (Uu is associated with an increased risk of bronchopulmonary dysplasia (BPD. While Uu is sensitive to erythromycin in vitro, the efficacy of intravenous (IV erythromycin to eliminate Uu from the airways has not been studied. Methods 17 very low birth weight infants with Uu positive tracheal aspirate (TA cultures were randomized to either 5 (8 infants or 10 days (9 infants of IV erythromycin lactobionate (40 mg/kg/day in 3 divided doses. Tracheal aspirate cultures for Uu were performed on days 0, 5, 10 and 15. Results Intravenous erythromycin failed to eliminate airway colonization in a large proportion of infants regardless of whether they received 5 or 10 days of treatment. Ureaplasma urealyticum was isolated from 4/15 (27% of TAs obtained at 5 days, 5/12 TAs (42% obtained at 10 days and 6/11(55% TAs obtained at 15 days (combined group data. Conclusions Erythromycin administered IV does not eliminate Uu from the airways in a large proportion of infants. Failure of erythromycin to eliminate Uu from the airways may contribute to the lack of efficacy of this drug in reducing the incidence of BPD in very low birth weight infants.

  9. [Laryngeal tube II : alternative airway for children?].

    Science.gov (United States)

    Schalk, R; Scheller, B; Peter, N; Rosskopf, W; Byhahn, C; Zacharowski, K; Meininger, D

    2011-06-01

    Difficult airway situations both expected and unexpected, present major challenges to every anesthesiologist, especially in pediatric anesthesia. However, the integration of extraglottic airway devices, such as the laryngeal mask, into the algorithm of difficult airways has improved the handling of difficult airway situations. A device for establishing a supraglottic airway, the laryngeal tube (LT), was introduced in 1999. The LT is an extraglottic airway designed to secure a patent airway during either spontaneous breathing or controlled ventilation. The design of the device has been revised several times and a further development is the LTS II/LTS-D, which provides an additional channel for the insertion of a gastric drain tube. This article reports on the successful use of the LTS II in 12 children aged from 2 days to 6 years when endotracheal intubation, alternative mask or laryngeal mask ventilation failed. Use of the LTS II was associated with a high level of success, securing the airway when other techniques had failed. The potential advantage of the LTS II over the standard LT is an additional suction port, which allows gastric tube placement and can be used as an indirect indicator of correct placement. With a modified insertion technique using an Esmarch manoeuvre, placement was simple and fast to perform. In emergency situations when direct laryngoscopy fails or is too time-consuming the LTS II tube is recommended as an alternative device to secure the airway. As with all extraglottic airway devices, familiarity and clinical experience with the respective device and the corresponding insertion technique are essential for safe and successful use, especially in emergency situations.

  10. Unique recognition of a low molecular weight Onchocerca volvulus antigen by IgG3 antibodies in chronic hyper-reactive oncho-dermatitis (Sowda).

    Science.gov (United States)

    Cabrera, Z; Buttner, D W; Parkhouse, R M

    1988-01-01

    Individual human Ig class responses to Onchocerca volvulus antigens have been evaluated by Western blotting using sera from cases of generalized onchocerciasis and chronic hyper-reactive onchocerciasis (Sowda). in all cases except IgG3 the patterns of recognition by human antibody classes were similar in Sowda and generalized onchocerciasis. Weak or undetectable responses were seen with IgG1, IgG2 and IgM. The total profiles of antigens recognized by the other Ig classes were different, although in some cases certain bands were commonly identified. The result with IgG3, however, was striking. Here, two major antigens (9 kD and 72kD) were recognized by IgG3 antibodies in Sowda sera but not generalized onchocerciasis sera. Furthermore, these two antigens were not recognised by any other Ig class, either in generalized or Sowda onchocerciasis, nor were they detected by antibodies of any class present in a collection of sera representative of other nematode infections. This difference in the IgG3 response was so pronounced that Sowda sera could be distinguished from generalized onchocerciasis sera by an IgG3-specific ELISA assay with a PBS parasite extract as the antigen. Thus, a correlation has been established between one particular clinical condition of onchocerciasis (Sowda) and a serological response, defined in terms of both the parasite antigens and an immunoglobulin class restricted antibody response. Images Fig. 1 Fig. 2 Fig. 5 PMID:3224441

  11. An airway tree-shape model for geodesic airway branch labeling

    DEFF Research Database (Denmark)

    Feragen, Aasa; Lo, Pechin Chien Pau; Gorbunova, Vladlena

    2011-01-01

    We present a mathematical airway tree-shape framework where airway trees are compared using geodesic distances. The framework consists of a rigorously dened shape space for treelike shapes, endowed with a metric such that the shape space is a geodesic metric space. This means that the distance be...... tree and a set of labeled airway trees are combined with a voting scheme to perform automatic branch labeling of segmented airways from the challenging EXACT'09 test set. In spite of the varying quality of the data, we obtain robust labeling results.......We present a mathematical airway tree-shape framework where airway trees are compared using geodesic distances. The framework consists of a rigorously dened shape space for treelike shapes, endowed with a metric such that the shape space is a geodesic metric space. This means that the distance...... between two tree-shapes can be realized as the length of the geodesic, or shortest deformation, connecting the two shapes. By computing geodesics between airway trees, as well as the corresponding airway deformation, we generate airway branch correspondences. Correspondences between an unlabeled airway...

  12. Postentry Processing of Recombinant Adeno-Associated Virus Type 1 and Transduction of the Ferret Lung Are Altered by a Factor in Airway Secretions

    OpenAIRE

    Yan, Ziying; Sun, Xingshen; Evans, Idil A.; Tyler, Scott R.; Song, Yi; Liu, Xiaoming; Sui, Hongshu; Engelhardt, John F.

    2013-01-01

    We recently created a cystic fibrosis ferret model that acquires neonatal lung infection. To develop lung gene therapies for this model, we evaluated recombinant adeno-associated virus (rAAV)-mediated gene transfer to the neonatal ferret lung. Unlike in vitro ferret airway epithelial (FAE) cells, in vivo infection of the ferret lung with rAAV1 required proteasome inhibitors to achieve efficient airway transduction. We hypothesized that differences in transduction between these two systems wer...

  13. Prevention of airway hyperresponsiveness induced by left ventricular dysfunction in rats

    Directory of Open Access Journals (Sweden)

    Petak Ferenc

    2012-12-01

    Full Text Available Abstract Background The effectiveness of strategies for treatment of the altered static lung volume and against the development of bronchial hyperreactivity (BHR following a left ventricular dysfunction (LVD induced by myocardial ischaemia was investigated in a rat model of sustained postcapillary pulmonary hypertension. Methods Airway resistance (Raw was identified from the respiratory system input impedance (Zrs in four groups of rats. End-expiratory lung volume (EELV was determined plethysmographically, and Zrs was measured under baseline conditions and following iv infusions of 2, 6 or 18 μg/kg/min methacholine. Sham surgery was performed in the rats in Group C, while the left interventricular coronary artery was ligated and Zrs and its changes following identical methacholine challenges were reassessed in the same rats 8 weeks later, during which no treatment was applied (Group I, or the animals were treated daily with a combination of an angiotensin enzyme converter inhibitor and a diuretic (enalapril and furosemide, Group IE, or a calcium channel blocker (diltiazem, Group ID. The equivalent dose of methacholine causing a 100% increase in Raw (ED50 was determined in each group. Diastolic pulmonary arterial pressure (PapD was assessed by introducing a catheter into the pulmonary artery. Results The sustained presence of a LVD increased PapD in all groups of rats, with variable but significant elevations in Groups I (p = 0.004, ID (p = 0.013 and IE (p = 0.006. A LVD for 8 weeks induced no changes in baseline Raw but elevated the EELV independently of the treatments. In Group I, BHR consistently developed following the LVD, with a significant decrease in ED50 from 10.0 ± 2.5 to 6.9 ± 2.5 μg/kg/min (p = 0.006. The BHR was completely abolished in both Groups ID and IE, with no changes in ED50 (9.5 ± 3.6 vs. 10.7 ± 4.7, p = 0.33 and 10.6 ± 2.1 vs. 9.8 ± 3.5 μg/kg/min p = 0.56, respectively

  14. The genus Prevotella in cystic fibrosis airways.

    Science.gov (United States)

    Field, Tyler R; Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2010-08-01

    Airway disease resulting from chronic bacterial colonization and consequential inflammation is the leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Although traditionally considered to be due to only a few pathogens, recent re-examination of CF airway microbiology has revealed that polymicrobial communities that include many obligate anaerobes colonize lower airways. The purpose of this study was to examine Prevotella species in CF airways by quantitative culture and phenotypic characterization. Expectorated sputum was transferred to an anaerobic environment immediately following collection and examined by quantitative microbiology using a variety of culture media. Isolates were identified as facultative or obligate anaerobes and the later group was identified by 16S rRNA sequencing. Prevotella spp. represented the majority of isolates. Twelve different species of Prevotella were recovered from 16 patients with three species representing 65% of isolates. Multiple Prevotella species were often isolated from the same sputum sample. These isolates were biochemically characterized using Rapid ID 32A kits (BioMérieux), and for their ability to produce autoinducer-2 and beta-lactamases. Considerable phenotypic variability between isolates of the same species was observed. The quantity and composition of Prevotella species within a patients' airway microbiome varied over time. Our results suggest that the diversity and dynamics of Prevotella in CF airways may contribute to airway disease. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  15. Post-extubation airway obstruction. Literature review

    Directory of Open Access Journals (Sweden)

    Álvaro SÁNCHEZ-TABERNERO

    2017-03-01

    Full Text Available Introduction and objective: airway obstruction after extubation in any surgery is a critical event with low incidence, which may require reintubation or tracheostomy, which often otolaryngologist is required. Objective: To determine the prevalence of BVA and its causes through systematic literature review. Method: Literature review in PubMed, Scopus and Cochrane clinical trials, meta-analysis, reviews and case series and control over airway obstruction after extubation that requires reintubation in adults. Results: 6 studies and one clinical practice guidelines were selected. The most common cause of extubation failure is blocking the airway for various reasons (pharyngeal muscle weakness residual effect -often farmacologycal-, laryngospasm, vocal cord paralysis, edema of upper respiratory tract, cervical postoperative hematoma, foreign bodies or secretions. Most cases of re-intubation occurred within 2 hours after extubation. Conclusions: The most common cause of failure after general anesthesia extubation is blocking the airway generally caused by residual neuromuscular blocking effect. Airway obstruction risk increases in airway and head and neck surgery. Difficult intubation guidlines have improved performance and reduced adverse events and similar strategies must be implemented in extubation. The procedure extubation and reintubation should be documented. Working groups airway must be multidisciplinary and include specialists in otolaryngology.

  16. Impact of bacterial infections on airway diseases

    Directory of Open Access Journals (Sweden)

    G. B. Toews

    2005-12-01

    Full Text Available Bacterial infections play an important role as aetiologic agents in acute exacerbations of chronic obstructive pulmonary disease (COPD. Modern investigational tools, including bronchoscopy, microbial molecular epidemiology and measurement of specific immunity have established that bacteria cause up to 50% of acute exacerbations in COPD. Acute exacerbations have enormous economic costs and contribute to morbidity, mortality and impairment in health related quality of life. Chronic bacterial persistence in the lower airways and lower respiratory tract in patients with COPD is not innocuous. It is likely to contribute to persistent airway inflammation and might contribute to acute airway exacerbations or progression of airway obstruction. Further investigation is required in these fertile areas of investigation. Bacteria also play a role in asthma exacerbations, but their role is less well defined than with patients with COPD. Mycoplasma pneumoniae may be associated with asthma chronicity. Chronic airway infection models document that M. pneumoniae plays a role in airway remodelling, including angiogenesis, vascular remodelling and airway wall thickening. Recent studies have identified patients with asthma as an at-risk group for invasive pneumococcal disease. The feasibility and cost effectiveness of a pneumococcal vaccination strategy among persons with asthma deserves careful, immediate attention.

  17. 21 CFR 868.2600 - Airway pressure monitor.

    Science.gov (United States)

    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 airway...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  19. Effect of Continuous Positive Airway Pressure on Airway Reactivity in Asthma. A Randomized, Sham-controlled Clinical Trial

    OpenAIRE

    Holbrook, Janet T.; Sugar, Elizabeth A.; Brown, Robert H., Jr.; Drye, Lea T.; Irvin, Charles G.; Schwartz, Alan R.; Tepper, Robert S.; Wise, Robert A; Yasin, Razan Z.; Busk, Michael F.

    2016-01-01

    Rationale: Studies have demonstrated that application of stress suppresses airway smooth muscle contractility. In animal models of asthma, continuous positive airway pressure (CPAP) reduced airway reactivity. Short-term studies of CPAP in patients with asthma showed reductions in airway reactivity.

  20. Anaerobic bacteria colonizing the lower airways in lung cancer patients

    Directory of Open Access Journals (Sweden)

    Anna Malm

    2011-07-01

    Full Text Available Anaerobes comprise most of the endogenous oropharyngeal microflora, and can cause infections of airways in lung cancer patients who are at high risk for respiratory tract infections. The aim of this study was to determine the frequency and species diversity of anaerobes in specimens from the lower airways of lung cancer patients. Sensitivity of the isolates to conventional antimicrobial agents used in anaerobe therapy was assessed. Respiratory secretions obtained by bronchoscopy from 30 lung cancer patients were cultured onto Wilkins- -Chalgren agar in anaerobic conditions at 37°C for 72–96 hours. The isolates were identified using microtest Api 20A. The minimal inhibitory concentrations for penicillin G, amoxicillin/clavulanate, piperacillin/tazobactam, cefoxitin, imipenem, clindamycin, and metronidazole were determined by E-test. A total of 47 isolates of anaerobic bacteria were detected in 22 (73.3% specimens. More than one species of anaerobe was found in 16 (53.3% samples. The most frequently isolated were Actinomyces spp. and Peptostreptococcus spp., followed by Eubacterium lentum, Veillonella parvula, Prevotella spp., Bacteroides spp., Lactobacillus jensenii. Among antibiotics used in the study amoxicillin/clavulanate and imipenem were the most active in vitro (0% and 2% resistant strains, respectively. The highest resistance rate was found for penicillin G and metronidazole (36% and 38% resistant strains, respectively. The results obtained confirm the need to conduct analyses of anaerobic microflora colonizing the lower respiratory tract in patients with lung cancer to monitor potential etiologic factors of airways infections, as well as to propose efficient, empirical therapy. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 263–266

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

    Science.gov (United States)

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

    2017-09-01

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

  2. Mucosal symptoms elicited by fragrance products in a population-based sample in relation to atopy and bronchial hyper-reactivity

    DEFF Research Database (Denmark)

    Elberling, J; Linneberg, A; Dirksen, A

    2005-01-01

    BACKGROUND: Exposure to perfume and fragrance products may, in some individuals, cause symptoms from the eyes and airways. The localization, character and risk factors of such symptoms in the general population are unknown. OBJECTIVE: To investigate both the localization and character of symptoms...

  3. The effects of cannabidiol on the antigen-induced contraction of airways smooth muscle in the guinea-pig.

    Science.gov (United States)

    Dudášová, A; Keir, S D; Parsons, M E; Molleman, A; Page, C P

    2013-06-01

    (-)-Δ(9)-Tetrahydrocannabinol has been demonstrated to have beneficial effects in the airways, but its psychoactive effects preclude its therapeutic use for the treatment of airways diseases. In the present study we have investigated the effects of (-)-cannabidiol, a non-psychoactive component of cannabis for its actions on bronchial smooth muscle in vitro and in vivo. Guinea-pig bronchial smooth muscle contractions induced by exogenously applied spasmogens were measured isometrically. In addition, contractile responses of bronchial smooth muscle from ovalbumin-sensitized guinea-pigs were investigated in the absence or presence of (-)-cannabidiol. Furthermore, the effect of (-)-cannabidiol against ovalbumin-induced airway obstruction was investigated in vivo in ovalbumin-sensitized guinea-pigs. (-)-Cannabidiol did not influence the bronchial smooth muscle contraction induced by carbachol, histamine or neurokinin A. In contrast, (-)-cannabidiol inhibited anandamide- and virodhamine-induced responses of isolated bronchi. A fatty acid amide hydrolase inhibitor, phenylmethanesulfonyl fluoride reversed the inhibitory effect of (-)-cannabidiol on anandamide-induced contractions. In addition, (-)-cannabidiol inhibited the contractile response of bronchi obtained from allergic guinea-pigs induced by ovalbumin. In vivo, (-)-cannabidiol reduced ovalbumin-induced airway obstruction. In conclusion, our results suggest that cannabidiol can influence antigen-induced airway smooth muscle tone suggesting that this molecule may have beneficial effects in the treatment of obstructive airway disorders. Copyright © 2013. Published by Elsevier Ltd.

  4. Generation of novel AAV variants by directed evolution for improved CFTR delivery to human ciliated airway epithelium.

    Science.gov (United States)

    Li, Wuping; Zhang, Liqun; Johnson, Jarrod S; Zhijian, Wu; Grieger, Joshua C; Ping-Jie, Xiao; Drouin, Lauren M; Agbandje-McKenna, Mavis; Pickles, Raymond J; Samulski, R Jude

    2009-12-01

    Recombinant adeno-associated virus (AAV) vectors expressing the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been used to deliver CFTR to the airway epithelium of cystic fibrosis (CF) patients. However, no significant CFTR function has been demonstrated likely due to low transduction efficiencies of the AAV vectors. To improve AAV transduction efficiency for human airway epithelium (HAE), we generated a chimeric AAV library and performed directed evolution of AAV on an in vitro model of human ciliated airway epithelium. Two independent and novel AAV variants were identified that contained capsid components from AAV-1, AAV-6, and/or AAV-9. The transduction efficiencies of the two novel AAV variants for human ciliated airway epithelium were three times higher than that for AAV-6. The novel variants were then used to deliver CFTR to ciliated airway epithelium from CF patients. Here we show that our novel AAV variants, but not the parental, AAV provide sufficient CFTR delivery to correct the chloride ion transport defect to ~25% levels measured in non-CF cells. These results suggest that directed evolution of AAV on relevant in vitro models will enable further improvements in CFTR gene transfer efficiency and the development of an efficacious and safe gene transfer vector for CF lung disease.

  5. Airway Tree Extraction with Locally Optimal Paths

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; Sporring, Jon; Pedersen, Jesper Johannes Holst

    2009-01-01

    This paper proposes a method to extract the airway tree from CT images by continually extending the tree with locally optimal paths. This is in contrast to commonly used region growing based approaches that only search the space of the immediate neighbors. The result is a much more robust method...... for tree extraction that can overcome local occlusions. The cost function for obtaining the optimal paths takes into account of an airway probability map as well as measures of airway shape and orientation derived from multi-scale Hessian eigen analysis on the airway probability. Significant improvements...... were achieved compared to a region growing based method, with up to 36% longer trees at a slight increase of false positive rate....

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

    Science.gov (United States)

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

  7. Prestretched airway smooth muscle response to length oscillation.

    Science.gov (United States)

    Al-Jumaily, Ahmed M; Roos, Kevin; Bessaguet, Sandy; Jo Avila, Miguel

    2017-01-01

    Airway smooth muscle (ASM) hyperconstriction is the cause of many respiratory diseases including asthma. In vitro testing has demonstrated that the active forces of ASM are reduced by length oscillation (LO) mimicking tidal breathing. In a previous study, we demonstrated that this force reduction can be further enhanced when superimposing oscillations (with certain frequencies and amplitudes) on this LO In contrast, it has been reported that pressurizing the lung may help in relieving asthmatic airway constrictions. Ultimately, this pressurizing stretches the ASM and may disturb the acto-myosin cross-bridges in a manner similar to LO; however, it is of a static rather than dynamic nature. This research investigates the effect of combining both prestretch- and LO-applications on contracted porcine ASM Isolated porcine ASM relaxation was tested with a 0.56%, 2%, or 4% stretch of its reference length (Lref) in addition to LO These oscillations are composed of a main wave mimicking the normal breathing (frequency of 0.33 Hz and amplitude of 4% Lref) and superimposed oscillations (frequencies of 20, 30, 40, 60 and 80 Hz and amplitude of 1% Lref). The oscillations were maintained for 10 min. The results demonstrate that a prestretch of 0.56% and 2% Lref does enhance the contracted ASM relaxation at certain superimposed length oscillations frequencies while of 4% Lref does not. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  8. Cortex phellodendri Extract Relaxes Airway Smooth Muscle

    OpenAIRE

    Qiu-Ju Jiang; Weiwei Chen; Hong Dan; Li Tan; He Zhu; Guangzhong Yang; Jinhua Shen; Yong-Bo Peng; Ping Zhao; Lu Xue; Meng-Fei Yu; Liqun Ma; Xiao-Tang Si; Zhuo Wang; Jiapei Dai

    2016-01-01

    Cortex phellodendri is used to reduce fever and remove dampness and toxin. Berberine is an active ingredient of C. phellodendri. Berberine from Argemone ochroleuca can relax airway smooth muscle (ASM); however, whether the nonberberine component of C. phellodendri has similar relaxant action was unclear. An n-butyl alcohol extract of C. phellodendri (NBAECP, nonberberine component) was prepared, which completely inhibits high K+- and acetylcholine- (ACH-) induced precontraction of airway smoo...

  9. PLUNC is a novel airway surfactant protein with anti-biofilm activity.

    Directory of Open Access Journals (Sweden)

    Lokesh Gakhar

    2010-02-01

    Full Text Available The PLUNC ("Palate, lung, nasal epithelium clone" protein is an abundant secretory product of epithelia present throughout the conducting airways of humans and other mammals, which is evolutionarily related to the lipid transfer/lipopolysaccharide binding protein (LT/LBP family. Two members of this family--the bactericidal/permeability increasing protein (BPI and the lipopolysaccharide binding protein (LBP--are innate immune molecules with recognized roles in sensing and responding to Gram negative bacteria, leading many to propose that PLUNC may play a host defense role in the human airways.Based on its marked hydrophobicity, we hypothesized that PLUNC may be an airway surfactant. We found that purified recombinant human PLUNC greatly enhanced the ability of aqueous solutions to spread on a hydrophobic surface. Furthermore, we discovered that PLUNC significantly reduced surface tension at the air-liquid interface in aqueous solutions, indicating novel and biologically relevant surfactant properties. Of note, surface tensions achieved by adding PLUNC to solutions are very similar to measurements of the surface tension in tracheobronchial secretions from humans and animal models. Because surfactants of microbial origin can disperse matrix-encased bacterial clusters known as biofilms [1], we hypothesized that PLUNC may also have anti-biofilm activity. We found that, at a physiologically relevant concentration, PLUNC inhibited biofilm formation by the airway pathogen Pseudomonas aeruginosa in an in vitro model.Our data suggest that the PLUNC protein contributes to the surfactant properties of airway secretions, and that this activity may interfere with biofilm formation by an airway pathogen.

  10. Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.

    Science.gov (United States)

    Bai, Jianwu; Smock, Steven L; Jackson, George R; MacIsaac, Kenzie D; Huang, Yongsheng; Mankus, Courtney; Oldach, Jonathan; Roberts, Brian; Ma, Yu-Lu; Klappenbach, Joel A; Crackower, Michael A; Alves, Stephen E; Hayden, Patrick J

    2015-01-01

    Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model. Air-liquid interface (ALI) human airway epithelial cell cultures were prepared from 6 asthmatic and 6 non-asthmatic donors. The effects of rhinovirus RV-A16 on ALI cultures were compared. Genome-wide gene expression changes in ALI cultures following HRV infection at 24 hours post exposure were further analyzed using RNA-seq technology. Cellular gene expression and cytokine/chemokine secretion were further evaluated by qPCR and a Luminex-based protein assay, respectively. ALI cultures were readily infected by HRV. RNA-seq analysis of HRV infected ALI cultures identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial structure and remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1, MUC5AC, CDHR3), and novel ones that were identified for the first time in this study (e.g. CCRL1). ALI-cultured human airway epithelial cells challenged with HRV are a useful translational model for the study of HRV-induced responses in airway epithelial cells, given that gene expression profile using this model largely recapitulates some important patterns of gene responses in patients during clinical HRV infection. Furthermore, our data emphasize that both abnormal airway epithelial structure and inflammatory signaling are two important asthma signatures, which can be further exacerbated by HRV infection.

  11. Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.

    Directory of Open Access Journals (Sweden)

    Jianwu Bai

    Full Text Available Human airway epithelial cells are the principal target of human rhinovirus (HRV, a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1 to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2 to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model.Air-liquid interface (ALI human airway epithelial cell cultures were prepared from 6 asthmatic and 6 non-asthmatic donors. The effects of rhinovirus RV-A16 on ALI cultures were compared. Genome-wide gene expression changes in ALI cultures following HRV infection at 24 hours post exposure were further analyzed using RNA-seq technology. Cellular gene expression and cytokine/chemokine secretion were further evaluated by qPCR and a Luminex-based protein assay, respectively.ALI cultures were readily infected by HRV. RNA-seq analysis of HRV infected ALI cultures identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial structure and remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1, MUC5AC, CDHR3, and novel ones that were identified for the first time in this study (e.g. CCRL1.ALI-cultured human airway epithelial cells challenged with HRV are a useful translational model for the study of HRV-induced responses in airway epithelial cells, given that gene expression profile using this model largely recapitulates some important patterns of gene responses in patients during clinical HRV infection. Furthermore, our data emphasize that both abnormal airway epithelial structure and inflammatory signaling are two important asthma signatures, which can be further exacerbated by HRV infection.

  12. Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease.

    Science.gov (United States)

    Cortjens, Bart; de Boer, Onno J; de Jong, Rineke; Antonis, Adriaan Fg; Sabogal Piñeros, Yanaika S; Lutter, René; van Woensel, Job Bm; Bem, Reinout A

    2016-02-01

    Human respiratory syncytial virus (RSV) is the most important cause of severe lower respiratory tract disease (LRTD) in young children worldwide. Extensive neutrophil accumulation in the lungs and occlusion of small airways by DNA-rich mucus plugs are characteristic features of severe RSV-LRTD. Activated neutrophils can release neutrophil extracellular traps (NETs), extracellular networks of DNA covered with antimicrobial proteins, as part of the first-line defence against pathogens. NETs can trap and eliminate microbes; however, abundant NET formation may also contribute to airway occlusion. In this study, we investigated whether NETs are induced by RSV and explored their potential anti-viral effect in vitro. Second, we studied NET formation in vivo during severe RSV-LRTD in infants and bovine RSV-LRTD in calves, by examining bronchoalveolar lavage fluid and lung tissue sections, respectively. NETs were visualized in lung cytology and tissue samples by DNA and immunostaining, using antibodies against citrullinated histone H3, elastase and myeloperoxidase. RSV was able to induce NET formation by human neutrophils in vitro. Furthermore, NETs were able to capture RSV, thereby precluding binding of viral particles to target cells and preventing infection. Evidence for the formation of NETs in the airways and lungs was confirmed in children with severe RSV-LRTD. Detailed histopathological examination of calves with RSV-LRTD showed extensive NET formation in dense plugs occluding the airways, either with or without captured viral antigen. Together, these results suggest that, although NETs trap viral particles, their exaggerated formation during severe RSV-LRTD contributes to airway obstruction. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. Ultrasound: A novel tool for airway imaging

    Directory of Open Access Journals (Sweden)

    Siddharthkumar Bhikhabhai Parmar

    2014-01-01

    Full Text Available Context: The scope of ultrasound is emerging in medical science, particularly outside traditional areas of radiology practice. Aims: We designed this study to evaluate feasibility of bedside sonography as a tool for airway assessment and to describe sonographic anatomy of airway. Settings and Design: A prospective, clinical study. Materials and Methods: We included 100 adult, healthy volunteers of either sex to undergo airway imaging systemically starting from floor of the mouth to the sternal notch in anterior aspect of neck by sonography. Results: We could visualize mandible and hyoid bone as a bright hyperechoic structure with hypoechoic acoustic shadow underneath. Epiglottis, thyroid cartilage, cricoid cartilage, and tracheal rings appeared hypoechoic. Vocal cords were visualized through thyroid cartilage. Interface between air and mucosa lining the airway produced a bright hyperechoic linear appearance. Artifacts created by intraluminal air prevented visualization of posterior pharynx, posterior commissure, and posterior wall of trachea. Conclusions: Ultrasound is safe, quick, noninvasive, repeatable, and bedside tool to assess the airway and can provide real-time dynamic images relevant for several aspects of airway management.

  14. Link between vitamin D and airway remodeling

    Directory of Open Access Journals (Sweden)

    Berraies A

    2014-04-01

    Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

  15. Airway foreign body in children

    Directory of Open Access Journals (Sweden)

    Marina GONZÁLEZ-HERRERO

    2017-11-01

    Full Text Available Introduction and objective: The aspiration of a foreign body in children is a frequent emergency in pediatrics, being potentially lethal. Method: Narrative review. Results: This pathology mainly affects children under 5 years of age with a peak of incidence between the first and third years of life. The clinic will depend on the type of foreign body (size, shape, possibility of breaking, organic or not, the age of the child and the location of the object. In our environment, the most frequent is the aspiration of nuts (peanuts and sunflower seeds. After the initial picture, an asymptomatic period tends to occur, which favors delayed diagnosis and leads to possible errors in the diagnosis. Discussion: An adequate clinical history and a high diagnostic suspicion are fundamental to favor an early treatment. The presence of a normal chest X-ray does not exclude the presence of a foreign body in the airway, so a bronchoscopy is indicated if the diagnostic suspicion is high. The treatment of choice is extraction by rigid bronchoscopy, being controversial the use of flexible fibrobronchoscope. Conclusions: Conclusions: The aspiration of a foreign body is a pediatric emergency that requires a diagnosis and early treatment. The highest incidence occurs in children under 3 years and more frequently in men. The most commonly aspirated material in our environment are nuts, mainly located in the bronchial tree. The initial episode may go unnoticed, delaying the diagnosis and may lead to progressive respiratory distress in the child. A detailed clinical history and suspicion of this pathology are essential in children at risk age who present with cough and dyspnea of sudden onset. The existence of a normal chest radiograph should not postpone bronchoscopy when there is high clinical suspicion. The treatment of choice for the extraction of foreign bodies in airways in children is rigid bronchoscopy, being controversial the use of the flexible fibrobronchoscope

  16. Aldose reductase inhibition prevents metaplasia of airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Umesh C S Yadav

    Full Text Available BACKGROUND: Goblet cell metaplasia that causes mucus hypersecretion and obstruction in the airway lumen could be life threatening in asthma and chronic obstructive pulmonary disease patients. Inflammatory cytokines such as IL-13 mediate the transformation of airway ciliary epithelial cells to mucin-secreting goblet cells in acute as well as chronic airway inflammatory diseases. However, no effective and specific pharmacologic treatment is currently available. Here, we investigated the mechanisms by which aldose reductase (AR regulates the mucus cell metaplasia in vitro and in vivo. METHODOLOGY/FINDINGS: Metaplasia in primary human small airway epithelial cells (SAEC was induced by a Th2 cytokine, IL-13, without or with AR inhibitor, fidarestat. After 48 h of incubation with IL-13 a large number of SAEC were transformed into goblet cells as determined by periodic acid-schiff (PAS-staining and immunohistochemistry using antibodies against Mucin5AC. Further, IL-13 significantly increased the expression of Mucin5AC at mRNA and protein levels. These changes were significantly prevented by treatment of the SAEC with AR inhibitor. AR inhibition also decreased IL-13-induced expression of Muc5AC, Muc5B, and SPDEF, and phosphorylation of JAK-1, ERK1/2 and STAT-6. In a mouse model of ragweed pollen extract (RWE-induced allergic asthma treatment with fidarestat prevented the expression of IL-13, phosphorylation of STAT-6 and transformation of epithelial cells to goblet cells in the lung. Additionally, while the AR-null mice were resistant, wild-type mice showed goblet cell metaplasia after challenge with RWE. CONCLUSIONS: The results show that exposure of SAEC to IL-13 caused goblet cell metaplasia, which was significantly prevented by AR inhibition. Administration of fidarestat to mice prevented RWE-induced goblet cell metaplasia and AR null mice were largely resistant to allergen induced changes in the lung. Thus our results indicate that AR inhibitors

  17. Aldose reductase inhibition prevents metaplasia of airway epithelial cells.

    Science.gov (United States)

    Yadav, Umesh C S; Aguilera-Aguirre, Leopoldo; Ramana, Kota V; Boldogh, Istvan; Srivastava, Satish K

    2010-12-28

    Goblet cell metaplasia that causes mucus hypersecretion and obstruction in the airway lumen could be life threatening in asthma and chronic obstructive pulmonary disease patients. Inflammatory cytokines such as IL-13 mediate the transformation of airway ciliary epithelial cells to mucin-secreting goblet cells in acute as well as chronic airway inflammatory diseases. However, no effective and specific pharmacologic treatment is currently available. Here, we investigated the mechanisms by which aldose reductase (AR) regulates the mucus cell metaplasia in vitro and in vivo. Metaplasia in primary human small airway epithelial cells (SAEC) was induced by a Th2 cytokine, IL-13, without or with AR inhibitor, fidarestat. After 48 h of incubation with IL-13 a large number of SAEC were transformed into goblet cells as determined by periodic acid-schiff (PAS)-staining and immunohistochemistry using antibodies against Mucin5AC. Further, IL-13 significantly increased the expression of Mucin5AC at mRNA and protein levels. These changes were significantly prevented by treatment of the SAEC with AR inhibitor. AR inhibition also decreased IL-13-induced expression of Muc5AC, Muc5B, and SPDEF, and phosphorylation of JAK-1, ERK1/2 and STAT-6. In a mouse model of ragweed pollen extract (RWE)-induced allergic asthma treatment with fidarestat prevented the expression of IL-13, phosphorylation of STAT-6 and transformation of epithelial cells to goblet cells in the lung. Additionally, while the AR-null mice were resistant, wild-type mice showed goblet cell metaplasia after challenge with RWE. The results show that exposure of SAEC to IL-13 caused goblet cell metaplasia, which was significantly prevented by AR inhibition. Administration of fidarestat to mice prevented RWE-induced goblet cell metaplasia and AR null mice were largely resistant to allergen induced changes in the lung. Thus our results indicate that AR inhibitors such as fidarestat could be developed as therapeutic agents to

  18. SIMPLE, TIMELY, SAFELY? LARYNGEAL MASK AND PEDIATRIC AIRWAY.

    Science.gov (United States)

    Karišik, Marijana

    2016-03-01

    Laryngeal mask airway (LMA) was a useful, powerful airway management device for routine pediatric airway management, pediatric difficult airway, and in pediatric emergency situations. Over years, various designs, induction and insertion techniques have been described. LMA provides ease of placement and removal as compared with endotracheal intubation, less traumatism for the respiratory tract, better tolerability by patients, improved hemodynamic stability during emergency, less coughing, less sore throat, avoidance of laryngoscopy, and hands free airway. On the other hand, LMA is not suitable to overcome functional airway problems and mechanical airway obstruction in children. Simple airway management in pediatric patients is normally easy in experienced hands, for anesthesiologists working in specialized hospitals with appropriate personnel and equipment that guarantee optimal safety in these patients. On the other hand, pediatric airway management is a great challenge for anesthesiologists working in departments with a small number of pediatric surgical procedures. Careful preoperative evaluation, preparation and training in the recognition of challenges in pediatric airway are essential for the management of the airway in children. LMA plays a special role in the management of difficult pediatric airway; as a supraglottic airway device, it is incorporated into difficult pediatric airway algorithms.

  19. Feasibility and speed of insertion of seven supraglottic airway devices under simulated airway conditions.

    Science.gov (United States)

    Robak, Oliver; Leonardelli, Marco; Zedtwitz-Liebenstein, Konstantin; Rützler, Kurt; Schuster, Ernst; Vaida, Sonia; Salem, Ramez; Frass, Michael

    2012-11-01

    Endotracheal intubation (ETI) is considered the gold standard for protecting the airway. Alternative devices for airway protection have been developed that can be used by untrained personnel, by those with less experience, and for when ETI is not possible. The main goals of our study were to evaluate the success rate and speed of insertion of different supraglottic airway devices and to determine whether the devices could be properly inserted under simulated critical conditions. Fifty medical students used an airway simulation trainer (Laerdal SimMan 3G) to assess the success rate and time used to insert seven different supraglottic airway devices under simulated physiologic and pathologic conditions in two different runs. Although all airway devices could be inserted without problems, only the Combitube and the EasyTube could be successfully inserted in simulations of trismus, limited mobility of the cervical spine, or a combination of pathologic conditions such as trismus plus limited mobility of the spine and trismus plus tongue edema. The insertion time was significantly longer with LMA Unique, Fastrach, and I-Gel devices in both the first and second runs. The Combitube and the EasyTube were most easily inserted under simulated conditions such as trismus, limited mobility of the cervical spine, and combined pathologic conditions. Although all devices are useful for establishing an airway by nontrained medical students in standard simulations, we suggest that the Combitube and the EasyTube may offer advantages in difficult airway situations.

  20. Airway management using the ProSeal laryngeal mask airway in a child with Goldenhar syndrome.

    Science.gov (United States)

    Aydogan, M S; Begec, Z; Erdogan, M A; Yücel, A; Ersoy, M O

    2012-04-01

    Children with congenital anomalies such as Goldenhar syndrome affecting the airway can be a problem for the anaesthesiologist. We present the case of an 18 month-old child with Goldenhar syndrome, in whom the ProSeal Laryngeal Mask Airway was successfully used for inguinal hernia surgery.

  1. Extracellular matrix in airway smooth muscle is associated with dynamics of airway function in asthma

    NARCIS (Netherlands)

    Yick, C. Y.; Ferreira, D. S.; Annoni, R.; von der Thüsen, J. H.; Kunst, P. W.; Bel, E. H.; Lutter, R.; Mauad, T.; Sterk, P. J.

    2012-01-01

    Background: Altered deposition of extracellular matrix (ECM) in the airway smooth muscle (ASM) layer as observed in asthma may influence ASM mechanical properties. We hypothesized that ECM in ASM is associated with airway function in asthma. First, we investigated the difference in ECM expression in

  2. Behavioral inhibition in rhesus monkeys (Macaca mulatta is related to the airways response, but not immune measures, commonly associated with asthma.

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    Katie Chun

    Full Text Available Behavioral inhibition reflects a disposition to react warily to novel situations, and has been associated with atopic diseases such as asthma. Retrospective work established the relationship between behavioral inhibition in rhesus monkeys (Macaca mulatta and airway hyperresponsiveness, but not atopy, and the suggestion was made that behavioral inhibition might index components of asthma that are not immune-related. In the present study, we prospectively examined the relationship between behavioral inhibition and airway hyperresponsiveness, and whether hormonal and immune measures often associated with asthma were associated with behavioral inhibition and/or airway hyperresponsiveness. In a sample of 49 yearling rhesus monkeys (mean=1.25 years, n=24 behaviorally inhibited animals, we measured in vitro cytokine levels (IL-4, IL-10, IL-12, IFN-γ in response to stimulation, as well as peripheral blood cell percentages, cortisol levels, and percentage of regulatory T-cells (CD3+CD4+CD25+FOXP3+. Airway reactivity was assessed using an inhaled methacholine challenge. Bronchoalveolar lavage was performed and the proportion of immune cells was determined. Behaviorally inhibited monkeys had airway hyperresponsiveness as indicated by the methacholine challenge (p=0.031, confirming our earlier retrospective result. Airway hyperresponsiveness was also associated with lower lymphocyte percentages in lavage fluid and marginally lower plasma cortisol concentrations. However, none of the tested measures was significantly related to both behavioral inhibition and airway hyperresponsiveness, and so could not mediate their relationship. Airway hyperresponsiveness is common to atopic and non-atopic asthma and behavioral inhibition has been related to altered autonomic activity in other studies. Our results suggest that behavioral inhibition might index an autonomically mediated reactive airway phenotype, and that a variety of stimuli (including inflammation within

  3. Airway clearance techniques for bronchiectasis.

    Science.gov (United States)

    Lee, Annemarie L; Burge, Angela T; Holland, Anne E

    2015-11-23

    People with non-cystic fibrosis bronchiectasis commonly experience chronic cough and sputum production, features that may be associated with progressive decline in clinical and functional status. Airway clearance techniques (ACTs) are often prescribed to facilitate expectoration of sputum from the lungs, but the efficacy of these techniques in a stable clinical state or during an acute exacerbation of bronchiectasis is unclear. Primary: to determine effects of ACTs on rates of acute exacerbation, incidence of hospitalisation and health-related quality of life (HRQoL) in individuals with acute and stable bronchiectasis. Secondary: to determine whether:• ACTs are safe for individuals with acute and stable bronchiectasis; and• ACTs have beneficial effects on physiology and symptoms in individuals with acute and stable bronchiectasis. We searched the Cochrane Airways Group Specialised Register of trials from inception to November 2015 and PEDro in March 2015, and we handsearched relevant journals. Randomised controlled parallel and cross-over trials that compared an ACT versus no treatment, sham ACT or directed coughing in participants with bronchiectasis. We used standard methodological procedures as expected by The Cochrane Collaboration. Seven studies involving 105 participants met the inclusion criteria of this review, six of which were cross-over in design. Six studies included adults with stable bronchiectasis; the other study examined clinically stable children with bronchiectasis. Three studies provided single treatment sessions, two lasted 15 to 21 days and two were longer-term studies. Interventions varied; some control groups received a sham intervention and others were inactive. The methodological quality of these studies was variable, with most studies failing to use concealed allocation for group assignment and with absence of blinding of participants and personnel for outcome measure assessment. Heterogeneity between studies precluded inclusion of

  4. Using Drugs to Probe the Variability of Trans-Epithelial Airway Resistance.

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    Kendra Tosoni

    Full Text Available Precision medicine aims to combat the variability of the therapeutic response to a given medicine by delivering the right medicine to the right patient. However, the application of precision medicine is predicated on a prior quantitation of the variance of the reference range of normality. Airway pathophysiology provides a good example due to a very variable first line of defence against airborne assault. Humans differ in their susceptibility to inhaled pollutants and pathogens in part due to the magnitude of trans-epithelial resistance that determines the degree of epithelial penetration to the submucosal space. This initial 'set-point' may drive a sentinel event in airway disease pathogenesis. Epithelia differentiated in vitro from airway biopsies are commonly used to model trans-epithelial resistance but the 'reference range of normality' remains problematic. We investigated the range of electrophysiological characteristics of human airway epithelia grown at air-liquid interface in vitro from healthy volunteers focusing on the inter- and intra-subject variability both at baseline and after sequential exposure to drugs modulating ion transport.Brushed nasal airway epithelial cells were differentiated at air-liquid interface generating 137 pseudostratified ciliated epithelia from 18 donors. A positively-skewed baseline range exists for trans-epithelial resistance (Min/Max: 309/2963 Ω·cm2, trans-epithelial voltage (-62.3/-1.8 mV and calculated equivalent current (-125.0/-3.2 μA/cm2; all non-normal, P<0.001. A minority of healthy humans manifest a dramatic amiloride sensitivity to voltage and trans-epithelial resistance that is further discriminated by prior modulation of cAMP-stimulated chloride transport.Healthy epithelia show log-order differences in their ion transport characteristics, likely reflective of their initial set-points of basal trans-epithelial resistance and sodium transport. Our data may guide the choice of the background set

  5. The effect of cathepsin K deficiency on airway development and TGF-β1 degradation

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    Saftig Paul

    2011-05-01

    Full Text Available Background Cathepsin K, a cysteine protease predominantly expressed in osteoclasts, is a major drug target for the treatment of osteoporosis. Recent findings, however, indicate that cathepsin K is also involved in non-skeletal metabolism. The development of fibrotic phenotypes in lung and skin is a concern for cathepsin K inhibitors presently evaluated in clinical trials. Cathepsin K is expressed in lung tissue and has been implicated in lung fibrosis. However, little is known about the role of cathepsin K in airway development and its effect on TGF-β1 degradation. Methods We investigated the effects of cathepsin K-deficiency on alterations in airway integrity, extracellular matrix composition, and TGF-β1 expression and degradation. Lung homogenates of wild-type and cathepsin K-deficient mice were used to evaluate their contents of collagen, glycosaminoglycans, and TGF-β1. The accessibility of TGF-β1 to cathepsin K-mediated degradation was determined in vitro and lung fibroblast proliferations in wild-type and cathepsin K-deficient cells were evaluated. Results Lung airway cathepsin K expression in wild-type mice remained constant between 1 and 6 months of age and the airway integrity was maintained. In contrast, after 2 months of age, all Ctsk-/- mice demonstrated increased airway epithelium thickness by 16-28%, a lower structural airway integrity (1-2 score units lower, elevated cytokeratin expression of 12%, increased α-actin and vimentin expression by 50% and 70%, increased area of smooth muscle cells by 15%, elevated hydroxyproline and GAGs content by 20% and 25%, and increased TGF-β1 expression by 25%. TGF-β1 proved an efficient substrate of cathepsin K and TGF-β1 protein content in lung was increased by a potent cathepsin inhibitor. Lung fibroblasts from Ctsk-/- mice after TGF-β1 treatment showed increased proliferation rates, increased levels of TGF-β1 by 30%, and increased ECM secretion. Conclusion This study suggests that

  6. Silibinin attenuates allergic airway inflammation in mice

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-26

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

  7. Astragaloside IV Ameliorates Airway Inflammation in an Established Murine Model of Asthma by Inhibiting the mTORC1 Signaling Pathway

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    Hualiang Jin

    2017-01-01

    Full Text Available Astragaloside IV (AS-IV, a main active constituent of Astragalus membranaceus, has been confirmed to have antiasthmatic effects. However, it remained unclear whether the beneficial effects of AS-IV on asthma were attributed to the mTOR inhibition; this issue was the focus of the present work. BALB/c mice were sensitized and challenged with ovalbumin followed with 3 weeks of rest/recovery and then reexposure to ovalbumin. AS-IV was administrated during the time of rest and reexposure. The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, cytokines (IL-4, IL-5, IL-13, IL-17, and INF-γ, and CD4+CD25+Foxp3+Treg cells in bronchoalveolar lavage fluid (BALF, and downstream proteins of mTORC1/2 signaling were examined. AS-IV markedly suppressed airway hyperresponsiveness and reduced IL-4, IL-5, and IL-17 levels and increased INF-γ levels in the BALF. Histological studies showed that AS-IV markedly decreased inflammatory infiltration in the lung tissues. Notably, AS-IV inhibited mTORC1 activity, whereas it had limited effects on mTORC2, as assessed by phosphorylation of mTORC1 and mTORC2 substrates S6 ribosomal protein, p70 S6 Kinase, and Akt, respectively. CD4+CD25+Foxp3+Treg cells in BALF were not significantly changed by AS-IV. Together, these results suggest that the antiasthmatic effects of AS-IV were at least partially from inhibiting the mTORC1 signaling pathway.

  8. Functional consequences of human airway smooth muscle phenotype plasticity

    NARCIS (Netherlands)

    Dekkers, Bart G J; Bos, I Sophie T; Zaagsma, Johan; Meurs, Herman

    BACKGROUND AND PURPOSE: Airway smooth muscle (ASM) phenotype plasticity, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to increased ASM mass and airway hyper-responsiveness in asthma. Further, increased expression of collagen I

  9. Airway Science curriculum demonstration project : summary of initial evaluation findings.

    Science.gov (United States)

    1988-10-01

    The performance, perceptions, and characteristics of Airway Science hires were compared with those of traditional hires. As of May 12, 1987. a total of 197 Airway Science candidates had been selected into FAA occupations. The demographic characterist...

  10. Optical imaging of subacute airway remodeling and adipose stem cell engraftment after airway injury.

    Science.gov (United States)

    Ahn, Yeh-Chan; Kim, Sung Won; Hwang, Sang Seok; Chae, Yu-Gyeong; Lee, Andrew Sungwan; Jung, Maan Hong; Chun, Bong Kwon; Lee, Sang Joon; Park, Eun-Kee; Oak, Chulho

    2013-12-20

    Acquired airway injury is frequently caused by endotracheal intubations, long-term tracheostomies, trauma, airway burns, and some systemic diseases. An effective and less invasive technique for both the early assessment and the early interventional treatment of acquired airway stenosis is therefore needed. Optical coherence tomography (OCT) has been proposed to have unique potential for early monitoring from the proliferative epithelium to the cartilage in acute airway injury. Additionally, stem cell therapy using adipose stem cells is being investigated as an option for early interventional treatment in airway and lung injury. Over the past decade, it has become possible to monitor the level of injury using OCT and to track the engraftment of stem cells using stem cell imaging in regenerative tissue. The purpose of this study was to assess the engraftment of exogenous adipose stem cells in injured tracheal epithelium with fluorescent microscopy and to detect and monitor the degree of airway injury in the same tracheal epithelium with OCT. OCT detected thickening of both the epithelium and basement membrane after tracheal scraping. The engraftment of adipose stem cells was successfully detected by fluorescent staining in the regenerative epithelium of injured tracheas. OCT has the potential to be a high-resolution imaging modality capable of detecting airway injury in combination with stem cell imaging in the same tracheal mucosa.

  11. Computed tomography assessment of airways throughout bronchial tree demonstrates airway narrowing in severe asthma.

    Science.gov (United States)

    Brillet, Pierre-Yves; Debray, Marie-Pierre; Golmard, Jean-Louis; Ould Hmeidi, Yahya; Fetita, Catalin; Taillé, Camille; Aubier, Michel; Grenier, Philippe A

    2015-06-01

    To analyze airway dimensions throughout the bronchial tree in severe asthmatic patients using multidetector row computed tomography (MDCT) focusing on airway narrowing. Thirty-two patients with severe asthma underwent automated (BronCare software) analysis of their right lung bronchi, with counts of airways >3 mm long arising from the main bronchi (airway count) and bronchial dimension quantification at segmental and subsegmental levels (lumen area [LA], wall area [WA], and WA%). Focal bronchial stenosis was defined as >50% narrowing of maximal LA on contiguous cross-sectional slices. Severe asthmatics were compared to 13 nonsevere asthmatic patients and nonasthmatic (pooled) subjects (Wilcoxon rank tests, then stepwise logistic regression). Finally, cluster analysis of severe asthmatic patients and stepwise logistic regression identified specific imaging subgroups. The most significant differences between severe asthmatic patients and the pooled subjects were bronchial stenosis (subsegmental and all bronchi: P bronchial stenosis: P = .009). Airway count was as discriminant as forced expiratory volume in 1 second/forced vital capacity (P = .01) to identify patients in each cluster, with both variables being correlated (r = 0.59, P = .005). Severe asthma-associated morphologic changes were characterized by focal bronchial stenoses and diffuse airway narrowing; the latter was associated with airflow obstruction. WA%, dependent on airway caliber, is the best parameter to identify severe asthmatic patients from pooled subjects. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-11-01

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

  13. Inefficient cationic lipid-mediated siRNA and antisense oligonucleotide transfer to airway epithelial cells in vivo

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    Hu Jim

    2006-02-01

    Full Text Available Abstract Background The cationic lipid Genzyme lipid (GL 67 is the current "gold-standard" for in vivo lung gene transfer. Here, we assessed, if GL67 mediated uptake of siRNAs and asODNs into airway epithelium in vivo. Methods Anti-lacZ and ENaC (epithelial sodium channel siRNA and asODN were complexed to GL67 and administered to the mouse airway epithelium in vivo Transfection efficiency and efficacy were assessed using real-time RT-PCR as well as through protein expression and functional studies. In parallel in vitro experiments were carried out to select the most efficient oligonucleotides. Results In vitro, GL67 efficiently complexed asODNs and siRNAs, and both were stable in exhaled breath condensate. Importantly, during in vitro selection of functional siRNA and asODN we noted that asODNs accumulated rapidly in the nuclei of transfected cells, whereas siRNAs remained in the cytoplasm, a pattern consistent with their presumed site of action. Following in vivo lung transfection siRNAs were only visible in alveolar macrophages, whereas asODN also transfected alveolar epithelial cells, but no significant uptake into conducting airway epithelial cells was seen. SiRNAs and asODNs targeted to β-galactosidase reduced βgal mRNA levels in the airway epithelium of K18-lacZ mice by 30% and 60%, respectively. However, this was insufficient to reduce protein expression. In an attempt to increase transfection efficiency of the airway epithelium, we increased contact time of siRNA and asODN using the in vivo mouse nose model. Although highly variable and inefficient, transfection of airway epithelium with asODN, but not siRNA, was now seen. As asODNs more effectively transfected nasal airway epithelial cells, we assessed the effect of asODN against ENaC, a potential therapeutic target in cystic fibrosis; no decrease in ENaC mRNA levels or function was detected. Conclusion This study suggests that although siRNAs and asODNs can be developed to inhibit

  14. Validation of airway wall measurements by optical coherence tomography in porcine airways.

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    Anthony M D Lee

    Full Text Available Examining and quantifying changes in airway morphology is critical for studying longitudinal pathogenesis and interventions in diseases such as chronic obstructive pulmonary disease and asthma. Here we present fiber-optic optical coherence tomography (OCT as a nondestructive technique to precisely and accurately measure the 2-dimensional cross-sectional areas of airway wall substructure divided into the mucosa (WAmuc, submucosa (WAsub, cartilage (WAcart, and the airway total wall area (WAt. Porcine lung airway specimens were dissected from freshly resected lung lobes (N = 10. Three-dimensional OCT imaging using a fiber-optic rotary-pullback probe was performed immediately on airways greater than 0.9 mm in diameter on the fresh airway specimens and subsequently on the same specimens post-formalin-fixation. The fixed specimens were serially sectioned and stained with H&E. OCT images carefully matched to selected sections stained with Movat's pentachrome demonstrated that OCT effectively identifies airway epithelium, lamina propria, and cartilage. Selected H&E sections were digitally scanned and airway total wall areas were measured. Traced measurements of WAmuc, WAsub, WAcart, and WAt from OCT images of fresh specimens by two independent observers found there were no significant differences (p>0.05 between the observer's measurements. The same wall area measurements from OCT images of formalin-fixed specimens found no significant differences for WAsub, WAcart and WAt, and a small but significant difference for WAmuc. Bland-Altman analysis indicated there were negligible biases between the observers for OCT wall area measurements in both fresh and formalin-fixed specimens. Bland-Altman analysis also indicated there was negligible bias between histology and OCT wall area measurements for both fresh and formalin-fixed specimens. We believe this study sets the groundwork for quantitatively monitoring pathogenesis and interventions in the airways

  15. Role of TRPV1 in inflammation-induced airway hypersensitivity

    OpenAIRE

    Lee, Lu-Yuan; Gu, Qihai

    2009-01-01

    Airway hypersensitivity is a common pathophysiological feature in various airway inflammatory diseases. Increasing evidence suggests that activation of the transient receptor potential vanilloid type 1 receptor (TRPV1) plays an important part in the manifestation of various symptoms of airway hypersensitivity. This mini-review focuses on recent studies that have revealed several potential contributing factors to the increase in TRPV1 sensitivity in pulmonary sensory neurons during airway infl...

  16. Dilemmas, Confusion, and Misconceptions Related to Small Airways Directed Therapy.

    Science.gov (United States)

    Lavorini, Federico; Pedersen, Søren; Usmani, Omar S

    2017-06-01

    During the past decade, there has been increasing evidence that the small airways (ie, airways misconceptions related to small airways directed therapy. To this end, we have reviewed all studies on small-particle aerosol therapy systematically to address the dilemmas, confusion, and misconceptions related to small airways directed therapy. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  17. Virus-induced airway inflammation and hyperresponsiveness in the guinea-pig is inhibited by levodropropizine.

    Science.gov (United States)

    Folkerts, G; van der Linde, H J; Omini, C; Nijkamp, F P

    1993-08-01

    Intratracheal Parainfluenza type 3 (PI-3) virus inoculation of guinea pigs leads to a non-specific airway hyperresponsiveness in vivo and in vitro which coincides with a significant increase in the number of inflammatory cells in the broncho-alveolar lavage fluid (90% increase, 4 days after inoculation). The activity of the bronchoalveolar cells, as measured by the chemiluminescence production of infected animals is significantly diminished (34.2%, 4 days after inoculation) after renewed stimulation with PI-3 virus in vitro as compared to the chemiluminescence production by bronchoalveolar cells obtained from control guinea pigs. Pretreatment of the guinea-pigs with the antitussive agent levodropropizine, administered intra-peritoneally twice a day for five successive days at a dose of 10 mg/kg, prevents the virus-induced airway hyperresponsiveness in vivo and in vitro, and inhibits the influx of broncho-alveolar cells. Levodropropizine at a dose of 1 mg/kg did not modulate these responses. Further, the decrease in chemiluminescence production of broncho-alveolar cells obtained from virus-infected animals after PI-3 virus stimulation in vitro was inhibited by levodropropizine (10 mg/kg). These data demonstrate the ability of levodropropizine to counteract the hyperresponsiveness phenomenon and the associated inflammatory event induced by PI-3 virus, an effect which may be due to its capacity to act on the peptidergic system or may be due to the anti-allergic/bronchoconstrictor property of this compound.

  18. Smoking is associated with shortened airway cilia.

    Directory of Open Access Journals (Sweden)

    Philip L Leopold

    2009-12-01

    Full Text Available Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting that cilia length must exceed the 6-7 microm airway surface fluid depth to generate force in the mucus layer, we hypothesized that cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers.Cilia length in normal nonsmokers and smokers was evaluated in aldehyde-fixed, paraffin-embedded endobronchial biopsies, and air-dried and hydrated samples were brushed from human airway epithelium via fiberoptic bronchoscopy. In 28 endobronchial biopsies, healthy smoker cilia length was reduced by 15% compared to nonsmokers (p<0.05. In 39 air-dried samples of airway epithelial cells, smoker cilia length was reduced by 13% compared to nonsmokers (p<0.0001. Analysis of the length of individual, detached cilia in 27 samples showed that smoker cilia length was reduced by 9% compared to nonsmokers (p<0.05. Finally, in 16 fully hydrated, unfixed samples, smoker cilia length was reduced 7% compared to nonsmokers (p<0.05. Using genome-wide analysis of airway epithelial gene expression we identified 6 cilia-related genes whose expression levels were significantly reduced in healthy smokers compared to healthy nonsmokers.Models predict that a reduction in cilia length would reduce mucociliary clearance, suggesting that smoking-associated shorter airway epithelial cilia play a significant role in the pathogenesis of smoking-induced lung disease.

  19. Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Bachert, Claus; Konge, Lars

    2015-01-01

    ) bronchial inflammation exists in all CRSwNP patients irrespective of clinical asthma status. Methods We collected biopsies from nasal polyps, inferior turbinates and bronchi of 27 CRSwNP patients and 6 controls. All participants were evaluated for lower airway disease according to international guidelines......Background It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma. Objective We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii...

  20. Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Bachert, Claus; Konge, Lars

    2015-01-01

    Background It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma. Objective We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii...... cytokines measured, IL-13 was significantly increased in bronchial biopsies from CRSwNP patients with, but not without asthma. Conclusion Our findings support the united airways concept; however, we did not find evidence for subclinical bronchial inflammation in CRSwNP patients without asthma. Finally...

  1. Metformin prevents the effects of Pseudomonas aeruginosa on airway epithelial tight junctions and restricts hyperglycaemia-induced bacterial growth.

    Science.gov (United States)

    Patkee, Wishwanath R A; Carr, Georgina; Baker, Emma H; Baines, Deborah L; Garnett, James P

    2016-04-01

    Lung disease and elevation of blood glucose are associated with increased glucose concentration in the airway surface liquid (ASL). Raised ASL glucose is associated with increased susceptibility to infection by respiratory pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. We have previously shown that the anti-diabetes drug, metformin, reduces glucose-induced S. aureus growth across in vitro airway epithelial cultures. The aim of this study was to investigate whether metformin has the potential to reduce glucose-induced P. aeruginosa infections across airway epithelial (Calu-3) cultures by limiting glucose permeability. We also explored the effect of P. aeruginosa and metformin on airway epithelial barrier function by investigating changes in tight junction protein abundance. Apical P. aeruginosa growth increased with basolateral glucose concentration, reduced transepithelial electrical resistance (TEER) and increased paracellular glucose flux. Metformin pre-treatment of the epithelium inhibited the glucose-induced growth of P. aeruginosa, increased TEER and decreased glucose flux. Similar effects on bacterial growth and TEER were observed with the AMP activated protein kinase agonist, 5-aminoimidazole-4-carboxamide ribonucleotide. Interestingly, metformin was able to prevent the P. aeruginosa-induced reduction in the abundance of tight junction proteins, claudin-1 and occludin. Our study highlights the potential of metformin to reduce hyperglycaemia-induced P. aeruginosa growth through airway epithelial tight junction modulation, and that claudin-1 and occludin could be important targets to regulate glucose permeability across airway epithelia and supress bacterial growth. Further investigation into the mechanisms regulating metformin and P. aeruginosa action on airway epithelial tight junctions could yield new therapeutic targets to prevent/suppress hyperglycaemia-induced respiratory infections, avoiding the use of antibiotics. © 2016 The

  2. In vivo imaging of the airway wall in asthma: fibered confocal fluorescence microscopy in relation to histology and lung function

    Directory of Open Access Journals (Sweden)

    Bel Elisabeth H

    2011-06-01

    Full Text Available Abstract Background Airway remodelling is a feature of asthma including fragmentation of elastic fibres observed in the superficial elastin network of the airway wall. Fibered confocal fluorescence microscopy (FCFM is a new and non-invasive imaging technique performed during bronchoscopy that may visualize elastic fibres, as shown by in vitro spectral analysis of elastin powder. We hypothesized that FCFM images capture in vivo elastic fibre patterns within the airway wall and that such patterns correspond with airway histology. We aimed to establish the concordance between the bronchial elastic fibre pattern in histology and FCFM. Second, we examined whether elastic fibre patterns in histology and FCFM were different between asthmatic subjects and healthy controls. Finally, the association between these patterns and lung function parameters was investigated. Methods In a cross-sectional study comprising 16 subjects (8 atopic asthmatic patients with controlled disease and 8 healthy controls spirometry and bronchoscopy were performed, with recording of FCFM images followed by endobronchial biopsy at the airway main carina. Elastic fibre patterns in histological sections and FCFM images were scored semi-quantitatively. Agreement between histology and FCFM was analysed using linearly weighted kappa κw. Results The patterns observed in histological sections and FCFM images could be divided into 3 distinct groups. There was good agreement between elastic fibre patterns in histology and FCFM patterns (κw 0.744. The semi-quantitative pattern scores were not different between asthmatic patients and controls. Notably, there was a significant difference in post-bronchodilator FEV1 %predicted between the different patterns by histology (p = 0.001 and FCFM (p = 0.048, regardless of asthma or atopy. Conclusion FCFM captures the elastic fibre pattern within the airway wall in humans in vivo. The association between post-bronchodilator FEV1 %predicted and

  3. Anti-Fas mAb-induced apoptosis and cytolysis of airway tissue eosinophils aggravates rather than resolves established inflammation

    Directory of Open Access Journals (Sweden)

    Persson Carl GA

    2005-08-01

    Full Text Available Abstract Background Fas receptor-mediated eosinophil apoptosis is currently forwarded as a mechanism resolving asthma-like inflammation. This view is based on observations in vitro and in airway lumen with unknown translatability to airway tissues in vivo. In fact, apoptotic eosinophils have not been detected in human diseased airway tissues whereas cytolytic eosinophils abound and constitute a major mode of degranulation of these cells. Also, Fas receptor stimulation may bypass the apoptotic pathway and directly evoke cytolysis of non-apoptotic cells. We thus hypothesized that effects of anti-Fas mAb in vivo may include both apoptosis and cytolysis of eosinophils and, hence, that established eosinophilic inflammation may not resolve by this treatment. Methods Weeklong daily allergen challenges of sensitized mice were followed by airway administration of anti-Fas mAb. BAL was performed and airway-pulmonary tissues were examined using light and electron microscopy. Lung tissue analysis for CC-chemokines, apoptosis, mucus production and plasma exudation (fibrinogen were performed. Results Anti-Fas mAb evoked apoptosis of 28% and cytolysis of 4% of eosinophils present in allergen-challenged airway tissues. Furthermore, a majority of the apoptotic eosinophils remained unengulfed and eventually exhibited secondary necrosis. A striking histopathology far beyond the allergic inflammation developed and included degranulated eosinophils, neutrophilia, epithelial derangement, plasma exudation, mucus-plasma plugs, and inducement of 6 CC-chemokines. In animals without eosinophilia anti-Fas evoked no inflammatory response. Conclusion An efficient inducer of eosinophil apoptosis in airway tissues in vivo, anti-Fas mAb evoked unprecedented asthma-like inflammation in mouse allergic airways. This outcome may partly reflect the ability of anti-Fas to evoke direct cytolysis of non-apoptotic eosinophils in airway tissues. Additionally, since most apoptotic tissue

  4. Rigid fibrescope Bonfils: use in simulated difficult airway by novices

    Directory of Open Access Journals (Sweden)

    Piepho Tim

    2009-07-01

    Full Text Available Abstract Background The Bonfils intubation fibrescope is a promising alternative device for securing the airway. We examined the success rate of intubation and the ease of use in standardized simulated difficult airway scenarios by physicians. We compared the Bonfils to a classical laryngoscope with Macintosh blade. Methods 30 physicians untrained in the use of rigid fibrescopes but experienced in airway management performed endotracheal intubation in an airway manikin (SimMan, Laerdal, Kent, UK with three different airway conditions. We evaluated the success rate using the Bonfils (Karl Storz, Tuttlingen, Germany or the Macintosh laryngoscope, the time needed for securing the airway, and subjective rating of both techniques. Results In normal airway all intubations were successful using laryngoscope (100% vs. 82% using the Bonfils (p Conclusion The Bonfils can be successfully used by physicians unfamiliar with this technique in an airway manikin. The airway could be secured with at least the same success rate as using a Macintosh laryngoscope in difficult airway scenarios. Use of the Bonfils did not delay intubation in the presence of a difficult airway. These results indicate that intensive special training is advised to use the Bonfils effectively in airway management.

  5. Editorial Intubation through supraglottic airways: Are we on target, or ...

    African Journals Online (AJOL)

    practitioner skill/experience make 'big data' studies of airway devices very challenging. Nonetheless, some developments have brought about dramatic changes in airway management and become enshrined into protocols and guidelines.2, 3. The ideal airway device would be reliably fast and easy to insert, cause no.

  6. Successful management of difficult airway: A case series

    Directory of Open Access Journals (Sweden)

    Balraj Hariharasudhan

    2016-01-01

    Full Text Available Management of difficult airway is widely recognized as one of the important tasks of an anesthesiologist. The problems related to it are known to be primary causes of life-threatening consequences. Herewith, we present a case series of difficult airway scenarios managed successfully with different techniques and airway gadgets. The following cases were managed successfully with appropriate airway techniques: 1 Ludwig′s angina for drainage with awake fiberoptic intubation, 2 temporomandibular joint (TMJ ankylosis for bilateral gap arthroplasty with fiberoptic intubation, 3 burn contractures for the release managed with intubating laryngeal mask airway (ILMA. Airway management is one of the vital aspects of clinical care provided by an anesthesiologist. The airway-related complications have significantly decreased due to better knowledge, skills of the anesthesiologist, and an array of airway gadgets. The three case scenarios of difficult airway were successfully managed with the appropriate airway gadgets suitable for each case without any untoward complication. Most airway problems can be solved with available gadgets and techniques, but clinical judgement borne of experience and expertise is crucial in implementing the skills in any difficult airway scenario.

  7. Airways inflammatory and atopy-related responses in athletes ...

    African Journals Online (AJOL)

    Repeated hyperventilation of unconditioned air, as well as air containing irritants and/or allergens has been suggested to cause thermal, mechanical, or osmotic airway trauma resulting in damage to the airway epithelium. Subsequent airway inflammatory responses may be responsible for the development of atopy-related

  8. Dysfunctional lung anatomy and small airways degeneration in COPD

    Directory of Open Access Journals (Sweden)

    Burgel PR

    2013-01-01

    Full Text Available Clémence Martin, Justine Frija, Pierre-Régis BurgelDepartment of Respiratory Medicine, Cochin Hospital, AP-HP and Université Paris Descartes, Sorbonne Paris Cité, Paris, FranceAbstract: Chronic obstructive pulmonary disease (COPD is characterized by incompletely reversible airflow obstruction. Direct measurement of airways resistance using invasive techniques has revealed that the site of obstruction is located in the small conducting airways, ie, bronchioles with a diameter < 2 mm. Anatomical changes in these airways include structural abnormalities of the conducting airways (eg, peribronchiolar fibrosis, mucus plugging and loss of alveolar attachments due to emphysema, which result in destabilization of these airways related to reduced elastic recoil. The relative contribution of structural abnormalities in small conducting airways and emphysema has been a matter of much debate. The present article reviews anatomical changes and inflammatory mechanisms in small conducting airways and in the adjacent lung parenchyma, with a special focus on recent anatomical and imaging data suggesting that the initial event takes place in the small conducting airways and results in a dramatic reduction in the number of airways, together with a reduction in the cross-sectional area of remaining airways. Implications of these findings for the development of novel therapies are briefly discussed.Keywords: emphysema, small airways disease, airway mucus, innate immunity, adaptive immunity

  9. Airway responsiveness to mannitol in asthma is associated with chymase-positive mast cells and eosinophilic airway inflammation

    DEFF Research Database (Denmark)

    Sverrild, Asger; Bergqvist, A; Baines, K J

    2016-01-01

    BACKGROUND: Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway...... levels of TSLP and CPA3. The degree of AHR to mannitol is correlated with the degree of eosinophilic inflammation in the airway submucosa....

  10. A randomised trial comparing the laryngeal mask airway Supreme™ with the laryngeal mask airway Unique™ in children.

    Science.gov (United States)

    Jagannathan, N; Sohn, L E; Sawardekar, A; Chang, E; Langen, K E; Anderson, K

    2012-02-01

    We conducted a randomised controlled trial comparing the laryngeal mask airway Supreme(™) with the laryngeal mask airway Unique(™) in children. Fifty children presenting for elective surgery were randomly assigned to receive either the laryngeal mask airway Supreme or laryngeal mask airway Unique. The outcomes measured were airway leak pressure, ease and time for insertion, insertion success rate, fibreoptic examination, incidence of gastric insufflation, ease of gastric tube placement through the laryngeal mask airway Supreme, quality of airway during anaesthetic maintenance and complications. Median (IQR [range]) time to successful device placement was shorter with the laryngeal mask airway Unique, 14.5 [13.5-16.3 (10.0-23.6)] s than with the laryngeal mask airway Supreme, 17.4 [14.8-19.8 (11.5-29.2)] s; p = 0.007. Median (IQR [range]) airway leak pressures for the laryngeal mask airway Supreme and laryngeal mask airway Unique were 20 [16-21 (12-22)] cmH(2)O and 15 [14-18 (10-24)] cmH(2)O, respectively (p = 0.001). The incidence of gastric insufflation was lower with the laryngeal mask airway Supreme (zero vs six patients), p = 0.01. In conclusion, the laryngeal mask airway Supreme performed as well as the laryngeal mask airway Unique and is a useful alternative for airway maintenance, particularly in children who require evacuation of gastric contents during anaesthesia. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

  11. Performance of Dry Powder Inhalers with Single Dosed Capsules in Preschool Children and Adults Using Improved Upper Airway Models

    Directory of Open Access Journals (Sweden)

    Sandra Lindert

    2014-02-01

    Full Text Available The pulmonary administration of pharmaceutical aerosols to patients is affected by age-dependent variations in the anatomy of the upper airways and the inhalation pattern. Considering this aspect, different upper airway models, representing the geometries of adults and preschool children, and a conventional induction port according to the European Pharmacopeia were used for in vitro testing of dry powder inhalers with single dosed capsules (Cyclohaler®, Handihaler® and Spinhaler®. Deposition measurements were performed using steady flow rates of 30 and 60 L/min for the Handihaler®/Spinhaler® and 30, 60 and 75 L/min for the Cyclohaler®. The inhalation volume was set at 1 L. For the Cyclohaler®, the in vitro testing was supplemented by a pediatric inhalation profile. Slight differences of pulmonary deposition between the idealized adult (11%–15% and pediatric (9%–11% upper airway model were observed for the Cyclohaler®. The applied pediatric inhalation profile resulted in a reduction of pulmonary deposition by 5% compared to steady conditions and indicated the influence of the inhalation pattern on the amount of pulmonary deposited particles. The comparison of two pediatric upper airway models showed no differences. The performance of the Handihaler® was similar to the Cyclohaler®. The Spinhaler® showed an insufficient performance and limited reproducibility in our investigations.

  12. Chronic Low Dose Chlorine Exposure Aggravates Allergic Inflammation and Airway Hyperresponsiveness and Activates Inflammasome Pathway

    Science.gov (United States)

    Kim, Sae-Hoon; Park, Da-Eun; Lee, Hyun-Seung; Kang, Hye-Ryun; Cho, Sang-Heon

    2014-01-01

    Background Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR). Methods Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro. Results Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro. Conclusion Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways. PMID:25202911

  13. The prolonged use of the laryngeal mask airway in a neonate with airway obstruction and Treacher Collins syndrome

    NARCIS (Netherlands)

    Bucx, Martin J. L.; Grolman, W.; Kruisinga, Frea H.; Lindeboom, Jerôme A. H.; van Kempen, Anne A. M. W.

    2003-01-01

    Upper airway obstruction and difficult tracheal intubation are often encountered in patients with Treacher Collins syndrome (mandibulofacial dysostosis). In this case report, the use of a laryngeal mask airway (LMA(TM)) in a 10-day-old newborn with severe Treacher Collins syndrome and acute airway

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

    Directory of Open Access Journals (Sweden)

    Satoru Fukuyama

    2011-01-01

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

  15. Management of difficult airway patients and the use of a difficult airway registry at a tertiary care pediatric hospital.

    Science.gov (United States)

    Sheeran, Paul W; Walsh, Brian K; Finley, Andre M; Martin, Aleta K; Brenski, Amy C

    2014-08-01

    Appropriate recognition and management of the pediatric difficult airway is essential. Two patient deaths in a 2-year period involving children with a known difficult airway led to the formation of the institution's multidisciplinary Difficult Airway Committee. Patients with a suspected difficult airway or a known difficult airway are entered into a registry of difficult airway patients. A note describing the airway and any experiences at airway manipulation is entered as part of a difficult airway note in the patient's electronic medical record as soon as the patient is recognized as having a difficult airway. A call system has been developed to mobilize expert emergency airway assistance for these patients. Multiple additional methods are employed to ensure that all hospital personnel are aware that these patients are difficult to intubate. Since inception almost 6 years ago, 164 patients (mean age 9.2 years) have been enrolled in the difficult airway registry. Eighty-seven patients (53%) had one of 28 identified syndromes or diagnoses. The most common reasons for airway obstruction were mandibular hypoplasia/micrognathia, decreased neck extension, and limited temporomandibular joint mobility. One hundred sixty-one patients (98%) in the registry were predicted by history or physical to have a difficult airway. The mortality of registry patients was 9.8% (n = 16) and was most commonly due to co-existing diseases. During the time period reviewed, there was one in-hospital death of a known difficult airway patient, in which expert airway assistance was not obtained in a timely fashion. The institution's difficult airway registry identifies patients with a suspected or known difficult airway. The presence of a difficult airway in children can usually be predicted based on history and physical examination by anesthesiologists and otolaryngologists. Providers without advanced airway skills, however, may not appreciate that an airway is difficult to intubate until

  16. Airway epithelial cells produce neurotrophins and promote the survival of eosinophils during allergic airway inflammation.

    Science.gov (United States)

    Hahn, Christian; Islamian, Ariyan Pirayesh; Renz, Harald; Nockher, Wolfgang Andreas

    2006-04-01

    Eosinophil-epithelial cell interactions make a major contribution to asthmatic airway inflammation. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and other members of the neurotrophin family, originally defined as a class of neuronal growth factors, are now recognized to support the survival and activation of immune cells. Neurotrophin levels are increased in bronchoalveolar lavage fluid during allergic asthma. We sought to investigate the role of neurotrophins as inflammatory mediators in eosinophil-epithelial cell interactions during the allergic immune response. Neurotrophin expression in the lung was investigated by means of immunohistochemistry and ELISA in a mouse model of chronic experimental asthma. Coculture experiments were performed with airway epithelial cells and bronchoalveolar lavage fluid eosinophils. Neurotrophin levels increased continuously during chronic allergic airway inflammation, and airway epithelial cells were the major source of NGF and BDNF within the inflamed lung. Epithelial neurotrophin production was upregulated by IL-1beta, TNF-alpha, and T(H)2 cytokines. Lung eosinophils expressed the BDNF and NGF receptors tropomyosin-related kinase (Trk) A and TrkB, and coculture with airway epithelial cells resulted in enhanced epithelial neurotrophin production, as well as in prolonged survival of eosinophils. Eosinophil survival was completely abolished in the presence of the neurotrophin receptor Trk antagonist K252a. During allergic inflammation, airway epithelial cells express increased amounts of NGF and BDNF that promote the survival of tissue eosinophils. Controlling epithelial neurotrophin production might be an important therapeutic target to prevent allergic airway eosinophilia. Attenuating the release of inflammatory mediators from the activated airway epithelium will become an important strategy to disrupt the pathogenesis of chronic allergic asthma.

  17. Airway inflammation in employees involved in cultivating Japanese mushrooms (bunashimeji).

    Science.gov (United States)

    Tsushima, Kenji; Yasuo, Masanori; Tanabe, Tsuyoshi; Yoshikawa, Sumiko; Yamazaki, Yoshitaka; Kubo, Keishi

    2008-06-01

    Chronic inhalation of spores may cause respiratory symptoms such as productive cough and sputum. The purpose of this study was to determine the clinical pathophysiology of airway inflammation caused by bunashimeji spores and to investigate whether the spores have direct toxic inflammatory effects. Sensitized employees with respiratory symptoms and a stimulation index (SI) > 200%, and non-sensitized employees with a SI < 200% were enrolled. They underwent sputum induction and chest high-resolution computed tomography (HRCT). The in vitro effect of bunashimeji spore solutions on normal human bronchial epithelial (NHBE) cell cultures was investigated using the air-liquid interface method. Bunashimeji spore solution was added at 10(4) or 10(6) spores per 20 microL/well. The interleukin (IL)-8 and epithelial neutrophil-activating peptide-78 (ENA-78) concentrations in the medium and IL-8 mRNA expression of NHBE cells were assessed after each stimulation. Sensitized employees were divided into 14 with normal HRCT and 9 with abnormal HRCT. Fifteen of the sensitized group and five of the non-sensitized group had a productive cough and sputum. The neutrophil counts in induced sputum were significantly higher in subjects with abnormal HRCT than in those with normal HRCT. IL-8 and ENA-78 concentrations following stimulation with 10(4) and 10(6) spores were significantly increased compared with PBS only on day 9. IL-8 mRNA expression due to spore stimulation was significantly increased compared with control. IL-8 mRNA expression with 10(6) spore stimulation was significantly increased on days 6 and 12 compared with 10(4) spores. The inhalation of spores directly produces toxic inflammatory effects in the airways, independent of the degree of sensitization.

  18. Recovery room nurses' knowledge regarding postoperative airway ...

    African Journals Online (AJOL)

    Adele

    9. Recovery room nurses' knowledge regarding postoperative airway emergencies in adults in private hospitals in Northern Gauteng,. South Africa. Correspondence: Dr ADH Botha email: annali.botha@up.ac.za. T van Huyssteen. Critical care unit, Zuid-Afrikaans Hospitaal, Muckleneuk, Pretoria, South Africa. ADH Botha.

  19. [Airway anatomy : Relevant structures in emergency medicine].

    Science.gov (United States)

    Schulze, M; Wree, A

    2017-09-01

    The subject of this article is the anatomy of the respiratory tract with an emphasis on the larynx. A differentiation is made between the upper and lower airways according to topographical and functional aspects, the limits of which are marked by the lower section of the larynx. The focus is on the anatomy of the structures involved, which are relevant for emergency medicine.

  20. Neuronal NOS localises to human airway cilia.

    Science.gov (United States)

    Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M

    2015-01-30

    Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Quantitative analysis of airway abnormalities in CT

    DEFF Research Database (Denmark)

    Petersen, Jens; Lo, Pechin Chien Pau; Nielsen, Mads

    2010-01-01

    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...

  2. Unique™ Laryngeal Mask airway versus Cobra™ Perilaryngeal ...

    African Journals Online (AJOL)

    Adele

    Introduction. Both the Unique™ LMA, and lately the Cobra™ PLA, is available in most of the larger state hospitals in South Africa. This study's objective is to evaluate and compare the learning curves for insertion of these two single-use airway devices. This is to ascertain which of these two devices is easier and safer to ...

  3. CT quantification of central airway in tracheobronchomalacia

    Energy Technology Data Exchange (ETDEWEB)

    Im, Won Hyeong; Jin, Gong Yong; Han, Young Min; Kim, Eun Young [Dept. of Radiology, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2016-05-15

    To know which factors help to diagnose tracheobronchomalacia (TBM) using CT quantification of central airway. From April 2013 to July 2014, 19 patients (68.0 ± 15.0 years; 6 male, 13 female) were diagnosed as TBM on CT. As case-matching, 38 normal subjects (65.5 ± 21.5 years; 6 male, 13 female) were selected. All 57 subjects underwent CT with end-inspiration and end-expiration. Airway parameters of trachea and both main bronchus were assessed using software (VIDA diagnostic). Airway parameters of TBM patients and normal subjects were compared using the Student t-test. In expiration, both wall perimeter and wall thickness in TBM patients were significantly smaller than normal subjects (wall perimeter: trachea, 43.97 mm vs. 49.04 mm, p = 0.020; right main bronchus, 33.52 mm vs. 42.69 mm, p < 0.001; left main bronchus, 26.76 mm vs. 31.88 mm, p = 0.012; wall thickness: trachea, 1.89 mm vs. 2.22 mm, p = 0.017; right main bronchus, 1.64 mm vs. 1.83 mm, p = 0.021; left main bronchus, 1.61 mm vs. 1.75 mm, p = 0.016). Wall thinning and decreased perimeter of central airway of expiration by CT quantification would be a new diagnostic indicators in TBM.

  4. Airway inflammation in mild cystic fibrosis.

    Science.gov (United States)

    Eckrich, Jonas; Zissler, Ulrich M; Serve, Friederike; Leutz, Patricia; Smaczny, Christina; Schmitt-Grohé, Sabina; Fussbroich, Daniela; Schubert, Ralf; Zielen, Stefan; Eickmeier, Olaf

    2017-01-01

    Airway infection and inflammation play major roles in the progression of cystic fibrosis (CF) lung disease. In patients with mild disease, airway inflammation is a clinically relevant and often underdiagnosed feature. Lung function, sputum cell counts, and cytokine profiles in CF with mild disease might be different in patients with and without involvement of small airway disease (SAD). Patients with mild CF (n=32) and 22 healthy controls were enrolled in this study. Patients with CF were assigned to two groups: (1) patients without SAD (n=19, median age 12.3years, MEF 25 >50% predicted), and (2) patients with SAD (n=13 median age, 13.2years, MEF 25 inflammation compared to controls as indicated by elevated levels of sputum biomarkers like total cells, neutrophils, and IL6. Our study demonstrated that patients with CF with mild disease defined by lung function might be further endotyped according to their involvement of SAD. In patients with CF and SAD, airway neutrophilic inflammation is more pronounced and is in part distinct from that seen in patients without SAD. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  5. Manual airway labeling has limited reproducibility

    DEFF Research Database (Denmark)

    Petersen, Jens; Feragen, Aasa; Thomsen, Laura Hohwü

    Purpose: Quantitative airway assessment is often performed in specific branches to enable comparison of measurements between patients and over time. Little is known on the accuracy in locating these branches. We determined inter- and intra-observer agreement of manual labeling of segmental bronch...

  6. Essential ultrasound techniques of the pediatric airway

    DEFF Research Database (Denmark)

    Stafrace, Samuel; Engelhardt, Thomas; Teoh, Wendy H

    2016-01-01

    Ultrasound of the airways is a technique which has been described in a number of recent articles and reviews highlighting the diagnostic possibilities and simple methodology. However, there is a paucity of information focusing specifically on such methods in children where equipment, technique, a...

  7. Qualitative analysis of unanticipated difficult airway management

    DEFF Research Database (Denmark)

    Rosenstock, C; Hansen, E G; Kristensen, M S

    2006-01-01

    Unanticipated difficult airway management (DAM) is a major challenge for the anaesthesiologist and is associated with a risk of severe patient damage. We analysed 24 cases of unanticipated DAM for actual case management and anaesthesiologists knowledge, technical and non-technical skills....... Anaesthesiologists' opinions, as well as environmental factors of importance for DAM proficiency, were also assessed....

  8. Allergic asthma and bronchial hyperreactivity

    NARCIS (Netherlands)

    Santing, Rudolf Eduard

    1993-01-01

    Asthma may effect 5-10% of the population in Western countries and is probably underdiagnosed (Mortagy et al., 1986). Despite improved possibilities for therapy and increased drug use morbidity and mortality are still increasing (Page, 1993). The social and financial burden of the disease is

  9. Indications of airway stenting for severe central airway obstruction due to advanced cancer.

    Science.gov (United States)

    Nagano, Hiroaki; Kishaba, Tomoo; Nei, Yuichirou; Yamashiro, Shin; Takara, Hiroaki

    2017-01-01

    Management of severe central airway obstruction due to advanced cancer is a medical and technical challenge. The impact of airway stenting on the clinical outcome of such patients is unclear. This single-center, retrospective study evaluated 21 patients who underwent airway stenting for advanced cancer. We examined predictors of the post-stenting mortality, including age, serum albumin, tracheal diameter, smoking, opioid use, respiratory failure, and performance status (PS). We also compared survival according to the PS. The mean survival period after stenting was 85.2 days. On univariate analysis, age, albumin, PS before airway stenting, respiratory failure, admission route, and PS grade were the candidates as possible predictors of prognosis after the procedure. On multivariate analysis, PS before airway stenting was identified as possible predictor of prognosis after stenting (HR 1.6180, 95% CI 0.969 to 2.7015, p = 0.066). The mean survival period after stenting was significantly longer in the good PS group, compared to the poor PS group (147.8 days vs. 38.2 days,p = 0.0346). Airway stenting for advanced cancer may be more effective for patients in good general condition than in those with poor performance status.

  10. Indications of airway stenting for severe central airway obstruction due to advanced cancer.

    Directory of Open Access Journals (Sweden)

    Hiroaki Nagano

    Full Text Available Management of severe central airway obstruction due to advanced cancer is a medical and technical challenge. The impact of airway stenting on the clinical outcome of such patients is unclear.This single-center, retrospective study evaluated 21 patients who underwent airway stenting for advanced cancer. We examined predictors of the post-stenting mortality, including age, serum albumin, tracheal diameter, smoking, opioid use, respiratory failure, and performance status (PS. We also compared survival according to the PS.The mean survival period after stenting was 85.2 days. On univariate analysis, age, albumin, PS before airway stenting, respiratory failure, admission route, and PS grade were the candidates as possible predictors of prognosis after the procedure. On multivariate analysis, PS before airway stenting was identified as possible predictor of prognosis after stenting (HR 1.6180, 95% CI 0.969 to 2.7015, p = 0.066. The mean survival period after stenting was significantly longer in the good PS group, compared to the poor PS group (147.8 days vs. 38.2 days,p = 0.0346.Airway stenting for advanced cancer may be more effective for patients in good general condition than in those with poor performance status.

  11. Airway epithelial cell tolerance to Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Verghese Margrith W

    2005-04-01

    Full Text Available Abstract Background The respiratory tract epithelium is a critical environmental interface that regulates inflammation. In chronic infectious airway diseases, pathogens may permanently colonize normally sterile luminal environments. Host-pathogen interactions determine the intensity of inflammation and thus, rates of tissue injury. Although many cells become refractory to stimulation by pathogen products, it is unknown whether the airway epithelium becomes either tolerant or hypersensitive in the setting of chronic infection. Our goals were to characterize the response of well-differentiated primary human tracheobronchial epithelial cells to Pseudomonas aeruginosa, to understand whether repeated exposure induced tolerance and, if so, to explore the mechanism(s. Methods The apical surface of well-differentiated primary human tracheobronchial epithelial cell cultures was repetitively challenged with Pseudomonas aeruginosa culture filtrates or the bacterial media control. Toxicity, cytokine production, signal transduction events and specific effects of dominant negative forms of signaling molecules were examined. Additional experiments included using IL-1β and TNFα as challenge agents, and performing comparative studies with a novel airway epithelial cell line. Results An initial challenge of the apical surface of polarized human airway epithelial cells with Pseudomonas aeruginosa culture filtrates induced phosphorylation of IRAK1, JNK, p38, and ERK, caused degradation of IκBα, generation of NF-κB and AP-1 transcription factor activity, and resulted in IL-8 secretion, consistent with activation of the Toll-like receptor signal transduction pathway. These responses were strongly attenuated following a second Pseudomonas aeruginosa, or IL-1β, but not TNFα, challenge. Tolerance was associated with decreased IRAK1 protein content and kinase activity and dominant negative IRAK1 inhibited Pseudomonas aeruginosa -stimulated NF-κB transcriptional

  12. Extrinsic airway compression secondary to pulmonary arterial conduits: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Donnelly, L.F. [Dept. of Radiology and Div. of Cardiothoracic Surgery, Children`s Hospital Medical Center, Cincinnati, OH (United States); Strife, J.L. [Dept. of Radiology and Div. of Cardiothoracic Surgery, Children`s Hospital Medical Center, Cincinnati, OH (United States); Bailey, W.W. [Dept. of Radiology and Div. of Cardiothoracic Surgery, Children`s Hospital Medical Center, Cincinnati, OH (United States)

    1997-03-01

    Abnormal enlargement or malposition of any vascular structure or mass adjacent to the airway can cause extrinsic airway compression. In children with previous surgery for congenitial heart disease, mass effect from prosthetic devices or alteration in the anatomic position of normal structures can lead to extrinsic airway compression. Because many children have complex medical problems after cardiac surgery, wheezing may be attributed to cardiac causes and airway compression may not be investigated. Furthermore, the distal airway compression seen in these children often is not visualized on chest radiographys. MR imaging can be useful in evaluating extrinsic airway compression in these patients. We present the MR imaging of two patients with symptomatic extrinsic airway compression secondary to pulmonary arterial conduits. (orig.)

  13. Predominant constitutive CFTR conductance in small airways

    Directory of Open Access Journals (Sweden)

    Lytle Christian

    2005-01-01

    Full Text Available Abstract Background The pathological hallmarks of chronic obstructive pulmonary disease (COPD are inflammation of the small airways (bronchiolitis and destruction of lung parenchyma (emphysema. These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter. Methods We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole. Results In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath of the bronchiole was small (mean ± sem: -3 ± 1 mV; n = 25, but when gluconate replaced luminal Cl-, the bionic Cl- diffusion potentials (-58 ± 3 mV; n = 25 were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl- permeability was at least 5 times greater than Na+ permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 μM+IBMX (100 μM, ATP (100 μM, or adenosine (100 μM, but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM, GlyH-101* (5–50 μM, and CFTRInh-172* (5 μM. RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways. Conclusion These results indicate that the small airway of the pig is characterized by a constitutively active Cl- conductance that is most likely due to CFTR.

  14. Role of airway epithelial barrier dysfunction in pathogenesis of asthma.

    Science.gov (United States)

    Gon, Yasuhiro; Hashimoto, Shu

    2018-01-01

    Bronchial asthma is characterized by persistent cough, increased sputum, and repeated wheezing. The pathophysiology underlying these symptoms is the hyper-responsiveness of the airway along with chronic airway inflammation. Repeated injury, repair, and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium; such changes are believed to have a significant association with the pathophysiology of asthma. Damage to the barrier functions of the airway epithelium enhances mucosal permeability of foreign substances in the airway epithelium of patients with asthma. Thus, epithelial barrier fragility is closely involved in releasing epithelial cytokines (e.g., TSLP, IL-25, and IL-33) because of the activation of airway epithelial cells, dendritic cells, and innate group 2 innate lymphoid cells (ILC2). Functional abnormalities of the airway epithelial cells along with the activation of dendritic cells, Th2 cells, and ILC2 form a single immunopathological unit that is considered to cause allergic airway inflammation. Here we use the latest published literature to discuss the potential pathological mechanisms regarding the onset and progressive severity of asthma with regard to the disruption of the airway epithelial function. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  15. Dynamics of Surfactant Liquid Plugs at Bifurcating Lung Airway Models

    Science.gov (United States)

    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.

  16. Update on the roles of distal airways in COPD

    Directory of Open Access Journals (Sweden)

    N. Roche

    2011-03-01

    Full Text Available This review is the summary of a workshop on the role of distal airways in chronic obstructive pulmonary disease (COPD, which took place in 2009 in Vence, France. The evidence showing inflammation and remodelling in distal airways and the possible involvement of these in the pathobiology, physiology, clinical manifestations and natural history of COPD were examined. The usefulness and limitations of physiological tests and imaging techniques for assessing distal airways abnormalities were evaluated. Ex vivo studies in isolated lungs and invasive measurements of airway resistance in living individuals have revealed that distal airways represent the main site of airflow limitation in COPD. Structural changes in small conducting airways, including increased wall thickness and obstruction by muco-inflammatory exudates, and emphysema (resulting in premature airway closure, were important determinants of airflow limitation. Infiltration of small conducting airways by phagocytes (macrophages and neutrophils, dendritic cells and T and B lymphocytes increased with airflow limitation. Distal airways abnormalities were associated with patient-related outcomes (e.g. dyspnoea and reduced health-related quality of life and with the natural history of the disease, as reflected by lung function decline and mortality. These data provide a clear rationale for targeting distal airways in COPD.

  17. Respuesta hemodinámica al estrés mental y físico en sujetos normotensos hiperreactivos: Efectos del Betabloqueo Cardiovascular response to mental and physical stress in hyper-reactive normotensive subjects: Beta blockade effect

    Directory of Open Access Journals (Sweden)

    Julio Przybylski

    2004-10-01

    Full Text Available El objetivo de nuestro trabajo fue estudiar la reactividad cardiovascular en personas sanas normotensas sin medicación, mediante la técnica, de Stroop de conflicto entre el color y la palabra (SCWCT, la respuesta anticipatoria de la presión arterial con el ejercicio (RA y la prueba ergométrica graduada (PEG. Se analizó el efecto de un betabloqueante beta1 selectivo: bisoprolol (B sobre la reactividad cardiovascular al estrés mental (EM y físico en personas hiperreactivas. Se estudiaron 42 personas, de los cuales fueron incluidas sólo 30 (21 mujeres y 9 varones que resultaron hiperreactivas, con una edad media de 42.5 años. Los mayores valores de la presión arterial sistólica (PAS y diastólica (PAD durante el EM fueron tomados como medida de reactividad, considerándose como respuesta hiperreactiva un aumento de 30 mm de Hg o mayor y/o 15 mm de Hg o mayor respectivamente. El efecto de una dosis diaria oral de 5 mg de B vs placebo (P fue estudiado en forma prospectiva, randomizada y doble ciego. Se analizaron los datos acerca de la reactividad en el SCWCT mediante el test exacto de Fisher. En los resultados, se observó una menor sensibilidad de RA y PEG vs SCWCT. Las 15 personas que recibieron P continuaron hiperreactivas en tanto que 6 de las 15 personas tratadas con B dejaron de ser reactivas (pThe aim of our study was to evaluate the cardiovascular reactivity in healthy normotensive subjects without medication, using mental and physical stress techniques: Stroop color word conflict test (SCWCT, anticipatory blood pressure response to exercise (ARE and stress testing (ST. We analized the effects of a selective beta 1 betablocker: bisoprolol (B on cardiovascular reactivity in our subjects (s. We studied 42 s, but only 30 (21 females and 9 males were included who were hyperreactives. The mean age was 42,5 years. The higher values of systolic (SBP and diastolic blood pressure (DBP during the mental stress (MS were taken as a measure of

  18. The degradation of airway tight junction protein under acidic conditions is probably mediated by transient receptor potential vanilloid 1 receptor

    Science.gov (United States)

    Xu, Rui; Li, Qi; Zhou, Jia; Zhou, Xiang-dong; Perelman, Juliy M.; Kolosov, Victor P.

    2013-01-01

    Acidic airway microenvironment is one of the representative pathophysiological features of chronic inflammatory respiratory diseases. Epithelial barrier function is maintained by TJs (tight junctions), which act as the first physical barrier against the inhaled substances and pathogens of airway. As previous studies described, acid stress caused impaired epithelial barriers and led the hyperpermeability of epithelium. However, the specific mechanism is still unclear. We have showed previously the existence of TRPV (transient receptor potential vanilloid) 1 channel in airway epithelium, as well as its activation by acidic stress in 16HBE cells. In this study, we explored the acidic stress on airway barrier function and TJ proteins in vitro with 16HBE cell lines. Airway epithelial barrier function was determined by measuring by TER (trans-epithelial electrical resistance). TJ-related protein [claudin-1, claudin-3, claudin-4, claudin-5, claudin-7 and ZO-1 (zonula occluden 1)] expression was examined by western blotting of insoluble fractions of cell extraction. The localization of TJ proteins were visualized by immunofluorescent staining. Interestingly, stimulation by pH 6.0 for 8 h slightly increased the epithelial resistance in 16HBE cells insignificantly. However, higher concentration of hydrochloric acid (lower than pH 5.0) did reduce the airway epithelial TER of 16HBE cells. The decline of epithelial barrier function induced by acidic stress exhibited a TRPV1-[Ca2+]i-dependent pathway. Of the TJ proteins, claudin-3 and claudin-4 seemed to be sensitive to acidic stress. The degradation of claudin-3 and claudin-4 induced by acidic stress could be attenuated by the specific TRPV1 blocker or intracellular Ca2+ chelator BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)]. PMID:24073800

  19. Thymol attenuates allergic airway inflammation in ovalbumin (OVA)-induced mouse asthma.

    Science.gov (United States)

    Zhou, Ershun; Fu, Yunhe; Wei, Zhengkai; Yu, Yuqiang; Zhang, Xichen; Yang, Zhengtao

    2014-07-01

    Thymol, a naturally occurring monocyclic phenolic compound derived from Thymus vulgaris (Lamiaceae), has been reported to exhibit anti-inflammatory property in vivo and vitro. However, the mechanism of thymol is not clear. The aim of the present study was to investigate the effects of thymol on allergic inflammation in OVA-induced mice asthma and explore its mechanism. The model of mouse asthma was established by the induction of OVA. Thymol was orally administered at a dose of 4, 8, and 16 mg/kg body weight 1h before OVA challenge. At 24h after the last challenge, mice were sacrificed, and the data were collected by various experimental methods. The results revealed that pretreatment with thymol reduced the level of OVA-specific IgE, inhibited recruitment of inflammatory cells into airway, and decreased the levels of IL-4, IL-5, and IL-13 in BALF. Moreover, the pathologic changes of lung tissues were obviously ameliorated and goblet cell hyperplasia was effectively inhibited by the pretreatment of thymol. In addition, thymol reduced the development of airway hyperresponsiveness and blocked the activation of NF-κB pathway. All data suggested that thymol ameliorated airway inflammation in OVA-induced mouse asthma, possibly through inhibiting NF-κB activation. These findings indicated that thymol may be used as an alternative agent for treating allergic asthma. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Raising awareness of upper airway diseases: Overview of management and prevention strategies

    Directory of Open Access Journals (Sweden)

    De-yun WANG

    2017-11-01

    Full Text Available The nose together with the paranasal sinuses is the main part of the upper airway, which is lined with pseudostratified columnar ciliated epithelium. There are several important physiological functions such as conditioning and filtration of the inspired air and the provision of end organ for the sense of smell. Besides the nose also fulfills a physical and immunological barrier as the nasal epithelium is the first site of interaction between the host tissue and foreign invaders, such as viruses, bacteria, fungi, allergens, and harmful particulates. Hence, nasal diseases such as rhinitis (allergic and infectious and rhinosinusitis are the most common health problems worldwide, affecting millions of people of all ages. In the past 10 to 20 years, our understanding of the immuno-pathophysiological mechanisms underlying the common nasal diseases has been significantly enhanced by in vivo and in vitro studies. This allows the development of novel therapeutic strategies designed to improve the physiological and immune defense functions of the nose, as well as for other common airway diseases. Since the dynamically external changes of atmosphere, environment (pollution and susceptible population, we are now facing some of new features on epidemiology and the types of upper airway diseases that require us to in-deep study the diseases through basic and clinical researches, so as to further understand the prevention, diagnosis and treatment of the diseases. DOI: 10.118555/j.issn.0577-7402.2017.10.01

  1. Dexamethasone and N-acetyl-cysteine attenuate Pseudomonas aeruginosa-induced mucus expression in human airways.

    Science.gov (United States)

    Sprenger, Lisa; Goldmann, Torsten; Vollmer, Ekkehard; Steffen, Armin; Wollenberg, Barbara; Zabel, Peter; Hauber, Hans-Peter

    2011-04-01

    Infection with Pseudomonas aeruginosa (PA) induces mucus hypersecretion in airways. Therapeutic options to attenuate excessive mucus expression are sparse. To investigate the effect of steroids and N-acetyl-cysteine (NAC) on PA-induced mucus expression. Calu-3 cells and explanted human mucosa from the upper airways were stimulated with either PA, lipopolysaccharide from alginate producing PA (smooth, sPA-LPS) or non-alginate producing PA (rough, rPA-LPS). Dexamethasone (DEX) and NAC were added in different concentrations. Expression of mucin (MUC5AC) gene and mucin protein expression was quantified using PAS (periodic acids Schiff) staining and real time PCR. PA, sPA-LPS or rPA-LPS significantly induced mucin protein and MUC5AC gene expression in Calu-3 cells and explanted mucosal tissue (P NAC significantly decreased PA-, sPA-LPS- and rPA-LPS-induced mucin protein expression both in vitro and ex vivo (P 0.05). Our data show that both an anti-inflammatory drug (DEX) and an anti-oxidative agent (NAC) can attenuate PA-induced mucus expression in human airways. These results support the use of steroids and NAC in clinical practice to treat PA-induced mucus hypersecretion. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Curcumin and anthocyanin inhibit pepsin-mediated cell damage and carcinogenic changes in airway epithelial cells.

    Science.gov (United States)

    Samuels, Tina L; Pearson, Amy C S; Wells, Clive W; Stoner, Gary D; Johnston, Nikki

    2013-10-01

    Laryngopharyngeal reflux (LPR) is associated with inflammatory and neoplastic airway diseases. Gastric pepsin internalized by airway epithelial cells during reflux contributes to oxidative stress, inflammation, and carcinogenesis. Several plant extracts and compounds inhibit digestive enzymes and inflammatory or neoplastic changes to the esophagus in models of gastroesophageal reflux. This study examined the potential of chemoprotective phytochemicals to inhibit peptic activity and mitigate pepsin-mediated damage of airway epithelial cells. Cultured human laryngeal and hypopharyngeal epithelial cells were pretreated with curcumin (10 micromol/L), ecabet sodium (125 microg/mL), and anthocyanin-enriched black-raspberry extract (100 microg/mL) 30 minutes before treatment with pepsin (0.1 mg/mL; 1 hour; pH 7). Controls were treated with media pH 7 or pepsin pH 7 without phytochemicals. Cell damage and proliferative changes were assessed by electron microscopy, cell count, thymidine analog incorporation, and real-time polymerase chain reaction array. Pepsin inhibition was determined by in vitro kinetic assay. Micromolar concentrations of curcumin, ecabet sodium, and black-raspberry extract inhibited peptic activity and pepsin-induced mitochondrial damage and hyperproliferation. Curcumin abrogated pepsin-mediated depression of tumor suppressor gene expression and altered the subcellular localization of pepsin following endocytosis. Several phytochemicals inhibit the pepsin-mediated cell damage underlying inflammatory or neoplastic manifestations of LPR. Dietary supplementation or adjunctive therapy with phytochemicals may represent novel preventive or therapeutic strategies for LPR-attributed disease.

  3. Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c

    NARCIS (Netherlands)

    Liu, Gang; Cooley, Marion A; Nair, Prema M; Donovan, Chantal; Hsu, Alan C; Jarnicki, Andrew G; Haw, Tatt Jhong; Hansbro, Nicole G; Ge, Qi; Brown, Alexandra C; Tay, Hock; Foster, Paul S; Wark, Peter A; Horvat, Jay C; Bourke, Jane E; Grainge, Chris L; Argraves, W Scott; Oliver, Brian G; Knight, Darryl A; Burgess, Janette K; Hansbro, Philip M

    2017-01-01

    Asthma is a chronic inflammatory disease of the airways. It is characterized by allergic airway inflammation, airway remodelling, and airway hyperresponsiveness (AHR). Asthma patients, in particular those with chronic or severe asthma, have airway remodelling that is associated with the accumulation

  4. Recent Developments in United Airways Disease

    OpenAIRE

    Ciprandi, Giorgio; Caimmi, Davide; Miraglia del Giudice, Michele; La Rosa, Mario; Salpietro, Carmelo; Marseglia, Gian Luigi

    2012-01-01

    The nose and lung are both part of the respiratory tract. Often the diseases affecting the nose and/or the bronchi are treated separately. However, in recent years, numerous studies have highlighted the fact that the respiratory system is a single entity and the concept of "united airway disease" has become more and more important. The unity of the respiratory tract is confirmed both from a morphological and from a functional point of view. Nevertheless, this concept is also confirmed for the...

  5. [Comparison of efficacy for laryngeal mask airway-Supreme(TM) versus common laryngeal mask airway in children].

    Science.gov (United States)

    Shangguan, Wang-ning; You, Shan; He, Wei; DI, Mei-qin; Xu, Jian; Li, Jun; Lian, Qing-quan

    2013-11-19

    To compare the efficacy of laryngeal mask airway-Supreme(TM) versus common laryngeal mask airway in children with general anesthesia. With local research ethics committee's approval and written informed parental consent, 100 children were randomly divided into groups L (size 2.0 common laryngeal mask airway) and S (size 2.0 laryngeal mask airway-Supreme(TM)) according to random number (n = 50 each). After anesthesia induction, a common laryngeal mask airway or laryngeal mask airway-Supreme(TM) was inserted and mechanically ventilated. Time and ease for insertion, insertion success rate, airway leak pressure, success rate and ease of disposal sputum collecting tube insertion in group S, quality of airway during anesthetic maintenance, abdominal circumference changes and complications within 24 h post-operation were measured. Compared with group L, abdominal circumference increased less in group S (0.90 ± 0.35 vs 0.43 ± 0.18 cm, n = 46, P children with mechanical ventilation, laryngeal mask airway-Supreme(TM) can be effectively applied to maintain a good airway. And the incidence of gastric insufflation is lower. It is particularly useful for those requiring evacuation of gastric contents during general anesthesia.

  6. Dynamic Properties of Human Bronchial Airway Tissues

    CERN Document Server

    Wang, Jau-Yi; Pallai, Prathap; Corrigan, Chris J; Lee, Tak H

    2011-01-01

    Young's Modulus and dynamic force moduli were measured on human bronchial airway tissues by compression. A simple and low-cost system for measuring the tensile-strengh of soft bio-materials has been built for this study. The force-distance measurements were undertaken on the dissected bronchial airway walls, cartilages and mucosa from the surgery-removed lungs donated by lung cancer patients with COPD. Young's modulus is estimated from the initial slope of unloading force-displacement curve and the dynamic force moduli (storage and loss) are measured at low frequency (from 3 to 45 Hz). All the samples were preserved in the PBS solution at room temperature and the measurements were perfomed within 4 hours after surgery. Young's modulus of the human bronchial airway walls are fond ranged between 0.17 and 1.65 MPa, ranged between 0.25 to 1.96 MPa for cartilages, and between 0.02 to 0.28 MPa for mucosa. The storage modulus are found varying 0.10 MPa with frequency while the loss modulus are found increasing from ...

  7. Exercise and airway injury in athletes.

    Science.gov (United States)

    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.

  8. THE BUFFER CAPACITY OF AIRWAY EPITHELIAL SECRETIONS

    Directory of Open Access Journals (Sweden)

    Dusik eKim

    2014-06-01

    Full Text Available The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF. The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 µl volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO3- is the major buffer. Peak buffer capacity (β increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO3- secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO3- secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions.

  9. The buffer capacity of airway epithelial secretions.

    Science.gov (United States)

    Kim, Dusik; Liao, Jie; Hanrahan, John W

    2014-01-01

    The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF). The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 μl) volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO(-) 3 is the major buffer. Peak buffer capacity (β) increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR)-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO(-) 3 secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO(-) 3 secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions.

  10. Impact of airway morphological changes on pulmonary flows in scoliosis

    Science.gov (United States)

    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.

  11. Secretoneurin induces airway mucus hypersecretion by enhancing the binding of EGF to NRP1.

    Science.gov (United States)

    Xu, Rui; Li, Qi; Zhou, Jia; Zhou, Xiangdong; Perelman, Juliy M; Kolosov, Victor P

    2014-01-01

    Secretoneurin(SN), a neuropeptide, has been considered a reliable marker of allergenic stimulation. However, the relationship between SN and the secretion of airway mucin remains unclear. In this study, we aimed to examine the in vitro relationship between SN and airway mucin over synthesis, as well as the signaling pathways involved. Exogenous SN was added to two human airway epithelial cell lines (16HBE and NCI-H292). Measured by real-time quantitative polymerase chain reaction (qPCR) and enzyme-linked immuno sorbent assay (ELISA) respectively, the intracellular mucin(MUC)5AC mRNA and MUC5AC protein of culture supernates exhibited a time- and dose-dependent increase after stimulation of SN. Based on the evidence of an increased phosphorylation of ERK1/2 induced by exogenous SN, we performed the radioactive binding assay. We failed to find direct binding of SN to either epidermal growth factor receptor (EGFR) or Neuropilin-1(NRP1), the co-receptor of EGFR. But we detected an enhanced binding of EGF to NRP1 in the two airway epithelial cell lines induced by exogenous SN. Either EGF neutralizing antibody or MEK specific inhibitor (PD-98059) could attenuate the over synthesis of MUC5AC induced by exogenous SN, indicating an endogenous EGF dependent mechanism in MUC5AC over synthesis induced by SN. We conclude that SN induces MUC5AC hypersecretion in a dose- and time-dependent manner; moreover, the MUC5AC over synthesis induced by SN is strongly associated with the enhanced binding of EGF to NRP1 and the activation of EGFR and ERK1/2 subsequently. © 2014 S. Karger AG, Basel.

  12. Effect of epithelium ATP release on cyclic pressure-induced airway mucus secretion.

    Science.gov (United States)

    Tong, Jin; Zhou, Xiang-Dong; Perelman, Juliy M; Kolosov, Victor P

    2014-02-01

    The cyclic mechanical effect of airflow during breathing creates the optimal airway hydration state. MUC (mucin) 5AC is an important component of the airway mucus. The formation of MUC5AC is related to ATP and intracellular calcium in the epithelial cells. In this study, we evaluated the effect of ATP release from intracellular calcium in epithelial cells on cyclic pressure-induced mucus secretion in the airway. 16HBE (human bronchial epithelial cells) were cultured in vitro on cyclically tilted cultured plates and divided into five groups: control, tilt, tilt and BAPTA-AM (1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid-acetoxymethyl ester), tilt and EGTA and tilt and RB-2 (reactive blue-2). The shear stress and compressive stress were induced by the surface tension of the liquid, atmospheric pressure and liquid gravity. Cell activity, MUC5AC mRNA expression level, MUC5AC protein expression level and ATP release and intracellular calcium changes were measured with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, RT-PCR (reverse transcription-PCR), HPLC and inverted fluorescence microscope, respectively. We detected that cyclic pressure significantly increased MUC5AC secretion and ATP release. The enhanced ATP release could be inhibited by both BAPTA-AM and RB-2, while EGTA did not have a suppressive effect. BAPTA-AM, EGTA and RB-2 did not obviously inhibit MUC5AC mRNA expression. Cyclic pressure did not induce MUC5AC secretion in the airway mucus epithelium via Ca(2+)-dependent ATP release, and nearly all Ca(2+) was provided by stored intracellular Ca(2). © 2014 The author(s).

  13. Secretoneurin Induces Airway Mucus Hypersecretion by Enhancing the Binding of EGF to NRP1

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    Rui Xu

    2014-02-01

    Full Text Available Aims: Secretoneurin(SN, a neuropeptide, has been considered a reliable marker of allergenic stimulation. However, the relationship between SN and the secretion of airway mucin remains unclear. In this study, we aimed to examine the in vitro relationship between SN and airway mucin over synthesis, as well as the signaling pathways involved. Methods and Results: Exogenous SN was added to two human airway epithelial cell lines (16HBE and NCI-H292. Measured by real-time quantitative polymerase chain reaction (qPCR and enzyme-linked immuno sorbent assay (ELISA respectively, the intracellular mucin(MUC5AC mRNA and MUC5AC protein of culture supernates exhibited a time- and dose-dependent increase after stimulation of SN. Based on the evidence of an increased phosphorylation of ERK1/2 induced by exogenous SN, we performed the radioactive binding assay. We failed to find direct binding of SN to either epidermal growth factor receptor (EGFR or Neuropilin-1(NRP1, the co-receptor of EGFR. But we detected an enhanced binding of EGF to NRP1 in the two airway epithelial cell lines induced by exogenous SN. Either EGF neutralizing antibody or MEK specific inhibitor (PD-98059 could attenuate the over synthesis of MUC5AC induced by exogenous SN, indicating an endogenous EGF dependent mechanism in MUC5AC over synthesis induced by SN. Conclusions: We conclude that SN induces MUC5AC hypersecretion in a dose- and time-dependent manner; moreover, the MUC5AC over synthesis induced by SN is strongly associated with the enhanced binding of EGF to NRP1 and the activation of EGFR and ERK1/2 subsequently.

  14. Effect of epithelium ATP release on cyclic pressure-induced airway mucus secretion

    Science.gov (United States)

    Tong, Jin; Zhou, Xiang-dong; Perelman, Juliy M.; Kolosov, Victor P.

    2013-01-01

    The cyclic mechanical effect of airflow during breathing creates the optimal airway hydration state. MUC (mucin) 5AC is an important component of the airway mucus. The formation of MUC5AC is related to ATP and intracellular calcium in the epithelial cells. In this study, we evaluated the effect of ATP release from intracellular calcium in epithelial cells on cyclic pressure-induced mucus secretion in the airway. 16HBE (human bronchial epithelial cells) were cultured in vitro on cyclically tilted cultured plates and divided into five groups: control, tilt, tilt and BAPTA–AM (1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid–acetoxymethyl ester), tilt and EGTA and tilt and RB-2 (reactive blue-2). The shear stress and compressive stress were induced by the surface tension of the liquid, atmospheric pressure and liquid gravity. Cell activity, MUC5AC mRNA expression level, MUC5AC protein expression level and ATP release and intracellular calcium changes were measured with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, RT–PCR (reverse transcription–PCR), HPLC and inverted fluorescence microscope, respectively. We detected that cyclic pressure significantly increased MUC5AC secretion and ATP release. The enhanced ATP release could be inhibited by both BAPTA–AM and RB-2, while EGTA did not have a suppressive effect. BAPTA–AM, EGTA and RB-2 did not obviously inhibit MUC5AC mRNA expression. Cyclic pressure did not induce MUC5AC secretion in the airway mucus epithelium via Ca2+-dependent ATP release, and nearly all Ca2+ was provided by stored intracellular Ca2+. PMID:27919041

  15. Exposure to ozone modulates human airway protease/antiprotease balance contributing to increased influenza A infection.

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    Matthew J Kesic

    Full Text Available Exposure to oxidant air pollution is associated with increased respiratory morbidities and susceptibility to infections. Ozone is a commonly encountered oxidant air pollutant, yet its effects on influenza infections in humans are not known. The greater Mexico City area was the primary site for the spring 2009 influenza A H1N1 pandemic, which also coincided with high levels of environmental ozone. Proteolytic cleavage of the viral membrane protein hemagglutinin (HA is essential for influenza virus infectivity. Recent studies suggest that HA cleavage might be cell-associated and facilitated by the type II transmembrane serine proteases (TTSPs human airway trypsin-like protease (HAT and transmembrane protease, serine 2 (TMPRSS2, whose activities are regulated by antiproteases, such as secretory leukocyte protease inhibitor (SLPI. Based on these observations, we sought to determine how acute exposure to ozone may modulate cellular protease/antiprotease expression and function, and to define their roles in a viral infection. We utilized our in vitro model of differentiated human nasal epithelial cells (NECs to determine the effects of ozone on influenza cleavage, entry, and replication. We show that ozone exposure disrupts the protease/antiprotease balance within the airway liquid. We also determined that functional forms of HAT, TMPRSS2, and SLPI are secreted from human airway epithelium, and acute exposure to ozone inversely alters their expression levels. We also show that addition of antioxidants significantly reduces virus replication through the induction of SLPI. In addition, we determined that ozone-induced cleavage of the viral HA protein is not cell-associated and that secreted endogenous proteases are sufficient to activate HA leading to a significant increase in viral replication. Our data indicate that pre-exposure to ozone disrupts the protease/antiprotease balance found in the human airway, leading to increased influenza susceptibility.

  16. Volatile organic compounds enhance allergic airway inflammation in an experimental mouse model.

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    Ulrike Bönisch

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

  17. Improving the safety of remote site emergency airway management.

    Science.gov (United States)

    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

  18. The site and nature of airway obstruction after lung transplantation.

    Science.gov (United States)

    Verleden, Stijn E; Vasilescu, Dragoş M; Willems, Stijn; Ruttens, David; Vos, Robin; Vandermeulen, Elly; Hostens, Jeroen; McDonough, John E; Verbeken, Erik K; Verschakelen, Johny; Van Raemdonck, Dirk E; Rondelet, Benoît; Knoop, Christiane; Decramer, Marc; Cooper, Joel; Hogg, James C; Verleden, Geert M; Vanaudenaerde, Bart M

    2014-02-01

    The chronic rejection of lung allografts is attributable to progressive small airway obstruction. To determine precisely the site and nature of this type of airway obstruction. Lungs from patients with rejected lung allografts treated by a second transplant (n = 7) were compared with unused donor (control) lungs (n = 7) using multidetector computed tomography (MDCT) to determine the percentage of visible airways obstructed in each airway generation, micro-computed tomography (microCT) to visualize the site of obstruction, and histology to determine the nature of this obstruction. The number of airways visible with MDCT was not different between rejected and control lungs. However, 10 ± 7% of observed airways greater than 2 mm in diameter, 50 ± 22% of airways between 1 and 2 mm in diameter, and 73 ± 10% of airways less than 1 mm in diameter were obstructed in the rejected lungs. MicroCT confirmed that the mean lumen diameter of obstructed airways was 647 ± 317 μm but showed no difference in either total number and cross-sectional area of the terminal bronchioles or in alveolar dimensions (mean linear intercept) between groups (P > 0.05). In addition, microCT demonstrated that only segments of the airways are obstructed. Histology confirmed a constrictive form of bronchiolitis caused by expansion of microvascular-rich granulation tissue in some locations and collagen-rich scar tissue in others. Chronic lung allograft rejection is associated with a progressive form of constrictive bronchiolitis that targets conducting airways while sparing larger airways as well as terminal bronchioles and the alveolar surface.

  19. Development of a Modular, Provider Customized Airway Trainer

    Science.gov (United States)

    2015-11-25

    data used to evaluate student performance. This transformation was done by the Airway Firmware on an Arduino Leonardo. The Airway Firmware transmitted...USB HID protocol, the Arduino Leonardo was selected. Figure 13: Electronics and Firmware W911NF-13-2-0033 Airway II Final Report...CREST U of MN Nov 2015 Page 12 of 35 The microchip, around which the Arduino Leonardo was built, readily supported USB HID through

  20. Polarized Airway Epithelial Models for Immunological Co-Culture Studies

    DEFF Research Database (Denmark)

    Papazian, Dick; Würtzen, Peter A; Hansen, Søren Werner Karlskov

    2016-01-01

    Epithelial cells line all cavities and surfaces throughout the body and play a substantial role in maintaining tissue homeostasis. Asthma and other atopic diseases are increasing worldwide and allergic disorders are hypothesized to be a consequence of a combination of dysregulation of the epithel......Epithelial cells line all cavities and surfaces throughout the body and play a substantial role in maintaining tissue homeostasis. Asthma and other atopic diseases are increasing worldwide and allergic disorders are hypothesized to be a consequence of a combination of dysregulation...... environment of both potential allergens and microflora. Limitations of these models prompt a need to develop new human cell-based in vitro models. A variety of co-culture systems for modelling the respiratory epithelium exist and are available to the scientific community. The models have become increasingly......-culture models to become powerful tools in the discovery of key molecules dictating immunity and/or tolerance, and for understanding the complex interplay that takes place between mucosa, airway epithelium and resident or infiltrating immune cells. This review focuses on current knowledge and the advantages...

  1. Point-of-care ultrasound (POCUS) of the upper airway.

    Science.gov (United States)

    You-Ten, Kong Eric; Siddiqui, Naveed; Teoh, Wendy H; Kristensen, Michael S

    2018-01-18

    Airway management is a critical skill in the practice of several medical specialities including anesthesia, emergency medicine, and critical care. Over the years mounting evidence has showed an increasing role of ultrasound (US) in airway management. The objective of this narrative review is to provide an overview of the indications for point-of-care ultrasound (POCUS) of the upper airway. The use of US to guide and assist clinical airway management has potential benefits for both provider and patient. Ultrasound can be utilized to determine airway size and predict the appropriate diameter of single-lumen endotracheal tubes (ETTs), double-lumen ETTs, and tracheostomy tubes. Ultrasonography can differentiate tracheal, esophageal, and endobronchial intubation. Ultrasonography of the neck can accurately localize the cricothyroid membrane for emergency airway access and similarly identify tracheal rings for US-guided tracheostomy. In addition, US can identify vocal cord dysfunction and pathology before induction of anesthesia. A rapidly growing body of evidence showing ultrasonography used in conjunction with hands-on management of the airway may benefit patient care. Increasing awareness and use of POCUS for many indications have resulted in technologic advancements and increased accessibility and portability. Upper airway POCUS has the potential to become the first-line non-invasive adjunct assessment tool in airway management.

  2. Dilemmas, Confusion, and Misconceptions Related to Small Airways Directed Therapy

    DEFF Research Database (Denmark)

    Lavorini, Federico; Pedersen, Søren; Usmani, Omar S.

    2017-01-01

    During the past decade, there has been increasing evidence that the small airways (ie, airways < 2 mm in internal diameter) contribute substantially to the pathophysiologic and clinical expression of asthma and COPD. The increased interest in small airways is, at least in part, a result of innova......During the past decade, there has been increasing evidence that the small airways (ie, airways COPD. The increased interest in small airways is, at least in part, a result...... benefit, compared with large-particle aerosol treatment. However, a number of questions remain unanswered about the pragmatic approach relevant for clinicians to consider the role of small airways directed therapy in the day-to-day management of asthma and COPD. We thus have tried to clarify the dilemmas......, confusion, and misconceptions related to small airways directed therapy. To this end, we have reviewed all studies on small-particle aerosol therapy systematically to address the dilemmas, confusion, and misconceptions related to small airways directed therapy....

  3. Vessel-guided airway segmentation based on voxel classification

    DEFF Research Database (Denmark)

    Lo, Pechin Chien Pau; Sporring, Jon; Ashraf, Haseem

    2008-01-01

    This paper presents a method for improving airway tree segmentation using vessel orientation information. We use the fact that an airway branch is always accompanied by an artery, with both structures having similar orientations. This work is based on a  voxel classification airway segmentation...... of the surroundings of a voxel, estimated based on a tube model, is to that of a neighboring vessel. The proposed method is tested on 20 CT images from different subjects selected randomly from a lung cancer screening study. Length of the airway branches from the results of the proposed method are significantly...

  4. Transient Mechanical Response of Lung Airway Tissue during Mechanical Ventilation

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    Israr Bin Muhammad Ibrahim

    2016-01-01

    Full Text Available Patients with acute lung injury, airway and other pulmonary diseases often require Mechanical Ventilation (MV. Knowledge of the stress/strain environment in lung airway tissues is very important in order to avoid lung injuries for patients undergoing MV. Airway tissue strains responsible for stressing the lung’s fiber network and rupturing the lung due to compliant airways are very difficult to measure experimentally. Multi-level modeling is adopted to investigate the transient mechanical response of the tissue under MV. First, airflow through a lung airway bifurcation (Generation 4–6 is modeled using Computational Fluid Dynamics (CFD to obtain air pressure during 2 seconds of MV breathing. Next, the transient air pressure was used in structural analysis to obtain mechanical strain experienced by the airway tissue wall. Structural analysis showed that airway tissue from Generation 5 in one bifurcation can stretch eight times that of airway tissue of the same generation number but with different bifurcation. The results suggest sensitivity of load to geometrical features. Furthermore, the results of strain levels obtained from the tissue analysis are very important because these strains at the cellular-level can create inflammatory responses, thus damaging the airway tissues.

  5. Selection and fabrication of a non-woven polycarbonate urethane cover for a tissue engineered airway stent.

    Science.gov (United States)

    Chen, Weiluan; Clauser, Johanna; Thiebes, Anja Lena; McGrath, Donnacha J; McHugh, Peter E; Steinseifer, Ulrich; Jockenhoevel, Stefan; Hennink, Wim E; Kok, Robbert Jan

    2016-11-30

    One of the major problems in end-stage bronchotracheal cancer is stenosis of the upper airways, either due to luminal ingrowth of the tumor or mucus plugging. Airway stents that suppress tumor ingrowth and sustain mucociliary transport can alleviate these problems in end-stage bronchial cancer. We evaluated different types of polymeric covers for a tissue engineered airway stent. The distinguishing feature of this stent concept is that respiratory epithelial cells can grow on the luminal surface of the stent which facilitates mucociliary clearance. To facilitate growth of epithelial cells at the air-liquid interface of the stent, we developed a polyurethane cover that allows transport of nutrients to the cells. Nonwoven polycarbonate urethane (PCU) covers were prepared by a spraying process and evaluated for their porosity and glucose permeability. Respiratory epithelial cells harvested from sheep trachea were cultured onto the selected PCU cover and remained viable at the air-liquid interface when cultured for 21days. Lastly, we evaluated the radial force of a PCU-covered nitinol stent, and showed the PCU covers did not adversely affect the mechanical properties of the stents for their intended application in the smaller bronchi. These in vitro data corroborate the design of a novel airway stent for palliative treatment of bronchotracheal stenosis by combination of stent-technology with tissue-engineered epithelial cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Inhibiting AKT Phosphorylation Employing Non-Cytotoxic Anthraquinones Ameliorates TH2 Mediated Allergic Airways Disease and Rhinovirus Exacerbation

    Science.gov (United States)

    Cesar de Souza Alves, Caio; Collison, Adam; Hatchwell, Luke; Plank, Maximilian; Morten, Matthew; Foster, Paul S.; Johnston, Sebastian L.; França da Costa, Cristiane; Vieira de Almeida, Mauro; Couto Teixeira, Henrique; Paula Ferreira, Ana; Mattes, Joerg

    2013-01-01

    Background Severe asthma is associated with T helper (TH) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro. Objective To determine the anti-inflammatory potential of anthraquinones in-vivo. Methods BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation. Results Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1α and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of TH2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung. Conclusion Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT. PMID:24223970

  7. Osteopontin That Is Elevated in the Airways during COPD Impairs the Antibacterial Activity of Common Innate Antibiotics.

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    Anele Gela

    Full Text Available Bacterial infections of the respiratory tract contribute to exacerbations and disease progression in chronic obstructive pulmonary disease (COPD. There is also an increased risk of invasive pneumococcal disease in COPD. The underlying mechanisms are not fully understood but include impaired mucociliary clearance and structural remodeling of the airways. In addition, antimicrobial proteins that are constitutively expressed or induced during inflammatory conditions are an important part of the airway innate host defense. In the present study, we show that osteopontin (OPN, a multifunctional glycoprotein that is highly upregulated in the airways of COPD patients co-localizes with several antimicrobial proteins expressed in the airways. In vitro, OPN bound lactoferrin, secretory leukocyte peptidase inhibitor (SLPI, midkine, human beta defensin-3 (hBD-3, and thymic stromal lymphopoietin (TSLP but showed low or no affinity for lysozyme and LL-37. Binding of OPN impaired the antibacterial activity against the important bacterial pathogens Streptococcus pneumoniae and Pseudomonas aeruginosa. Interestingly, OPN reduced lysozyme-induced killing of S. pneumoniae, a finding that could be explained by binding of OPN to the bacterial surface, thereby shielding the bacteria. A fragment of OPN generated by elastase of P. aeruginosa retained some inhibitory effect. Some antimicrobial proteins have additional functions. However, the muramidase-activity of lysozyme and the protease inhibitory function of SLPI were not affected by OPN. Taken together, OPN can contribute to the impairment of innate host defense by interfering with the function of antimicrobial proteins, thus increasing the vulnerability to acquire infections during COPD.

  8. Reduction of Eosinophils in Small Airways by Inhaled Steroids is Insufficient in Patients with Adult Asthma

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    Hiroshi Tanaka

    2006-01-01

    Conclusions: It was speculated that inhaled CFC-BDP and DP-FP might deposit mainly in large airways and fail to fully reach small airways, consequently allowing eosinophilic inflammation to continue in small airways.

  9. Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology.

    Science.gov (United States)

    Hüttemann, Maik; Lee, Icksoo; Gao, Xiufeng; Pecina, Petr; Pecinova, Alena; Liu, Jenney; Aras, Siddhesh; Sommer, Natascha; Sanderson, Thomas H; Tost, Monica; Neff, Frauke; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Naton, Beatrix; Rathkolb, Birgit; Rozman, Jan; Favor, Jack; Hans, Wolfgang; Prehn, Cornelia; Puk, Oliver; Schrewe, Anja; Sun, Minxuan; Höfler, Heinz; Adamski, Jerzy; Bekeredjian, Raffi; Graw, Jochen; Adler, Thure; Busch, Dirk H; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Weissmann, Norbert; Doan, Jeffrey W; Bassett, David J P; Grossman, Lawrence I

    2012-09-01

    Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial electron transport chain. The purpose of this study was to analyze the function of lung-specific cytochrome c oxidase subunit 4 isoform 2 (COX4i2) in vitro and in COX4i2-knockout mice in vivo. COX was isolated from cow lung and liver as control and functionally analyzed. COX4i2-knockout mice were generated and the effect of the gene knockout was determined, including COX activity, tissue energy levels, noninvasive and invasive lung function, and lung pathology. These studies were complemented by a comprehensive functional screen performed at the German Mouse Clinic (Neuherberg, Germany). We show that isolated cow lung COX containing COX4i2 is about twice as active (88 and 102% increased activity in the presence of allosteric activator ADP and inhibitor ATP, respectively) as liver COX, which lacks COX4i2. In COX4i2-knockout mice, lung COX activity and cellular ATP levels were significantly reduced (-50 and -29%, respectively). Knockout mice showed decreased airway responsiveness (60% reduced P(enh) and 58% reduced airway resistance upon challenge with 25 and 100 mg methacholine, respectively), and they developed a lung pathology deteriorating with age that included the appearance of Charcot-Leyden crystals. In addition, there was an interesting sex-specific phenotype, in which the knockout females showed reduced lean mass (-12%), reduced total oxygen consumption rate (-8%), improved glucose tolerance, and reduced grip force (-14%) compared to wild-type females. Our data suggest that high activity lung COX is a central determinant of airway function and is required for maximal airway responsiveness and healthy lung function. Since airway constriction requires energy, we propose a model in which reduced tissue ATP levels explain protection from airway hyperresponsiveness, i.e., absence of COX4i2 leads to reduced lung COX activity and ATP levels, which results in impaired airway constriction and

  10. Effects of Theophylline on Chronic Inflammatory Lung Injury Induced by LPS Exposure in Guinea Pigs

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    Yoshio Kaneko

    2007-01-01

    Conclusions: Theophylline improved airway injury as well as airway hyperreactivity induced by repetitive exposure of the guinea pigs to LPS. These results suggest that theophylline treatment has ameliorative effects on airway disease with chronic inflammation.

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

    Science.gov (United States)

    Shipkowski, Kelly Anne

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

  12. Coal fly ash impairs airway antimicrobial peptides and increases bacterial growth.

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    Jennifer A Borcherding

    Full Text Available Air pollution is a risk factor for respiratory infections, and one of its main components is particulate matter (PM, which is comprised of a number of particles that contain iron, such as coal fly ash (CFA. Since free iron concentrations are extremely low in airway surface liquid (ASL, we hypothesize that CFA impairs antimicrobial peptides (AMP function and can be a source of iron to bacteria. We tested this hypothesis in vivo by instilling mice with Pseudomonas aeruginosa (PA01 and CFA and determine the percentage of bacterial clearance. In addition, we tested bacterial clearance in cell culture by exposing primary human airway epithelial cells to PA01 and CFA and determining the AMP activity and bacterial growth in vitro. We report that CFA is a bioavailable source of iron for bacteria. We show that CFA interferes with bacterial clearance in vivo and in primary human airway epithelial cultures. Also, we demonstrate that CFA inhibits AMP activity in vitro, which we propose as a mechanism of our cell culture and in vivo results. Furthermore, PA01 uses CFA as an iron source with a direct correlation between CFA iron dissolution and bacterial growth. CFA concentrations used are very relevant to human daily exposures, thus posing a potential public health risk for susceptible subjects. Although CFA provides a source of bioavailable iron for bacteria, not all CFA particles have the same biological effects, and their propensity for iron dissolution is an important factor. CFA impairs lung innate immune mechanisms of bacterial clearance, specifically AMP activity. We expect that identifying the PM mechanisms of respiratory infections will translate into public health policies aimed at controlling, not only concentration of PM exposure, but physicochemical characteristics that will potentially cause respiratory infections in susceptible individuals and populations.

  13. Fitness of isogenic colony morphology variants of Pseudomonas aeruginosa in murine airway infection.

    Directory of Open Access Journals (Sweden)

    Elza Rakhimova

    Full Text Available Chronic lung infections with Pseudomonas aeruginosa are associated with the diversification of the persisting clone into niche specialists and morphotypes, a phenomenon called 'dissociative behaviour'. To explore the potential of P. aeruginosa to change its morphotype by single step loss-of-function mutagenesis, a signature-tagged mini-Tn5 plasposon library of the cystic fibrosis airway isolate TBCF10839 was screened for colony morphology variants under nine different conditions in vitro. Transposon insertion into 1% of the genome changed colony morphology into eight discernable morphotypes. Half of the 55 targets encode features of primary or secondary metabolism whereby quinolone production was frequently affected. In the other half the transposon had inserted into genes of the functional categories transport, regulation or motility/chemotaxis. To mimic dissociative behaviour of isogenic strains in lungs, pools of 25 colony morphology variants were tested for competitive fitness in an acute murine airway infection model. Six of the 55 mutants either grew better or worse in vivo than in vitro, respectively. Metabolic proficiency of the colony morphology variant was a key determinant for survival in murine airways. The most common morphotype of self-destructive autolysis did unexpectedly not impair fitness. Transposon insertions into homologous genes of strain PAO1 did not reproduce the TBCF10839 mutant morphotypes for 16 of 19 examined loci pointing to an important role of the genetic background on colony morphology. Depending on the chosen P. aeruginosa strain, functional genome scans will explore other areas of the evolutionary landscape. Based on our discordant findings of mutant phenotypes in P. aeruginosa strains PAO1, PA14 and TBCF10839, we conclude that the current focus on few reference strains may miss modes of niche adaptation and dissociative behaviour that are relevant for the microevolution of complex traits in the wild.

  14. Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates.

    Science.gov (United States)

    Longest, P Worth; Tian, Geng; Khajeh-Hosseini-Dalasm, Navvab; Hindle, Michael

    2016-12-01

    The objective of this study was to compare aerosol deposition predictions of a new whole-airway CFD model with available in vivo data for a dry powder inhaler (DPI) considered across multiple inhalation waveforms, which affect both the particle size distribution (PSD) and particle deposition. The Novolizer DPI with a budesonide formulation was selected based on the availability of 2D gamma scintigraphy data in humans for three different well-defined inhalation waveforms. Initial in vitro cascade impaction experiments were conducted at multiple constant (square-wave) particle sizing flow rates to characterize PSDs. The whole-airway CFD modeling approach implemented the experimentally determined PSDs at the point of aerosol formation in the inhaler. Complete characteristic airway geometries for an adult were evaluated through the lobar bronchi, followed by stochastic individual pathway (SIP) approximations through the tracheobronchial region and new acinar moving wall models of the alveolar region. It was determined that the PSD used for each inhalation waveform should be based on a constant particle sizing flow rate equal to the average of the inhalation waveform's peak inspiratory flow rate (PIFR) and mean flow rate [i.e., AVG(PIFR, Mean)]. Using this technique, agreement with the in vivo data was acceptable with <15% relative differences averaged across the three regions considered for all inhalation waveforms. Defining a peripheral to central deposition ratio (P/C) based on alveolar and tracheobronchial compartments, respectively, large flow-rate-dependent differences were observed, which were not evident in the original 2D in vivo data. The agreement between the CFD predictions and in vivo data was dependent on accurate initial estimates of the PSD, emphasizing the need for a combination in vitro-in silico approach. Furthermore, use of the AVG(PIFR, Mean) value was identified as a potentially useful method for characterizing a DPI aerosol at a constant flow rate.

  15. Deposition of graphene nanomaterial aerosols in human upper airways.

    Science.gov (United States)

    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 naomaterials inevitably could become airborne in the workplace during manufacturing processes. The inhalation and subsequent deposition of graphene nanomaterial aerosols in the human respiratory tract could potentially result in adverse health effects to exposed workers. Therefore, investigating the deposition of graphene nanomaterial aerosols in the human airways is an indispensable component of an integral approach to graphene occupational health. For this reason, this study carried out a series of airway replica deposition experiments to obtain original experimental data for graphene aerosol airway deposition. In this study, graphene aerosols were generated, size classified, and delivered into human airway replicas (nasal and oral-to-lung airways). The deposition fraction and deposition efficiency of graphene aerosol in the airway replicas were obtained by a novel experimental approach. The experimental results acquired showed that the fractional deposition of graphene aerosols in airway sections studied were all less than 4%, and the deposition efficiency in each airway section was generally lower than 0.03. These results indicate that the majority of the graphene nanomaterial aerosols 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.

  16. Imaging Acute Airway Obstruction in Infants and Children.

    Science.gov (United States)

    Darras, Kathryn E; Roston, Alexandra T; Yewchuk, Lila K

    2015-01-01

    Acute airway obstruction is much more common in infants and children than in adults because of their unique anatomic and physiologic features. Even in young patients with partial airway occlusion, symptoms can be severe and potentially life-threatening. Factors that predispose children to airway compromise include the orientation of their larynx, the narrow caliber of their trachea, and their weak intercostal muscles. Because the clinical manifestations of acute airway obstruction are often nonspecific, clinicians often rely on the findings at imaging to establish a diagnosis. Several key anatomic features of the pediatric airway make it particularly susceptible to respiratory distress, and the imaging recommendations for children suspected of having acute airway obstruction are presented. Although cross-sectional imaging may be helpful, the diagnosis can often be established by using radiographs alone. Radiographs of the chest and upper airway should be routinely acquired; however, for the child who is in severe distress, a single lateral radiographic view may be all that is necessary. The purpose of this article is to provide an imaging approach to acquired causes of acute airway obstruction in children, including (a) abnormalities affecting the upper portion of the airway, such as croup, acute epiglottitis, retropharyngeal infection, and foreign bodies, and (b) abnormalities affecting the lower portion of the airway, such as asthma, bronchiolitis, and foreign bodies. It is essential that the radiologist recognize key imaging findings and understand the pathophysiologic features of acute airway obstruction because in most cases, when the cause is identified, the condition responds well to prompt management. (©)RSNA, 2015.

  17. Baicalein reduces airway injury in allergen and IL-13 induced airway inflammation.

    Directory of Open Access Journals (Sweden)

    Ulaganathan Mabalirajan

    Full Text Available 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.

  18. Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness

    NARCIS (Netherlands)

    deBruinWeller, MS; Weller, FR; RijssenbeekNouwens, LHM; Jansen, HM; deMonchy, JGR

    In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in

  19. Airway Measurement for Airway Remodeling Defined by Post-Bronchodilator FEV1/FVC in Asthma: Investigation Using Inspiration-Expiration Computed Tomography

    OpenAIRE

    Chae, Eun Jin; Kim, Tae-Bum; Cho, You Sook; Park, Chan-Sun; Seo, Joon Beom; Kim, Namkug; Moon, Hee-Bom

    2010-01-01

    Purpose Airway remodeling may be responsible for irreversible airway obstruction in asthma, and a low post-bronchodilator FEV1/FVC ratio can be used as a noninvasive marker of airway remodeling. We investigated correlations between airway wall indices on computed tomography (CT) and various clinical indices, including post-bronchodilator FEV1/FVC ratio, in patients with asthma. Methods Volumetric CT was performed on 22 stable asthma patients who were taking inhaled corticosteroids. Airway dim...

  20. MOEBIUS SYNDROME: CHALLENGES OF AIRWAY MANAGEMENT.

    Science.gov (United States)

    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.

  1. Water permeability in human airway epithelium

    DEFF Research Database (Denmark)

    Pedersen, Peter Steen; Procida, Kristina; Larsen, Per Leganger

    2005-01-01

    Osmotic water permeability (P(f)) was studied in spheroid-shaped human airway epithelia explants derived from nasal polyps by the use of a new improved tissue collection and isolation procedure. The fluid-filled spheroids were lined with a single cell layer with the ciliated apical cell membrane...... facing the outside. They were capable of surviving hours of experiment involving continuous superfusion of the bathing medium and changes of osmolarity. A new image analysis technique was developed for measuring the spheroid diameters, giving high time and measurement resolutions. The transepithelial P...

  2. Mucoactive agents for airway mucus hypersecretory diseases.

    Science.gov (United States)

    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

  3. Upper airway stimulation therapy and prior airway surgery for obstructive sleep apnea.

    Science.gov (United States)

    Mahmoud, Ahmad F; Thaler, Erica R

    2017-10-31

    To determine if patients with prior airway surgery for obstructive sleep apnea (OSA) had increased benefit following implantation with hypoglossal nerve stimulator. Retrospective chart review at a single institution tertiary academic care center. Following implantation with hypoglossal nerve stimulator device, the outcomes of patients who underwent prior airway surgery for OSA were compared with those who did not. Primary outcome measures included apnea-hypopnea index (AHI) and nadir oxyhemoglobin saturation (NOS) as measured by polysomnography. Secondary outcome measures included Epworth Sleepiness Scale. Forty-seven patients underwent implantation with hypoglossal nerve stimulator. Of these, 30 patients had undergone prior airway surgery for OSA, whereas 16 did not. Mean preoperative AHI and NOS were 39.3 ± 2.8 and 78% ± 1.8% for all patients, 39.4 ± 3.7 and 79% ± 14% for patients with prior airway surgery, and 39.1 ± 4.0 and 77% ± 2.6% for patients without prior surgery. Mean postoperative AHI and NOS were 3.9 ± 1.2 and 91% ± 0.4% for all patients, 4.2 ± 1.7 and 91% ± 0.5% for patients with prior surgery, and 3.4 ± 1.5 and 93% ± 0.6% for patients without prior surgery (P = 0.756 and 0.053, respectively). Overall, patients had significant improvement following implantation with hypoglossal nerve stimulator. Prior airway surgery had no statistically significant effect on postoperative AHI or NOS. 4. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  4. Resistin-like molecule-β (RELM-β) targets airways fibroblasts to effect remodelling in asthma: from mouse to man.

    Science.gov (United States)

    Fang, C L; Yin, L J; Sharma, S; Kierstein, S; Wu, H F; Eid, G; Haczku, A; Corrigan, C J; Ying, S

    2015-05-01

    RELM-β has been implicated in airways inflammation and remodelling in murine models. Its possible functions in human airways are largely unknown. The aim was to address the hypothesis that RELM-β plays a role in extracellular matrix deposition in asthmatic airways. The effects of RELM-β gene deficiency were studied in a model of allergen exposure in mice sensitised and challenged with Aspergillus fumigatus (Af). RELM-β expression was investigated in bronchial biopsies from asthmatic patients. Direct regulatory effects of RELM-β on human lung fibroblasts were examined using primary cultures and the MRC5 cell line in vitro. Sensitisation and challenge of wild-type mice with Af-induced release of RELM-β with a time course coincident with that of procollagen in the airways. Af-induced expression of mRNA encoding some, but not all ECM in the lung parenchyma was attenuated in RELM-β-/- mice. RELM-β expression was significantly increased in the bronchial submucosa of human asthmatics compared with controls, and its expression correlated positively with that of fibronectin and α-smooth muscle actin. In addition to epithelial cells, macrophages, fibroblasts and vascular endothelial cells formed the majority of cells expressing RELM-β in the submucosa. Exposure to RELM-β increased TGF-β1, TGF-β2, collagen I, fibronectin, smooth muscle α-actin, laminin α1, and hyaluronan and proteoglycan link protein 1 (Hapl1) production as well as proliferation by human lung fibroblasts in vitro. These changes were associated with activation of ERK1/2 in MRC5 cells. The data are consistent with the hypothesis that elevated RELM-β expression in asthmatic airways contributes to airways remodelling at least partly by increasing fibroblast proliferation and differentiation with resulting deposition of extracellular matrix proteins. © 2014 John Wiley & Sons Ltd.

  5. A clinical comparison of disposable airway devices | Strydom ...

    African Journals Online (AJOL)

    They all received a standardised anaesthetic with propofol, fentanyl and isoflurane in 40% O2/N2O. Insertion technique, mask sizes and maximum cuff volumes were per manufacturer's instructions. The cuff was inflated to achieve an adequate airway seal (no audible leak at an airway pressure of 20cm H2O), or to the ...

  6. Plethysmographic measurements of specific airway resistance in young children

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Nielsen, Kim G

    2005-01-01

    Validated methods for lung function measurements in young children are lacking. Plethysmographic measurement of specific airway resistance (sRaw) provides such a method applicable from 2 years of age. sRaw gauges airway resistance from the measurements of the pressure changes driving the airflow...

  7. Difficult airways: a reliable “Plan B”

    African Journals Online (AJOL)

    2010-11-15

    Nov 15, 2010 ... supraglottic airway (SGA) or cricothyroidotomy is anticipated to be difficult. We describe the transtracheal placement of a central venous catheter (CVC) as a means to establish rescue jet ventilation in a patient with a difficult airway who was unwilling to undergo a tracheostomy under local anaesthesia.

  8. Airway management: A survey of training and practices of Nigerian ...

    African Journals Online (AJOL)

    2014-02-21

    Feb 21, 2014 ... Background: Airway management is an integral part of anesthetist's training and clinical practice. Studies have suggested that opportunities for anesthesia trainees to learn and practice endotracheal intubation have decreased over time. We sought to examine the current training and practices of airway ...

  9. Nitrogen Dioxide Exposure and Airway Responsiveness in Individuals with Asthma

    Science.gov (United States)

    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...

  10. Airway management: A survey of training and practices of Nigerian ...

    African Journals Online (AJOL)

    Background: Airway management is an integral part of anesthetist's training and clinical practice. Studies have suggested that opportunities for anesthesia trainees to learn and practice endotracheal intubation have decreased over time. We sought to examine the current training and practices of airway management by ...

  11. Repair of damaged supraglottic airway devices: A novel method

    Directory of Open Access Journals (Sweden)

    Kapoor Dheeraj

    2010-06-01

    Full Text Available Abstract 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.

  12. Airway smooth muscle and fibroblasts in the pathogenesis of asthma

    NARCIS (Netherlands)

    Johnson, Peter R A; Burgess, Janette K

    2004-01-01

    Asthma is a disease characterized by marked structural changes within the airway wall. These changes include deposition of extracellular matrix proteins and an increase in the numbers of airway smooth muscle cells and subepithelial fibroblasts. Both these cell types possess properties that would

  13. Bacteria isolated from the airways of paediatric patients with ...

    African Journals Online (AJOL)

    Knowledge of which bacteria are found in the airways of paediatric patients with bronchiectasis unrelated to cystic fibrosis. (CF) is important in defining empirical antibiotic guidelines for the treatment of acute infective exacerbations. Objective. To describe the bacteria isolated from the airways of children with non-CF ...

  14. Mortality by Level of Emphysema and Airway Wall Thickness

    DEFF Research Database (Denmark)

    Johannessen, Ane; Skorge, Trude Duelien; Bottai, Matteo

    2013-01-01

    There is limited knowledge of the prognostic value of quantitative computed tomography (CT) measures of emphysema and airway wall thickness (AWT) on mortality.......There is limited knowledge of the prognostic value of quantitative computed tomography (CT) measures of emphysema and airway wall thickness (AWT) on mortality....

  15. Airway skills training using a human patient simulator | Moodley ...

    African Journals Online (AJOL)

    ... of airway management skills using the simulator. Participant satisfaction was much better in the simulator group. The importance of psychomotor reinforcement should be borne in mind when designing simulation courses. Keywords: human patient simulator, simulation, airway management, psychomotor skills ...

  16. Vitamin D and markers of airway inflammation in asthma

    Directory of Open Access Journals (Sweden)

    Hala Mohamed Shalaby Samaha

    2015-10-01

    Conclusion: The lower the vitamin D level deficiency or insufficiency, the more the asthma exacerbation, the less the asthma control, the higher the serum level of IgE and higher FENO. Also low vitamin D associated with airway remodeling is presented by small airway affection and HRCT findings.

  17. Intra‑Operative Airway Management in Patients with Maxillofacial ...

    African Journals Online (AJOL)

    Background: Despite advancements in airway management, treatment of fractures in the maxillofacial region under general anesthesia remains a unique anesthetic challenge. We reviewed the pattern of airway management in patients with maxillofacial fractures and assessed those challenges associated with the different ...

  18. ORIGINAL ARTICLE ORIG Is airway diameter measured accurately ...

    African Journals Online (AJOL)

    tracheal or bronchial stenoses includes bronchoscopy and CT (computed tomography).2 This process affords the opportunity to study aspects of CT relating to airway stenosis. Axial CT scans produce excellent resolution in the horizontal plane, but the extent of airway disease may be underestimated if only axial images are ...

  19. Point-of-care ultrasound (POCUS) of the upper airway

    DEFF Research Database (Denmark)

    You-Ten, Kong Eric; Siddiqui, Naveed; Teoh, Wendy H

    2018-01-01

    Airway management is a critical skill in the practice of several medical specialities including anesthesia, emergency medicine, and critical care. Over the years mounting evidence has showed an increasing role of ultrasound (US) in airway management. The objective of this narrative review is to p...

  20. Airway and respiratory complications in children undergoing cleft lip ...

    African Journals Online (AJOL)

    Objectives: Anatomical abnormalities associated with cleft lip and palate increase the risk of airway complications. The aim of this study was to determine the incidence of intra-operative airway and respiratory complications during cleft lip and palate repair and identify risk factors. Design: Observational study in which fifty ...

  1. Perioperative adverse airway events in cleft lip and palate repair ...

    African Journals Online (AJOL)

    Background: Airway-related problems account for the majority of anaesthetic morbidity in paediatric anaesthesia, but more so for cleft lip and palate repair. The aim of this study was to assess the frequency, pattern, management and outcome of adverse airway events during the perioperative period in cleft lip and palate ...

  2. Neurotrophins in chronic allergic airway inflammation and remodeling.

    Science.gov (United States)

    Renz, Harald; Kiliç, Ayşe

    2012-01-01

    Allergic asthma is a chronic inflammatory disease characterized by the production of allergen-specific IgE antibodies, TH2 inflammation, airway hyperresponsiveness and airway remodeling. Airway remodeling represents the disease-limiting stage during disease progression, and the underlying cellular molecular network resulting in airway remodeling are still poorly defined. In addition to the well-established TH2-dependent inflammatory response, several lines of investigation reveal that this regulation in the peripheral central nervous system contributes to disease development, exacerbation and progression. Several members of the neurotrophin family (e.g. nerve growth factor, brain-derived neurotrophic factor) are important transmitters of signals between the immune and the nervous system. Recent data indicate that NGF contributes to the development of airway remodeling in an inflammation and TGF-independent manner. These and other data open the opportunity to therapeutically interfere also on this level of regulation as a novel approach. Copyright © 2012 S. Karger AG, Basel.

  3. Lack of national consensus in preoperative airway assessment

    DEFF Research Database (Denmark)

    Kehlet Nørskov, Anders; Rosenstock, Charlotte V; Lundstrøm, Lars H

    2016-01-01

    that Danish airway assessment was lacking uniformity. We aimed to examine whether multivariable risk assessment tools and predictors for difficult intubation and mask ventilation were used systematically. METHODS: Heads of anaesthesia departments were sent a six-question survey at the beginning of 2012. We......INTRODUCTION: Difficult airway management is associated with an increased risk of morbidity and mortality. Several preoperative risk factors associated with airway management difficulties have been proposed; however, no clear guideline for airway assessments exists. We therefore hypothesised...... asked if systematic risk assessment tools, particularly the Simplified Airway Risk Index (SARI), and predictors for difficult intubation and mask ventilation were used. Additionally, we asked if any risk factors were pre-printed on the anaesthesia record. RESULTS: In all, 29 of 31 (94%) departments...

  4. A hierarchical scheme for geodesic anatomical labeling of airway trees

    DEFF Research Database (Denmark)

    Feragen, Aasa; Petersen, Jens; Owen, Megan

    2012-01-01

    centerline tree, which is relatively unaffected by pathology. A thorough leave-one-patient-out evaluation of the algorithm is made on 40 segmented airway trees from 20 subjects labeled by 2 medical experts. We evaluate accuracy, reproducibility and robustness in patients with Chronic Obstructive Pulmonary......We present a fast and robust supervised algorithm for label- ing anatomical airway trees, based on geodesic distances in a geometric tree-space. Possible branch label configurations for a given unlabeled air- way tree are evaluated based on the distances to a training set of labeled airway trees....... In tree-space, the airway tree topology and geometry change continuously, giving a natural way to automatically handle anatomical differences and noise. The algorithm is made efficient using a hierarchical approach, in which labels are assigned from the top down. We only use features of the airway...

  5. A fungal protease allergen provokes airway hyperresponsiveness in asthma

    Science.gov (United States)

    Balenga, Nariman A.; Klichinsky, Michael; Xie, Zhihui; Chan, Eunice C.; Zhao, Ming; Jude, Joseph; Laviolette, Michel; Panettieri, Reynold A.; Druey, Kirk M.

    2015-01-01

    Asthma, a common disorder that affects more than 250 million people worldwide, is defined by exaggerated bronchoconstriction to inflammatory mediators including acetylcholine, bradykinin, and histamine—also termed airway hyper-responsiveness Nearly 10% of people with asthma have severe, treatment-resistant disease, which is frequently associated with IgE sensitization to ubiquitous fungi, typically Aspergillus fumigatus. Here we show that a major Aspergillus fumigatus allergen, Asp f13, which is a serine protease, alkaline protease 1 (Alp 1), promotes airway hyper-responsiveness by infiltrating the bronchial submucosa and disrupting airway smooth muscle cell-extracellular matrix interactions. Alp 1-mediated extracellular matrix degradation evokes pathophysiological RhoA-dependent Ca2+ sensitivity and bronchoconstriction. These findings support a pathogenic mechanism in asthma and other lung diseases associated with epithelial barrier impairment, whereby airway smooth muscle cells respond directly to inhaled environmental allergens to generate airway hyper-responsiveness. PMID:25865874

  6. Estudo da hiper-responsividade brônquica em pacientes portadores de refluxo gastroesofágico Bronchial hyperreactivity in patients with gastroesophageal reflux disease

    Directory of Open Access Journals (Sweden)

    Mônica Silveira Lapa

    2005-08-01

    Full Text Available OBJETIVO: O intuito deste trabalho foi evidenciar a existência desse reflexo vagal, através de uma broncoprovocação, em pacientes portadores de refluxo gastroesofágico. MÉTODOS: Onze pacientes com endoscopia sem evidências de refluxo gastroesofágico ou hérnia hiatal (grupo controle e dez pacientes com hérnia hiatal ou refluxo gastroesofágico foram submetidos à broncoprovocação com carbacol. RESULTADOS: O teste foi positivo em 5 dos pacientes com hérnia hiatal ou refluxo gastroesofágico (50%, e em 3 do grupo controle (27% (p = 0,64. CONCLUSÃO: A hipótese de que as vias aéreas de pacientes com refluxo gastroesofágico sem sintomas asmatiformes anteriores possam ser mais responsivas do que as de pacientes sem refluxo gastroesofágico permanece não comprovada.OBJECTIVE: To identify this vagal reflex using bronchial provocation tests in patients with gastroesophageal reflux disease. METHODS: The study group was composed of 10 patients presenting endoscopic evidence of hiatal hernia or gastroesophageal reflux disease, and the control group consisted of 11 patients presenting no evidence of either condition. All subjects were submitted to bronchial provocation with carbachol. RESULTS: The provocation test was positive in 5 (50% of the study group patients and 3 (27% of the control group patients (p = 0.64. CONCLUSION: The hypothesis that the airways of patients with gastroesophageal reflux disease (and no history of asthma-like respiratory symptoms might be more responsive than those of individuals without the disease remains unproven.

  7. Cortex phellodendri Extract Relaxes Airway Smooth Muscle

    Directory of Open Access Journals (Sweden)

    Qiu-Ju Jiang

    2016-01-01

    Full Text Available Cortex phellodendri is used to reduce fever and remove dampness and toxin. Berberine is an active ingredient of C. phellodendri. Berberine from Argemone ochroleuca can relax airway smooth muscle (ASM; however, whether the nonberberine component of C. phellodendri has similar relaxant action was unclear. An n-butyl alcohol extract of C. phellodendri (NBAECP, nonberberine component was prepared, which completely inhibits high K+- and acetylcholine- (ACH- induced precontraction of airway smooth muscle in tracheal rings and lung slices from control and asthmatic mice, respectively. The contraction induced by high K+ was also blocked by nifedipine, a selective blocker of L-type Ca2+ channels. The ACH-induced contraction was partially inhibited by nifedipine and pyrazole 3, an inhibitor of TRPC3 and STIM/Orai channels. Taken together, our data demonstrate that NBAECP can relax ASM by inhibiting L-type Ca2+ channels and TRPC3 and/or STIM/Orai channels, suggesting that NBAECP could be developed to a new drug for relieving bronchospasm.

  8. Cortex phellodendri Extract Relaxes Airway Smooth Muscle

    Science.gov (United States)

    Jiang, Qiu-Ju; Chen, Weiwei; Dan, Hong; Tan, Li; Zhu, He; Yang, Guangzhong; Shen, Jinhua; Peng, Yong-Bo; Zhao, Ping; Xue, Lu; Yu, Meng-Fei; Ma, Liqun; Si, Xiao-Tang; Wang, Zhuo; Dai, Jiapei; Qin, Gangjian; Zou, Chunbin; Liu, Qing-Hua

    2016-01-01

    Cortex phellodendri is used to reduce fever and remove dampness and toxin. Berberine is an active ingredient of C. phellodendri. Berberine from Argemone ochroleuca can relax airway smooth muscle (ASM); however, whether the nonberberine component of C. phellodendri has similar relaxant action was unclear. An n-butyl alcohol extract of C. phellodendri (NBAECP, nonberberine component) was prepared, which completely inhibits high K+- and acetylcholine- (ACH-) induced precontraction of airway smooth muscle in tracheal rings and lung slices from control and asthmatic mice, respectively. The contraction induced by high K+ was also blocked by nifedipine, a selective blocker of L-type Ca2+ channels. The ACH-induced contraction was partially inhibited by nifedipine and pyrazole 3, an inhibitor of TRPC3 and STIM/Orai channels. Taken together, our data demonstrate that NBAECP can relax ASM by inhibiting L-type Ca2+ channels and TRPC3 and/or STIM/Orai channels, suggesting that NBAECP could be developed to a new drug for relieving bronchospasm. PMID:27239213

  9. [Airway injuries due to blunt chest trauma].

    Science.gov (United States)

    Okabayashi, Kan; Hamatake, D; Yoshida, Y; Nakajima, H; Shirakusa, T; Yamasaki, S

    2006-10-01

    Although the incidence of blunt chest trauma is very high, the mediastinal tracheobronchial injuries are quite rare. The airway injuries are thought to be one of the most urgent clinical conditions in thoracic surgery, and we are requested to make not only a rapid and sharp diagnosis but also an appropriate treatment plan considering combined injuries. We present 9 cases of tracheobronchial injuries due to blunt chest trauma in recent years. The average age of these patients is 26.1 years, and they are consisted of 6 male and 3 female. The cause of trauma is traffic accident in 7, and occupational crane accident in 2. Bronchoplasty were done in 5 cases (right main bronchus in 2, left main bronchus in 1, trunks intermediate bronchus in 1, and the spur between middle and lower lobe in 1), membranous-tracheoplasty with right pneumonectomy in 1, left pneumonectomy in 1, conservative treatment in 2. Postoperative mortality is occurred in 1 case who was suffering from multiple injuries including severe head injury and contralateral lung contusion. Tracheobronchial plasties should be chosen if possible to preserve lung function for the patient suffering from airway injuries.

  10. An upper airway obstruction emergency: Ludwig angina.

    Science.gov (United States)

    Chou, Yu-Kung; Lee, Chao-Yi; Chao, Hai-Hsuan

    2007-12-01

    Ludwig angina remains a potentially lethal disease, rapidly spreading bilateral cellulitis of the submental, sublingual, and submandibular spaces, which bears the threat for rapid airway obstruction. Since the introduction of antibiotics in 1940s, the mortality was reduced significantly. This resulted in the rare occurrence of the disease, leaving many physicians with limited experience of Ludwig angina. Although the occurrence of Ludwig angina in adults is rare, its presence in the pediatric edentulous population is even more uncommon. Because the unfamiliarity with this disease is now increasing, unnecessary delaying diagnosis or inadequate management may occur and may result in serious complications. This presentation will consist of a historical review, discussion of pathophysiology, followed by clinical presentation, etiology, bacteriology, and management. With early diagnosis, airway observation and management, aggressive intravenous antibiotic therapy, and judicious surgical intervention, the disease should resolve without complications. In addition, the source of infection should be determined and eliminated if possible. A thoughtful, individualized management strategy seems to be the most reasonable approach to the disease.

  11. Continuous positive airway pressure therapy: new generations.

    LENUS (Irish Health Repository)

    Garvey, John F

    2012-02-01

    Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea syndrome (OSAS). However, CPAP is not tolerated by all patients with OSAS and alternative modes of pressure delivery have been developed to overcome pressure intolerance, thereby improving patient comfort and adherence. Auto-adjustable positive airway pressure (APAP) devices may be utilised for the long-term management of OSAS and may also assist in the initial diagnosis of OSAS and titration of conventional CPAP therapy. Newer modalities such as C-Flex and A-Flex also show promise as treatment options in the future. However, the evidence supporting the use of these alternative modalities remains scant, in particular with regard to long-term cardiovascular outcomes. In addition, not all APAP devices use the same technological algorithms and data supporting individual APAP devices cannot be extrapolated to support all. Further studies are required to validate the roles of APAP, C-Flex and A-Flex. In the interim, standard CPAP therapy should continue as the mainstay of OSAS management.

  12. Continuous positive airway pressure therapy: new generations.

    LENUS (Irish Health Repository)

    Garvey, John F

    2010-02-01

    Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea syndrome (OSAS). However, CPAP is not tolerated by all patients with OSAS and alternative modes of pressure delivery have been developed to overcome pressure intolerance, thereby improving patient comfort and adherence. Auto-adjustable positive airway pressure (APAP) devices may be utilised for the long-term management of OSAS and may also assist in the initial diagnosis of OSAS and titration of conventional CPAP therapy. Newer modalities such as C-Flex and A-Flex also show promise as treatment options in the future. However, the evidence supporting the use of these alternative modalities remains scant, in particular with regard to long-term cardiovascular outcomes. In addition, not all APAP devices use the same technological algorithms and data supporting individual APAP devices cannot be extrapolated to support all. Further studies are required to validate the roles of APAP, C-Flex and A-Flex. In the interim, standard CPAP therapy should continue as the mainstay of OSAS management.

  13. Airway Responsiveness to Psychological Processes in Asthma and Health

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    Thomas eRitz

    2012-09-01

    Full Text Available Psychosocial factors have been found to impact airway pathophysiology in respiratory disease with considerable consistency. Influences on airway mechanics have been studied particularly well. The goal of this article is to review the literature on airway responses to psychological stimulation, discuss potential pathways of influence, and present a well-established emotion-induction paradigm to study airway obstruction elicited by unpleasant stimuli. Observational studies have found systematic associations between lung function and daily mood changes. The laboratory –based paradigm of bronchoconstrictive suggestion has been used successfully to elicit airway obstruction in a substantial proportion of asthmatic individuals. Other studies have demonstrated an enhancement of airway responses to standard airway challenges with exercise, allergens, or methacholine. Standardized emotion-induction techniques have consistently shown airway constriction during unpleasant stimulation, with surgery, blood and injury stimuli being particularly powerful. Findings with various forms of stress induction have been more mixed. A number of methodological factors may account for variability across studies, such as choice of measurement technique, temporal association between stimulation and measurement, and the specific quality and intensity of the stimulus material, in particular the extent of implied action-orientation. Research has also begun to elucidate physiological processes associated with psychologically induced airway responses, with vagal excitation and ventilatory influences being the most likely candidate pathways, whereas the role of specific central nervous system pathways and inflammatory processes has been less studied. The technique of emotion-induction using films has the potential to become a standardized challenge paradigm for the further exploration of airway hyperresponsiveness mediated by central nervous system processes.

  14. Mucociliary clearance, airway inflammation and nasal symptoms in urban motorcyclists

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    Tereza C.S. Brant

    2014-01-01

    Full Text Available OBJECTIVES: There is evidence that outdoor workers exposed to high levels of air pollution exhibit airway inflammation and increased airway symptoms. We hypothesized that these workers would experience increased airway symptoms and decreased nasal mucociliary clearance associated with their exposure to air pollution. METHODS: In total, 25 non-smoking commercial motorcyclists, aged 18-44 years, were included in this study. These drivers work 8-12 hours per day, 5 days per week, driving on urban streets. Nasal mucociliary clearance was measured by the saccharine transit test; airway acidification was measured by assessing the pH of exhaled breath condensate; and airway symptoms were measured by the Sino-nasal Outcome Test-20 questionnaire. To assess personal air pollution exposure, the subjects used a passive-diffusion nitrogen dioxide (NO2 concentration-monitoring system during the 14 days before each assessment. The associations between NO2 and the airway outcomes were analyzed using the Mann-Whitney test and the Chi-Square test. Clinicaltrials.gov: NCT01976039. RESULTS: Compared with clearance in healthy adult males, mucociliary clearance was decreased in 32% of the motorcyclists. Additionally, 64% of the motorcyclists had airway acidification and 92% experienced airway symptoms. The median personal NO2 exposure level was 75 mg/m3 for these subjects and a significant association was observed between NO2 and impaired mucociliary clearance (p = 0.036. CONCLUSION: Non-smoking commercial motorcyclists exhibit increased airway symptoms and airway acidification as well as decreased nasal mucociliary clearance, all of which are significantly associated with the amount of exposure to air pollution.

  15. Comparison of pulsed versus continuous oxygen delivery using realistic adult nasal airway replicas

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    Chen JZ

    2017-08-01

    Full Text Available John Z Chen,1 Ira M Katz,2 Marine Pichelin,2 Kaixian Zhu,3 Georges Caillibotte,2 Michelle L Noga,4 Warren H Finlay,1 Andrew R Martin1 1Department of Mechanical Engineering, University of Alberta, Edmonton, AB, Canada; 2Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, Les Loges-en-Josas, 3Centre Explor!, Air Liquide Healthcare, Gentilly, France; 4Radiology and Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada Background: Portable oxygen concentrators (POCs typically include pulse flow (PF modes to conserve oxygen. The primary aims of this study were to develop a predictive in vitro model for inhaled oxygen delivery using a set of realistic airway replicas, and to compare PF for a commercial POC with steady flow (SF from a compressed oxygen cylinder. Methods: Experiments were carried out using a stationary compressed oxygen cylinder, a POC, and 15 adult nasal airway replicas based on airway geometries derived from medical images. Oxygen delivery via nasal cannula was tested at PF settings of 2.0 and 6.0, and SF rates of 2.0 and 6.0 L/min. A test lung simulated three breathing patterns representative of a chronic obstructive pulmonary disease patient at rest, during exercise, and while asleep. Volume-averaged fraction of inhaled oxygen (FiO2 was calculated by analyzing oxygen concentrations sampled at the exit of each replica and inhalation flow rates over time. POC pulse volumes were also measured using a commercial O2 conserver test system to attempt to predict FiO2 for PF. Results: Relative volume-averaged FiO2 using PF ranged from 68% to 94% of SF values, increasing with breathing frequency and tidal volume. Three of 15 replicas failed to trigger the POC when used with the sleep breathing pattern at the 2.0 setting, and four of 15 replicas failed to trigger at the 6.0 setting. FiO2 values estimated from POC pulse characteristics followed similar trends but were lower than those derived from

  16. Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling

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    Yuan Ma

    2016-01-01

    Full Text Available Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA- sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs were challenged by tumor necrosis factor alpha (TNF-α. The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS/mitogen-activated protein kinase (MAPK evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL- 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2′,7′-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were

  17. Upregulation of gelatinases and epithelial-mesenchymal transition in small airway remodeling associated with chronic exposure to wood smoke.

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    Yimin Zou

    Full Text Available BACKGROUND: Peribronchiolar fibrosis is an important feature of small airway remodeling (SAR in cigarette smoke-induced COPD. The aim of this study was to investigate the role of gelatinases (MMP9, MMP2 and epithelial-mesenchymal transition (EMT in SAR related to wood smoke (WS exposure in a rat model. METHODS: Forty-eight female Sprague-Dawley rats were randomly divided into the WS group, the cigarette smoke (CS group and the clean air control group. After 4 to 7 months of smoke exposure, lung tissues were examined with morphometric measurements, immunohistochemistry and Western blotting. Serum MMP9 and TIMP1 concentrations were detected by ELISA. In vitro, primary rat tracheal epithelial cells were stimulated with wood smoke condensate for 7 days. RESULTS: The COPD-like pathological alterations in rats exposed chronically to WS were similar to those exposed to CS; the area of collagen deposition was significantly increased in the small airway walls of those exposed to WS or CS for 7 months. The expression of gelatinases in rats induced by WS or CS exposure was markedly increased in whole lung tissue, and immunohistochemistry showed that MMP9, MMP2 and TIMP1 were primarily expressed in the airway epithelium. The serum levels of MMP9 and TIMP1 were significantly higher in rats secondary to WS or CS exposure. Few cells that double immunostained for E-cadherin and vimentin were observed in the airway subepithelium of rats exposed to WS for 7 months (only 3 of these 8 rats. In vitro, the expression of MMP9 and MMP2 proteins was upregulated in primary rat tracheal epithelial cells following exposure to wood smoke condensate for 7 days by Western blotting; positive immunofluorescent staining for vimentin and type I collagen was also observed. CONCLUSIONS: These findings suggest that the upregulation of gelatinases and EMT might play a role in SAR in COPD associated with chronic exposure to wood smoke.

  18. 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.

    Science.gov (United States)

    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 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 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. © 2015 The Association of Anaesthetists of Great Britain and Ireland.

  19. Pediatric Trainees Managing a Difficult Airway: Comparison of Laryngeal Mask Airway, Direct, and Video-Assisted Laryngoscopy

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    Art Ambrosio MD

    2017-05-01

    Full Text Available Objective Difficult airway management is a key skill required by all pediatric physicians, yet training on multiple modalities is lacking. The objective of this study was to compare the rate of, and time to, successful advanced infant airway placement with direct laryngoscopy, video-assisted laryngoscopy, and laryngeal mask airway (LMA in a difficult airway simulator. This study is the first to compare the success with 3 methods for difficult airway management among pediatric trainees. Study Design Randomized crossover pilot study. Setting Tertiary academic medical center. Methods Twenty-two pediatric residents, interns, and medical students were tested. Participants were provided 1 training session by faculty using a normal infant manikin. Subjects then performed all 3 of the aforementioned advanced airway modalities in a randomized order on a difficult airway model of a Robin sequence. Success was defined as confirmed endotracheal intubation or correct LMA placement by the testing instructor in ≤120 seconds. Results Direct laryngoscopy demonstrated a significantly higher placement success rate (77.3% than video-assisted laryngoscopy (36.4%, P = .0117 and LMA (31.8%, P = .0039. Video-assisted laryngoscopy required a significantly longer amount of time during successful intubations (84.8 seconds; 95% CI, 59.4-110.1 versus direct laryngoscopy (44.9 seconds; 95% CI, 33.8-55.9 and LMA placement (36.6 seconds; 95% CI, 24.7-48.4. Conclusions Pediatric trainees demonstrated significantly higher success using direct laryngoscopy in a difficult airway simulator model. However, given the potential lifesaving implications of advanced airway adjuncts, including video-assisted laryngoscopy and LMA placement, more extensive training on adjunctive airway management techniques may be useful for trainees.

  20. L-ornithine derived polyamines in cystic fibrosis airways.

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    Hartmut Grasemann

    Full Text Available Increased arginase activity contributes to airway nitric oxide (NO deficiency in cystic fibrosis (CF. Whether down-stream products of arginase activity contribute to CF lung disease is currently unknown. The objective of this study was to test whether L-ornithine derived polyamines are present in CF airways and contribute to airway pathophysiology. Polyamine concentrations were measured in sputum of patients with CF and in healthy controls, using liquid chromatography-tandem mass spectrometry. The effect of spermine on airway smooth muscle mechanical properties was assessed in bronchial segments of murine airways, using a wire myograph. Sputum polyamine concentrations in stable CF patients were similar to healthy controls for putrescine and spermidine but significantly higher for spermine. Pulmonary exacerbations were associated with an increase in sputum and spermine levels. Treatment for pulmonary exacerbations resulted in decreases in arginase activity, L-ornithine and spermine concentrations in sputum. The changes in sputum spermine with treatment correlated significantly with changes in L-ornithine but not with sputum inflammatory markers. Incubation of mouse bronchi with spermine resulted in an increase in acetylcholine-induced force and significantly reduced nitric oxide-induced bronchial relaxation. The polyamine spermine is increased in CF airways. Spermine contributes to airways obstruction by reducing the NO-mediated smooth muscle relaxation.

  1. [Nasal obstruction and compliance to nasal positive airway pressure].

    Science.gov (United States)

    Nowak, C; Bourgin, P; Portier, F; Genty, E; Escourrou, P; Bobin, S

    2003-06-01

    Obstructive sleep apnea syndrome is a very common disease. Nasal continuous positive airway pressure is a useful and efficient treatment but compliance depends on several factors including the degree of nasal obstruction. The aim of this study was to evaluate the effects of surgical correction of nasal obstruction on compliance to nasal continuous positive airway pressure in obstructive sleep apnea syndrome. This retrospective study (from March 1998 to March 2000) included ten patients suffering from a severe obstructive sleep apnea syndrome (apnea-hypopnea index greater than 30 per hour) treated by nasal continuous positive airway pressure for at least three months and presenting an anatomic nasal obstruction limiting the use of nasal continuous positive airway pressure. Surgical procedures included one septoplasty, two inferior turbinectomies and seven septoplasties with turbinectomies. The post-operative polysomnography showed that surgical correction of nasal obstruction had no effect on obstructive sleep apnea syndrome severity (no significative change of apnea hypopnea index after surgery) but allowed the use of lower nasal continuous positive airway pressure levels (7.1 mmHg after surgery versus 10 mmHg before) and improved compliance to treatment (six compliant patients after surgery versus no compliant patient before). These results were compared with those published in the literature. An examination of the nose has to be performed before initiating nasal continuous positive airway pressure. If nasal continuous positive airway pressure cannot be tolerated because of nasal obstruction, surgery is required to improve compliance and tolerance to treatment.

  2. Optimizing education in difficult airway management: meeting the challenge.

    Science.gov (United States)

    Myatra, Sheila N; Kalkundre, Rupali S; Divatia, Jigeeshu V

    2017-09-21

    The last 2 decades have seen a vast change in the science and technology of airway management. As a result, there is an increasing need to equip anesthesiologists with the new knowledge and skills for the safe management of a difficult airway. In addition to knowledge and expertise, human factors and nontechnical skills (NTS), including situational awareness, communication and team work, play an important role during difficult airway management and contribute to the outcome. Didactic sessions are useful to impart knowledge. Self-learning, interactive discussions, simulation and debriefing are important tools for teaching and training in difficult airway management. Manikin training and simulation enable development of technical as well as NTS without subjecting patients to risk and allow multiple training sessions of relatively uncommon scenarios. Guidelines are useful teaching tools, whereas cognitive tools such as the Vortex approach may be useful during a difficult airway. There is need for research on difficult airway management and optimized training methods. Research is also required to determine the barriers to adoption of guidelines and strategies to ensure widespread dissemination and implementation of guidelines and best practices for difficult airway management.

  3. A comparison of supraglottic airway i-gel™ vs. classic laryngeal mask airway in small children.

    Science.gov (United States)

    Lee, Ju-Hyun; Cho, Hyun-Seok; Shin, Won-Jung; Yang, Hong-Seuk

    2014-02-01

    i-gel™ is a new single-use supraglottic airway device without an inflatable cuff. This study was designed to compare the usefulness of i-gel™ versus a classic laryngeal mask airway (cLMA) in small children. Sixty-three children (age range : 4-72 months) were randomly assigned to an i-gel™ or cLMA group. We evaluated hemodynamic data, airway sealing ability, the success rate of insertion, and adverse events including an inadvertent sliding out during ventilation. Demographic data and hemodynamic data obtained immediately after the insertion of these devices did not differ between the two groups. The success rates for insertion on the first attempt were 77 and 84% for i-gel™ and cLMA, respectively (P = 0.54), and the overall success rates were 87 and 100% respectively (P = 0.14). There were no significant differences in terms of airway leak pressure. The inserted i-gel™ inadvertently slid out in 8 of 31 patients but only one sliding out case occurred in the cLMA group (P = 0.02). There were no differences between the groups in terms of other side effects (e.g., coughing, bleeding) associated with the use of i-gel™ and cLMA (P = 0.75 and 0.49, respectively). Oropharyngeal leak pressure and insertion success rate of i-gel™ are similar to those of cLMA. However, i-gel™ is prone to inadvertent sliding out of the mouth in small children. Therefore, it is recommended that the i-gel™ should be secured more tightly to avoid displacement of the device.

  4. Reduced Baseline Airway Caliber Relates to Larger Airway Sensitivity to Rostral Fluid Shift in Asthma

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    Swati A. Bhatawadekar

    2017-12-01

    Full Text Available Background: We have previously shown that when asthmatics go supine, fluid shifts out of the legs, accumulates in the thorax, and exacerbates lower airway narrowing. In the retrospective analysis of our previous work presented here, we test the hypothesis that the sensitivity of this process relates inversely to baseline caliber of the lower airways.Methods: Eighteen healthy (six women and sixteen asthmatic subjects (nine women sat for 30 min, and then lay supine for 30 min. While supine, lower body positive pressure (LBPP, 40 mm Hg was applied to displace fluid from the legs similar in amount to the overnight fluid shift. Respiratory resistance and reactance at 5 Hz (R5 and X5 and leg and thoracic fluid volumes (LFV and TFV were measured at the beginning and end of the supine period.Results: With LBPP, healthy, and asthmatic subjects had similar changes in the LFV and TFV (p = 0.3 and 0.1, respectively. Sensitivity to fluid shift, defined by ΔR5/ΔTFV, was larger in the asthmatics than in the healthy subjects (p = 0.0001, and correlated with baseline R5 in the supine position in the asthmatics (p = 0.7, p = 0.003. No such association was observed in the healthy subjects (p = 0.6. In the asthmatics, women showed a greater reduction in X5 than men with LBPP (p = 0.009.Conclusions: Smaller baseline airway caliber, as assessed by larger R5, was associated with increased sensitivity to fluid shift in the supine position. We conclude that asthmatics with narrower small airways such as obese asthma patients, women with asthma and those with severe asthma may be more sensitive to the effects fluid shift while supine as during sleep.

  5. Airway remodeling and its reversibility in equine asthma

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    Jean-Pierre Lavoie

    2017-06-01

    Full Text Available Despite effective therapies for controlling its clinical manifestations, human asthma remains an incurable disease. It is now recognized that inflammation induced structural changes (remodeling of the airways are responsible for the progressive loss of lung function in asthmatic patients. However, the peripheral airways, where most of the remodeling occurs in severe asthmatic patients, cannot be safely sampled in humans, and therefore, little is known of the effects of current therapies at reversing the established asthmatic remodeling, especially those occurring in the peripheral airways. Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, experiments in which the disease is artificially induced have been shown to have limited translational potential for humans. To the contrary, horses naturally suffer from an asthma-like condition which shares marked similarities with human asthma making this model unique to investigate the kinetics, reversibility, as well as the physiological consequences of tissue remodeling (Bullone and Lavoie 2015. We reported an increased deposition of smooth muscle, collagen and elastic fibers in the peripheral airways of affected horses, which was correlated with the lung function (Herszberg et al., 2006; Setlakwe et al., 2014. The airway subepithelial collagen depositions were almost completely reversed with 6 to 12 months of treatment with either antigen avoidance or inhaled corticosteroids (ICS administration, and there was a modest (30% on average decrease in airway smooth muscle (Leclere et al., 2011. A recent study also found that ICS combined with long-acting ß2-agonists drugs (LABA and ICS monotherapy similarly induced a 30% decrease of the airway smooth muscle mass at 3 months (Buollone, 2017. However, only ICS/LABA and antigen avoidance decreased airway luminal neutrophilia. The findings indicate the enhance therapeutic effect of ICS

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

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    Sonia R Rosner

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

  7. Continuous positive airway pressure titration in infants with severe upper airway obstruction or bronchopulmonary dysplasia.

    Science.gov (United States)

    Khirani, Sonia; Ramirez, Adriana; Aloui, Sabrina; Leboulanger, Nicolas; Picard, Arnaud; Fauroux, Brigitte

    2013-07-26

    Noninvasive continuous positive airway pressure (CPAP) is recognized as an effective treatment for severe airway obstruction in young children. The aim of the present study was to compare a clinical setting with a physiological setting of noninvasive CPAP in infants with nocturnal alveolar hypoventilation due to severe upper airway obstruction (UAO) or bronchopulmonary dysplasia (BPD). The breathing pattern and respiratory muscle output of all consecutive infants due to start CPAP in our noninvasive ventilation unit were retrospectively analysed. CPAP set on clinical noninvasive parameters (clinical CPAP) was compared to CPAP set on the normalization or the maximal reduction of the oesophageal pressure (Poes) and transdiaphragmatic pressure (Pdi) swings (physiological CPAP). Expiratory gastric pressure (Pgas) swing was measured. The data of 12 infants (mean age 10 ± 8 mo) with UAO (n = 7) or BPD (n = 5) were gathered. The mean clinical CPAP (8 ± 2 cmH₂O) was associated with a significant decrease in Poes and Pdi swings. Indeed, Poes swing decreased from 31 ± 15 cmH₂O during spontaneous breathing to 21 ± 10 cmH₂O during CPAP (P Poes swing 11 ± 5 cm H₂O; P Poes and Pgas, is superior to a clinical setting, based on clinical noninvasive parameters. Expiratory abdominal activity was present during spontaneous breathing and decreased in the physiological CPAP setting.

  8. Effect of intravenous magnesium sulphate on airway calibre and airway reactivity to histamine in asthmatic subjects.

    Science.gov (United States)

    Hill, J M; Britton, J

    1996-11-01

    In a randomized, double-blind, placebo controlled cross-over study we have investigated the effect of intravenous magnesium on airway calibre and airway reactivity to histamine in 20 subjects with mild to moderate asthma. After baseline measurements of forced expiratory volume in one second (FEV1), subjects received 100 ml normal saline with or without 2 g of magnesium sulphate by infusion over 20 min. Measurements of FEV1 were repeated at 5 min intervals throughout the infusion, and the provocative dose of histamine required to drop the FEV1 by 20% from baseline (PD20FEV1) was determined at 20 min. The area under the curve (AUC) in litre minutes for change from baseline in FEV1 between 0 and 20 min was significantly higher on the magnesium study day (mean difference in AUC (95% CI) 1.71 (0.02-3.4), P = 0.049). The increase in FEV1 from baseline with magnesium relative to saline was maximal at 20 min (mean difference (95% CI) 0.13 (0.02-0.23) l, P = 0.01). Log PD20FEV1 to histamine was not significantly different after magnesium and saline (mean difference in log PD20FEV1 (95% CI) 0.04 (-0.19 to 0.27), P = 0.7). We conclude that intravenous magnesium is a weak bronchodilator but does not alter airway reactivity at this dose in stable asthmatic subjects.

  9. Airway Management Evolution – In a Search for an Ideal Extraglottic Airway Device

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    Pavel Michálek

    2014-01-01

    Full Text Available 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.

  10. [Classic laryngeal mask airway vs COBRA-PLA device for airway maintenance during minor urological procedures].

    Science.gov (United States)

    Wrońska-Sewruk, Agnieszka; Nestorowicz, Andrzej; Kowalczyk, Michał

    2009-01-01

    In recent years, different supraglottic airway devices became popular and new constructions have been proposed. We compared a classic laryngeal mask airway (LMA-classic) with the COBRA-PLA device (a LMA of different design). Fifty adult ASA 1 and 2 adult patients, scheduled for minor urological interventions were randomly allocated to receive the LMA-Classic or the COBRA-PLA. Time to secure airway was shorter for the LMA-Classic (16.8+/- 5 sec vs 33.0 +/- 19.6 sec; p<0.0001). The leak pressure was higher in the COBRA group (29.0+/- 7.5 vs 22.2 +/- 3.5 cm H2O; p=0.001). The cuff pressure, necessary for obtaining adequate seal, was higher for the LMA (83.6 +/- 14.1 vs 60.2 +/- 16.4 cm H2O; p<0.0001). We did not observe statistically significant differences in heart rate, arterial blood pressure, pulse oximetry and frequency of sore throat. The LMA-classic was easier to insert but the COBRA device had more effective seal. These differences were not clinically important; both devices were found equally effective.

  11. An update on newer pediatric supraglottic airways with recommendations for clinical use.

    Science.gov (United States)

    Jagannathan, Narasimhan; Ramsey, Melissa A; White, Michelle C; Sohn, Lisa

    2015-04-01

    Supraglottic airways are an established part of routine and emergency pediatric airway management, including use in difficult airways and neonatal resuscitation. With the introduction of newer supraglottic airways in children, efficacy can only be determined by comparing these devices with those that are already well established (laryngeal mask airway Classic and laryngeal mask airway ProSeal). This narrative review aims to present the current literature on these newer supraglottic airways and give recommendations for their use in various clinical scenarios based on the existing evidence. © 2015 John Wiley & Sons Ltd.

  12. Ludwig's angina and airway considerations: a case report.

    Science.gov (United States)

    Kulkarni, Anand H; Pai, Swarupa D; Bhattarai, Basant; Rao, Sumesh T; Ambareesha, M

    2008-06-20

    Patients with deep neck infections present challenging airways for an anesthesiologist. Patients with Ludwig's angina may die as a result of the inability to effectively manage the airway. Here we discuss the anesthetic management with fiberoptic intubation of a 45-year-old man with Ludwig's angina scheduled for emergency drainage. Awake fiberoptic intubation under topical anesthesia may be the ideal method to secure the airway in advanced cases of Ludwig's angina. When fiberoptic bronchoscopy is not feasible, not available or has failed, an awake tracheostomy may be the preferred option.

  13. Reproducibility of airway luminal size in asthma measured by HRCT.

    Science.gov (United States)

    Brown, Robert H; Henderson, Robert J; Sugar, Elizabeth A; Holbrook, Janet T; Wise, Robert A

    2017-10-01

    Brown RH, Henderson RJ, Sugar EA, Holbrook JT, Wise RA, on behalf of the American Lung Association Airways Clinical Research Centers. Reproducibility of airway luminal size in asthma measured by HRCT. J Appl Physiol 123: 876-883, 2017. First published July 13, 2017; doi:10.1152/japplphysiol.00307.2017.-High-resolution CT (HRCT) is a well-established imaging technology used to measure lung and airway morphology in vivo. However, there is a surprising lack of studies examining HRCT reproducibility. The CPAP Trial was a multicenter, randomized, three-parallel-arm, sham-controlled 12-wk clinical trial to assess the use of a nocturnal continuous positive airway pressure (CPAP) device on airway reactivity to methacholine. The lack of a treatment effect of CPAP on clinical or HRCT measures provided an opportunity for the current analysis. We assessed the reproducibility of HRCT imaging over 12 wk. Intraclass correlation coefficients (ICCs) were calculated for individual airway segments, individual lung lobes, both lungs, and air trapping. The ICC [95% confidence interval (CI)] for airway luminal size at total lung capacity ranged from 0.95 (0.91, 0.97) to 0.47 (0.27, 0.69). The ICC (95% CI) for airway luminal size at functional residual capacity ranged from 0.91 (0.85, 0.95) to 0.32 (0.11, 0.65). The ICC measurements for airway distensibility index and wall thickness were lower, ranging from poor (0.08) to moderate (0.63) agreement. The ICC for air trapping at functional residual capacity was 0.89 (0.81, 0.94) and varied only modestly by lobe from 0.76 (0.61, 0.87) to 0.95 (0.92, 0.97). In stable well-controlled asthmatic subjects, it is possible to reproducibly image unstimulated airway luminal areas over time, by region, and by size at total lung capacity throughout the lungs. Therefore, any changes in luminal size on repeat CT imaging are more likely due to changes in disease state and less likely due to normal variability.NEW & NOTEWORTHY There is a surprising lack of

  14. The effects of rhinovirus infections on allergic airway responses.

    Science.gov (United States)

    Gern, J E; Busse, W W

    1995-10-01

    Although it has long been recognized that the common cold is a potent trigger for symptoms of asthma, the mechanisms underlying the association between upper respiratory infection and increased lower airway obstruction remain obscure. The use of experimental infection of volunteers with or without respiratory allergies has enabled direct comparisons of common cold symptoms in these two groups. Furthermore, techniques such as bronchoalveolar lavage and segmental antigen challenge have been used to directly sample lower airway fluids and tissues during acute viral infection. This review summarizes the findings of studies examining the separate and combined effects of rhinovirus infection and allergen exposure on airway physiology and inflammation.

  15. Airway management of an unusual case of recurrent rhinoscleroma

    Directory of Open Access Journals (Sweden)

    Nita D′souza

    2011-01-01

    Full Text Available Rhinoscleroma is a rare entity encountered in anesthesia practice. We discuss the management of a patient after its recurrence, involving the upper respiratory tract i.e. nasopharynx and oropharynx, which compromised the airway. The pateint was referred for anesthesia on three different occasions with different presentations owing to the recurrence of symptoms.The presence of an oropharyngeal membrane with a small opening made airway management a challenge. The patient was successfully managed on all three occasions. Imaging facilitated assessment and subsequent airway management.

  16. Nasal deformities resulting from flow driver continuous positive airway pressure.

    Science.gov (United States)

    Robertson, N J; McCarthy, L S; Hamilton, P A; Moss, A L

    1996-11-01

    Over a period of six months, seven cases were documented of trauma to the nose as a result of flow driver continuous positive airway pressure in babies of very low birthweight (VLBW). There was a complication rate of 20% in the babies who required it. Deformities consisted of columella nasi necrosis which can occur within three days, flaring of nostrils which worsens with duration of continuous positive airway pressure, and snubbing of the nose which persists after prolonged continuous positive airway pressure. These complications should be preventable by modifications to the mechanism and method of use.

  17. Ultrasonography - A viable tool for airway assessment

    Directory of Open Access Journals (Sweden)

    Preethi B Reddy

    2016-01-01

    Full Text Available Background and Aims: Accurate prediction of the Cormack-Lehane (CL grade preoperatively can help in better airway management of the patient during induction of anaesthesia. Our aim was to determine the utility of ultrasonography in predicting CL grade. Methods: We studied 100 patients undergoing general endotracheal anaesthesia. Mallampati (MP class, thyromental distance (TMD and sternomental distance (SMD were noted. Ultrasound measurements of the anterior neck soft tissue thickness at the level of the hyoid (ANS-Hyoid, anterior neck soft tissue thickness at the level of the vocal cords (ANS-VC and ratio of the depth of the pre-epiglottic space (Pre-E to the  distance from the epiglottis to the mid-point of the distance between the vocal cords (E-VC were obtained. CL grade was noted during intubation. Chi-square test was employed to determine if there was any statistical difference in the measurements of patients with different CL grades. Sensitivity, specificity, positive predictive value (PPV, negative predictive value (NPV and accuracy were calculated for the various parameters. Results: The incidence of difficult intubation was 14%. An ANS-VC >0.23 cm had a sensitivity of 85.7% in predicting a CL Grade of 3 or 4, which was higher than that of MP class, TMD and SMD. However, the specificity, PPV and accuracy were lower than the physical parameters. The NPV was comparable. Conclusion: Ultrasound is a useful tool in airway assessment. ANS-VC >0.23 cm is a potential predictor of difficult intubation. ANS-Hyoid is not indicative of difficult intubation. The ratio Pre-E/E-VC has a low to moderate predictive value.

  18. Ultrasonography - A viable tool for airway assessment.

    Science.gov (United States)

    Reddy, Preethi B; Punetha, Pankaj; Chalam, Kolli S

    2016-11-01

    Accurate prediction of the Cormack-Lehane (CL) grade preoperatively can help in better airway management of the patient during induction of anaesthesia. Our aim was to determine the utility of ultrasonography in predicting CL grade. We studied 100 patients undergoing general endotracheal anaesthesia. Mallampati (MP) class, thyromental distance (TMD) and sternomental distance (SMD) were noted. Ultrasound measurements of the anterior neck soft tissue thickness at the level of the hyoid (ANS-Hyoid), anterior neck soft tissue thickness at the level of the vocal cords (ANS-VC) and ratio of the depth of the pre-epiglottic space (Pre-E) to the distance from the epiglottis to the mid-point of the distance between the vocal cords (E-VC) were obtained. CL grade was noted during intubation. Chi-square test was employed to determine if there was any statistical difference in the measurements of patients with different CL grades. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for the various parameters. The incidence of difficult intubation was 14%. An ANS-VC >0.23 cm had a sensitivity of 85.7% in predicting a CL Grade of 3 or 4, which was higher than that of MP class, TMD and SMD. However, the specificity, PPV and accuracy were lower than the physical parameters. The NPV was comparable. Ultrasound is a useful tool in airway assessment. ANS-VC >0.23 cm is a potential predictor of difficult intubation. ANS-Hyoid is not indicative of difficult intubation. The ratio Pre-E/E-VC has a low to moderate predictive value.

  19. Regulated Mucin Secretion from Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Kenneth Bruce Adler

    2013-09-01

    Full Text Available Secretory epithelial cells of the proximal airways synthesize and secrete gel-forming polymeric mucins. The secreted mucins adsorb water to form mucus that is propelled by neighboring ciliated cells, providing a mobile barrier which removes inhaled particles and pathogens from the lungs. Several features of the intracellular trafficking of mucins make the airway secretory cell an interesting comparator for the cell biology of regulated exocytosis. Polymeric mucins are exceedingly large molecules (up to 3x10^6 D per monomer whose folding and initial polymerization in the ER requires the protein disulfide isomerase Agr2. In the Golgi, mucins further polymerize to form chains and possibly branched networks comprising more than 20 monomers. The large size of mucin polymers imposes constraints on their packaging into transport vesicles along the secretory pathway. Sugar side chains account for >70% of the mass of mucins, and their attachment to the protein core by O-glycosylation occurs in the Golgi. Mature polymeric mucins are stored in large secretory granules ~1 um in diameter. These are translocated to the apical membrane to be positioned for exocytosis by cooperative interactions among MARCKS, cysteine string protein (CSP, HSP70 and the cytoskeleton. Mucin granules undergo exocytic fusion with the plasma membrane at a low basal rate and a high stimulated rate. Both rates are mediated by a regulated exocytic mechanism as indicated by phenotypes in both basal and stimulated secretion in mice lacking Munc13-2, a sensor of the second messengers calcium and diacylglycerol (DAG. Basal secretion is induced by low levels of activation of P2Y2 purinergic and A3 adenosine receptors by extracellular ATP released in paracrine fashion and its metabolite adenosine. Stimulated secretion is induced by high levels of the same ligands, and possibly by inflammatory mediators as well. Activated receptors are coupled to phospholipase C by Gq, resulting in the

  20. Notch signaling prevents mucous metaplasia in mouse conducting airways during postnatal development

    Science.gov (United States)

    Tsao, Po-Nien; Wei, Shu-Chen; Wu, Ming-Fang; Huang, Miao-Tzu; Lin, Hsien-Yi; Lee, Ming-Cheng; Lin, Kurt Ming-Chao; Wang, I-Jong; Kaartinen, Vesa; Yang, Liang-Tung; Cardoso, Wellington V.

    2011-01-01

    Goblet cell metaplasia and mucus overproduction contribute to the pathogenesis of chronic lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). Notch signaling regulates cell fate decisions and is crucial in controlling goblet cell differentiation in the gut epithelium. Little is known, however, about how endogenous Notch signaling influences the goblet cell differentiation program that takes place in the postnatal lung. Using a combination of genetic and in vitro approaches here we provide evidence of a novel role for Notch in restricting goblet cell differentiation in the airway epithelium during the postnatal period. Conditional inactivation of the essential Notch pathway component Pofut1 (protein O-fucosyltransferase1) in Tgfb3-Cre-expressing mice resulted in an aberrant postnatal airway phenotype characterized by marked goblet cell metaplasia, decreased Clara cell number and increase in ciliated cells. The presence of the same phenotype in mice in which the Notch transcriptional effector Rbpjk was deleted indicated the involvement of the canonical Notch pathway. Lineage study in vivo suggested that goblet cells originated from a subpopulation of Clara cells largely present in proximal airways in which Notch was disrupted. The phenotype was confirmed by a panel of goblet cell markers, showed no changes in cell proliferation or altered expression of proinflammatory cytokines and was associated with significant downregulation of the bHLH transcriptional repressor Hes5. Luciferase reporter analysis suggested that Notch directly repressed MUC5AC transcription in lung epithelial cells. The data suggested that during postnatal life Notch is required to prevent Clara cells from differentiating into goblet cells. PMID:21791528

  1. Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway inflammation in mice.

    Science.gov (United States)

    Pouwels, Simon D; Zijlstra, G Jan; van der Toorn, Marco; Hesse, Laura; Gras, Renee; Ten Hacken, Nick H T; Krysko, Dmitri V; Vandenabeele, Peter; de Vries, Maaike; van Oosterhout, Antoon J M; Heijink, Irene H; Nawijn, Martijn C

    2016-02-15

    Recent data indicate a role for airway epithelial necroptosis, a regulated form of necrosis, and the associated release of damage-associated molecular patterns (DAMPs) in the development of chronic obstructive pulmonary disease (COPD). DAMPs can activate pattern recognition receptors (PRRs), triggering innate immune responses. We hypothesized that cigarette smoke (CS)-induced epithelial necroptosis and DAMP release initiate airway inflammation in COPD. Human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract (CSE), and necrotic cell death (membrane integrity by propidium iodide staining) and DAMP release (i.e., double-stranded DNA, high-mobility group box 1, heat shock protein 70, mitochondrial DNA, ATP) were analyzed. Subsequently, BEAS-2B cells were exposed to DAMP-containing supernatant of CS-induced necrotic cells, and the release of proinflammatory mediators [C-X-C motif ligand 8 (CXCL-8), IL-6] was evaluated. Furthermore, mice were exposed to CS in the presence and absence of the necroptosis inhibitor necrostatin-1, and levels of DAMPs and inflammatory cell numbers were determined in bronchoalveolar lavage fluid. CSE induced a significant increase in the percentage of necrotic cells and DAMP release in BEAS-2B cells. Stimulation of BEAS-2B cells with supernatant of CS-induced necrotic cells induced a significant increase in the release of CXCL8 and IL-6, in a myeloid differentiation primary response gene 88-dependent fashion. In mice, exposure of CS increased the levels of DAMPs and numbers of neutrophils in bronchoalveolar lavage fluid, which was statistically reduced upon treatment with necrostatin-1. Together, we showed that CS exposure induces necrosis of bronchial epithelial cells and subsequent DAMP release in vitro, inducing the production of proinflammatory cytokines. In vivo, CS exposure induces neutrophilic airway inflammation that is sensitive to necroptosis inhibition. Copyright © 2016 the American Physiological Society.

  2. Innate Immune Signaling Activated by MDR Bacteria in the Airway

    Science.gov (United States)

    Parker, Dane; Ahn, Danielle; Cohen, Taylor; Prince, Alice

    2015-01-01

    Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation. PMID:26582515

  3. Team processes in airway facilities operations control centers.

    Science.gov (United States)

    2000-07-01

    In October 2000, the Airway Facilities organization plans to transition the National Airspace System (NAS) monitoring responsibilities to three regional Operations Control Centers (OCCs). Teams in these facilities will be different from those that cu...

  4. Targeting transcription factor lysine acetylation in inflammatory airway diseases

    NARCIS (Netherlands)

    van den Bosch, Thea; Kwiatkowski, Marcel; Bischoff, Rainer; Dekker, Frank J

    2017-01-01

    Asthma and chronic obstructive pulmonary disease are inflammatory airway diseases for which alternative therapeutic strategies are urgently needed. Interestingly, HDAC inhibitors show anti-inflammatory effects in mouse models for these diseases. Here we explore underlying mechanisms that may explain

  5. Surface Airways Observations (SAO) Hourly Data 1928-1948 (CDMP)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The dataset consists of hourly U.S. surface airways observations (SAO). These observations extend as far back as 1928, from the time when commercial aviation began...

  6. Childhood asthma after bacterial colonization of the airway in neonates

    DEFF Research Database (Denmark)

    Bisgaard, H.; Hermansen, M.N.; Buchvald, F.

    2007-01-01

    Pathological features of the airway in young children with severe recurrent wheeze suggest an association between bacterial colonization and the initiating events of early asthma. We conducted a study to investigate a possible association between bacterial colonization of the hypopharynx...

  7. Airway dysfunction in elite swimmers: prevalence, impact, and challenges.

    Science.gov (United States)

    Lomax, Mitch

    2016-01-01

    The prevalence of airway dysfunction in elite swimmers is among the highest in elite athletes. The traditional view that swimmers naturally gravitate toward swimming because of preexisting respiratory disorders has been challenged. There is now sufficient evidence that the higher prevalence of bronchial tone disorders in elite swimmers is not the result of a natural selection bias. Rather, the combined effects of repeated chlorine by-product exposure and chronic endurance training can lead to airway dysfunction and atopy. This review will detail the underpinning causes of airway dysfunction observed in elite swimmers. It will also show that airway dysfunction does not prevent success in elite level swimming. Neither does it inhibit lung growth and might be partially reversible when elite swimmers retire from competition.

  8. Autophagy and airway fibrosis: Is there a link?

    Science.gov (United States)

    Kota, Anudeep; Deshpande, Deepak; Haghi, Mehra; Oliver, Brian; Sharma, Pawan

    2017-01-01

    In the past decade, an emerging process named "autophagy" has generated intense interest in many chronic lung diseases. Tissue remodeling and fibrosis is a common feature of many airway diseases, and current therapies do not prevent or reverse these structural changes. Autophagy has evolved as a conserved process for bulk degradation and recycling of cytoplasmic components to maintain basal cellular homeostasis and healthy organelle populations in the cell. Furthermore, autophagy serves as a cell survival mechanism and can also be induced by chemical and physical stress to the cell. Accumulating evidence demonstrates that autophagy plays an essential role in vital cellular processes, including tissue remodeling. This review will discuss some of the recent advancements made in understanding the role of this fundamental process in airway fibrosis with emphasis on airway remodeling, and how autophagy can be exploited as a target for airway remodeling in asthma and chronic obstructive pulmonary disease.

  9. 76 FR 11978 - Proposed Amendment of Federal Airways; Alaska

    Science.gov (United States)

    2011-03-04

    ... Federal airways in Alaska. Due to construction of wind turbines on Fire Island, AK, the Anchorage VOR is... promulgated, will not have a significant economic impact on a substantial number of small entities under the...

  10. Maternal smoking during pregnancy induces airway remodelling in mice offspring

    NARCIS (Netherlands)

    Blacquiere, M. J.; Timens, W.; Melgert, B. N.; Geerlings, M.; Postma, D. S.; Hylkema, M. N.

    Children from smoking mothers have an increased risk of developing asthma for reasons largely unknown. The effects of maternal smoking during pregnancy on remodelling, allergic airway inflammation and hyperresponsiveness in offspring were investigated in an experimental asthma model. Mice were

  11. Spirometry screening for airway obstruction in asymptomatic smokers.

    Science.gov (United States)

    Wisnivesky, Juan; Skloot, Gwen; Rundle, Andrew; Revenson, Tracey A; Neugut, Alfred

    2014-07-01

    Screening spirometry might help identify patients with chronic obstructive pulmonary disease (COPD) at an earlier stage. In this study, we evaluated the prevalence of airway obstruction in a cohort of asymptomatic smokers who underwent spirometry as part of a routine health maintenance examination. The study cohort consisted of a consecutive sample of 386 asymptomatic smokers (≥5 pack-years) without a history of COPD or asthma, who completed spirometry testing as part of a routine health maintenance examination. Overall, 9 study subjects (2.3%, 95% confidence interval: 1.1-4.4%) had evidence of airway obstruction on spirometry. Univariate and multiple regression analyses showed that the risk of airway obstruction was not significantly associated with age, sex, race, smoking history or past history of respiratory symptoms. Spirometry screening of asymptomatic smokers may help detect a small number of patients with airway obstruction who are at high risk for COPD.

  12. Modulation of airway epithelial antiviral immunity by fungal exposure

    National Research Council Canada - National Science Library

    Zhu, Lingxiang; Lee, Boram; Zhao, Fangkun; Zhou, Xu; Chin, Vanessa; Ling, Serena C; Chen, Yin

    2014-01-01

    .... However, their interactions have not been investigated. In the present study, we tested the effect of Alt exposure on virus-induced airway epithelial immunity using live virus and a synthetic viral mimicker, double-stranded RNA (dsRNA...

  13. Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma

    NARCIS (Netherlands)

    de Groot, Jantina C; van Roon, Eric; Storm, Huib; Veeger, Nic J G M; Zwinderman, Aeilko H; Hiemstra, Pieter S; Bel, Elisabeth H D; Ten Brinke, Anneke

    2015-01-01

    BACKGROUND: Low levels of vitamin D are associated with asthma severity, airway remodeling, and exacerbation rate increase, especially in nonatopic asthma. Reduced steroid responsiveness or impaired antimicrobial defense might be underlying mechanisms. OBJECTIVE: We sought to evaluate the effect of

  14. Airway dysfunction in elite swimmers: prevalence, impact, and challenges

    Directory of Open Access Journals (Sweden)

    Lomax M

    2016-05-01

    Full Text Available Mitch Lomax Department of Sport and Exercise Science, University of Portsmouth, Portsmouth, UK Abstract: The prevalence of airway dysfunction in elite swimmers is among the highest in elite athletes. The traditional view that swimmers naturally gravitate toward swimming because of preexisting respiratory disorders has been challenged. There is now sufficient evidence that the higher prevalence of bronchial tone disorders in elite swimmers is not the result of a natural selection bias. Rather, the combined effects of repeated chlorine by-product exposure and chronic endurance training can lead to airway dysfunction and atopy. This review will detail the underpinning causes of airway dysfunction observed in elite swimmers. It will also show that airway dysfunction does not prevent success in elite level swimming. Neither does it inhibit lung growth and might be partially reversible when elite swimmers retire from competition. Keywords: exercise, aquatic athletes, bronchoconstriction

  15. Mechanics of airflow in the human nasal airways.

    Science.gov (United States)

    Doorly, D J; Taylor, D J; Schroter, R C

    2008-11-30

    The mechanics of airflow in the human nasal airways is reviewed, drawing on the findings of experimental and computational model studies. Modelling inevitably requires simplifications and assumptions, particularly given the complexity of the nasal airways. The processes entailed in modelling the nasal airways (from defining the model, to its production and, finally, validating the results) is critically examined, both for physical models and for computational simulations. Uncertainty still surrounds the appropriateness of the various assumptions made in modelling, particularly with regard to the nature of flow. New results are presented in which high-speed particle image velocimetry (PIV) and direct numerical simulation are applied to investigate the development of flow instability in the nasal cavity. These illustrate some of the improved capabilities afforded by technological developments for future model studies. The need for further improvements in characterising airway geometry and flow together with promising new methods are briefly discussed.

  16. Susceptibility to Lower Respiratory Infections in Childhood is Associated with Perturbation of the Cytokine Response to Pathogenic Airway Bacteria

    DEFF Research Database (Denmark)

    Vissing, Nadja Hawwa; Larsen, Jeppe Madura; Rasmussen, Morten Arendt

    2016-01-01

    BACKGROUND: Neonatal colonization of the airways with respiratory pathogens is associated with increased risk of lower respiratory infections (LRI) in early childhood. Therefore, we hypothesized that children developing LRI have an aberrant immune response to pathogenic bacteria in infancy...... of 411 children born of mothers with asthma. LRI incidence was prospectively captured from 6-monthly planned visits and visits at acute respiratory episodes. The in vitro systemic immune response to H. influenzae, M. catarrhalis and S. pneumoniae was characterized by the production of TNF-α, IFN-γ, IL-2...

  17. Transplantation of Airway Epithelial Stem/Progenitor Cells: A Future for Cell-Based Therapy.

    Science.gov (United States)

    Ghosh, Moumita; Ahmad, Shama; White, Carl W; Reynolds, Susan D

    2017-01-01

    Cell therapy has the potential to cure disease through replacement of malfunctioning cells. Although the tissue stem cell (TSC) is thought to be the optimal therapeutic cell, transplantation of TSC/progenitor cell mixtures has saved lives. We previously purified the mouse tracheobronchial epithelial TSCs and reported that in vitro amplification generated numerous TSCs. However, these cultures also contained TSC-derived progenitor cells and TSC repurification by flow cytometry compromised TSC self-renewal. These limitations prompted us to determine if a TSC/progenitor cell mixture would repopulate the injured airway epithelium. We developed a cell transplantation protocol and demonstrate that transplanted mouse and human tracheobronchial epithelial TSC/progenitor cell mixtures are 20-25% of airway epithelial cells, actively contribute to epithelial repair, and persist for at least 43 days. At 2 weeks after transplantation, TSCs/progenitor cells differentiated into the three major epithelial cell types: basal, secretory, and ciliated. We conclude that cell therapy that uses adult tracheobronchial TSCs/progenitor cells is an effective therapeutic option.

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

    Directory of Open Access Journals (Sweden)

    Ignacio M Fenoy

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

  19. Development of characteristic upper tracheobronchial airway models for testing pharmaceutical aerosol delivery.

    Science.gov (United States)

    Walenga, Ross L; Tian, Geng; Longest, P Worth

    2013-09-01

    Characteristic models of the upper conducting airways are needed to evaluate the performance of existing pharmaceutical inhalers and to develop new respiratory drug delivery strategies. Previous studies have focused on the development of characteristic mouth-throat (MT) geometries for orally inhaled products; however, characteristic upper tracheobronchial (TB) geometries are currently not available. In this study, a new characteristic model of the upper TB airways for an average adult male was developed based on an analysis of new and existing anatomical data. Validated computational fluid dynamics (CFD) simulations were used to evaluate the deposition of monodisperse and realistic polydisperse aerosols from multiple inhalers. Comparisons of deposition results between the new model and a simpler geometry were used to identify the effects of different anatomical features on aerosol deposition. The CFD simulations demonstrated a good match to regional pharmaceutical aerosol deposition from in vitro experiments in the same geometry. The deposition of both monodisperse and pharmaceutical aerosols was increased in the new TB geometry as a result of additional anatomical detail on a regional and highly localized basis. Tracheal features including an accurate coronal angle, asymmetry, and curvature produced a skewed laryngeal jet and significantly increased regional deposition. Branch curvature and realistic cross-sections increased deposition in the remainder of the TB model. A hexahedral mesh style was utilized to provide the best solution. In conclusion, a number of physiological features in the upper TB region were shown to influence deposition and should be included in a characteristic model of respiratory drug delivery.

  20. Prostaglandin E2 induces expression of MAPK phosphatase 1 (MKP-1) in airway smooth muscle cells.

    Science.gov (United States)

    Rumzhum, Nowshin N; Ammit, Alaina J

    2016-07-05

    Prostaglandin E2 (PGE2) is a prostanoid with diverse actions in health and disease. In chronic respiratory diseases driven by inflammation, PGE2 has both positive and negative effects. An enhanced understanding of the receptor-mediated cellular signalling pathways induced by PGE2 may help us separate the beneficial properties from unwanted actions of this important prostaglandin. PGE2 is known to exert anti-inflammatory and bronchoprotective actions in human airways. To date however, whether PGE2 increases production of the anti-inflammatory protein MAPK phosphatase 1 (MKP-1) was unknown. We address this herein and use primary cultures of human airway smooth muscle (ASM) cells to show that PGE2 increases MKP-1 mRNA and protein upregulation in a concentration-dependent manner. We explore the signalling pathways responsible and show that PGE2-induces CREB phosphorylation, not p38 MAPK activation, in ASM cells. Moreover, we utilize selective antagonists of EP2 (PF-04418948) and EP4 receptors (GW 627368X) to begin to identify EP-mediated functional outcomes in ASM cells in vitro. Taken together with earlier studies, our data suggest that PGE2 increases production of the anti-inflammatory protein MKP-1 via cAMP/CREB-mediated cellular signalling in ASM cells and demonstrates that EP2 may, in part, be involved. Copyright © 2016 Elsevier B.V. All rights reserved.