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Sample records for airway narrowing responses

  1. Distribution of airway narrowing responses across generations and at branching points, assessed in vitro by anatomical optical coherence tomography

    Directory of Open Access Journals (Sweden)

    Eastwood Peter R

    2010-01-01

    Full Text Available Abstract Background Previous histological and imaging studies have shown the presence of variability in the degree of bronchoconstriction of airways sampled at different locations in the lung (i.e., heterogeneity. Heterogeneity can occur at different airway generations and at branching points in the bronchial tree. Whilst heterogeneity has been detected by previous experimental approaches, its spatial relationship either within or between airways is unknown. Methods In this study, distribution of airway narrowing responses across a portion of the porcine bronchial tree was determined in vitro. The portion comprised contiguous airways spanning bronchial generations (#3-11, including the associated side branches. We used a recent optical imaging technique, anatomical optical coherence tomography, to image the bronchial tree in three dimensions. Bronchoconstriction was produced by carbachol administered to either the adventitial or luminal surface of the airway. Luminal cross sectional area was measured before and at different time points after constriction to carbachol and airway narrowing calculated from the percent decrease in luminal cross sectional area. Results When administered to the adventitial surface, the degree of airway narrowing was progressively increased from proximal to distal generations (r = 0.80 to 0.98, P Conclusions Our findings demonstrate that the bronchial tree expresses intrinsic serial heterogeneity, such that narrowing increases from proximal to distal airways, a relationship that is influenced by the route of drug administration but not by structural variations accompanying branching sites.

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

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Diamant, Zuzana

    2009-01-01

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

  3. Tracheal granulation as a cause of unrecognized airway narrowing

    OpenAIRE

    Gaurav Bhatia; Valsamma Abraham; Linjo Louis

    2012-01-01

    Tracheostomy is one of the most common elective surgical procedures performed in critically ill patients. The most frequent late complication after tracheostomy is the development of granulation tissue, a complication that may cause airway occlusion or result in airway stenosis. We report the successful management of a patient with tracheal granulation presenting as an unrecognised cause of difficulty breathing.

  4. 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.

  5. 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...... inflammation in adolescent elite swimmers. Methods: We performed a cross-sectional study on adolescent elite swimmers (n = 33) and 2 control groups: unselected adolescents (n = 35) and adolescents with asthma (n = 212). The following tests were performed: questionnaire, exhaled nitric oxide (FeNO), spirometry...... years of intense training and competition. This leads us to believe that elite swimmers do not have particularly susceptible airways when they take up competitive swimming when young, but that they develop respiratory symptoms, airway inflammation, and AHR during their swimming careers Udgivelsesdato...

  6. 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...

  7. 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

    2003-01-01

    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

  8. Airway Responsiveness to Psychological Processes in Asthma and Health

    Directory of Open Access Journals (Sweden)

    Thomas eRitz

    2012-09-01

    Full Text Available Psychosocial factors have been found to impact airway pathophysiology in respiratory disease with considerable consistency. Influences on airway mechanics have been studied particularly well. The goal of this article is to review the literature on airway responses to psychological stimulation, discuss potential pathways of influence, and present a well-established emotion-induction paradigm to study airway obstruction elicited by unpleasant stimuli. Observational studies have found systematic associations between lung function and daily mood changes. The laboratory –based paradigm of bronchoconstrictive suggestion has been used successfully to elicit airway obstruction in a substantial proportion of asthmatic individuals. Other studies have demonstrated an enhancement of airway responses to standard airway challenges with exercise, allergens, or methacholine. Standardized emotion-induction techniques have consistently shown airway constriction during unpleasant stimulation, with surgery, blood and injury stimuli being particularly powerful. Findings with various forms of stress induction have been more mixed. A number of methodological factors may account for variability across studies, such as choice of measurement technique, temporal association between stimulation and measurement, and the specific quality and intensity of the stimulus material, in particular the extent of implied action-orientation. Research has also begun to elucidate physiological processes associated with psychologically induced airway responses, with vagal excitation and ventilatory influences being the most likely candidate pathways, whereas the role of specific central nervous system pathways and inflammatory processes has been less studied. The technique of emotion-induction using films has the potential to become a standardized challenge paradigm for the further exploration of airway hyperresponsiveness mediated by central nervous system processes.

  9. Small Airway Dysfunction and Abnormal Exercise Responses

    Science.gov (United States)

    Petsonk, Edward L.; Stansbury, Robert C.; Beeckman-Wagner, Lu-Ann; Long, Joshua L.; Wang, Mei Lin

    2016-01-01

    Rationale Coal mine dust exposure can cause symptoms and loss of lung function from multiple mechanisms, but the roles of each disease process are not fully understood. Objectives We investigated the implications of small airway dysfunction for exercise physiology among a group of workers exposed to coal mine dust. Methods Twenty coal miners performed spirometry, first breathing air and then helium-oxygen, single-breath diffusing capacity, and computerized chest tomography, and then completed cardiopulmonary exercise testing. Measurements and Main Results Six participants meeting criteria for small airway dysfunction were compared with 14 coal miners who did not. At submaximal workload, miners with small airway dysfunction used a higher proportion of their maximum voluntary ventilation and had higher ventilatory equivalents for both O2 and CO2. Regression modeling indicated that inefficient ventilation was significantly related to small airway dysfunction but not to FEV1 or diffusing capacity. At the end of exercise, miners with small airway dysfunction had 27% lower O2 consumption. Conclusions Small airway abnormalities may be associated with important inefficiency of exercise ventilation. In dust-exposed individuals with only mild abnormalities on resting lung function tests or chest radiographs, cardiopulmonary exercise testing may be important in defining causes of exercise intolerance. PMID:27073987

  10. Seasonal Fluctuations in Airway Responsiveness in Elite Endurance Athletes

    OpenAIRE

    Howard B Hemingson; Davis, Beth E.; Cockcroft, Donald W

    2004-01-01

    BACKGROUND: It has been suggested that exposure to winter training conditions (irritants in indoor facilities and/or cold, dry air in the outdoors) can increase airway responsiveness in elite endurance athletes.OBJECTIVES: It has yet to be elucidated whether elite endurance athletes experience seasonal fluctuations in their airway responsiveness.METHODS: Eighteen members of a varsity cross-country running team underwent screening procedures and five members were enrolled in the study. Each at...

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

    Science.gov (United States)

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

  12. Postnatal exposure history and airways: oxidant stress responses in airway explants.

    Science.gov (United States)

    Murphy, Shannon R; Schelegle, Edward S; Edwards, Patricia C; Miller, Lisa A; Hyde, Dallas M; Van Winkle, Laura S

    2012-12-01

    Postnatally, the lung continues to grow and differentiate while interacting with the environment. Exposure to ozone (O(3)) and allergens during postnatal lung development alters structural elements of conducting airways, including innervation and neurokinin abundance. These changes have been linked with development of asthma in a rhesus monkey model. We hypothesized that O(3) exposure resets the ability of the airways to respond to oxidant stress and that this is mediated by changes in the neurokinin-1 receptor (NK-1R). Infant rhesus monkeys received episodic exposure to O(3) biweekly with or without house dust mite antigen (HDMA) from 6 to 12 months of age. Age-matched monkeys were exposed to filtered air (FA). Microdissected airway explants from midlevel airways (intrapulmonary generations 5-8) for four to six animals in each of four groups (FA, O(3), HDMA, and HDMA+O(3)) were tested for NK-1R gene responses to acute oxidant stress using exposure to hydrogen peroxide (1.2 mM), a lipid ozonide (10 μM), or sham treatment for 4 hours in vitro. Airway responses were measured using real-time quantitative RT-PCR of NK-1R and IL-8 gene expression. Basal NK-1R gene expression levels were not different between the exposure groups. Treatment with ozonide or hydrogen peroxide did not change NK-1R gene expression in animals exposed to FA, HDMA, or HDMA+O(3). However, treatment in vitro with lipid ozonide significantly increased NK-1R gene expression in explants from O(3)-exposed animals. We conclude that a history of prior O(3) exposure resets the steady state of the airways to increase the NK-1R response to subsequent acute oxidant stresses. PMID:22962062

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

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

  14. Mechanisms of airway responses to esophageal acidification in cats.

    Science.gov (United States)

    Lang, Ivan M; Haworth, Steven T; Medda, Bidyut K; Forster, Hubert; Shaker, Reza

    2016-04-01

    Acid in the esophagus causes airway constriction, tracheobronchial mucous secretion, and a decrease in tracheal mucociliary transport rate. This study was designed to investigate the neuropharmacological mechanisms controlling these responses. In chloralose-anesthetized cats (n = 72), we investigated the effects of vagotomy or atropine (100 μg·kg(-1)·30 min(-1) iv) on airway responses to esophageal infusion of 0.1 M PBS or 0.1 N HCl at 1 ml/min. We quantified 1) diameter of the bronchi, 2) tracheobronchial mucociliary transport rate, 3) tracheobronchial mucous secretion, and 4) mucous content of the tracheal epithelium and submucosa. We found that vagotomy or atropine blocked the airway constriction response but only atropine blocked the increase in mucous output and decrease in mucociliary transport rate caused by esophageal acidification. The mucous cells of the mucosa produced more Alcian blue- than periodic acid-Schiff (PAS)-stained mucosubstances, and the mucous cells of the submucosa produced more PAS- than Alcian blue-stained mucosubstances. Selective perfusion of the different segments of esophagus with HCl or PBS resulted in significantly greater production of PAS-stained mucus in the submucosa of the trachea adjacent to the HCl-perfused esophagus than in that adjacent to the PBS-perfused esophagus. In conclusion, airway constriction caused by esophageal acidification is mediated by a vagal cholinergic pathway, and the tracheobronchial transport response is mediated by cholinergic receptors. Acid perfusion of the esophagus selectively increases production of neutral mucosubstances of the apocrine glands by a local mechanism. We hypothesize that the airway responses to esophageal acid exposure are part of the innate, rather than acute emergency, airway defense system. PMID:26846551

  15. Innate immune response in CF airway epithelia: hyperinflammatory?

    Science.gov (United States)

    Machen, Terry E

    2006-08-01

    The lack of functional cystic fibrosis (CF) transmembrane conductance regulator (CFTR) in the apical membranes of CF airway epithelial cells abolishes cAMP-stimulated anion transport, and bacteria, eventually including Pseudomonas aeruginosa, bind to and accumulate in the mucus. Flagellin released from P. aeruginosa triggers airway epithelial Toll-like receptor 5 and subsequent NF-kappaB signaling and production and release of proinflammatory cytokines that recruit neutrophils to the infected region. This response has been termed hyperinflammatory because so many neutrophils accumulate; a response that damages CF lung tissue. We first review the contradictory data both for and against the idea that epithelial cells exhibit larger-than-normal proinflammatory signaling in CF compared with non-CF cells and then review proposals that might explain how reduced CFTR function could activate such proinflammatory signaling. It is concluded that apparent exaggerated innate immune response of CF airway epithelial cells may have resulted not from direct effects of CFTR on cellular signaling or inflammatory mediator production but from indirect effects resulting from the absence of CFTRs apical membrane channel function. Thus, loss of Cl-, HCO3-, and glutathione secretion may lead to reduced volume and increased acidification and oxidation of the airway surface liquid. These changes concentrate proinflammatory mediators, reduce mucociliary clearance of bacteria and subsequently activate cellular signaling. Loss of apical CFTR will also hyperpolarize basolateral membrane potentials, potentially leading to increases in cytosolic [Ca2+], intracellular Ca2+, and NF-kappaB signaling. This hyperinflammatory effect of CF on intracellular Ca2+ and NF-kappaB signaling would be most prominently expressed during exposure to both P. aeruginosa and also endocrine, paracrine, or nervous agonists that activate Ca2+ signaling in the airway epithelia. PMID:16825601

  16. Histamine airway hyper-responsiveness and mortality from chronic obstructive pulmonary disease : a cohort study

    NARCIS (Netherlands)

    Hospers, JJ; Postma, DS; Rijcken, B; Weiss, ST; Schouten, JP

    2000-01-01

    Background Smoking and airway lability, which is expressed by histamine airway hyper-responsiveness, are known risk factors for development of respiratory symptoms. Smoking is also associated with increased mortality risks. We studied whether airway hyper-responsiveness is associated with increased

  17. Airway responses to NO2 and allergen in asthmatics

    OpenAIRE

    Barck, Charlotte

    2005-01-01

    Nitrogen dioxide (N02), a gas produced by combustion, is a common environmental air pollutant. Individuals with asthma are more sensitive to N02 exposure than healthy subjects, according to results from controlled human-exposure studies. N02 can enhance the asthmatic response to inhaled allergen. The mechanisms for N02's enhancing effect on the asthmatic reaction to allergen appear to be related to an increased inflammatory reaction in the airways. The general aim of the ...

  18. Effects of nitrogen dioxide on airway responsiveness in allergic asthma

    OpenAIRE

    Strand, Victoria

    1998-01-01

    Asthma is one of the most common chronic diseases in the industrialized world and its prevalence is increasing. Clinical symptoms of airway obstruction and bronchial hyper responsiveness can be induced by specific agents, such as allergens and non-specific stimuli, such as cold air and irritants. In order to avoid exacerbation it is important to identify these stimuli and to study how they interact with each other and amplify inflammation in asthma. Nitrogen dioxide (NO2) is...

  19. RESPONSE OF NONLINEAR OSCILLATOR UNDER NARROW-BAND RANDOM EXCITATION

    Institute of Scientific and Technical Information of China (English)

    戎海武; 王向东; 孟光; 徐伟; 方同

    2003-01-01

    The principal resonance of Duffing oscillator to narrow-band random parametricexcitation was investigated. The method of multiple scales was used to determine theequations of modulation of amplitude and phase. The behavior, stability and bifurcation ofsteady state response were studied by means of qualitative analyses. The effects of damping,detuning, bandwidth and magnitudes of deterministic and random excitations wereanalyzed. The theoretical analyses were verified by numerical results. Theoretical analysesand numerical simulations show that when the intensity of the random excitation increases,the nontrivial steady state solution may change from a limit cycle to a diffused limit cycle.Under some conditions the system may have two ,steady state solutions.

  20. Narrow band noise response of a Belleville spring resonator.

    Science.gov (United States)

    Lyon, Richard H

    2013-09-01

    This study of nonlinear dynamics includes (i) an identification of quasi-steady states of response using equivalent linearization, (ii) the temporal simulation of the system using Heun's time step procedure on time domain analytic signals, and (iii) a laboratory experiment. An attempt has been made to select material and measurement parameters so that nearly the same systems are used and analyzed for all three parts of the study. This study illustrates important features of nonlinear response to narrow band excitation: (a) states of response that the system can acquire with transitions of the system between those states, (b) the interaction between the noise source and the vibrating load in which the source transmits energy to or draws energy from the load as transitions occur; (c) the lag or lead of the system response relative to the source as transitions occur that causes the average frequencies of source and response to differ; and (d) the determination of the state of response (mass or stiffness controlled) by observation of the instantaneous phase of the influence function. These analyses take advantage of the use of time domain analytic signals that have a complementary role to functions that are analytic in the frequency domain.

  1. Nasal airway responses to nasal continuous positive airway pressure breathing: An in-vivo pilot study.

    Science.gov (United States)

    White, David E; Bartley, Jim; Shakeel, Muhammad; Nates, Roy J; Hankin, Robin K S

    2016-06-14

    The nasal cycle, through variation in nasal airflow partitioning, allows the upper airway to accommodate the contrasting demands of air conditioning and removal of entrapped air contaminants. The purpose of this study was to investigate the influence of nasal continuous positive airway pressure (nCPAP) breathing has on both nasal airflow partitioning and nasal geometry. Using a custom-made nasal mask, twenty healthy participants had the airflow in each naris measured during normal nasal breathing followed by nCPAP breathing. Eight participants also underwent magnetic resonance imaging (MRI) of the nasal region during spontaneous nasal breathing, and then nCPAP breathing over a range of air pressures. During nCPAP breathing, a simultaneous reduction in airflow through the patent airway together with a corresponding increase in airway flow within the congested nasal airway were observed in sixteen of the twenty participants. Nasal airflow resistance is inversely proportional to airway cross-sectional area. MRI data analysis during nCPAP breathing confirmed airway cross-sectional area reduced along the patent airway while the congested airway experienced an increase in this parameter. During awake breathing, nCPAP disturbs the normal inter-nasal airflow partitioning. This could partially explain the adverse nasal drying symptoms frequently reported by many users of this therapy. PMID:27173595

  2. Airway response to methacholine following eucapnic voluntary hyperpnea in athletes.

    Directory of Open Access Journals (Sweden)

    Valérie Bougault

    Full Text Available To evaluate the changes in airway responsiveness to methacholine inhalation test (MIT when performed after an eucapnic voluntary hyperpnea challenge (EVH in athletes.Two MIT preceded (visit 1 or not (visit 2 by an EVH, were performed in 28 athletes and 24 non-athletes. Twelve athletes and 13 non-athletes had airway hyperresponsiveness (AHR to methacholine, and 11 athletes and 11 non-athletes had AHR to EVH (EVH+.The MIT PC20 post-EVH was significantly lower compared to baseline MIT PC20 by 1.3±0.7 doubling-concentrations in EVH+ athletes only (p<0.0001. No significant change was observed in EVH- athletes and EVH+/EVH- non-athletes. A significant correlation between the change in MIT PC20 post-EVH and EVH+/EVH- status and athlete/nonathlete status was found (Adjusted R2=0.26 and p<0.001. Three (11% athletes and one (4% non-athlete had a change in the diagnosis of AHR when MIT was performed consecutively to EVH.The responsiveness to methacholine was increased by a previous indirect challenge in EVH+ athletes only. The mechanisms for such increase remain to be determined. MIT and EVH should ideally be performed on separate occasions as there is a small but possible risk to obtain a false-positive response to methacholine when performed immediately after the EVH.ClinicalTrials.gov NCT00686491.

  3. Depletion of OX-8 lymphocytes from the blood and airways using monoclonal antibodies enhances the late airway response in rats.

    OpenAIRE

    Olivenstein, R.; Renzi, P M; Yang, J P; P. Rossi; Laberge, S.; Waserman, S; Martin, J.G.

    1993-01-01

    Recent evidence supports a role for T lymphocytes in allergic airway responses. We hypothesized that reducing blood T suppressor cells (Ts) might increase the late airway response (LR). Sprague-Dawley (SD) rats were sensitized with ovalbumin (OA). On days 8, 10, and 12, post-sensitization test SD (n = 14) received monoclonal antibody intravenously (OX-8; 1 mg) specific to rat Ts. Controls received saline (n = 7) or mouse ascites IgG (n = 7). On day 14, animals were challenged with OA aerosol ...

  4. Airway response to inhaled salbutamol in hyperthyroid and hypothyroid patients before and after treatment.

    OpenAIRE

    Harrison, R N; Tattersfield, A. E.

    1984-01-01

    For many years the development of thyrotoxicosis has been known to cause a deterioration in asthma but the mechanism is unknown. We have studied the effect of thyroid function on airway beta adrenergic responsiveness in 10 hyperthyroid and six hypothyroid subjects before and after treatment of their thyroid disease. Airway adrenergic responsiveness was assessed by measuring specific airway conductance (sGaw) after increasing doses of inhaled salbutamol (10-410 micrograms). After treatment the...

  5. Plasticity of airway epithelial cell transcriptome in response to flagellin.

    Directory of Open Access Journals (Sweden)

    Joan G Clark

    Full Text Available Airway epithelial cells (AEC are critical components of the inflammatory and immune response during exposure to pathogens. AECs in monolayer culture and differentiated epithelial cells in air-liquid interface (ALI represent two distinct and commonly used in vitro models, yet differences in their response to pathogens have not been investigated. In this study, we compared the transcriptional effects of flagellin on AECs in monolayer culture versus ALI culture using whole-genome microarrays and RNA sequencing. We exposed monolayer and ALI AEC cultures to flagellin in vitro and analyzed the transcriptional response by microarray and RNA-sequencing. ELISA and RT-PCR were used to validate changes in select candidates. We found that AECs cultured in monolayer and ALI have strikingly different transcriptional states at baseline. When challenged with flagellin, monolayer AEC cultures greatly increased transcription of numerous genes mapping to wounding response, immunity and inflammatory response. In contrast, AECs in ALI culture had an unexpectedly muted response to flagellin, both in number of genes expressed and relative enrichment of inflammatory and immune pathways. We conclude that in vitro culturing methods have a dramatic effect on the transcriptional profile of AECs at baseline and after stimulation with flagellin. These differences suggest that epithelial responses to pathogen challenges are distinctly different in culture models of intact and injured epithelium.

  6. Plasticity of airway epithelial cell transcriptome in response to flagellin.

    Science.gov (United States)

    Clark, Joan G; Kim, Kyoung-Hee; Basom, Ryan S; Gharib, Sina A

    2015-01-01

    Airway epithelial cells (AEC) are critical components of the inflammatory and immune response during exposure to pathogens. AECs in monolayer culture and differentiated epithelial cells in air-liquid interface (ALI) represent two distinct and commonly used in vitro models, yet differences in their response to pathogens have not been investigated. In this study, we compared the transcriptional effects of flagellin on AECs in monolayer culture versus ALI culture using whole-genome microarrays and RNA sequencing. We exposed monolayer and ALI AEC cultures to flagellin in vitro and analyzed the transcriptional response by microarray and RNA-sequencing. ELISA and RT-PCR were used to validate changes in select candidates. We found that AECs cultured in monolayer and ALI have strikingly different transcriptional states at baseline. When challenged with flagellin, monolayer AEC cultures greatly increased transcription of numerous genes mapping to wounding response, immunity and inflammatory response. In contrast, AECs in ALI culture had an unexpectedly muted response to flagellin, both in number of genes expressed and relative enrichment of inflammatory and immune pathways. We conclude that in vitro culturing methods have a dramatic effect on the transcriptional profile of AECs at baseline and after stimulation with flagellin. These differences suggest that epithelial responses to pathogen challenges are distinctly different in culture models of intact and injured epithelium. PMID:25668187

  7. Postnatal Exposure History and Airways: Oxidant Stress Responses in Airway Explants

    OpenAIRE

    Murphy, Shannon R.; Schelegle, Edward S.; Edwards, Patricia C.; Lisa A. Miller; Hyde, Dallas M.; Van Winkle, Laura S.

    2012-01-01

    Postnatally, the lung continues to grow and differentiate while interacting with the environment. Exposure to ozone (O3) and allergens during postnatal lung development alters structural elements of conducting airways, including innervation and neurokinin abundance. These changes have been linked with development of asthma in a rhesus monkey model. We hypothesized that O3 exposure resets the ability of the airways to respond to oxidant stress and that this is mediated by changes in the neurok...

  8. Distinct effects of endogenous interleukin-23 on eosinophilic airway inflammation in response to different antigens

    OpenAIRE

    Rika Ogawa; Yusuke Suzuki; Shizuko Kagawa; Katsunori Masaki; Koichi Fukunaga; Akihiko Yoshimura; Seitaro Fujishima; Takeshi Terashima; Tomoko Betsuyaku; Koichiro Asano

    2015-01-01

    Background: The role of interleukin (IL)-23 in asthma pathophysiology is still controversial. We examined its role in allergic airway inflammation in response to two distinct antigens using IL-23-deficient mice. Methods: Allergic airway inflammation was evaluated in wild-type and IL-23p19−/− mice. Mice were sensitized to ovalbumin (OVA) or house dust mite (HDM) by intraperitoneal injection of antigen and their airways were then exposed to the same antigen. Levels of antigen-specific immuno...

  9. Compensatory responses to upper airway obstruction in obese apneic men and women

    OpenAIRE

    Chin, Chien-Hung; Kirkness, Jason P.; Patil, Susheel P.; McGinley, Brian M.; Smith, Philip L.; Schwartz, Alan R.; Schneider, Hartmut

    2011-01-01

    Defective structural and neural upper airway properties both play a pivotal role in the pathogenesis of obstructive sleep apnea. A more favorable structural upper airway property [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] has been documented for women. However, the role of sex-related modulation in compensatory responses to upper airway obstruction (UAO), independent of the passive Pcrit, remains unclear. Obese apneic men and women underwent a standard polysomno...

  10. Th17 Responses in Chronic Allergic Airway Inflammation Abrogate Regulatory T cell-mediated Tolerance and Contribute to Airway Remodeling

    OpenAIRE

    Zhao, Jingyue; Lloyd, Clare M.; Noble, Alistair

    2012-01-01

    The role of Th17 responses in airway remodeling in asthma is currently unknown. We demonstrate that both parenteral and mucosal allergen sensitization followed by allergen inhalation leads to Th17-biased lung immune responses. Unlike Th17 cells generated in vitro, lung Th17 cells did not produce TNF-α or IL-22. Eosinophilia predominated in acute inflammation while neutrophilia and IL-17 increased in chronic disease. Allergen-induced tolerance involved Foxp3, Helios and GARP expressing regulat...

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

    Science.gov (United States)

    Shipkowski, Kelly Anne

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

  12. Nonstationary Narrow-Band Response and First-Passage Probability

    DEFF Research Database (Denmark)

    Krenk, Steen

    1979-01-01

    The notion of a nonstationary narrow-band stochastic process is introduced without reference to a frequency spectrum, and the joint distribution function of two consecutive maxima is approximated by use of an envelope. Based on these definitions the first passage problem is treated as a Markov po...

  13. 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.

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

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    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.

  15. A PAF receptor antagonist inhibits acute airway inflammation and late-phase responses but not chronic airway inflammation and hyperresponsiveness in a primate model of asthma

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    R. H. Gundel

    1992-01-01

    Full Text Available We have examined the effects of a PAF receptor antagonist, WEB 2170, on several indices of acute and chronic airway inflammation and associated changes in lung function in a primate model of allergic asthma. A single oral administration WEB 2170 provided dose related inhibition of the release of leukotriene C4 (LTC4 and prostaglandin D2 (PGD2 recovered and quantified in bronchoalveolar lavage (BAL fluid obtained during the acute phase response to inhaled antigen. In addition, oral WEB 2170 treatment in dual responder primates blocked the acute influx of neutrophils into the airways as well as the associated late-phase airway obstruction occurring 6 h after antigen inhalation. In contrast, a multiple dosing regime with WEB 2170 (once a day for 7 consecutive days failed to reduce the chronic airway inflammation (eosinophilic and associated airway hyperresponsiveness to inhaled methacholine that is characteristic of dual responder monkeys. Thus, we conclude that the generation of PAF following antigen inhalation contributes to the development of lipid mediators, acute airway inflammation and associated late-phase airway obstruction in dual responder primates; however, PAF does not play a significant role in the maintenance of chronic airway inflammation and associated airway hyperresponsiveness in this primate model.

  16. TRPM8 mechanism of autonomic nerve response to cold in respiratory airway

    Directory of Open Access Journals (Sweden)

    Wang Cong-Yi

    2008-06-01

    Full Text Available Abstract Breathing cold air without proper temperature exchange can induce strong respiratory autonomic responses including cough, airway constriction and mucosal secretion, and can exacerbate existing asthma conditions and even directly trigger an asthma attack. Vagal afferent fiber is thought to be involved in the cold-induced respiratory responses through autonomic nerve reflex. However, molecular mechanisms by which vagal afferent fibers are excited by cold remain unknown. Using retrograde labeling, immunostaining, calcium imaging, and electrophysiological recordings, here we show that a subpopulation of airway vagal afferent nerves express TRPM8 receptors and that activation of TRPM8 receptors by cold excites these airway autonomic nerves. Thus activation of TRPM8 receptors may provoke autonomic nerve reflex to increase airway resistance. This putative autonomic response may be associated with cold-induced exacerbation of asthma and other pulmonary disorders, making TRPM8 receptors a possible target for prevention of cold-associated respiratory disorders.

  17. Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection

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    King Nicholas JC

    2006-05-01

    Full Text Available Abstract Background Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscle cells (HASM. We hypothesised that rhinovirus induction of inflammatory cytokine release from airway smooth muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells. Methods HASM cells, isolated from either asthmatic or non-asthmatic subjects, were infected with rhinovirus. Cytokine production was assayed by ELISA, ICAM-1 cell surface expression was assessed by FACS, and the transcription regulation of IL-6 was measured by luciferase activity. Results RV-induced IL-6 release was significantly greater in HASM cells derived from asthmatic subjects compared to non-asthmatic subjects. This response was RV specific, as 5% serum- induced IL-6 release was not different in the two cell types. Whilst serum stimulated IL-8 production in cells from both subject groups, RV induced IL-8 production in only asthmatic derived HASM cells. The transcriptional induction of IL-6 was differentially regulated via C/EBP in the asthmatic and NF-κB + AP-1 in the non-asthmatic HASM cells. Conclusion This study demonstrates augmentation and differential transcriptional regulation of RV specific innate immune response in HASM cells derived from asthmatic and non-asthmatics, and may give valuable insight into the mechanisms of RV-induced asthma exacerbations.

  18. Cough sensitivity and extrathoracic airway responsiveness to inhaled capsaicin in chronic cough patients.

    OpenAIRE

    Cho, You Sook; Lee, Chang-Keun; Yoo, Bin; Moon, Hee-Bom

    2002-01-01

    Enhanced cough response has been frequently observed in chronic cough. Recently, extrathoracic airway constriction to inhaled histamine was demonstrated in some chronic cough patients. However, relation between extrathoracic airway hyperresponsiveness (EAHR) and cough sensitivity determined by capsaicin inhalation is unclear in each etiological entity of chronic cough. Seventy-seven patients, with dry cough persisting for 3 or more weeks, normal spirometry and chest radiography, and 15 contro...

  19. Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.

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    Winfried Möller

    Full Text Available Endotoxin (Lipopolysaccharide, LPS is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alveoli to targeted LPS inhalation in order to understand the role of LPS challenge in airway disease.In healthy volunteers without any bronchial hyperresponsiveness we targeted sequentially 1, 5 and 20 µg LPS to the airways and 5 µg LPS to the alveoli using controlled aerosol bolus inhalation. Inflammatory parameters were assessed during a 72 h time period. LPS deposited in the airways induced dose dependent systemic responses with increases of blood neutrophils (peaking at 6 h, Interleukin-6 (peaking at 6 h, body temperature (peaking at 12 h, and CRP (peaking at 24 h. 5 µg LPS targeted to the alveoli caused significantly stronger effects compared to 5 µg airway LPS deposition. Local responses were studied by measuring lung function (FEV(1 and reactive oxygen production, assessed by hydrogen peroxide (H(2O(2 in fractionated exhaled breath condensate (EBC. FEV(1 showed a dose dependent decline, with lowest values at 12 h post LPS challenge. There was a significant 2-fold H(2O(2 induction in airway-EBC at 2 h post LPS inhalation. Alveolar LPS targeting resulted in the induction of very low levels of EBC-H(2O(2.Targeting LPS to the alveoli leads to stronger systemic responses compared to airway LPS targeting. Targeted LPS inhalation may provide a novel model of airway inflammation for studying the role of LPS contamination of air pollution in lung diseases, exacerbation and anti-inflammatory drugs.

  20. The role of intracellular calcium signals in inflammatory responses of polarised cystic fibrosis human airway epithelia.

    Science.gov (United States)

    Ribeiro, Carla Maria Pedrosa

    2006-01-01

    Hyperinflammatory host responses to bacterial infection have been postulated to be a key step in the pathogenesis of cystic fibrosis (CF) lung disease. Previous studies have indicated that the CF airway epithelium itself contributes to the hyperinflammation of CF airways via an excessive inflammatory response to bacterial infection. However, it has been controversial whether the hyperinflammation of CF epithelia results from mutations in the CF transmembrane conductance regulator (CFTR) and/or is a consequence of persistent airways infection. Recent studies have demonstrated that intracellular calcium (Ca2+i) signals consequent to activation of apical G protein-coupled receptors (GPCRs) by pro-inflammatory mediators are increased in CF airway epithelia. Because of the relationship between Ca2+i mobilisation and inflammatory responses, the mechanism for the increased Ca2+i signals in CF was investigated and found to result from endoplasmic reticulum (ER) Ca2+ store expansion. The ER Ca2+ store expansion imparts a hyperinflammatory phenotype to chronically infected airway epithelia as a result of the larger Ca2+i mobilisation coupled to an excessive inflammatory response following GPCR activation. The ER expansion is not dependent on ER retention of misfolded DeltaF508 CFTR, but reflects an epithelial response acquired following persistent luminal airway infection. With respect to the mechanism of ER expansion in CF, the current view is that chronic airway epithelial infection triggers an unfolded protein response as a result of the increased flux of newly synthesised inflammatory mediators and defensive factors into the ER compartment. This unfolded protein response is coupled to X-box binding protein 1 (XBP-1) mRNA splicing and transcription of genes associated with the expansion of the protein-folding capacity of the ER (e.g. increases in ER chaperones and ER membranes). These studies have revealed a novel adaptive response in chronically infected airway epithelia

  1. Hemodynamic responses and upper airway morbidity following tracheal intubation in patients with hypertension: conventional laryngoscopy versus an intubating laryngeal mask airway

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    Elif Bengi Sener

    2012-01-01

    Full Text Available OBJECTIVES: We compared hemodynamic responses and upper airway morbidity following tracheal intubation via conventional laryngoscopy or intubating laryngeal mask airway in hypertensive patients. METHODS: Forty-two hypertensive patients received a conventional laryngoscopy or were intubated with a intubating laryngeal mask airway. Anesthesia was induced with propofol, fentanyl, and cis-atracurium. Measurements of systolic and diastolic blood pressures, heart rate, rate pressure product, and ST segment changes were made at baseline, preintubation, and every minute for the first 5 min following intubation. The number of intubation attempts, the duration of intubation, and airway complications were recorded. RESULTS: The intubation time was shorter in the conventional laryngoscopy group than in the intubating laryngeal mask airway group (16.33 ± 10.8 vs. 43.04±19.8 s, respectively (p<0.001. The systolic and diastolic blood pressures in the intubating laryngeal mask airway group were higher than those in the conventional laryngoscopy group at 1 and 2 min following intubation (p<0.05. The rate pressure product values (heart rate x systolic blood pressure at 1 and 2 min following intubation in the intubating laryngeal mask airway group (15970.90 ± 3750 and 13936.76 ± 2729, respectively were higher than those in the conventional laryngoscopy group (13237.61 ± 3413 and 11937.52 ± 3160, respectively (p<0.05. There were no differences in ST depression or elevation between the groups. The maximum ST changes compared with baseline values were not significant between the groups (conventional laryngoscopy group: 0.328 mm versus intubating laryngeal mask airway group: 0.357 mm; p = 0.754. The number and type of airway complications were similar between the groups. CONCLUSION: The intense and repeated oropharyngeal and tracheal stimulation resulting from intubating laryngeal mask airway induces greater pressor responses than does stimulation resulting from

  2. Phase and Amplitude Responses of Narrow-Band Optical Filter Measured by Microwave Network Analyzer

    OpenAIRE

    Wang, Hsi-Cheng; Ho, Keang-Po

    2006-01-01

    The phase and amplitude responses of a narrow-band optical filter are measured simultaneously using a microwave network analyzer. The measurement is based on an interferometric arrangement to split light into two paths and then combine them. In one of the two paths, a Mach-Zehnder modulator generates two tones without carrier and the narrow-band optical filter just passes through one of the tones. The temperature and environmental variations are removed by separated phase and amplitude averag...

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

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    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

  4. Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    Hansel, Nadia N.; Pare, Peter D.; Rafaels, Nicholas; Sin, Don D.; Sandford, Andrew; Daley, Denise; Vergara, Candelaria; Huang, Lili; Elliott, W. Mark; Pascoe, Chris D.; Arsenault, Bryna A.; Postma, Dirkje S.; Boezen, Marieke H.; Bosse, Yohan; van den Berge, Maarten; Hiemstra, Pieter S.; Cho, Michael H.; Litonjua, Augusto A.; Sparrow, David; Ober, Carole; Wise, Robert A.; Connett, John; Neptune, Enid R.; Beaty, Terri H.; Ruczinski, Ingo; Mathias, Rasika A.; Barnes, Kathleen C.

    2015-01-01

    Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina

  5. Distinct effects of endogenous interleukin-23 on eosinophilic airway inflammation in response to different antigens

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    Rika Ogawa

    2015-09-01

    Conclusions: Different antigens induced IL-23 at different part of the body in our similar asthma models. Endogenous IL-23 production at the site of antigen sensitization facilitates type-2 immune responses, whereas IL-23 production and subsequent IL-17A synthesis in the airways suppresses allergic inflammation.

  6. Secretory response induced by essential oils on airway surface fluid: a pharmacological MRI study.

    Science.gov (United States)

    Nicolato, Elena; Boschi, Federico; Marzola, Pasquina; Sbarbati, Andrea

    2009-07-30

    Using pharmacological magnetic resonance imaging, we have performed an in vivo evaluation of the secretory response induced by essential oils in the rat airway. Aim of the work was to establish a computerized method to assess the efficacy of volatile compounds in spatially localized areas without the bias derived by subjective evaluation. Magnetic resonance experiments were carried out using a 4.7 T horizontal magnet. In the trachea, airway surface fluid was easily identified for its high intensity signal. The tracheal glands were also easily visible. The oesophageal lumen was usually collapsed and was identifiable only in the presence of intraluminal liquid. Scotch pine essential oil inhalation significantly increased the surface fluid in the middle portion of the trachea and the increase was visible at both 5 and 10 min. A lesser secretory response was detected after rosemary essential oil inhalation even though the response was significant with respect to the control in particular at 10 min. No secretory response was detected after peppermint essential oil inhalation both at 5 and 10 min. The data obtained in the present work demonstrate a chemically induced airway secretion. The availability of a pharmacological magnetic resonance imaging approach opens new perspectives to test the action of volatile compounds on the airway. PMID:19422906

  7. Arsenic alters ATP-dependent Ca²+ signaling in human airway epithelial cell wound response.

    Science.gov (United States)

    Sherwood, Cara L; Lantz, R Clark; Burgess, Jefferey L; Boitano, Scott

    2011-05-01

    Arsenic is a natural metalloid toxicant that is associated with occupational inhalation injury and contaminates drinking water worldwide. Both inhalation of arsenic and consumption of arsenic-tainted water are correlated with malignant and nonmalignant lung diseases. Despite strong links between arsenic and respiratory illness, underlying cell responses to arsenic remain unclear. We hypothesized that arsenic may elicit some of its detrimental effects on the airway through limitation of innate immune function and, specifically, through alteration of paracrine ATP (purinergic) Ca²+ signaling in the airway epithelium. We examined the effects of acute (24 h) exposure with environmentally relevant levels of arsenic (i.e., immune functions (e.g., ciliary beat, salt and water transport, bactericide production, and wound repair). Arsenic-induced compromise of such airway defense mechanisms may be an underlying contributor to chronic lung disease. PMID:21357385

  8. Siblings Promote a Type 1/Type 17-oriented immune response in the airways of asymptomatic neonates

    DEFF Research Database (Denmark)

    Wolsk, Helene Mygind; Chawes, Bo L.; Følsgaard, Nilofar V.;

    2016-01-01

    BACKGROUND: Siblings have been shown to reduce the risk of later asthma and allergy, but the mechanism driving this association is unknown. The objective was to study whether siblings affect the airway immune response in healthy neonates. We hypothesized that siblings exert immune modulatory...... effects on neonates mirrored in the airway mucosa. METHODS: We measured 20 immune-mediators related to the Type 1, Type 2, Type 17 or regulatory immune pathways in the airway mucosa of 571 one-month-old asymptomatic neonates from the Copenhagen Prospective Studies on Asthma in Childhood2010 birth...... effect. These findings may represent an in-utero immune priming effect of the fetal immune system caused by previous pregnancies as the effect was attenuated with time since last childbirth or presence of unidentified microbes, but further studies are needed to confirm our findings....

  9. Response of airway epithelial cells to double-stranded RNA in an allergic environment

    OpenAIRE

    Herbert, Cristan; Zeng, Qing-Xiang; Shanmugasundaram, Ramesh; Garthwaite, Linda; Oliver, Brian G.; Kumar, Rakesh K.

    2014-01-01

    Background Respiratory viral infections are the most common trigger of acute exacerbations in patients with allergic asthma. The anti-viral response of airway epithelial cells (AEC) may be impaired in asthmatics, while cytokines produced by AEC may drive the inflammatory response. We investigated whether AEC cultured in the presence of Th2 cytokines associated with an allergic environment exhibited altered responses to double-stranded RNA, a virus-like stimulus. Methods We undertook prelimina...

  10. Specific immune responses against airway epithelial cells in a transgenic mouse-trachea transplantation model for obliterative airway disease

    NARCIS (Netherlands)

    Qu, N; de Haan, A; Harmsen, MC; Kroese, FGM; de Leij, LFMH; Prop, J

    2003-01-01

    Background. Immune injury to airway epithelium is suggested to play a central role in the pathogenesis of obliterative bronchiolitis (OB) after clinical lung transplantation. In several studies, a rejection model of murine trachea transplants is used, resulting in obliterative airway disease (OAD) w

  11. Onset of obesity in carboxypeptidase E-deficient mice and effect on airway responsiveness and pulmonary responses to ozone

    OpenAIRE

    Johnston, Richard A.; Zhu, Ming; Hernandez, Christopher B.; Williams, Erin S.; Shore, Stephanie A.

    2010-01-01

    When compared with lean, wild-type mice, obese Cpefat mice, 14 wk of age and older, manifest innate airway hyperresponsiveness (AHR) to intravenous methacholine and enhanced pulmonary inflammation following acute exposure to ozone (O3). The purpose of this study was to examine the onset of these augmented pulmonary responses during the onset of obesity. Thus airway responsiveness and O3-induced pulmonary inflammation and injury were examined in 7- and 10-wk-old Cpefat and age-matched, wild-ty...

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

    DEFF Research Database (Denmark)

    Sverrild, Asger; Bergqvist, Anders; Baines, Katherine J;

    2016-01-01

    BACKGROUND: Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway...... tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell-associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol. METHODS: Airway hyperresponsiveness to inhaled mannitol was measured in 23 non......-smoking, corticosteroid-free asthmatic individuals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were divided into phenotypes based on the presence of chymase. mRNA expression of mast cell-associated genes was measured by real-time PCR. RESULTS...

  13. Alteration of airway responsiveness mediated by receptors in ovalbumin-induced asthmatic E3 rats

    Institute of Scientific and Technical Information of China (English)

    Jing-wen LONG; Xu-dong YANG; Lei CAO; She-min LU; Yong-xiao CAO

    2009-01-01

    Aim:Airway hyperresponsiveness is a constant feature of asthma.The aim of the present study was to investigate airway hyperreactivity mediated by contractile and dilative receptors in an ovalbumin (OVA)-induced model of rat asthma.Methods:Asthmatic E3 rats were prepared by intraperitoneal injection with OVA/aluminum hydroxide and then challenged with intranasal instillation of OVA-PBS two weeks later.The myograph method was used to measure the responses of constriction and dilatation in the trachea,main bronchi and lobar bronchi.Results:In asthmatic E3 rata,β2 adrenoceptor-mediated relaxation of airway smooth muscle pre-contracted with 5-HT was inhibited,and there were no obvious difference in relaxation compared with normal E3 rats.Contraction of lobar bronchi mediated by 5-HT and sarafotoxin 6c was more potent than in the trachea or main bronchi.Airway contractions mediated by the endothelin (ET)A receptor,ETB receptor and M3 muscarinic receptor were augmented,and the augmented contraction was most obvious in lobar bronchi.The order of efficacy of contraction for lobar bronchi induced by agonists was ET-1,sarafotoxin 6c>ACh>5-HT.OX8 (an antibody against CD8+ T cells) strongly shifted and 0X35 (an antibody against CD4+ T cells) modestly shifted isoprenaline-induced concentration-relaxation curves in a nonparallel fashion to the left with an increased Rmax in asthmatic rats and sarafotoxin 6c-induced concentration-contractile curves to the right with a decreased Emax.Conclusion:The inhibition of airway relaxation and the augmentation of contraction mediated by receptors contribute to airway hyperresponsiveness and involve CD8+ and CD4+ T cells.

  14. Airway Responsiveness: Role of Inflammation, Epithelium Damage and Smooth Muscle Tension

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    K. I. Gourgoulianis

    1999-01-01

    Full Text Available The purpose of this study was the effect of epithelium damage on mechanical responses of airway smooth muscles under different resting tension. We performed acetylcholine (ACh (10-5M-induced contraction on tracheal strips from 30 rabbits in five groups (0.5, 1, 1.5, 2 and 2.5 g before and after epithelium removal. At low resting tension (0.5-1.5g, the epithelium removal decreased the ACh-induced contractions. At 2g resting tension, the epithelium removal increased the ACh-induced contractions of airways with intact epithelium about 20%. At 2.5 g resting tension, the elevation of contraction is about 25% (p<0.01. Consequently, after epithelium loss, the resting tension determines the airway smooth muscles responsiveness. In asthma, mediators such as ACh act on already contracted inflammatory airways, which results in additional increase of contraction. In contrast, low resting tension, a condition that simulates normal tidal breathing, protects from bronchoconstriction even when the epithelium is damaged.

  15. TRPM8 mechanism of autonomic nerve response to cold in respiratory airway

    OpenAIRE

    Wang Cong-Yi; Tominaga Makoto; Johnson Richard D; Chen Meng; Ling Jennifer X; Xing Hong; Gu Jianguo

    2008-01-01

    Abstract Breathing cold air without proper temperature exchange can induce strong respiratory autonomic responses including cough, airway constriction and mucosal secretion, and can exacerbate existing asthma conditions and even directly trigger an asthma attack. Vagal afferent fiber is thought to be involved in the cold-induced respiratory responses through autonomic nerve reflex. However, molecular mechanisms by which vagal afferent fibers are excited by cold remain unknown. Using retrograd...

  16. Role of SHIP-1 in the adaptive immune responses to aeroallergen in the airway.

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    Sukit Roongapinun

    Full Text Available BACKGROUND: Th2-dominated inflammatory response in the airway is an integral component in the pathogenesis of allergic asthma. Accumulating evidence supports the notion that the phosphoinositide 3-kinase (PI3K pathway is involved in the process. We previously reported that SHIP-1, a negative regulator of the PI3K pathway, is essential in maintaining lung immunohomeostasis, potentially through regulation of innate immune cells. However, the function of SHIP-1 in adaptive immune response in the lung has not been defined. We sought to determine the role of SHIP-1 in adaptive immunity in response to aeroallergen stimulation in the airway. METHODOLOGY/PRINCIPAL FINDINGS: SHIP-1 knockout (SHIP-1-/- mice on BALB/c background were immunized with ovalbumin (OVA plus aluminum hydroxide, a strong Th2-inducing immunization, and challenged with OVA. Airway and lung inflammation, immunoglobulin response, Th2 cytokine production and lymphocyte response were analyzed and compared with wild type mice. Even though there was mild spontaneous inflammation in the lung at baseline, SHIP-1-/- mice showed altered responses, including less cell infiltration around the airways but more in the parenchyma, less mucus production, decreased Th2 cytokine production, and diminished serum OVA-specific IgE, IgG1, but not IgG2a. Naïve and OVA sensitized SHIP-1-/- T cells produced a lower amount of IL-4. In vitro differentiated SHIP-1-/- Th2 cells produced less IL-4 compared to wild type Th2 cells upon T cell receptor stimulation. CONCLUSIONS/SIGNIFICANCE: These findings indicate that, in contrast to its role as a negative regulator in the innate immune cells, SHIP-1 acts as a positive regulator in Th2 cells in the adaptive immune response to aeroallergen. Thus any potential manipulation of SHIP-1 activity should be adjusted according to the specific immune response.

  17. Exposure of neonates to Respiratory Syncytial Virus is critical in determining subsequent airway response in adults

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    Daly Melissa

    2006-08-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the most common cause of acute bronchiolitis in infants and the elderly. Furthermore, epidemiological data suggest that RSV infection during infancy is a potent trigger of subsequent wheeze and asthma development. However, the mechanism by which RSV contributes to asthma is complex and remains largely unknown. A recent study indicates that the age of initial RSV infection is a key factor in determining airway response to RSV rechallenge. We hypothesized that severe RSV infection during neonatal development significantly alters lung structure and the pulmonary immune micro-environment; and thus, neonatal RSV infection is crucial in the development of or predisposition to allergic inflammatory diseases such as asthma. Methods To investigate this hypothesis the present study was conducted in a neonatal mouse model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old mice were infected with RSV (2 × 105 TCID50/g body weight and allowed to mature to adulthood. To determine if neonatal RSV infection predisposed adult animals to enhanced pathophysiological responses to allergens, these mice were then sensitized and challenged with ovalbumin. Various endpoints including lung function, histopathology, cytokine production, and cellularity in bronchoalveolar lavage were examined. Results RSV infection in neonates alone led to inflammatory airway disease characterized by airway hyperreactivity, peribronchial and perivascular inflammation, and subepithelial fibrosis in adults. If early RSV infection was followed by allergen exposure, this pulmonary phenotype was exacerbated. The initial response to neonatal RSV infection resulted in increased TNF-α levels in bronchoalveolar lavage. Interestingly, increased levels of IL-13 and mucus hyperproduction were observed almost three months after the initial infection with RSV. Conclusion Neonatal RSV exposure results in long term

  18. Surfactant and allergic airway inflammation.

    Science.gov (United States)

    Winkler, Carla; Hohlfeld, Jens M

    2013-01-01

    Pulmonary surfactant is a complex mixture of unique proteins and lipids that covers the airway lumen. Surfactant prevents alveolar collapse and maintains airway patency by reducing surface tension at the air-liquid interface. Furthermore, it provides a defence against antigen uptake by binding foreign particles and enhancing cellular immune responses. Allergic asthma is associated with chronic airway inflammation and presents with episodes of airway narrowing. The pulmonary inflammation and bronchoconstriction can be triggered by exposure to allergens or pathogens present in the inhaled air. Pulmonary surfactant has the potential to interact with various immune cells which orchestrate allergen- or pathogen-driven episodes of airway inflammation. The complex nature of surfactant allows multiple sites of interaction, but also makes it susceptible to external alterations, which potentially impair its function. This duality of modulating airway physiology and immunology during inflammatory conditions, while at the same time being prone to alterations accompanied by restricted function, has stimulated numerous studies in recent decades, which are reviewed in this article. PMID:23896983

  19. Effect of parenchymal stiffness on canine airway size with lung inflation.

    Directory of Open Access Journals (Sweden)

    Robert H Brown

    Full Text Available Although airway patency is partially maintained by parenchymal tethering, this structural support is often ignored in many discussions of asthma. However, agonists that induce smooth muscle contraction also stiffen the parenchyma, so such parenchymal stiffening may serve as a defense mechanism to prevent airway narrowing or closure. To quantify this effect, specifically how changes in parenchymal stiffness alter airway size at different levels of lung inflation, in the present study, we devised a method to separate the effect of parenchymal stiffening from that of direct airway narrowing. Six anesthetized dogs were studied under four conditions: baseline, after whole lung aerosol histamine challenge, after local airway histamine challenge, and after complete relaxation of the airways. In each of these conditions, we used High resolution Computed Tomography to measure airway size and lung volume at five different airway pressures (0, 12, 25, 32, and 45 cm H(2O. Parenchymal stiffening had a protective effect on airway narrowing, a fact that may be important in the airway response to deep inspiration in asthma. When the parenchyma was stiffened by whole lung aerosol histamine challenge, at every lung volume above FRC, the airways were larger than when they were directly challenged with histamine to the same initial constriction. These results show for the first time that a stiff parenchyma per se minimizes the airway narrowing that occurs with histamine challenge at any lung volume. Thus in clinical asthma, it is not simply increased airway smooth muscle contraction, but perhaps a lack of homogeneous parenchymal stiffening that contributes to the symptomatic airway hyperresponsiveness.

  20. Establishment of Allergic Airway Inflammation Model in Late- phase Response of Sprague- Dawley Rats

    Institute of Scientific and Technical Information of China (English)

    朱敏敏; 傅诚章; 周钦海

    2002-01-01

    Objective To establish allergic airway inflammation model in late-phase airwayreaction of Sprague-Dawley (SD) rats. Methods Thirty-six SD rats were randomly divided intothree groups: control group (Group Ⅰ),single challenge group (Group Ⅱ),consecutive challenge group(Group Ⅲ). The rats in Group Ⅱ and Group Ⅲ were sensitized twice by injection of ovalbumin (OA) to-gether with aluminum hydroxide and Bordetella pertussis as adjuvants, followed by challenge withaerosolized OA for 20 min once in Group Ⅱ or one time on each day for one week in Group Ⅲ . Therats in Group Ⅰ received 0.9 % saline by injection and inhalation. Results Conpared uith groupⅠ , there were positive symptoms observed in the group Ⅱ and group Ⅲ; the amount of total leucocytesand eosinophil percentage in brochoalveolar lauage fluid (BALF) significantly increased (P<0.05 orP <0.01 respectively) in Group Ⅱ or Ⅲ; histopathologic changes of lung showed acute allergic inflam-mation changes in Group Ⅱ : Disrupted epithelium damaged subepithelial structure and eosinophil infiltra-tion the in the airway wall. As for the Group Ⅲ , there were allergen-induced characteristic features ofchronic allergic airways inflammation: hypertrophy and hyperplasia of bronchial smooth muscle, gobletcell hyperplasia , basement membrane thickening, eosinophil infiltration, edema. Conclusion The mod-el of allergic airway inflammation in late-phase response of SD rats was successfully established by OAsensitization (twice) and consecutive challenge.

  1. Numerical simulations of dynamic response of narrow conical structures due to ice actions

    Energy Technology Data Exchange (ETDEWEB)

    Dalane, O.; Loset, S. [Norwegian Univ. of Science and Technology, Trondheim (Norway); Xu, N.; Yue, Q. [Dalian Univ. of Technology, Dalian (China); Tuomo, K. [Norwegian Univ. of Science and Technology, Trondheim (Norway)]|[Karna Research and Consulting, Helsinki (Finland)

    2008-07-01

    The design of an offshore drilling platform in the Bohai Bay of North China was recently modified in an effort to reduce vibrations resulting from ice action. This paper presented a theoretical example where a conical structure was exposed to sheet ice action. The dynamic analysis for the structure was based on a narrow cone where rubble build-up does not influence the ice action. Both field data and recent theoretical studies showed that the time-varying ice action and the structural response constitute a narrow-band random process under these conditions. According to structural dynamic studies, the time of exposure can be a significant parameter if the response has a narrow-band character. The numerical simulation is influenced by such ice action since there is a possibility that the real response will be underestimated if the time of a numerical simulation is not sufficiently long. This paper addressed this problem by using a numerical method based on data obtained from full-scale structures deployed in the Bohai Bay. The purpose was to determine the time required to reach a maximum response while the key parameters of the load model vary randomly. The simulation results were compared with a similar analysis performed on full-scale data. 21 refs., 11 figs.

  2. Chronic exposure to a beta 2-adrenoceptor agonist increases the airway response to methacholine.

    Science.gov (United States)

    Witt-Enderby, P A; Yamamura, H I; Halonen, M; Palmer, J D; Bloom, J W

    1993-09-01

    Scheduled chronic administration of beta 2-adrenoceptor agonist bronchodilators in patients with asthma recently has been reported to be associated with a worsening of symptoms and an increase in bronchial responsiveness. We wanted to determine whether a 28-day in vivo exposure to albuterol (beta 2-adrenoceptor agonist) altered the response of rabbit airways to the cholinergic agonist methacholine. We found, using in vitro tissue bath techniques, that in mainstem bronchi from rabbits given a 28-day exposure to albuterol, maximum contraction to methacholine was increased in the albuterol-treated group (control group = 1.10 +/- 0.11 g vs. treated group = 1.50 +/- 0.13 g, P airway smooth muscle to methacholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7901034

  3. Treating asthma means treating airway smooth muscle cells

    NARCIS (Netherlands)

    Zuyderduyn, S; Sukkar, M B; Fust, A; Dhaliwal, S; Burgess, J K

    2008-01-01

    Asthma is characterised by airway hyperresponsiveness, airway inflammation and airway remodelling. Airway smooth muscle cells are known to be the main effector cells of airway narrowing. In the present paper, studies will be discussed that have led to a novel view of the role of airway smooth muscle

  4. Surfactant Protein D modulates allergen particle uptake and inflammatory response in a human epithelial airway model

    Directory of Open Access Journals (Sweden)

    Schleh Carsten

    2012-02-01

    Full Text Available Abstract Background Allergen-containing subpollen particles (SPP are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP-D. The aim of the present study was to investigate the influence of SP-D in a complex three-dimensional human epithelial airway model, which simulates the most important barrier functions of the epithelial airway. The uptake of SPP as well as the secretion of pro-inflammatory cytokines was investigated. Methods SPP were isolated from timothy grass and subsequently fluorescently labeled. A human epithelial airway model was built by using human Type II-pneumocyte like cells (A549 cells, human monocyte derived macrophages as well as human monocyte derived dendritic cells. The epithelial cell model was incubated with SPP in the presence and absence of surfactant protein D. Particle uptake was evaluated by confocal microscopy and advanced computer-controlled analysis. Finally, human primary CD4+ T-Cells were added to the epithelial airway model and soluble mediators were measured by enzyme linked immunosorbent assay or bead array. Results SPP were taken up by epithelial cells, macrophages, and dendritic cells. This uptake coincided with secretion of pro-inflammatory cytokines and chemokines. SP-D modulated the uptake of SPP in a cell type specific way (e.g. increased number of macrophages and epithelial cells, which participated in allergen particle uptake and led to a decreased secretion of pro-inflammatory cytokines. Conclusion These results display a possible mechanism of how SP-D can modulate the inflammatory response to inhaled allergen.

  5. Lymphocyte Gene Expression Characteristic of Immediate Airway Responses (IAR) and Methacholine (MCH) Hyperresponsiveness in Mice Sensitized and Challenged with Isocyanates

    Science.gov (United States)

    Exposure to isocyanates has been associated with occupational airway diseases, including asthma. Previously we reported on respiratory and immune responses following dermal sensitization and intranasal challenge of BALB/c mice with 6 different isocyanates. The purpose of this st...

  6. 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. OBJEC...

  7. Cessation of dexamethasone exacerbates airway responses to methacholine in asthmatic mice.

    Science.gov (United States)

    Stengel, Peter W; Nickell, Laura E; Wolos, Jeffrey A; Snyder, David W

    2007-06-01

    In asthmatic mice, dexamethasone (30.0 mg/kg) was administered orally once daily on Days 24-27. One hour after dexamethasone on Day 25-27, the mice were exposed to ovalbumin aerosols. Twenty-eight days after the initial ovalbumin immunization, we found that dexamethasone reduced methacholine-induced pulmonary gas trapping and inhibited bronchoalveolar lavage eosinophils and neutrophils. However, five days after the last dose of dexamethasone and last ovalbumin aerosol exposure in other asthmatic mice, the airway obstructive response to methacholine was exacerbated in dexamethasone-treated mice compared to vehicle-treated mice on Day 32. Further, eosinophils, but not neutrophils, were still inhibited after cessation of dexamethasone. Thus, discontinuing dexamethasone worsened methacholine-induced pulmonary gas trapping of asthmatic mice in the absence of eosinophilic airway inflammation.

  8. Chitin-Induced Airway Epithelial Cell Innate Immune Responses Are Inhibited by Carvacrol/Thymol

    Science.gov (United States)

    Erle, David J.

    2016-01-01

    Chitin is produced in large amounts by fungi, insects, and other organisms and has been implicated in the pathogenesis of asthma. Airway epithelial cells are in direct contact with environmental particles and serve as the first line of defense against inhaled allergens and pathogens. The potential contributions of airway epithelial cells to chitin-induced asthma remain poorly understood. We hypothesized that chitin directly stimulates airway epithelial cells to release cytokines that promote type 2 immune responses and to induce expression of molecules which are important in innate immune responses. We found that chitin exposure rapidly induced the expression of three key type 2-promoting cytokines, IL-25, IL-33 and TSLP, in BEAS-2B transformed human bronchial epithelial cells and in A549 and H292 lung carcinoma cells. Chitin also induced the expression of the key pattern recognition receptors TLR2 and TLR4. Chitin induced the expression of miR-155, miR-146a and miR-21, each of which is known to up-regulate the expression of pro-inflammatory cytokines. Also the expression of SOCS1 and SHIP1 which are known targets of miR-155 was repressed by chitin treatment. The monoterpene phenol carvacrol (Car) and its isomer thymol (Thy) are found in herbal essential oils and have been shown to inhibit allergic inflammation in asthma models. We found that Car/Thy inhibited the effects of chitin on type 2-promoting cytokine release and on the expression of TLRs, SOCS1, SHIP1, and miRNAs. Car/Thy could also efficiently reduce the protein levels of TLR4, inhibit the increase in TLR2 protein levels in chitin plus Car/Thy-treated cells and increase the protein levels of SHIP1 and SOCS1, which are negative regulators of TLR-mediated inflammatory responses. We conclude that direct effects of chitin on airway epithelial cells are likely to contribute to allergic airway diseases like asthma, and that Car/Thy directly inhibits epithelial cell pro-inflammatory responses to chitin. PMID

  9. Children with asthma by school age display aberrant immune responses to pathogenic airway bacteria as infants

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura; Pedersen, Susanne Brix; Thysen, Anna Hammerich;

    2014-01-01

    BackgroundAsthma is a highly prevalent chronic lung disease that commonly originates in early childhood. Colonization of neonatal airways with the pathogenic bacterial strains Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae is associated with increased risk of later...... Prospective Studies on Asthma in Childhood birth cohort was followed prospectively, and asthma was diagnosed at age 7 years. The immune response to H influenzae, M catarrhalis, and S pneumoniae was analyzed in 292 infants using PBMCs isolated and stored since the age of 6 months. The immune response...

  10. Triggers of airway inflammation.

    Science.gov (United States)

    Kerrebijn, K F

    1986-01-01

    Most asthmatics have hyperresponsive airways. This makes them more sensitive than non-asthmatics to bronchoconstricting environmental exposures which, in their turn, may enhance responsiveness. Airway inflammation is considered to be a key determinant of airway hyperresponsiveness: the fact that chronic airway inflammation in cystic fibrosis does not lead to airway hyperresponsiveness of any importance indicates, however, that the role of airway inflammation is complex and incompletely elucidated. The main inducers of airway inflammation are viral infections, antigens, occupational stimuli and pollutants. Although exercise, airway cooling and hyper- or hypotonic aerosols are potent stimuli of bronchoconstriction, it is questionable if airway inflammation is involved in their mode of action. Each of the above-mentioned stimuli is discussed, with emphasis laid on the relation of symptoms to mechanisms. PMID:3533597

  11. Neurturin influences inflammatory responses and airway remodeling in different mouse asthma models.

    Science.gov (United States)

    Mauffray, Marion; Domingues, Olivia; Hentges, François; Zimmer, Jacques; Hanau, Daniel; Michel, Tatiana

    2015-02-15

    Neurturin (NTN) was previously described for its neuronal activities, but recently, we have shown that this factor is also involved in asthma physiopathology. However, the underlying mechanisms of NTN are unclear. The aim of this study was to investigate NTN involvement in acute bronchial Th2 responses, to analyze its interaction with airway structural cells, and to study its implication in remodeling during acute and chronic bronchial inflammation in C57BL/6 mice. We analyzed the features of allergic airway inflammation in wild-type and NTN(-/-) mice after sensitization with two different allergens, OVA and house dust mite. We showed that NTN(-/-) dendritic cells and T cells had a stronger tendency to activate the Th2 pathway in vitro than similar wild-type cells. Furthermore, NTN(-/-) mice had significantly increased markers of airway remodeling like collagen deposition. NTN(-/-) lung tissues showed higher levels of neutrophils, cytokine-induced neutrophil chemoattractant, matrix metalloproteinase 9, TNF-α, and IL-6. Finally, NTN had the capacity to decrease IL-6 and TNF-α production by immune and epithelial cells, showing a direct anti-inflammatory activity on these cells. Our findings support the hypothesis that NTN could modulate the allergic inflammation in different mouse asthma models. PMID:25595789

  12. Social Stress Enhances Allergen-Induced Airway Inflammation in Mice and Inhibits Corticosteroid Responsiveness of Cytokine Production

    OpenAIRE

    Bailey, Michael; Kierstein, Sonja; Sharma, Satish; Spaits, Matthew; Kinsey, Steven G.; Tliba, Omar; Amrani, Yassine; John F Sheridan; Panettieri, Reynold A.; Haczku, Angela

    2009-01-01

    Chronic psychosocial stress exacerbates asthma but the underlying mechanisms remain poorly understood. We hypothesized that psychosocial stress aggravates allergic airway inflammation by altering innate immune cell function. The effects of stress on airway inflammation, lung function and glucocorticoid responsiveness were studied in a novel in vivo murine model of combined social disruption stress and allergic sensitization. The effects of corticosterone were assessed on cytokine profile and ...

  13. Distribution of radioactive aerosol in the airways of children and adolescents with bronchial hyper-responsiveness

    International Nuclear Information System (INIS)

    The purpose of this study was to examine the relationship between the pulmonary distribution of inhaled radioaerosol, bronchial responsiveness, and lung function in children and adolescents. The participating subjects were divided into three groups: (1) 14 asthmatics with bronchial hyper-responsiveness (BHR), (2) five non-asthmatic subjects with BHR, and (3) 20 controls without BHR. Pulmonary distribution of [99Tcm] albumin radioaerosol, maximal expiratory flow when 25% of forced vital capacity remain to be exhaled (MEF25), and bronchial responsiveness to inhaled histamine were measured. Twenty subjects (52%) has irregular central distribution and 19 subjects (48%) had regular distribution of radioaerosol in their lungs. No difference in distribution of radioaerosol was found between the three groups of children. The median MEF25 among non-asthmatic subjects (80% predicted) was lower than that found in controls (92% predicted) but higher than that found in asthmatic subjects (55% predicted). A relationship was found between reduced flow at the peripheral airways, as indicated by MEF25 and the degree of central distribution of radioaerosol. Furthermore, subjects with irregular central distribution of radioaerosol had an increase degree of bronchial responsiveness. In conclusion, children and adolescents who have flow rates in the peripheral airways or increased degree of bronchial responsiveness tend to have abnormal distribution of radioaerosols. (author)

  14. Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling.

    Science.gov (United States)

    Ma, Yuan; Ge, Ai; Zhu, Wen; Liu, Ya-Nan; Ji, Ning-Fei; Zha, Wang-Jian; Zhang, Jia-Xiang; Zeng, Xiao-Ning; Huang, Mao

    2016-01-01

    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 abolished by morin

  15. Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    Ahmed Tahir

    2012-01-01

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

  17. Comparison of dexmedetomidine and lignocaine on attenuation of airway and pressor responses during tracheal extubation

    Directory of Open Access Journals (Sweden)

    Vivek Bharti Sharma

    2014-01-01

    Full Text Available Background: Haemodynamic stability and rapid emergence after general anaesthesia used in spinal surgery is a common practice, the goal of which is to permit early neurological motor and sensory examination. Extubation is almost always associated with hypertension, increased airway response and arrhythmias. We have compared the effects of the α-2 agonist Dexmedetomidine and Lignocaine given at the end of the procedure on attenuation of airway and pressor responses following tracheal extubation. This study is a randomised, placebo-controlled, double-blinded study. Materials and Methods: Sixty ASA I-III patients, aged 18-70 years, scheduled to undergo spinal surgery at the level of thoracic, lumbar or sacral region were randomly divided into three groups. Balanced general anaesthesia comprising standard procedures and drugs were used for monitoring, induction and maintenance. At the last skin suture, inhalation anaesthetic was discontinued. After turning the patient supine and return of spontaneous efforts, in Group D Dexmedetomidine 0.5 μg/kg, in Group L Lignocaine 1.5 mg/kg and in Group P normal saline (10 ml were administered as bolus intravenously over 60 seconds. Systolic, diastolic and mean arterial pressures and heart rate were recorded before intravenous administration and also every minute for 3 minutes, at 5, 10 and 15 minutes post-extubation. Duration of emergence and extubation were noted and attenuation of airway response and quality of extubation was evaluated on cough grading. Results: Mean arterial pressures and heart rate were higher in Group L and Group P than in Group D but not statistically significant. The duration of emergence, extubation and recovery were comparable in all the groups (P > 0.05. Extubation Quality Scores was 1 in 80%, 2 in 20% in Group D; in Group L, the quality scores were 1 for 55%, 2 for 45% and I Group P 1 for 35%, 2 for 45% and 3 for 20% of the patients. The requirement of rescue analgesia was also less

  18. Relationship among bacterial colonization, airway inflam- mation, and bronchodilator response in patients with stable chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Bronchodilator reversibility, a response of airway to bronchodilator, occurred in 64% of stable patients with chronic obstructive pulmonary disease (COPD).1 In patients with COPD who have a significant response to bronchodilators, a clinical and functional response to inhaled corticosteroids is similar to that in asthmatics.2

  19. The effects of inhaled corticosteroids on intrinsic responsiveness and histology of airways from infant monkeys exposed to house dust mite allergen and ozone

    International Nuclear Information System (INIS)

    Inhaled corticosteroids (ICS) are recommended to treat infants with asthma, some with intermittent asthma. We previously showed that exposing infant monkeys to allergen/ozone resulted in asthma-like characteristics of their airways. We evaluated the effects of ICS on histology and intrinsic responsiveness of allergen/ozone-exposed and normal infant primate airways. Infant monkeys were exposed by inhalation to (1) filtered air and saline, (2) house dust mite allergen (HDMA) + ozone and saline, (3) filtered air and ICS (budesonide) or (4) HDMA + ozone and ICS. Allergen/ozone exposures started at 1 month and ICS at 3 months of age. At 6 months of age, methacholine-induced changes in luminal area of airways in proximal and distal lung slices were determined using videomicrometry, followed by histology of the same slices. Proximal airway responsiveness was increased by allergen/ozone and by ICS. Eosinophil profiles were increased by allergen/ozone in both proximal and distal airways, an effect that was decreased by ICS in distal airways. In both allergen/ozone- and air-exposed monkeys, ICS increased the number of alveolar attachments in distal airways, decreased mucin in proximal airways and decreased epithelial volume in both airways. ICS increased smooth muscle in air-exposed animals while decreasing it in allergen/ozone-exposed animals in both airways. In proximal airways, there was a small but significant positive correlation between smooth muscle and airway responsiveness, as well as between alveolar attachments and responsiveness. ICS change morphology and function in normal airways as well as allergen/ozone-exposed airways, suggesting that they should be reserved for infants with active symptoms

  20. Effect of reproterol either alone or combined with disodium cromoglycate on airway responsiveness to methacholine.

    Science.gov (United States)

    Kanniess, Frank; Jörres, Rudolf A; Magnussen, Helgo

    2005-01-01

    Regular use of inhaled beta2-agonists might lead to tolerance as reflected in a loss of bronchoprotection. In vitro-data suggest that this might be prevented by disodium cromoglycate (DSCG). Therefore, we studied the effect of the beta2-agonist reproterol in combination with DSCG. In a cross-over design, 19 subjects with airway hyperresponsiveness inhaled either placebo, 1mg reproterol, 2 mg DSCG, or 1mg reproterol plus 2 mg DSCG 4x daily over 2 weeks. Treatment periods were separated by > or = 7 days. Before and at the end of periods, lung function and methacholine responsiveness were determined in the morning, and 6h later the bronchodilator effect and the protection against methacholine-induced bronchoconstriction. Reproterol or DSCG or their combination did not exert detrimental effects on lung function, airway responsiveness, or bronchodilator capacity. However, bronchoprotection was significantly reduced (p DSCG, the respective changes being 0.59, 0.96 and 1.37 doubling concentrations. All changes were small as compared to intraindividual variability. In this model all treatments except with DSCG caused a significant but small loss of protection against methacholine-induced bronchoconstriction. Thus, tolerance was not prevented by 2 weeks of additional treatment with DSCG, in contrast to in vitro findings. PMID:15939309

  1. Airway hyperresponsiveness; smooth muscle as the principal actor.

    Science.gov (United States)

    Lauzon, Anne-Marie; Martin, James G

    2016-01-01

    Airway hyperresponsiveness (AHR) is a defining characteristic of asthma that refers to the capacity of the airways to undergo exaggerated narrowing in response to stimuli that do not result in comparable degrees of airway narrowing in healthy subjects. Airway smooth muscle (ASM) contraction mediates airway narrowing, but it remains uncertain as to whether the smooth muscle is intrinsically altered in asthmatic subjects or is responding abnormally as a result of the milieu in which it sits. ASM in the trachea or major bronchi does not differ in its contractile characteristics in asthmatics, but the more pertinent peripheral airways await complete exploration. The mass of ASM is increased in many but not all asthmatics and therefore cannot be a unifying hypothesis for AHR, although when increased in mass it may contribute to AHR. The inability of a deep breath to reverse or prevent bronchial narrowing in asthma may reflect an intrinsic difference in the mechanisms that lead to softening of contracted ASM when subjected to stretch. Cytokines such as interleukin-13 and tumor necrosis factor-α promote a more contractile ASM phenotype. The composition and increased stiffness of the matrix in which ASM is embedded promotes a more proliferative and pro-inflammatory ASM phenotype, but the expected dedifferentiation and loss of contractility have not been shown. Airway epithelium may drive ASM proliferation and/or molecular remodeling in ways that may lead to AHR. In conclusion, AHR is likely multifactorial in origin, reflecting the plasticity of ASM properties in the inflammatory environment of the asthmatic airway. PMID:26998246

  2. Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Pisi R

    2015-06-01

    Full Text Available Roberta Pisi,1 Marina Aiello,1 Andrea Zanini,2 Panagiota Tzani,1 Davide Paleari,3 Emilio Marangio,1 Antonio Spanevello,2,4 Gabriele Nicolini,5 Alfredo Chetta1 1Department of Clinical and Experimental Medicine, University of Parma, Parma, 2Division of Pneumology, IRCCS Rehabilitation Institute of Tradate, Salvatore Maugeri Foundation, Tradate, 3Medical Department, Chiesi Farmaceutici SpA, Parma, 4Department of Clinical and Experimental Medicine, University of Insubria, Varese, 5Corporate Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy Background: We investigated whether a relationship between small airways dysfunction and bronchodilator responsiveness exists in patients with chronic obstructive pulmonary disease (COPD.Methods: We studied 100 (20 female; mean age: 68±10 years patients with COPD (forced expiratory volume in 1 second [FEV1]: 55% pred ±21%; FEV1/forced vital capacity [FVC]: 53%±10% by impulse oscillometry system. Resistance at 5 Hz and 20 Hz (R5 and R20, in kPa·s·L-1 and the fall in resistance from 5 Hz to 20 Hz (R5 – R20 were used as indices of total, proximal, and peripheral airway resistance; reactance at 5 Hz (X5, in kPa·s·L-1 was also measured. Significant response to bronchodilator (salbutamol 400 µg was expressed as absolute (≥0.2 L and percentage (≥12% change relative to the prebronchodilator value of FEV1 (flow responders, FRs and FVC (volume responders, VRs.Results: Eighty out of 100 participants had R5 – R20 >0.03 kPa·s·L-1 (> upper normal limit and, compared to patients with R5 – R20 ≤0.030 kPa·s·L-1, showed a poorer health status, lower values of FEV1, FVC, FEV1/FVC, and X5, along with higher values of residual volume/total lung capacity and R5 (P<0.05 for all comparisons. Compared to the 69 nonresponders and the 8 FRs, the 16 VRs had significantly higher R5 and R5 – R20 values (P<0.05, lower X5 values (P<0.05, and greater airflow obstruction and lung

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

    Directory of Open Access Journals (Sweden)

    Li Yin Drake

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

  4. [Cardiovascular responses during laryngeal mask airway insertion in normotensive, hypertensive and chronic renal failure patients].

    Science.gov (United States)

    Yamauchi, M; Igarashi, M; Tsunoda, K; Edanaga, M; Suzuki, H; Tohdoh, Y; Namiki, A

    1999-08-01

    The hemodynamic response to the insertion of the laryngeal mask airway (LM) following induction with propofol 2 mg.kg-1 was assessed and compared in normotensive (Normal), hypertensive (HT) and chronic renal failure (CRF) patients (n = 23 in each group). Before induction, in HT and CRF groups blood pressure and rate pressure products (RPP) were higher than in Normal group (P < 0.05). Although blood pressure and RPP were decreased in every patient by induction with propofol, no patients needed vasopressor drugs. The decreases of blood pressure and RPP were larger in HT and CRF groups than in Normal group (P < 0.05). There were no differences between groups in heart rate and rate of successful LM insertion. We concluded that LM insertion with propofol 2 mg.kg-1 was an effective induction method preventing the adverse circulatory responses in normotensive, hypertensive and chronic renal failure patients. PMID:10481421

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-15

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

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

    International Nuclear Information System (INIS)

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

  7. Morning-evening changes in airway responsiveness to methacholine in normal and asthmatic subjects: analysis using partial flow-volume curves.

    OpenAIRE

    Heaton, R W; Gillett, M K; Snashall, P. D.

    1988-01-01

    In eight normal and eight asthmatic subjects airway responsiveness to methacholine was measured by means of partial flow-volume loops at 0800 and 1800 hours on the same day. Airway responsiveness was lower in the evening in both normal and asthmatic subjects.

  8. Recruited alveolar macrophages, in response to airway epithelial-derived monocyte chemoattractant protein 1/CCl2, regulate airway inflammation and remodeling in allergic asthma.

    Science.gov (United States)

    Lee, Yong Gyu; Jeong, Jong Jin; Nyenhuis, Sharmilee; Berdyshev, Evgeny; Chung, Sangwoon; Ranjan, Ravi; Karpurapu, Manjula; Deng, Jing; Qian, Feng; Kelly, Elizabeth A B; Jarjour, Nizar N; Ackerman, Steven J; Natarajan, Viswanathan; Christman, John W; Park, Gye Young

    2015-06-01

    Although alveolar macrophages (AMs) from patients with asthma are known to be functionally different from those of healthy individuals, the mechanism by which this transformation occurs has not been fully elucidated in asthma. The goal of this study was to define the mechanisms that control AM phenotypic and functional transformation in response to acute allergic airway inflammation. The phenotype and functional characteristics of AMs obtained from human subjects with asthma after subsegmental bronchoprovocation with allergen was studied. Using macrophage-depleted mice, the role and trafficking of AM populations was determined using an acute allergic lung inflammation model. We observed that depletion of AMs in a mouse allergic asthma model attenuates Th2-type allergic lung inflammation and its consequent airway remodeling. In both human and mouse, endobronchial challenge with allergen induced a marked increase in monocyte chemotactic proteins (MCPs) in bronchoalveolar fluid, concomitant with the rapid appearance of a monocyte-derived population of AMs. Furthermore, airway allergen challenge of allergic subjects with mild asthma skewed the pattern of AM gene expression toward high levels of the receptor for MCP1 (CCR2/MCP1R) and expression of M2 phenotypic proteins, whereas most proinflammatory genes were highly suppressed. CCL2/MCP-1 gene expression was prominent in bronchial epithelial cells in a mouse allergic asthma model, and in vitro studies indicate that bronchial epithelial cells produced abundant MCP-1 in response to house dust mite allergen. Thus, our study indicates that bronchial allergen challenge induces the recruitment of blood monocytes along a chemotactic gradient generated by allergen-exposed bronchial epithelial cells. PMID:25360868

  9. Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Hansel, Nadia N; Paré, Peter D; Rafaels, Nicholas; Sin, Don D; Sandford, Andrew; Daley, Denise; Vergara, Candelaria; Huang, Lili; Elliott, W Mark; Pascoe, Chris D; Arsenault, Bryna A; Postma, Dirkje S; Boezen, H Marike; Bossé, Yohan; van den Berge, Maarten; Hiemstra, Pieter S; Cho, Michael H; Litonjua, Augusto A; Sparrow, David; Ober, Carole; Wise, Robert A; Connett, John; Neptune, Enid R; Beaty, Terri H; Ruczinski, Ingo; Mathias, Rasika A; Barnes, Kathleen C

    2015-08-01

    Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina (San Diego, CA) Human660W-Quad BeadChip on European Americans with COPD from the Lung Health Study. Linear regression models with correlated meta-analyses, including data from baseline (n = 2,814) and Year 5 (n = 2,657), were used to test for common genetic variants associated with airway responsiveness. Genotypic imputation was performed using reference 1000 Genomes Project data. Expression quantitative trait loci (eQTL) analyses in lung tissues were assessed for the top 10 markers identified, and immunohistochemistry assays assessed protein staining for SGCD and MYH15. Four genes were identified within the top 10 associations with airway responsiveness. Markers on chromosome 9p21.2 flanked by LINGO2 met a predetermined threshold of genome-wide significance (P < 9.57 × 10(-8)). Markers on chromosomes 3q13.1 (flanked by MYH15), 5q33 (SGCD), and 6q21 (PDSS2) yielded suggestive evidence of association (9.57 × 10(-8) < P ≤ 4.6 × 10(-6)). Gene expression studies in lung tissue showed single nucleotide polymorphisms on chromosomes 5 and 3 to act as eQTL for SGCD (P = 2.57 × 10(-9)) and MYH15 (P = 1.62 × 10(-6)), respectively. Immunohistochemistry confirmed localization of SGCD protein to airway smooth muscle and vessels and MYH15 to airway epithelium, vascular endothelium, and inflammatory cells. We identified novel loci associated with airway responsiveness in a GWAS among smokers with COPD. Risk alleles on chromosomes 5 and 3 acted as eQTLs for SGCD and MYH15 messenger RNA, and these proteins were expressed in lung cells relevant to the development of airway responsiveness. PMID:25514360

  10. Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Paré, Peter D.; Rafaels, Nicholas; Sin, Don D.; Sandford, Andrew; Daley, Denise; Vergara, Candelaria; Huang, Lili; Elliott, W. Mark; Pascoe, Chris D.; Arsenault, Bryna A.; Postma, Dirkje S.; Boezen, H. Marike; Bossé, Yohan; van den Berge, Maarten; Hiemstra, Pieter S.; Cho, Michael H.; Litonjua, Augusto A.; Sparrow, David; Ober, Carole; Wise, Robert A.; Connett, John; Neptune, Enid R.; Beaty, Terri H.; Ruczinski, Ingo; Mathias, Rasika A.; Barnes, Kathleen C.

    2015-01-01

    Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina (San Diego, CA) Human660W-Quad BeadChip on European Americans with COPD from the Lung Health Study. Linear regression models with correlated meta-analyses, including data from baseline (n = 2,814) and Year 5 (n = 2,657), were used to test for common genetic variants associated with airway responsiveness. Genotypic imputation was performed using reference 1000 Genomes Project data. Expression quantitative trait loci (eQTL) analyses in lung tissues were assessed for the top 10 markers identified, and immunohistochemistry assays assessed protein staining for SGCD and MYH15. Four genes were identified within the top 10 associations with airway responsiveness. Markers on chromosome 9p21.2 flanked by LINGO2 met a predetermined threshold of genome-wide significance (P < 9.57 × 10−8). Markers on chromosomes 3q13.1 (flanked by MYH15), 5q33 (SGCD), and 6q21 (PDSS2) yielded suggestive evidence of association (9.57 × 10−8 < P ≤ 4.6 × 10−6). Gene expression studies in lung tissue showed single nucleotide polymorphisms on chromosomes 5 and 3 to act as eQTL for SGCD (P = 2.57 × 10−9) and MYH15 (P = 1.62 × 10−6), respectively. Immunohistochemistry confirmed localization of SGCD protein to airway smooth muscle and vessels and MYH15 to airway epithelium, vascular endothelium, and inflammatory cells. We identified novel loci associated with airway responsiveness in a GWAS among smokers with COPD. Risk alleles on chromosomes 5 and 3 acted as eQTLs for SGCD and MYH15 messenger RNA, and these proteins were expressed in lung cells relevant to the development of airway responsiveness. PMID:25514360

  11. Response Properties of a Newly Identified Tristratified Narrow Field Amacrine Cell in the Mouse Retina.

    Directory of Open Access Journals (Sweden)

    G S Newkirk

    Full Text Available Amacrine cells were targeted for whole cell recording using two-photon fluorescence microscopy in a transgenic mouse line in which the promoter for dopamine receptor 2 drove expression of green fluorescent protein in a narrow field tristratified amacrine cell (TNAC that had not been studied previously. Light evoked a multiphasic response that was the sum of hyperpolarizing and depolarization synaptic inputs consistent with distinct dendritic ramifications in the off and on sublamina of the inner plexiform layer. The amplitude and waveform of the response, which consisted of an initial brief hyperpolarization at light onset followed by recovery to a plateau potential close to dark resting potential and a hyperpolarizing response at the light offset varied little over an intensity range from 0.4 to ~10^6 Rh*/rod/s. This suggests that the cell functions as a differentiator that generates an output signal (a transient reduction in inhibitory input to downstream retina neurons that is proportional to the derivative of light input independent of its intensity. The underlying circuitry appears to consist of rod and cone driven on and off bipolar cells that provide direct excitatory input to the cell as well as to GABAergic amacrine cells that are synaptically coupled to TNAC. Canonical reagents that blocked excitatory (glutamatergic and inhibitory (GABA and glycine synaptic transmission had effects on responses to scotopic stimuli consistent with the rod driven component of the proposed circuit. However, responses evoked by photopic stimuli were paradoxical and could not be interpreted on the basis of conventional thinking about the neuropharmacology of synaptic interactions in the retina.

  12. Deficiency of FHL2 attenuates airway inflammation in mice and genetic variation associates with human bronchial hyper-responsiveness

    NARCIS (Netherlands)

    Kurakula, K.; Vos, M.; Logiantara, A.; Roelofs, J. J. T. H.; Nieuwenhuis, M. A.; Koppelman, G. H.; Postma, D. S.; Brandsma, C. A.; Sin, D. D.; Bosse, Y.; Nickle, D. C.; van Rijt, L. S.; de Vries, C. J. M.

    2015-01-01

    Background: Asthma is an inflammatory disease that involves airway hyper-responsiveness and mucus hypersecretion. The LIM-only protein FHL2 is a crucial modulator of multiple signal transduction pathways and functions as a scaffold in specific protein protein interactions. Objective: We sought to in

  13. Role of M2 Muscarinic Receptor in the Airway Response to Methacholine of Mice Selected for Minimal or Maximal Acute Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Juciane Maria de Andrade Castro

    2013-01-01

    Full Text Available Airway smooth muscle constriction induced by cholinergic agonists such as methacholine (MCh, which is typically increased in asthmatic patients, is regulated mainly by muscle muscarinic M3 receptors and negatively by vagal muscarinic M2 receptors. Here we evaluated basal (intrinsic and allergen-induced (extrinsic airway responses to MCh. We used two mouse lines selected to respond maximally (AIRmax or minimally (AIRmin to innate inflammatory stimuli. We found that in basal condition AIRmin mice responded more vigorously to MCh than AIRmax. Treatment with a specific M2 antagonist increased airway response of AIRmax but not of AIRmin mice. The expression of M2 receptors in the lung was significantly lower in AIRmin compared to AIRmax animals. AIRmax mice developed a more intense allergic inflammation than AIRmin, and both allergic mouse lines increased airway responses to MCh. However, gallamine treatment of allergic groups did not affect the responses to MCh. Our results confirm that low or dysfunctional M2 receptor activity is associated with increased airway responsiveness to MCh and that this trait was inherited during the selective breeding of AIRmin mice and was acquired by AIRmax mice during allergic lung inflammation.

  14. The Role of Airway Epithelial Cells in Response to Mycobacteria Infection

    Directory of Open Access Journals (Sweden)

    Yong Li

    2012-01-01

    Full Text Available Airway epithelial cells (AECs are part of the frontline defense against infection of pathogens by providing both a physical barrier and immunological function. The role of AECs in the innate and adaptive immune responses, through the production of antimicrobial molecules and proinflammatory factors against a variety of pathogens, has been well established. Tuberculosis (TB, a contagious disease primarily affecting the lungs, is caused by the infection of various strains of mycobacteria. In response to mycobacteria infection, epithelial expression of Toll-like receptors and surfactant proteins plays the most prominent roles in the recognition and binding of the pathogen, as well as the initiation of the immune response. Moreover, the antimicrobial substances, proinflammatory factors secreted by AECs, composed a major part of the innate immune response and mediation of adaptive immunity against the pathogen. Thus, a better understanding of the role and mechanism of AECs in response to mycobacteria will provide insight into the relationship of epithelial cells and lung immunocytes against TB, which may facilitate our understanding of the pathogenesis and immunological mechanism of pulmonary tuberculosis disease.

  15. Remodeling of the pulmonary circulation - a novel response to allergic airway inflammation

    OpenAIRE

    Rydell-Törmänen, Kristina

    2008-01-01

    Asthma is characterized, not only by inflammation but also by airway and vascular remodeling. Airway remodeling is established early in disease, structural alterations have been found in children, and is thought to contribute to asthma symptoms. Unfortunately, airway remodeling is considered difficult to reverse and it seldom resolves completely. Studies of vascular involvement in asthma have mainly focused on the tracheal and bronchial microcirculation, as these vessels are relatively easy t...

  16. Pharmacology of airway smooth muscle proliferation

    NARCIS (Netherlands)

    Gosens, Reinoud; Roscioni, Sara S.; Dekkers, Bart G. J.; Pera, Tonio; Schmidt, Martina; Schaafsma, Dedmer; Zaagsma, Johan; Meurs, Herman

    2008-01-01

    Airway smooth muscle thickening is a pathological feature that contributes significantly to airflow limitation and airway hyperresponsiveness in asthma. Ongoing research efforts aimed at identifying the mechanisms responsible for the increased airway smooth muscle mass have indicated that hyperplasi

  17. Effects of superoxide generating systems on muscle tone, cholinergic and NANC responses in cat airway.

    Science.gov (United States)

    Bauer, V; Nakajima, T; Pucovsky, V; Onoue, H; Ito, Y

    2000-02-14

    To study the possible role of reactive oxygen species in airway hyperreactivity, we examined the effects of the superoxide anion radical (O(2)(-)) generating systems, pyrogallol and xanthine with xanthine oxidase, on muscle tone, excitatory and inhibitory neurotransmission in the cat airway. Smooth muscle contraction or non-adrenergic non-cholinergic (NANC) relaxation evoked by electrical field stimulation (EFS) were measured before or after O(2)(-) generating systems with or without diethydithiocarbamic acid (DEDTCA), an inhibitor of endogenous superoxide dismutase (SOD). Resting membrane potential or excitatory junction potential (EJP) were also measured in vitro. Both pyrogallol and xanthine/xanthine oxidase produced biphasic changes in basal and elevated (by 5-HT) muscle tone. After SOD pretreatment, both systems consistently produced a prolonged contraction, thereby indicating that O(2)(-) was converted to H(2)O(2) by the action of SOD and as a result the actions of O(2)(-) were lost but those of H(2)O(2) introduced. The O(2)(-) showed no significant effect on smooth muscle contraction or EJP evoked by EFS, however after DEDTCA pretreatment, it evoked initial enhancement followed by suppression of the contraction and EJP. DEDTCA pretreatment ameliorated the inhibitory action of pyrogallol and xanthine/xanthine oxidase on the NANC relaxation, probably because O(2)(-) could combine with endogenous NO to form peroxynitrite. These results indicate that the O(2)(-) generating systems have multiple actions, presumably due to the presence and simultaneous action of at least two different reactive oxygen species (O(2)(-) and H(2)O(2)). While H(2)O(2) seems to be responsible for elevation of muscle tone and augmentation of smooth muscle contraction by EFS, O(2)(-) inhibits muscle tone, cholinergic and NANC neurotransmission.

  18. T lymphocytes promote the antiviral and inflammatory responses of airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Lan Jornot

    Full Text Available HYPOTHESIS: T cells modulate the antiviral and inflammatory responses of airway epithelial cells to human rhinoviruses (HRV. METHODS: Differentiated primary human nasal epithelial cells (HNEC grown on collagen-coated filters were exposed apically to HRV14 for 6 h, washed thoroughly and co-cultured with anti-CD3/CD28 activated T cells added in the basolateral compartment for 40 h. RESULTS: HRV14 did not induce IFNγ, NOS2, CXCL8 and IL-6 in HNEC, but enhanced expression of the T cell attractant CXCL10. On the other hand, HNEC co-cultured with activated T cells produced CXCL10 at a level several orders of magnitude higher than that induced by HRV14. Albeit to a much lower degree, activated T cells also induced CXCL8, IL-6 and NOS2. Anti-IFNγ antibodies and TNF soluble receptor completely blocked CXCL10 upregulation. Furthermore, a significant correlation was observed between epithelial CXCL10 mRNA expression and the amounts of IFNγ and TNF secreted by T cells. Likewise, increasing numbers of T cells to a constant number of HNEC in co-cultures resulted in increasing epithelial CXCL10 production, attaining a plateau at high IFNγ and TNF levels. Hence, HNEC activation by T cells is induced mainly by IFNγ and/or TNF. Activated T cells also markedly inhibited viral replication in HNEC, partially through activation of the nitric oxide pathway. CONCLUSION: Cross-talk between T cells and HNEC results in activation of the latter and increases their contribution to airway inflammation and virus clearance.

  19. MicroRNA Mediated Chemokine Responses in Human Airway Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Mythili Dileepan

    Full Text Available Airway smooth muscle (ASM cells play a critical role in the pathophysiology of asthma due to their hypercontractility and their ability to proliferate and secrete inflammatory mediators. microRNAs (miRNAs are gene regulators that control many signaling pathways and thus serve as potential therapeutic alternatives for many diseases. We have previously shown that miR-708 and miR-140-3p regulate the MAPK and PI3K signaling pathways in human ASM (HASM cells following TNF-α exposure. In this study, we investigated the regulatory effect of these miRNAs on other asthma-related genes. Microarray analysis using the Illumina platform was performed with total RNA extracted from miR-708 (or control miR-transfected HASM cells. Inhibition of candidate inflammation-associated gene expression was further validated by qPCR and ELISA. The most significant biologic functions for the differentially expressed gene set included decreased inflammatory response, cytokine expression and signaling. qPCR revealed inhibition of expression of CCL11, CXCL10, CCL2 and CXCL8, while the release of CCL11 was inhibited in miR-708-transfected cells. Transfection of cells with miR-140-3p resulted in inhibition of expression of CCL11, CXCL12, CXCL10, CCL5 and CXCL8 and of TNF-α-induced CXCL12 release. In addition, expression of RARRES2, CD44 and ADAM33, genes known to contribute to the pathophysiology of asthma, were found to be inhibited in miR-708-transfected cells. These results demonstrate that miR-708 and miR-140-3p exert distinct effects on inflammation-associated gene expression and biological function of ASM cells. Targeting these miRNA networks may provide a novel therapeutic mechanism to down-regulate airway inflammation and ASM proliferation in asthma.

  20. Effect of different bronchodilators on airway smooth muscle responsiveness to contractile agents.

    Science.gov (United States)

    Gustafsson, B; Persson, C G

    1991-05-01

    "Functional antagonism" is often used to describe the general relaxant effect of beta 2 agonists and xanthines and their ability to protect the airways against bronchoconstrictor stimuli. This study in guinea pig isolated trachea addresses the question of whether the capacity of these drugs to protect against constrictor stimuli is related to smooth muscle relaxation. Three antimuscarinic drugs were also examined to determine whether antagonism of mediators other than muscarinic agonists might contribute to bronchodilatation by these antimuscarinic drugs. Terbutaline (1.1 x 10(-7), 2.2 x 10(-7) M), theophylline (2.2 x 10(-4), 4.4 x 10(-4) M), and enprofylline (5.2 x 10(-5), 1.0 x 10(-4) M) relaxed the tracheal tension that remained after indomethacin treatment. They did not, however, alter the carbachol concentration-response curve significantly. In addition, neither theophylline (2.2 x 10(-4) M) nor terbutaline (1.1 x 10(-7) M) altered histamine induced contraction. Atropine sulphate, glycopyrrolate, and ipratropium bromide had EC50 values of 10(-9) - 10(-8) M for relaxation of carbachol induced contractions, whereas concentrations of 10(-6) - 10(-3) M or greater were required to relax contractions induced by allergen and nine other non-muscarinic mediators. It is suggested that bronchodilatation by antimuscarinic drugs in vivo is due to inhibition of acetylcholine induced bronchoconstriction alone and that beta 2 agonists and xanthines have poor ability to protect airway smooth muscle against constrictor stimuli. Hence mechanisms other than bronchodilatation and "functional antagonism" should be considered to explain the protection against constrictor stimuli in asthma seen with beta 2 agonists and xanthines. PMID:2068693

  1. Exhaled nitric oxide predicts airway hyper-responsiveness to hypertonic saline in children that wheeze

    NARCIS (Netherlands)

    de Meer, G; van Amsterdam, JGC; Janssen, NAH; Meijer, E; Brunekreef, B; STEERENBERG, PA

    2005-01-01

    Background: Exhaled nitric oxide (eNO) has shown good validity for the assessment of airway inflammation in asthmatic children. In large-scale epidemiological studies, this method would be preferred above airway challenge tests, because it is a quick and easy applicable tool. Objective: In this stud

  2. A GM-CSF/IL-33 Pathway Facilitates Allergic Airway Responses to Sub-Threshold House Dust Mite Exposure

    OpenAIRE

    Alba Llop-Guevara; Chu, Derek K.; Walker, Tina D; Susanna Goncharova; Ramzi Fattouh; Silver, Jonathan S.; Cheryl Lynn Moore; Xie, Juliana L.; Paul M O'Byrne; Anthony J. Coyle; Roland Kolbeck; Humbles, Alison A.; Martin R Stämpfli; Manel Jordana

    2014-01-01

    Allergic asthma is a chronic immune-inflammatory disease of the airways. Despite aeroallergen exposure being universal, allergic asthma affects only a fraction of individuals. This is likely related, at least in part, to the extent of allergen exposure. Regarding house dust mite (HDM), we previously identified the threshold required to elicit allergic responses in BALB/c mice. Here, we investigated the impact of an initial immune perturbation on the response to sub-threshold HDM exposure. We ...

  3. Airway Smooth Muscle Growth in Asthma: Proliferation, Hypertrophy, and Migration

    OpenAIRE

    Bentley, J. Kelley; Hershenson, Marc B.

    2008-01-01

    Increased airway smooth muscle mass is present in fatal and non-fatal asthma. However, little information is available regarding the cellular mechanism (i.e., hyperplasia vs. hypertrophy). Even less information exists regarding the functional consequences of airway smooth muscle remodeling. It would appear that increased airway smooth muscle mass would tend to increase airway narrowing and airflow obstruction. However, the precise effects of increased airway smooth muscle mass on airway narro...

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

    Directory of Open Access Journals (Sweden)

    Aimi Steven

    2011-03-01

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

  5. Response of Differentiated Human Airway Epithelia to Alcohol Exposure and Klebsiella pneumoniae Challenge

    Directory of Open Access Journals (Sweden)

    Sammeta V. Raju

    2013-07-01

    Full Text Available Alcohol abuse has been associated with increased susceptibility to pulmonary infection. It is not fully defined how alcohol contributes to the host defense compromise. Here primary human airway epithelial cells were cultured at an air-liquid interface to form a differentiated and polarized epithelium. This unique culture model allowed us to closely mimic lung infection in the context of alcohol abuse by basolateral alcohol exposure and apical live bacterial challenge. Application of clinically relevant concentrations of alcohol for 24 h did not significantly alter epithelial integrity or barrier function. When apically challenged with viable Klebsiella pneumoniae, the cultured epithelia had an enhanced tightness which was unaffected by alcohol. Further, alcohol enhanced apical bacterial growth, but not bacterial binding to the cells. The cultured epithelium in the absence of any treatment or stimulation had a base-level IL-6 and IL-8 secretion. Apical bacterial challenge significantly elevated the basolateral secretion of inflammatory cytokines including IL-2, IL-4, IL-6, IL-8, IFN-γ, GM-CSF, and TNF-α. However, alcohol suppressed the observed cytokine burst in response to infection. Addition of adenosine receptor agonists negated the suppression of IL-6 and TNF-α. Thus, acute alcohol alters the epithelial cytokine response to infection, which can be partially mitigated by adenosine receptor agonists.

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

    Directory of Open Access Journals (Sweden)

    Alba Llop-Guevara

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

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

    Science.gov (United States)

    Llop-Guevara, Alba; Chu, Derek K; Walker, Tina D; Goncharova, Susanna; Fattouh, Ramzi; Silver, Jonathan S; Moore, Cheryl Lynn; Xie, Juliana L; O'Byrne, Paul M; Coyle, Anthony J; Kolbeck, Roland; Humbles, Alison A; Stämpfli, Martin R; Jordana, Manel

    2014-01-01

    Allergic asthma is a chronic immune-inflammatory disease of the airways. Despite aeroallergen exposure being universal, allergic asthma affects only a fraction of individuals. This is likely related, at least in part, to the extent of allergen exposure. Regarding house dust mite (HDM), we previously identified the threshold required to elicit allergic responses in BALB/c mice. Here, we investigated the impact of an initial immune perturbation on the response to sub-threshold HDM exposure. We show that transient GM-CSF expression in the lung facilitated robust eosinophilic inflammation, long-lasting antigen-specific Th2 responses, mucus production and airway hyperresponsiveness. This was associated with increased IL-33 levels and activated CD11b(+) DCs expressing OX40L. GM-CSF-driven allergic responses were significantly blunted in IL-33-deficient mice. IL-33 was localized on alveolar type II cells and in vitro stimulation of human epithelial cells with GM-CSF enhanced intracellular IL-33 independently of IL-1α. Likewise, GM-CSF administration in vivo resulted in increased levels of IL-33 but not IL-1α. These findings suggest that exposures to environmental agents associated with GM-CSF production, including airway infections and pollutants, may decrease the threshold of allergen responsiveness and, hence, increase the susceptibility to develop allergic asthma through a GM-CSF/IL-33/OX40L pathway. PMID:24551140

  8. Distending Pressure Did Not Activate Acute Phase or Inflammatory Responses in the Airways and Lungs of Fetal, Preterm Lambs.

    Directory of Open Access Journals (Sweden)

    Rebecca Y Petersen

    Full Text Available Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP is being increasingly used clinically to transition preterm infants at birth.To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs.The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF, bronchoalveolar lavage fluid (BAL, right mainstem bronchi and peripheral lung tissue were evaluated for inflammation.Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used.Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep.

  9. Airway inflammatory response to ozone in subjects with different asthma severity

    Energy Technology Data Exchange (ETDEWEB)

    Vagaggini, B.; Carnevali, S.; Macchioni, P. [Univ. of Pisa, Cardio-Thoracic Dept., Respiratory patho-physiology (IT)] (and others)

    1999-07-01

    The aim of this study was to evaluate whether ozone exposure induces a similar airway inflammatory response in subjects with different degrees of asthma severity. Two groups of asthmatic subjects were studied: seven with intermittent mild asthma not requiring regular treatment (group A); and seven with persistent mild asthma requiring regular treatment with inhaled corticosteroids and long-acting {beta}{sub 2}-agonists (group B). All subjects were exposed, in a randomized cross-over design, to air or O{sub 3} (0.26 parts per million (ppm) for 2 h with intermittent exercise); subjects in group B withdrew from regular treatment 72 h before each exposure. Before the exposure, and 1 and 2 h after the beginning of the exposure they performed a pulmonary function test, and a questionnaire was completed to obtain a total symptom score (TSS). Six hours after the end of the exposure, hypertonic saline (HS) sputum induction was conducted. Sputum cell percentages, eosinophil cationic protein (ECP) and interleukin (IL)-8 concentrations in the sputum supernatant were measured. TSS significantly increased and forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) significantly decreased after O{sub 3} exposure in comparison with air exposure in group A, whereas no changes were observed in group B except for a significant decrement of FEV1 2 h after the beginning of O{sub 3} exposure. Sputum neutrophil percentage was significantly higher after O{sub 3} exposure than after air exposure in both groups (Group A: 70.2% (28-87) versus 26.6% (8.6-73.2); Group B: 62.1% (25-82.4) versus 27.9% (14.4-54)). IL-8 was higher in sputum supernatant collected 6 h after O{sub 3} exposure than after air, only in group A. No change due to O{sub 3} has been found in sputum eosinophil percentage and ECP concentration in both groups. In conclusion, the degree of airway response to a short-term exposure to ozone is different in subjects with asthma of different severity. The

  10. Comparative study of hemodynamic responses to orotracheal intubation with intubating laryngeal mask airway and direct laryngoscope

    Institute of Scientific and Technical Information of China (English)

    ZHANG Guo-hua; XUE Fu-shan; SUN Hai-yan; LI Cheng-wen; SUN Hai-tao; LI Ping; LIU Kun-peng

    2006-01-01

    Background Intubating laryngeal mask airway (ILMA) offers a new approach for orotracheal intubation and is expected to produce less cardiovascular stress responses. However, the available studies provide inconsistent results. The purpose of this study was to identify whether there is a clinically relevant difference in hemodynamic responses to orotracheal intubation by using ILMA and direct laryngoscope (DLS).Methods A total of 53 adult patients, ASA physical status Ⅰ-Ⅱ, scheduled for elective plastic surgery under general anesthesia requiring the orotracheal intubation, were randomly allocated to either DLS or ILMA groups.After a standard intravenous anesthesia induction, orotracheal intubation was performed. Noninvasive blood pressure and heart rate were recorded before (baseline values) and after anesthesia induction (post-induction values), at intubation and every minute for the first 5 minutes after intubation. The data were analyzed using Chisquare test, paired and unpaired Student's t test, and repeated-measures analysis of variance as appropriate.Results The mean intubation time in the ILMA group was longer than that in the DLS group (P<0.05). The blood pressure and heart rate increased significantly after intubation in the two groups compared to the postinduction values (P<0.05), but the maximum value of blood pressure during the observation did not exceed the baseline value, while the maximum value of heart rate was higher than the baseline (P<0.05). During the observation, there were no significant differences in blood pressure and heart rate among each time point and in the maximum values between the two groups.Conclusions Orotracheal intubations by using ILMA and DLS produce similar hemodynamic response. ILMA has no advantage in attenuating the hemodynamic responses to orotracheal intubation compared with DLS.

  11. Conquering the difficult airway.

    Science.gov (United States)

    Gandy, William E

    2008-01-01

    Every medic should practice regularly for the inevitable difficult airway case. Practice should include review of the causes of difficult airways, as well as skill practice. Having a preassembled airway kit can make your response to an unexpected difficult situation easier. Of all the devices mentioned, the bougie is the airway practitioner's best friend. Using the BURP technique, if not contraindicated, together with the bougie will enable you to intubate many difficult patients with confidence. Remember, "If your patient cannot breathe, nothing else matters. PMID:18251307

  12. Differential Inflammatory Response to Inhaled Lipopolysaccharide Targeted Either to the Airways or the Alveoli in Man

    OpenAIRE

    Möller, Winfried; Heimbeck, Irene; Hofer, Thomas P J; Khadem Saba, Gülnaz; Neiswirth, Margot; Frankenberger, Marion; Ziegler-Heitbrock, Löms

    2012-01-01

    Endotoxin (Lipopolysaccharide, LPS) is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alveoli to targeted LPS inhalation in order to understand the role of LPS challenge in airway disease. In healthy volunteers without any bronchial hyperresponsiveness we targeted sequentially 1, 5 and...

  13. The Pentax airway scope versus the Macintosh laryngoscope: Comparison of hemodynamic responses and concentrations of plasma norepinephrine to tracheal intubation

    OpenAIRE

    Lee, Heeseung

    2013-01-01

    Background The Pentax Airway Scope (AWS) is a video laryngoscope designed to facilitate tracheal intubation with a high-resolution image. The Pentax AWS has been reported to cause less hemodynamic stress than the Macintosh laryngoscope. The aims of this study are to investigate the differences in hemodynamic responses and norepinephrine concentrations to tracheal intubation between procedures using he Pentax AWS and the Macintosh laryngoscope. Methods Forty patients (American Society of Anest...

  14. Role of CO2 responsiveness and breathing efficiency in determining exercise capacity of patients with chronic airway obstruction.

    Science.gov (United States)

    Chonan, T; Hida, W; Kikuchi, Y; Shindoh, C; Takishima, T

    1988-12-01

    We examined the role of CO2 responsiveness and breathing efficiency in limiting exercise capacity in 15 patients with chronic airway obstruction (FEV1 = 0.88 +/- 0.25 L, mean +/- SD). Responses of minute ventilation and P0.1 (mouth pressure 0.1 s after the onset of occluded inspiration) to hypercapnia (delta VE/delta PCO2, delta P0.1/delta PCO2) were measured by rebreathing, and the ratio of the two (delta VE/delta P0.1) was defined as an index of breathing efficiency during hyperventilation. Exercise capacity was measured as symptom-limited, maximal oxygen consumption (VO2max/BW) in an incremental treadmill test and also as the 12-min walking distance (TMD). All patients discontinued the treadmill test because of dyspnea, and the exercise capacity correlated with the degree of airway obstruction, although there was a wide variability among patients with comparable FEV1. There were no significant correlations between the responses to CO2 and exercise capacity. However, there was a significant correlation between delta VE/delta P0.1 and VO2max/BW (r = 0.87, p less than 0.001) or TMD (r = 0.78, p less than 0.001), and these correlations remained significant even when the relational effects of FEV1 were taken out. These results support the hypothesis that airway obstruction and breathing efficiency are important, but that CO2 responsiveness is not a major factor in determining the exercise capacity of patients with chronic airway obstruction.

  15. Nonadrenergic, noncholinergic responses stabilize smooth muscle tone, with and without parasympathetic activation, in guinea-pig isolated airways.

    Science.gov (United States)

    Lindén, A; Löfdahl, C G; Ullman, A; Skoogh, B E

    1993-03-01

    In guinea-pig isolated airways, nonadrenergic, noncholinergic (NANC) neural responses converge towards a similar level of smooth muscle tone, via a contraction when the tone is low prior to stimulation, and via a relaxation when the tone is high prior to stimulation. We wanted to assess the effect of simultaneous parasympathetic activation on these converging NANC responses, with and without the addition of sympathetic activation. In guinea-pig isolated airways, the spontaneous airway tone was initially abolished by indomethacin (10 microM). In one series, adrenergic depletion by guanethidine (10 microM) was then established, with and without cholinergic blockade by atropine (1 microM). In another series, either cholinergic blockade by atropine (1 microM) or no blockade was utilized. Responses to electrical field stimulation (1,200 mA, 0.5 ms, 3 Hz for 240 s) were studied with no induced tone, at a moderate (0.3 microM) and at a near-maximum (6 microM), histamine-induced tone. The mean level of the tonus equilibrium (% of maximum tone) was higher with the simultaneous NANC and parasympathetic activation than with NANC activation alone (75% compared with 44%, in the main bronchus, n = 8). The level of the tonus equilibrium was also higher with the simultaneous NANC, sympathetic and parasympathetic activation than with NANC and sympathetic activation only (49% compared with 21%, in the main bronchus, n = 8). The pattern was similar in the distal trachea. In conclusion, NANC neural responses can stabilize smooth muscle tone, and this stabilizing effect can be modulated by both parasympathetic and sympathetic activation, in guinea-pig isolated airways. PMID:8472834

  16. Regulation of cyclooxygenase-2 expression by cAMP response element and mRNA stability in a human airway epithelial cell line exposed to zinc

    Science.gov (United States)

    Exposure to zinc-laden particulate matter in ambient and occupational settings has been associated with proinflammatory responses in the lung. Cyclooxygenase 2-derived eicosanoids are important modulators of airway inflammation. In this study, we characterized the transcriptional...

  17. Effect of montelukast combined with procaterol treatment on airway remodeling and inflammatory response in children with mycoplasma pneumonia

    Institute of Scientific and Technical Information of China (English)

    Jian-Mei Zhang; Fen-Xia Zhang; Yan Jia; Min Wang; Jue Bai

    2016-01-01

    Objective:To study the effect of montelukast combined with procaterol treatment on airway remodeling and inflammatory response in children with mycoplasma pneumonia.Methods:A total of 60 mycoplasma pneumonia children with acute asthma attack treated in our hospital were selected and randomly divided into two groups, observation group received conventional anti-infection, cough-relieving and sputum-reducing combined with montelukast and procaterol spasmolysis and asthma-relieving treatment, control group received conventional anti-infection, cough-relieving and sputum-reducing combined with procaterol spasmolysis and asthma-relieving treatment, and then the degree of airway remodeling and inflammatory response was compared between two groups.Results:Serum MCP-4, MDC and CysLTs levels of both groups 1 week after treatment were significantly lower than those before treatment and serum MCP-4, MDC and CysLTs levels of observation group after treatment were lower than those of control group; 1 week after treatment, LD and the proportion of Treg in induced sputum of observation group were significantly higher than those of control group, WT, WA%, PEF25, PEF50 and PEF75 as well as FN1 and Col-1 levels and the proportion of Th17 in induced sputum were significantly lower than those of control group, and FVC, PEF and FEV1 were not different from those of control group.Conclusions:Montelukast combined with procaterol treatment can significantly improve the airway remodeling and inflammatory response in mycoplasma pneumonia children with acute asthma attack.

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

    Directory of Open Access Journals (Sweden)

    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

  19. 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...

  20. Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium

    International Nuclear Information System (INIS)

    Highlights: ► Cadmium induces secretion of IL-6 and IL-8 by two distinct pathways. ► Cadmium increases NAPDH oxidase activity leading to Erk activation and IL-8 secretion. ► Curcumin prevents cadmium-induced secretion of both IL-6 and IL-8 by airway cells. ► Curcumin could be use to suppress lung inflammation due to cadmium inhalation. -- Abstract: Cadmium is a toxic metal present in the environment and its inhalation can lead to pulmonary disease such as lung cancer and chronic obstructive pulmonary disease. These lung diseases are characterized by chronic inflammation. Here we show that exposure of human airway epithelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal pro-inflammatory cytokines known to play an important role in pulmonary inflammation. We also determined that two distinct pathways controlled secretion of these proinflammatory cytokines by human airway epithelial cells as cadmium-induced IL-6 secretion occurs via an NF-κB dependent pathway, whereas IL-8 secretion involves the Erk1/2 signaling pathway. Interestingly, the natural antioxidant curcumin could prevent both cadmium-induced IL-6 and IL-8 secretion by human airway epithelial cells. In conclusion, curcumin could be used to prevent airway inflammation due to cadmium inhalation.

  1. Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Rennolds, Jessica; Malireddy, Smitha; Hassan, Fatemat; Tridandapani, Susheela; Parinandi, Narasimham [Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH 43210 (United States); Boyaka, Prosper N. [Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210 (United States); Cormet-Boyaka, Estelle, E-mail: Estelle.boyaka@osumc.edu [Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH 43210 (United States)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Cadmium induces secretion of IL-6 and IL-8 by two distinct pathways. Black-Right-Pointing-Pointer Cadmium increases NAPDH oxidase activity leading to Erk activation and IL-8 secretion. Black-Right-Pointing-Pointer Curcumin prevents cadmium-induced secretion of both IL-6 and IL-8 by airway cells. Black-Right-Pointing-Pointer Curcumin could be use to suppress lung inflammation due to cadmium inhalation. -- Abstract: Cadmium is a toxic metal present in the environment and its inhalation can lead to pulmonary disease such as lung cancer and chronic obstructive pulmonary disease. These lung diseases are characterized by chronic inflammation. Here we show that exposure of human airway epithelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal pro-inflammatory cytokines known to play an important role in pulmonary inflammation. We also determined that two distinct pathways controlled secretion of these proinflammatory cytokines by human airway epithelial cells as cadmium-induced IL-6 secretion occurs via an NF-{kappa}B dependent pathway, whereas IL-8 secretion involves the Erk1/2 signaling pathway. Interestingly, the natural antioxidant curcumin could prevent both cadmium-induced IL-6 and IL-8 secretion by human airway epithelial cells. In conclusion, curcumin could be used to prevent airway inflammation due to cadmium inhalation.

  2. Using optical coherence tomography (OCT) imaging in the evaluation of airway dynamics (Conference Presentation)

    Science.gov (United States)

    Szabari, Margit V.; Kelly, Vanessa J.; Applegate, Matthew B.; Chee, Chunmin; Tan, Khay M.; Hariri, Lida P.; Harris, R. Scott; Winkler, Tilo; Suter, Melissa J.

    2016-03-01

    Asthma is a chronic disease resulting in periodic attacks of coughing and wheezing due to temporarily constricted and clogged airways. The pathophysiology of asthma and the process of airway narrowing are not completely understood. Appropriate in vivo imaging modality with sufficient spatial and temporal resolution to dynamically assess the behavior of airways is missing. Optical coherence tomography (OCT) enables real-time evaluation of the airways during dynamic and static breathing maneuvers. Our aim was to visualize the structure and function of airways in healthy and Methacholine (MCh) challenged lung. Sheep (n=3) were anesthetized, mechanically ventilated and imaged with OCT in 4 dependent and 4 independent airways both pre- and post-MCh administration. The OCT system employed a 2.4 Fr (0.8 mm diameter) catheter and acquired circumferential cross-sectional images in excess of 100 frames per second during dynamic tidal breathing, 20 second static breath-holds at end-inspiration and expiration pressure, and in a response to a single deep inhalation. Markedly different airway behavior was found in dependent versus non-dependent airway segments before and after MCh injection. OCT is a non-ionizing light-based imaging modality, which may provide valuable insight into the complex dynamic behavior of airway structure and function in the normal and asthmatic lung.

  3. The effect of prolonged exposure to NO{sub 2} from birth on airways responsiveness in rabbits sensitized at birth

    Energy Technology Data Exchange (ETDEWEB)

    Douglas, G.J.; Page, C.P. [University of London, Dept. of Pharmacology, King`s College, London (United Kingdom); Price, J.F. [King`s college Hospital, Dept. of Thoracic Medicine, London (United Kingdom)

    1995-02-01

    Our aim was to determine whether daily exposure to 4 ppm nitrogen dioxide (NO{sub 2}) from birth until 3 months of age influenced the development of airways hyperresponsiveness and atopic sensitivity in immunized rabbits. Littermate New Zealand White (NZW) rabbits were immunized within 24 h of birth by i.p. injection of house dust mite antigen in Al(OH){sub 3} gel, and exposed to either ambient air or 4 ppm NO{sub 2} for 2 h-day{sup -1}, 5 days-week{sup -1}. At 3 months, bronchoalveolar lavage (BAL) and serum samples were obtained. Airways responsiveness was measured as the provocative concentrations (mg{sup .}ml{sup -1}) of histamine or methacholine required to elicit a 50% increase in airway resistance (RLPC50) and a 35% decrease in dynamic compliance (CdynPC35). There were no differences in total cell or differential cell counts recovered in BAL fluid between control and NO{sub 2} exposed animals. Airways responsiveness did not differ between groups of animals (histamine RLPC50 values: air (n{sub 1}5) versus NO{sub 2} (n=13), respectively, 9.98{+-}1.32 versus 16.43{+-}1.45 mg{sup .}ml{sup -1}; CdynPC35 values: 16.60{+-}1.44 versus 14.95{+-}1.43 mg{sup .}ml{sup -1}; methacololine RLPC50 values: air (n=14) versus NO{sub 2} (n=12), respectively, 2.18{sup +}-{sup 1}.51 versus 2.21{+-}1.32 mg{sup .}ml{sup -1}; CdynPC35 values: 2.64{+-}1.41 versus 2.85{+-}1.31 mg{sup .}ml{sup -1}). There was no difference in sensitization between groups of animals exposed to air or NO{sub 2}, evaluated either by cutaneous responsiveness to intradermal antigen, or serum immunoglobulin E (IgE) levels assessed by the passive cutaneous anaphylaxis (PCA) reaction. We conclude that daily inalhation of 4ppm NO{sub 2} during the first three months of life does not affect airways responsiveness and atopic status of rabbits sensitized at birth. The lack of influence of NO{sub 2} in this model may be related to the i.p. route of immunization. (au) (36 refs.)

  4. Noninvasive assessment of pulmonary vascular and airway response to physiologic stimuli with high-resolution CT

    International Nuclear Information System (INIS)

    This paper reports on reactivity of pulmonary vasculature under various stimuli studied invasively with perfused isolated lung models. We used high- resolution CT (HRCT) to demonstrate noninvasively the effects of hypoxia and volume variation on pulmonary circulation and airways. Five anesthetized and ventilated pigs were examined with HRCT (10 contiguous 2-mm sections through the lower lobes) during varying oxygen tensions and intravascular volume states. Blood pressures, pulmonary artery pressures, blood gas levels, and cardiac indexes (thermodilution) were measured. HRCT scans were digitized, and vessel and airway areas were determined with use of a computer edging process

  5. Airway hyperresponsiveness; smooth muscle as the principal actor [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Anne-Marie Lauzon

    2016-03-01

    Full Text Available Airway hyperresponsiveness (AHR is a defining characteristic of asthma that refers to the capacity of the airways to undergo exaggerated narrowing in response to stimuli that do not result in comparable degrees of airway narrowing in healthy subjects. Airway smooth muscle (ASM contraction mediates airway narrowing, but it remains uncertain as to whether the smooth muscle is intrinsically altered in asthmatic subjects or is responding abnormally as a result of the milieu in which it sits. ASM in the trachea or major bronchi does not differ in its contractile characteristics in asthmatics, but the more pertinent peripheral airways await complete exploration. The mass of ASM is increased in many but not all asthmatics and therefore cannot be a unifying hypothesis for AHR, although when increased in mass it may contribute to AHR. The inability of a deep breath to reverse or prevent bronchial narrowing in asthma may reflect an intrinsic difference in the mechanisms that lead to softening of contracted ASM when subjected to stretch. Cytokines such as interleukin-13 and tumor necrosis factor-α promote a more contractile ASM phenotype. The composition and increased stiffness of the matrix in which ASM is embedded promotes a more proliferative and pro-inflammatory ASM phenotype, but the expected dedifferentiation and loss of contractility have not been shown. Airway epithelium may drive ASM proliferation and/or molecular remodeling in ways that may lead to AHR. In conclusion, AHR is likely multifactorial in origin, reflecting the plasticity of ASM properties in the inflammatory environment of the asthmatic airway.

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

    OpenAIRE

    Kim Seung-Hyung; Kim Bok-Kyu; Lee Young-Cheol

    2012-01-01

    Abstract Background Allergic asthma is a chronic inflammatory lung disease that is characterized by airway hyperresponsiveness (AHR) to allergens, airway oedema, increased mucus secretion, excess production of T helper-2 (Th2) cytokines, and eosinophil accumulation in the lungs. Corni fructus (CF) is a fruit of Cornus officinalis Sieb. Et. Zucc. (Cornaceae) and has been used in traditional Korean medicine as an anti-inflammatory, analgesic, and diuretic agent. To investigate the anti-asthmati...

  7. Flow cytometry of sputum: assessing inflammation and immune response elements in the bronchial airways**

    Science.gov (United States)

    Rationale: The evaluation of sputum leukocytes by flow cytometry is an opportunity to assess characteristics of cells residing in the central airways, yet it is hampered by certain inherent properties of sputum including mucus and large amounts of contaminating cells and debris. ...

  8. A RANDOMIZED CLINICAL TRIAL OF COMPARISON OF PRESSOR RESPONSE DURING AND AFTER TRACHIAL EXTUBATION AND LMA (LARYNGEAL MASK AIRWAY REMOVAL IN CONTROLLED HYPERTENSIVE PATIENTS

    Directory of Open Access Journals (Sweden)

    Srinivas Rao

    2015-10-01

    Full Text Available BACKGROUND : The primary goal of an anaesthesiologist is to maintain a patent airway during general anaesthesia. Endotracheal intubation is considered as gold standard for securing an unobstructed airway. Endotracheal intubation and extubation cause reflex cardiovascul ar responses due to mechanical stimulation of the upper respiratory tract. Several methods have been used for attenuating these cardiovascular responses. Each method or drug that is used for attenuating these pressor responses has its own associated sequel ae or disadvantages. Most certain method of avoiding adrenergic responses would be to avoid both laryngoscopy and endotracheal intubation. Use of laryngeal mask airway has also shown lesser haemodynamic response as no laryngoscopy is required for its place ment. AIM : To compare the haemodynamic responses associated with laryngeal mask airway removal and endotracheal extubation in controlled hypertensive patients undergoing elective surgical procedures. DESIGN : A prospective randomized comparative study. METH ODS : The study was conducted in eighty - controlled hypertensive patients in the age group 35 - 65 years belongs to ASA grade 1&2 scheduled for elective surgical procedure. Patients were allocated in a randomized manner by the envelop method, into two groups o ne undergoing endotracheal tube intubation (Group T and other group undergoing laryngeal mask airway insertion (Group L. At the end of the procedure. Endotracheal extubation and laryngeal mask airway removal was carried out when patient was completely co nscious and responded to verbal commands. Pulse rate and blood pressure were recorded for the study at the following intervals; A. Pre induction., B. Just before extubation or laryngeal mask removal (Baseline value, C. 1, 2, 3, 5 and 10 minutes after e xtubation., Rate pressure product and mean arterial pressure at those intervals were calculated. RESULTS : After airway instrumentation, in patients of group T, mean

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

    Directory of Open Access Journals (Sweden)

    Kim Seung-Hyung

    2012-03-01

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

  10. Basophil-associated OX40 Ligand Participates in the Initiation of Th2 Responses during Airway Inflammation*

    Science.gov (United States)

    Di, Caixia; Lin, Xiaoliang; Zhang, Yanjie; Zhong, Wenwei; Yuan, Yufan; Zhou, Tong; Liu, Junling; Xia, Zhenwei

    2015-01-01

    Asthma is characterized by increased airway submucosal infiltration of T helper (Th) cells and myeloid cells that co-conspire to sustain a chronic inflammation. While recent studies have demonstrated that the myeloid basophils promote Th2 cells in response to various types of allergens, the underlying mechanisms are poorly understood. Here, we found for the first time that in a mouse model of allergic asthma basophils highly expressed OX40 ligand (OX40L) after activation. Interestingly, blockade of OX40-OX40L interaction suppressed basophils-primed Th2 cell differentiation in vitro and ameliorated ovalbumin (OVA)-induced allergic eosinophilic inflammation mediated by Th2 activation. In accordance, the adoptive transfer of basophils derived from mediastinal lymph nodes (MLN) of OVA-immunized mice triggered a robust Th2 response and eosinophilic inflammation in wild-type mice but largely muted in OX40−/− mice and mice receiving OX40L-blocked basophils. Taken together, our results reveal a critical role of OX40L presented by the activated basophils to initiate Th2 responses in an allergic asthma model, implicating OX40-OX40L signaling as a potential therapeutic target in the treatment of allergic airway inflammation. PMID:25839234

  11. Basophil-associated OX40 ligand participates in the initiation of Th2 responses during airway inflammation.

    Science.gov (United States)

    Di, Caixia; Lin, Xiaoliang; Zhang, Yanjie; Zhong, Wenwei; Yuan, Yufan; Zhou, Tong; Liu, Junling; Xia, Zhenwei

    2015-05-15

    Asthma is characterized by increased airway submucosal infiltration of T helper (Th) cells and myeloid cells that co-conspire to sustain a chronic inflammation. While recent studies have demonstrated that the myeloid basophils promote Th2 cells in response to various types of allergens, the underlying mechanisms are poorly understood. Here, we found for the first time that in a mouse model of allergic asthma basophils highly expressed OX40 ligand (OX40L) after activation. Interestingly, blockade of OX40-OX40L interaction suppressed basophils-primed Th2 cell differentiation in vitro and ameliorated ovalbumin (OVA)-induced allergic eosinophilic inflammation mediated by Th2 activation. In accordance, the adoptive transfer of basophils derived from mediastinal lymph nodes (MLN) of OVA-immunized mice triggered a robust Th2 response and eosinophilic inflammation in wild-type mice but largely muted in OX40(-/-) mice and mice receiving OX40L-blocked basophils. Taken together, our results reveal a critical role of OX40L presented by the activated basophils to initiate Th2 responses in an allergic asthma model, implicating OX40-OX40L signaling as a potential therapeutic target in the treatment of allergic airway inflammation. PMID:25839234

  12. Mycoplasma ovipneumoniae induces inflammatory response in sheep airway epithelial cells via a MyD88-dependent TLR signaling pathway.

    Science.gov (United States)

    Xue, Di; Ma, Yan; Li, Min; Li, Yanan; Luo, Haixia; Liu, Xiaoming; Wang, Yujiong

    2015-01-15

    Mycoplasma ovipneumoniae (M. ovipneumoniae) is a bacterium that specifically infects sheep and goat and causes ovine infectious pleuropneumonia. In an effort to understand the pathogen-host interaction between the M. ovipneumoniae and airway epithelial cells, we investigated the host inflammatory response using a primary air-liquid interface (ALI) epithelial culture model generated from bronchial epithelial cells of Ningxia Tan sheep (Ovis aries). The ALI culture of sheep bronchial epithelial cells showed a fully differentiated epithelium comprising distinct epithelial types, including the basal, ciliated and goblet cells. Exposure of ALI cultures to M. ovipneumoniae led to increased expression of Toll-like receptors (TLRs), and components of the myeloid differentiation factor 88 (MyD88)-dependent TLR signaling pathway, including the MyD88, TNF receptor-associated factor 6 (TRAF6), IL-1 receptor-associated kinases (IRAKs) and nuclear factor-kappa B (NF-κB), as well as subsequent pro-inflammatory cytokines in the epithelial cells. Of interest, infection with M. ovipneumoniae failed to induce the expression of TANK-binding kinase 1 (TBK1), TRAF3 and interferon regulatory factor 3 (IRF3), key components of the MyD88-independent signaling pathway. These results suggest that the MyD88-dependent TLR pathway may play a crucial role in sheep airway epithelial cells in response to M. ovipneumoniae infection, which also indicate that the ALI culture system may be a reliable model for investigating pathogen-host interactions between M. ovipneumoniae and airway epithelial cells.

  13. Airway and Extracellular Matrix Mechanics in COPD

    OpenAIRE

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

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases worldwide, and is characterized by airflow obstruction that is not fully reversible with treatment. Even though airflow obstruction is caused by airway smooth muscle contraction, the extent of airway narrowing depends on a range of other structural and functional determinants that impact on active and passive tissue mechanics. Cells and extracellular matrix in the airway and parenchymal compartments respond b...

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

    Science.gov (United States)

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

    2006-06-01

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

  15. Airway responsiveness to leukotriene C4 (LTC4), leukotriene E4 (LTE4) and histamine in aspirin-sensitive asthmatic subjects.

    Science.gov (United States)

    Christie, P E; Schmitz-Schumann, M; Spur, B W; Lee, T H

    1993-11-01

    We wanted to determine whether the airway response to inhaled leukotriene C4 (LTC4) is similar to inhaled leukotriene E4 (LTE4) in aspirin-sensitive asthma and, therefore, determined airway responsiveness to histamine, LTC4 and LTE4 in seven aspirin-sensitive subjects and 13 control asthmatic subjects, who were tolerant of aspirin. The concentration of inhaled lysine-aspirin which produced a 15% fall in forced expiratory volume in one second (FEV1) (PC15) was determined in aspirin-sensitive asthmatic subjects. The dose of histamine, LTC4 and LTE4 which produced a 35% fall in specific airways conductance (PD35sGaw) was determined by linear interpolation from the log dose response curve. There was no correlation between the PC15 for lysine-aspirin and the airway reactivity to inhaled LTC4 or LTE4. There was no difference in airway response to histamine and LTC4 between any of the groups of asthmatic subjects. There was a rank order of potency LTC4 > LTE4 > histamine in both groups, with LTC4 approximately 1,000 fold more potent than histamine in both groups. Aspirin-sensitive asthmatic subjects were significantly more responsive to LTE4 (p = 0.02) than aspirin-tolerant asthmatic subjects. The relative responsiveness of LTE4 to histamine (PD35 histamine/PD35 LTE4) was significantly greater in aspirin-sensitive asthmatic subjects compared to aspirin-tolerant asthmatic subjects (p = 0.05). There was no difference in relative responsiveness of LTC4 to histamine between aspirin-sensitive or aspirin-tolerant asthmatic subjects. We conclude that the airways of aspirin-sensitive asthmatic subjects demonstrate a selective hyperresponsiveness to LTE4, which is not observed for LTC4. PMID:8112440

  16. Activation of tumor necrosis factor receptor 1 in airway smooth muscle: a potential pathway that modulates bronchial hyper-responsiveness in asthma?

    Directory of Open Access Journals (Sweden)

    Panettieri Reynold A

    2000-07-01

    Full Text Available Abstract The cellular and molecular mechanisms that are involved in airway hyper-responsiveness are unclear. Current studies suggest that tumor necrosis factor (TNF-α, a cytokine that is produced in considerable quantities in asthmatic airways, may potentially be involved in the development of bronchial hyper-responsiveness by directly altering the contractile properties of the airway smooth muscle (ASM. The underlying mechanisms are not known, but growing evidence now suggests that most of the biologic effects of TNF-α on ASM are mediated by the p55 receptor or tumor necrosis factor receptor (TNFR1. In addition, activation of TNFR1 coupled to the tumor necrosis factor receptor-associated factor (TRAF2-nuclear factor-κB (NF-κB pathway alters calcium homeostasis in ASM, which appears to be a new potential mechanism underlying ASM hyper-responsiveness.

  17. Comparison of hemodynamic and metabolic stress responses caused by endotracheal tube and Proseal laryngeal mask airway in laparoscopic cholecystectomy

    Directory of Open Access Journals (Sweden)

    Handan Güleç

    2012-01-01

    Full Text Available Background: We aimed to compare hemodynamic and endocrine alterations caused by stress response due to Proseal laryngeal mask airway and endotracheal tube usage in laparoscopic cholecystectomy. Materials and Methods: Sixty-three ASA I-II patients scheduled for elective laparoscopic cholecystectomy were included in the study. Patients were randomly allocated into two groups of endotracheal tube and Proseal laryngeal mask airway. Standard general anaesthesia was performed in both groups with the same drugs in induction and maintenance of anaesthesia. After anaesthesia induction and 20 minutes after CO 2 insufflations, venous blood samples were obtained for measuring adrenalin, noradrenalin, dopamine and cortisol levels. Hemodynamic and respiratory parameters were recorded at the 1 st , 5 th , 15 th , 30 th and 45 th minutes after the insertion of airway devices. Results: No statistically significant differences in age, body mass index, gender, ASA physical status, and operation time were found between the groups (p > 0.05. Changes in hemodynamic and respiratory parameters were not statistically significant when compared between and within groups (p > 0.05. Although no statistically significant differences were observed between and within groups when adrenalin, noradrenalin and dopamine values were compared, serum cortisol levels after CO 2 insufflation in PLMA group were significantly lower than the ETT group (p = 0.024. When serum cortisol levels were compared within groups, cortisol levels 20 minutes after CO 2 insufflation were significantly higher (46.1 (9.5-175.7 and 27.0 (8.3-119.4 in the ETT and PLMA groups, respectively than cortisol levels after anaesthesia induction (11.3 (2.8-92.5 and 16.6 (4.4-45.4 in the ETT and PLMA groups, respectively in both groups (p = 0.001. Conclusion: PLMA usage is a suitable, effective and safe alternative to ETT in laparoscopic cholecystectomy patients with lower metabolic stress.

  18. Nonlinear Optical Response of Disordered J Aggregates in the Motional Narrowing Limit

    NARCIS (Netherlands)

    Knoester, Jasper

    1995-01-01

    We discuss the theory of nonlinear optical response of molecular aggregates with frequency disorder. In contrast to the usual modeling, we allow for spatial correlations in the disorder. We show that the joint distribution of all multi-exciton frequencies can be determined analytically to first orde

  19. Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation

    OpenAIRE

    LAMBRECHT, Bart; Veerman, M De; Coyle, Anthony; Gutierrez-Ramos, J C; Thielemans, Kris; Pauwels, R. A.

    2000-01-01

    textabstractThe aim of this study was to investigate whether dendritic cells (DCs) can induce sensitization to aeroallergen in a mouse model of allergic asthma. Ovalbumin-pulsed (OVA-pulsed) or unpulsed myeloid DCs that were injected into the airways of naive mice migrated into the mediastinal lymph nodes. When challenged 2 weeks later with an aerosol of OVA, activated CD4 and CD8 lymphocytes, eosinophils, and neutrophils were recruited to the lungs of actively immunized mice. These CD4(+) ly...

  20. Low-frequency ionospheric sounding with Narrow Bipolar Event lightning radio emissions: regular variabilities and solar-X-ray responses

    Directory of Open Access Journals (Sweden)

    A. R. Jacobson

    2007-11-01

    Full Text Available We present refinements of a method of ionospheric D-region sounding that makes opportunistic use of powerful (109–1011 W broadband lightning radio emissions in the low-frequency (LF; 30–300 kHz band. Such emissions are from "Narrow Bipolar Event" (NBE lightning, and they are characterized by a narrow (10-μs, simple emission waveform. These pulses can be used to perform time-delay reflectometry (or "sounding" of the D-region underside, at an effective LF radiated power exceeding by orders-of-magnitude that from man-made sounders. We use this opportunistic sounder to retrieve instantaneous LF ionospheric-reflection height whenever a suitable lightning radio pulse from a located NBE is recorded. We show how to correct for three sources of "regular" variability, namely solar zenith angle, radio-propagation range, and radio-propagation azimuth. The residual median magnitude of the noise in reflection height, after applying the regression corrections for the three regular variabilities, is on the order of 1 km. This noise level allows us to retrieve the D-region-reflector-height variation with solar X-ray flux density for intensity levels at and above an M-1 flare. The instantaneous time response is limited by the occurrence rate of NBEs, and the noise level in the height determination is typically in the range ±1 km.

  1. Relationship between airway responsiveness to mannitol and to methacholine and markers of airway inflammation, peak flow variability and quality of life in asthma patients

    DEFF Research Database (Denmark)

    Porsbjerg, C.; Brannan, J.D.; Anderson, S.D.;

    2008-01-01

    -three adult non-smoking asthmatics (28 females, 18-56 years) who were not taking inhaled steroids were challenged with mannitol (up to 635 mg) and methacholine (up to 8 mu mol). Induced sputum eosinophils, exhaled nitric oxide (eNO), peak flow variation and clinical severity of asthma according to the Global...... AHR to mannitol, and in 88% of asthma patients with AHR to methacholine, the eNO level was > 20 p.p.b. Sputum% eosinophils >1% was measured in 70% of asthma patients with AHR to mannitol and in 77% of asthma patients with AHR to methacholine. In asthma patients without AHR, 15% had an eNO level >20p......Background Airway hyperresponsiveness (AHR) to stimuli that cause bronchial smooth muscle (BSM) contraction indirectly through the release of endogenous mediators is thought to reflect air-way inflammation more closely compared with AHR measured by stimuli that act directly on BSM. Methods Fifty...

  2. Eosinophilic airway inflammation in COPD

    OpenAIRE

    Saha, Shironjit; Brightling, Christopher E.

    2006-01-01

    Chronic obstructive pulmonary disease is a common condition and a major cause of mortality. COPD is characterized by irreversible airflow obstruction. The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation. The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages. Although eosinophilic airway inflammation is usually considered a f...

  3. Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP and CCL11/eotaxin-1 in human asthmatic airways.

    Directory of Open Access Journals (Sweden)

    Gustavo Nino

    Full Text Available BACKGROUND: Thymic stromal lymphoproetin (TSLP is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. METHODS: Primary human bronchial epithelial cells (HBEC from control (n = 3 and asthmatic (n = 3 donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI conditions and treated apically with dsRNA (viral surrogate or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC from normal (n = 3 and asthmatic (n = 3 donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20 vs. non-asthmatic uninfected controls (n = 20. Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay. RESULTS: Our data demonstrate that: 1 Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2 TSLP exposure induces unidirectional (apical secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3 Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1. CONCLUSIONS: There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

  4. S-nitrosothiols regulate cell-surface pH buffering by airway epithelial cells during the human immune response to rhinovirus.

    Science.gov (United States)

    Carraro, Silvia; Doherty, Joseph; Zaman, Khalequz; Gainov, Iain; Turner, Ronald; Vaughan, John; Hunt, John F; Márquez, Javier; Gaston, Benjamin

    2006-05-01

    Human rhinovirus infection is a common trigger for asthma exacerbations. Asthma exacerbations and rhinovirus infections are both associated with markedly decreased pH and ammonium levels in exhaled breath condensates. This observation is thought to be related, in part, to decreased activity of airway epithelial glutaminase. We studied whether direct rhinovirus infection and/or the host immune response to the infection decreased airway epithelial cell surface pH in vitro. Interferon-gamma and tumor necrosis factor-alpha, but not direct rhinovirus infection, decreased pH, an effect partly associated with decreased ammonium concentrations. This effect was 1) prevented by nitric oxide synthase inhibition; 2) independent of cyclic GMP; 3) associated with an increase in endogenous airway epithelial cell S-nitrosothiol concentration; 4) mimicked by the exogenous S-nitrosothiol, S-nitroso-N-acetyl cysteine; and 5) independent of glutaminase expression and activity. We then confirmed that decreased epithelial pH inhibits human rhinovirus replication in airway epithelial cells. These data suggest that a nitric oxide synthase-dependent host response to viral infection mediated by S-nitrosothiols, rather than direct infection itself, plays a role in decreased airway surface pH during human rhinovirus infection. This host immune response may serve to protect the lower airways from direct infection in the normal host. In patients with asthma, however, this fall in pH could be associated with the increased mucus production, augmented inflammatory cell degranulation, bronchoconstriction, and cough characteristic of an asthma exacerbation. PMID:16603595

  5. Cigarette smoke extracts promote vascular smooth muscle cell proliferation and enhances contractile responses in the vasculature and airway

    DEFF Research Database (Denmark)

    Xu, Cang-Bao; Lei, Ying; Chen, Qingwen;

    2010-01-01

    Cigarette smoke exposure is a strong risk factor for cardiovascular and respiratory diseases. However, the knowledge about how cigarette smoke induces damage to vasculature and airway is limited. The present study was designed to examine the effects of cigarette smoke particles extracted by heptane...... (heptane-soluble smoke particles, HSP), by water (water-soluble smoke particles, WSP) and by DMSO (DMSO-soluble smoke particles, DSP), which represent lipophilic, hydrophilic and ambiphoteric constituents from the cigarette smoke, respectively. Human aortic smooth muscle cell (HASMC) proliferation...... responses to sarafotoxin 6c, U46619 or bradykinin in rat mesenteric artery and/or in bronchi. ERK1/2 is activated by HSP and DSP in HASMCs and inhibition of ERK1/2 abrogated the smoke extracts-induced HASMC proliferation, while blockage of nicotinic receptors had no effects, suggesting that the toxic...

  6. Role of Inhaled Steroids in Vascular Airway Remodelling in Asthma and COPD

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    Alfredo Chetta

    2012-01-01

    Full Text Available In chronic obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD, changes in bronchial microvasculature are present in response to inflammatory stimuli. Vascular changes may significantly contribute to airway wall remodelling. Angiogenesis and vascular leakage are prevalent in asthma, while vasodilation and vascular leakage dominate in COPD. An endothelial dysfunction may be present both in asthma and in COPD. Vascular changes may occur simultaneously with the thickening of the airway wall and the narrowing of the bronchial lumen. Consequently, pharmacological control of bronchial vascular remodelling may be crucial for symptom control in asthma and COPD. In asthmatic airways, inhaled steroids can downregulate vascular remodelling by acting on proangiogenic factors. Additionally, studies on combination therapy with long-acting β2-agonists and inhaled steroids have provided evidence of a possible synergistic action on components of vascular remodelling in asthma. In COPD, there is less experimental evidence on the effect of inhaled steroids on airway microvascular changes. Importantly, vascular endothelial growth factor (VEGF, the most specific growth factor for vascular endothelium, is crucially involved in the pathophysiology of airway vascular remodelling, both in asthma and COPD. The inhibition of VEGF and its receptor may be useful in the treatment of the vascular changes in the airway wall.

  7. IFN-γ, IL-4 and IL-13 modulate responsiveness of human airway smooth muscle cells to IL-13

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    Michoud Marie-Claire

    2008-12-01

    Full Text Available Abstract Background IL-13 is a critical mediator of allergic asthma and associated airway hyperresponsiveness. IL-13 acts through a receptor complex comprised of IL-13Rα1 and IL-4Rα subunits with subsequent activation of signal transducer and activator of transcription 6 (STAT6. The IL-13Rα2 receptor may act as a decoy receptor. In human airway smooth muscle (HASM cells, IL-13 enhances cellular proliferation, calcium responses to agonists and induces eotaxin production. We investigated the effects of pre-treatment with IL-4, IL-13 and IFN-γ on the responses of HASM cells to IL-13. Methods Cultured HASM were examined for expression of IL-13 receptor subunits using polymerase chain reaction, immunofluorescence microscopy and flow cytometry. Effects of cytokine pre-treatment on IL-13-induced cell responses were assessed by looking at STAT6 phosphorylation using Western blot, eotaxin secretion and calcium responses to histamine. Results IL-13Rα1, IL-4Rα and IL-13Rα2 subunits were expressed on HASM cells. IL-13 induced phosphorylation of STAT6 which reached a maximum by 30 minutes. Pre-treatment with IL-4, IL-13 and, to a lesser degree, IFN-γ reduced peak STAT6 phosphorylation in response to IL-13. IL-13, but not IFN-γ, pre-treatment abrogated IL-13-induced eotaxin secretion. Pre-treatment with IL-4 or IL-13 abrogated IL-13-induced augmentation of the calcium transient evoked by histamine. Cytokine pre-treatment did not affect expression of IL-13Rα1 and IL-4Rα but increased expression of IL-13Rα2. An anti-IL-13Rα2 neutralizing antibody did not prevent the cytokine pre-treatment effects on STAT6 phosphorylation. Cytokine pre-treatment increased SOCS-1, but not SOCS-3, mRNA expression which was not associated with significant increases in protein expression. Conclusion Pre-treatment with IL-4 and IL-13, but not IFN-γ, induced desensitization of the HASM cells to IL-13 as measured by eotaxin secretion and calcium transients to histamine

  8. Airway responses and inflammation in subjects with asthma after four days of repeated high-single-dose allergen challenge

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    Schulze Johannes

    2012-09-01

    Full Text Available Abstract Background Both standard and low-dose allergen provocations are an established tool in asthma research to improve our understanding of the pathophysiological mechanism of allergic asthma. However, clinical symptoms are less likely to be induced. Therefore, we designed a protocol for repetitive high-dose bronchial allergen challenges to generate clinical symptoms and airway inflammation. Methods A total of 27 patients aged 18 to 40 years with positive skin-prick tests and mild asthma underwent repetitive high-dose allergen challenges with household dust mites for four consecutive days. Pulmonary function and exhaled NO were measured at every visit. Induced sputum was analysed before and after the allergen challenges for cell counts, ECP, IL-5, INF-γ, IL-8, and the transcription factor Foxp3. Results We found a significant decrease in pulmonary function, an increased use of salbutamol and the development of a late asthmatic response and bronchial hyperresponsiveness, as well as a significant induction of eNO, eosinophils, and Th-2 cytokines. Repeated provocation was feasible in the majority of patients. Two subjects had severe adverse events requiring prednisolone to cope with nocturnal asthma symptoms. Conclusions Repeated high-dose bronchial allergen challenges resulted in severe asthma symptoms and marked Th-2-mediated allergic airway inflammation. The high-dose challenge model is suitable only in an attenuated form in diseased volunteers for proof-of-concept studies and in clinical settings to reduce the risk of severe asthma exacerbations. Trial registration ClinicalTrials.govNCT00677209

  9. 18F-FDG Uptake Rate Is a Biomarker of Eosinophilic Inflammation and Airway Response in Asthma

    OpenAIRE

    Harris, R. Scott; Venegas, José G.; Wongviriyawong, Chanikarn; Winkler, Tilo; Kone, Mamary; Musch, Guido; Vidal Melo, Marcos F.; De Prost, Nicolas; Daniel L Hamilos; Afshar, Roshi; Cho, Josalyn; Luster, Andrew D.; Medoff, Benjamin D.

    2011-01-01

    In asthma, the relationship among airway inflammation, airway hyperresponsiveness, and lung function is poorly understood. Methods to noninvasively assess these relationships in human subjects are needed. We sought to determine whether 18F-FDG uptake rate (Ki, min−1) could serve as a biomarker of eosinophilic inflammation and local lung function.

  10. Directional Secretory Response of Double Stranded RNA-Induced Thymic Stromal Lymphopoetin (TSLP) and CCL11/Eotaxin-1 in Human Asthmatic Airways

    OpenAIRE

    Nino, Gustavo; Huseni, Shehlanoor; Perez, Geovanny F; Pancham, Krishna; Mubeen, Humaira; Abbasi, Aleeza; Wang, Justin; Eng, Stephen; Colberg-Poley, Anamaris M.; Pillai, Dinesh K; Rose, Mary C.

    2014-01-01

    Background Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. Methods Primary human bronchial epithelial cells (HBEC) from con...

  11. Mean airway pressure and response to inhaled nitric oxide in neonatal and pediatric patients.

    Science.gov (United States)

    Hoffman, George M; Nelin, Leif D

    2005-01-01

    Inhaled nitric oxide (iNO) can improve oxygenation and ventilation-perfusion (V/Q) matching by reduction of shunt (Qs/Qt) in patients with hypoxemic lung disease. Because the improvement in V/Q matching must occur by redistribution of pulmonary blood flow, and because high airway pressure (Paw) increases physiologic dead space (Vd/Vt), we hypothesized that high Paw may limit the improvement in V/Q matching during iNO treatment. iNO 0-50 ppm was administered during mechanical ventilation. Mechanical ventilator settings were at the discretion of the attending physician. Qs/Qt and Vd/Vt were derived from a tripartite lung model with correction for shunt-induced dead space. Data from 62 patients during 153 trials were analyzed for effects of Paw and iNO on Qs/Qt and Vd/Vt. Baseline Qs/Qt was slightly increased at Paw 16-23 cmH2O (p < 0.05), while Vd/Vt increased progressively with higher Paw (p < 0.002). Therapy with iNO significantly reduced Qs/Qt (p < 0.001) at all levels of mean Paw, reaching a maximum reduction at 16-23 cmH2O (p < 0.05), such that Qs/Qt during iNO treatment was similar at all levels of Paw. During iNO treatment, a reduction in Vd/Vt occurred only at Paw of 8-15 cmH2O (p < 0.05), and the positive relationship between Vd/Vt and Paw was maintained. These differential effects on Qs/Qt and Vd/Vt suggest that both high and low Paw may limit improvement in gas exchange with iNO. Analysis of gas exchange using this corrected tripartite lung model may help optimize ventilatory strategies during iNO therapy. PMID:16465603

  12. Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice.

    Science.gov (United States)

    Shieh, Ying-Hua; Huang, Huei-Mei; Wang, Ching-Chiung; Lee, Chen-Chen; Fan, Chia-Kwung; Lee, Yueh-Lun

    2015-02-01

    Zerumbone is a sesquiterpene compound isolated from the rhizome of wild ginger, Zingiber zerumbet Smith. The rhizomes of the plant are used as a spice and traditional medicine. Zerumbone was shown to possess anticarcinogenic, anti-inflammatory, and antioxidant properties. However, the antiallergic activity and the underlying mechanism of zerumbone have not been reported. Herein, we investigated the immunomodulatory effects of zerumbone on antigen-presenting dendritic cells (DCs) in vitro and its potential therapeutic effects against ovalbumin (OVA)-induced T helper 2 (Th2)-mediated asthma in mice. In the presence of zerumbone, lipopolysaccharide-activated bone marrow-derived DCs enhanced T cell proliferation and Th1 cell polarization in an allogeneic mixed lymphocyte reaction. In animal experiments, mice were sensitized and challenged with OVA, and were orally treated with different doses of zerumbone after sensitization. Circulating titers of OVA-specific antibodies, airway hyperresponsiveness to methacholine, histological changes in lung tissues, the cell composition and cytokine levels in bronchoalveolar lavage fluid, and cytokine profiles of spleen cells were assessed. Compared to OVA-induced hallmarks of asthma, oral administration of zerumbone induced lower OVA-specific immunoglobulin E (IgE) and higher IgG2a antibody production, attenuated airway hyperresponsiveness, prevented eosinophilic pulmonary infiltration, and ameliorated mucus hypersecretion. Zerumbone treatment also reduced the production of eotaxin, keratinocyte-derived chemokine (KC), interleukin (IL)-4, IL-5, IL-10, and IL-13, and promoted Th1 cytokine interferon (IFN)-γ production in asthmatic mice. Taken together, these results suggest that zerumbone exhibits an antiallergic effect via modulation of Th1/Th2 cytokines in an asthmatic mouse model. PMID:25573403

  13. 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.

  14. Effect of vascular endothelial growth factor and its receptor KDR on human airway smooth muscle cells proliferation

    Institute of Scientific and Technical Information of China (English)

    ZOU hui; XU Yong-jian; ZHANG Zhen-xiang

    2005-01-01

    @@ Airway remodeling with inflammatory cell infiltration, epithelial shedding, basement membrane thickening and increased mass of airway smooth muscle (ASM) is an important determinant of bronchial obstruction and hyperresponsiveness in asthma.1,2 Increased ASM mass is by far the most important abnormality responsible for excessive airway narrowing and compliance of the airway wall in asthma.1-3 ASM growth and proliferation in asthma is a complex phenomenon of which the underlying mechanisms are difficult to investigate in vivo. The increased amount of ASM in asthmatics is an indication of abnormal cell proliferation and growth, but little is known regarding the molecular mechanisms and factors that regulate ASM cell proliferation and growth in asthma.

  15. Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Emily F A van 't Wout

    2015-06-01

    Full Text Available Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA. Efficient functioning of the endoplasmic reticulum (ER is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded protein response" (UPR. Bacterial infection and Toll-like receptor activation trigger the UPR most likely due to the increased demand for protein folding of inflammatory mediators. In this study, we show that cell-free conditioned medium of the PAO1 strain of P. aeruginosa, containing secreted virulence factors, induces ER stress in primary bronchial epithelial cells as evidenced by splicing of XBP1 mRNA and induction of CHOP, GRP78 and GADD34 expression. Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA. Using various mutant strains and purified virulence factors, we identified pyocyanin and AprA as inducers of ER stress. However, the induction of GADD34 was mediated by an ER stress-independent integrated stress response (ISR which was at least partly dependent on the iron-sensing eIF2α kinase HRI. Our data strongly suggest that this increased GADD34 expression served to protect against Pseudomonas-induced, iron-sensitive cell cytotoxicity. In summary, virulence factors from P. aeruginosa induce ER stress in airway epithelial cells and also trigger the ISR to improve cell survival of the host.

  16. Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells.

    Science.gov (United States)

    van 't Wout, Emily F A; van Schadewijk, Annemarie; van Boxtel, Ria; Dalton, Lucy E; Clarke, Hanna J; Tommassen, Jan; Marciniak, Stefan J; Hiemstra, Pieter S

    2015-06-01

    Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA). Efficient functioning of the endoplasmic reticulum (ER) is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded protein response" (UPR). Bacterial infection and Toll-like receptor activation trigger the UPR most likely due to the increased demand for protein folding of inflammatory mediators. In this study, we show that cell-free conditioned medium of the PAO1 strain of P. aeruginosa, containing secreted virulence factors, induces ER stress in primary bronchial epithelial cells as evidenced by splicing of XBP1 mRNA and induction of CHOP, GRP78 and GADD34 expression. Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA. Using various mutant strains and purified virulence factors, we identified pyocyanin and AprA as inducers of ER stress. However, the induction of GADD34 was mediated by an ER stress-independent integrated stress response (ISR) which was at least partly dependent on the iron-sensing eIF2α kinase HRI. Our data strongly suggest that this increased GADD34 expression served to protect against Pseudomonas-induced, iron-sensitive cell cytotoxicity. In summary, virulence factors from P. aeruginosa induce ER stress in airway epithelial cells and also trigger the ISR to improve cell survival of the host. PMID:26083346

  17. Translocation of particles and inflammatory responses after exposure to fine particles and nanoparticles in an epithelial airway model

    Directory of Open Access Journals (Sweden)

    Musso Claudia

    2007-09-01

    Full Text Available Abstract Background Experimental studies provide evidence that inhaled nanoparticles may translocate over the airspace epithelium and cause increased cellular inflammation. Little is known, however, about the dependence of particle size or material on translocation characteristics, inflammatory response and intracellular localization. Results Using a triple cell co-culture model of the human airway wall composed of epithelial cells, macrophages and dendritic cells we quantified the entering of fine (1 μm and nano-sized (0.078 μm polystyrene particles by laser scanning microscopy. The number distribution of particles within the cell types was significantly different between fine and nano-sized particles suggesting different translocation characteristics. Analysis of the intracellular localization of gold (0.025 μm and titanium dioxide (0.02–0.03 μm nanoparticles by energy filtering transmission electron microscopy showed differences in intracellular localization depending on particle composition. Titanium dioxide nanoparticles were detected as single particles without membranes as well as in membrane-bound agglomerations. Gold nanoparticles were found inside the cells as free particles only. The potential of the different particle types (different sizes and different materials to induce a cellular response was determined by measurements of the tumour necrosis factor-α in the supernatants. We measured a 2–3 fold increase of tumour necrosis factor-α in the supernatants after applying 1 μm polystyrene particles, gold nanoparticles, but not with polystyrene and titanium dioxide nanoparticles. Conclusion Quantitative laser scanning microscopy provided evidence that the translocation and entering characteristics of particles are size-dependent. Energy filtering transmission electron microscopy showed that the intracellular localization of nanoparticles depends on the particle material. Both particle size and material affect the cellular

  18. Interpretation of bronchodilator response in patients with obstructive airways disease. The Dutch Chronic Non-Specific Lung Disease (CNSLD) Study Group.

    OpenAIRE

    Brand, P L; Quanjer, P. H.; Postma, D. S.; Kerstjens, H.A.; Koëter, G. H.; Dekhuijzen, P. N.; Sluiter, H J

    1992-01-01

    BACKGROUND: There is no agreement on how a bronchodilator response should be expressed. Ideally, the index used should be able to distinguish asthma from chronic obstructive lung disease and be independent of initial FEV1. METHODS: Two hundred and seventy four adults (aged 18-60 years) outpatients with obstructive airways disease were studied. Patients were divided into syndrome groups on the basis of a standardised history: asthma (n = 99), asthmatic bronchitis (n = 88), and chronic obstruct...

  19. Human rhinovirus induced cytokine/chemokine responses in human airway epithelial and immune cells.

    Directory of Open Access Journals (Sweden)

    Devi Rajan

    Full Text Available Infections with human rhinovirus (HRV are commonly associated with acute upper and lower respiratory tract disease and asthma exacerbations. The role that HRVs play in these diseases suggests it is important to understand host-specific or virus-specific factors that contribute to pathogenesis. Since species A HRVs are often associated with more serious HRV disease than species B HRVs, differences in immune responses they induce should inform disease pathogenesis. To identify species differences in induced responses, we evaluated 3 species A viruses, HRV 25, 31 and 36 and 3 species B viruses, HRV 4, 35 and 48 by exposing human PBMCs to HRV infected Calu-3 cells. To evaluate the potential effect of memory induced by previous HRV infection on study responses, we tested cord blood mononuclear cells that should be HRV naïve. There were HRV-associated increases (significant increase compared to mock-infected cells for one or more HRVs for IP-10 and IL-15 that was unaffected by addition of PBMCs, for MIP-1α, MIP-1β, IFN-α, and HGF only with addition of PBMCs, and for ENA-78 only without addition of PBMCs. All three species B HRVs induced higher levels, compared to A HRVs, of MIP-1α and MIP-1β with PBMCs and ENA-78 without PBMCs. In contrast, addition of CBMCs had less effect and did not induce MIP-1α, MIP-1β, or IFN-α nor block ENA-78 production. Addition of CBMCs did, however, increase IP-10 levels for HRV 35 and HRV 36 infection. The presence of an effect with PBMCs and no effect with CBMCs for some responses suggest differences between the two types of cells possibly because of the presence of HRV memory responses in PBMCs and not CBMCs or limited response capacity for the immature CBMCs relative to PBMCs. Thus, our results indicate that different HRV strains can induce different patterns of cytokines and chemokines; some of these differences may be due to differences in memory responses induced by past HRV infections, and other differences

  20. CT demonstration of pharyngeal narrowing in adult obstructive sleep apnea

    International Nuclear Information System (INIS)

    Sleep apnea is a major cause of daytime hypersomnolence. Among the proposed etiologies, focal obstruction of the airways at the level of the pharynx has been suggested but not proven. Using computed tomography, the cross-sectional area of the airway can be readily assessed. Thirty-three adults with clinically proven sleep apnea and 12 normal adults underwent systematic computed tomography of the neck. Significant airway narrowing was demonstrated in all the patients with obstructive sleep apnea, whereas no such narrowing was seen in the controls. In 11, the narrowing was at a single level, whereas in 22 patients two or more levels were affected. This study has shown that a structurally abnormal airway may serve as an anatomic substrate for the development of sleep apnea. On the basis of this evidence, uvulopalatopharyngoplasty has been performed in two patients with relief of symptoms in one

  1. Airway responses to eucapnic hyperpnea, exercise, and methacholine in elite swimmers

    DEFF Research Database (Denmark)

    Pedersen, Lise; Winther, S.; Backer, V.;

    2008-01-01

    Purpose: The International Olympic Committee Medical Commission (IOC-MC) requires athletes to provide the result of an objective test to support a diagnosis of asthma or exercise-induced bronchoconstriction (EIB) if they want to inhale a beta-2-agonist. The purpose of the study was to evaluate the......) test, a field-based exercise test (FBT), a laboratory-based exercise test (LBT), and a methacholine challenge. The criteria suggested by the IOC-MC were used to define a positive response to the challenges (EVH, field test, and laboratory test: minimum 10% decrease in FBT; methacholine: PD20 <= 2 mu...... cutoff for methacholine (PD20 <= 8 mu mol). Conclusions: The EVH test is the test that diagnoses most swimmers with an abnormal response to hyperpnea, but not all cases of EIB are identified with the EVH test. Performing a methacholine test using IOC-MC's cutoff value does not improve the chances of...

  2. Aerobic Exercise Attenuates Airway Inflammatory Responses in a Mouse Model of Atopic Asthma

    OpenAIRE

    Pastva, Amy; Estell, Kim; Schoeb, Trenton R.; Atkinson, T. Prescott; Schwiebert, Lisa M

    2004-01-01

    Recent reports indicate that aerobic exercise improves the overall physical fitness and health of asthmatic patients. The specific exercise-induced improvements in the pathology of asthma and the mechanisms by which these improvements occur, however, are ill-defined; thus, the therapeutic potential of exercise in the treatment of asthma remains unappreciated. Using an OVA-driven mouse model, we examined the role of aerobic exercise in modulating inflammatory responses associated with atopic a...

  3. Measures of reversibility in response to bronchodilators in chronic airflow obstruction: relation to airway calibre.

    OpenAIRE

    Weir, D C; Sherwood Burge, P

    1991-01-01

    A study was carried out to examine the independence from starting prebronchodilator FEV1 of four indices commonly used to express airflow (FEV1) reversibility in response to bronchodilators. In 121 patients with chronic airflow obstruction with a mean prebronchodilator FEV1 of 1.81 (43.9% of predicted values) the change in FEV1 expressed as a percentage of the patient's predicted FEV1 was the least dependent on starting FEV1. Reversibility, expressed as a percentage of the prebronchodilator v...

  4. Interactions between inhalant allergen extracts and airway epithelial cells : Effect on cytokine production and cell detachment

    NARCIS (Netherlands)

    Tomee, JFC; van Weissenbruch, R; de Monchy, JGR; Kauffman, HF

    1998-01-01

    Background: The factors responsible for inducing or maintaining airway inflammation are poorly understood. Various studies have focussed on the mechanisms leading to allergic airway inflammation in patients with asthma and rhinitis. The observation of local airway inflammation in nonallergic patient

  5. 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.

  6. Time- and concentration-dependent genomic responses of the rat airway to inhaled nickel subsulfide

    International Nuclear Information System (INIS)

    Objective: To provide insights into the mode of action for Ni3S2 lung carcinogenicity by examining gene expression changes in target cells after inhalation exposure. Methods: Gene expression changes were determined in micro-dissected lung broncho-alveolar cells from Fischer 344 rats following inhalation of Ni3S2 at 0.0, 0.04, 0.08, 0.15, and 0.60 mg/m3 (0.03, 0.06, 0.11, and 0.44 mg Ni/m3) for one and four weeks (6 h/day, 5 days/week). Results: Broncho-alveolar lavage fluid evaluation and lung histopathology provided evidence of inflammation only at the two highest concentrations, which were similar to those tested in the 2-year bioassay. The number of statistically significant up- and down-regulated genes decreased markedly from one to four weeks of exposure, suggesting adaptation. Cell signal pathway enrichment at both time-points primarily reflected responses to toxicity, including inflammatory and proliferative signaling. While proliferative signaling was up-regulated at both time points, some inflammatory signaling reversed from down-regulation at 1 week to up-regulation at 4 weeks. Conclusions: These results support a mode of action for Ni3S2 carcinogenicity driven by chronic toxicity, inflammation and proliferation, leading to mis-replication, rather than by direct genotoxicity. Benchmark dose (BMD) analysis identified the lowest pathway transcriptional BMD exposure concentration as 0.026 mg Ni/m3, for apoptosis/survival signaling. When conducted on the basis of lung Ni concentration the lowest pathway BMD was 0.64 μg Ni/g lung, for immune/inflammatory signaling. Implications: These highly conservative BMDs could be used to derive a point of departure in a nonlinear risk assessment for Ni3S2 toxicity and carcinogenicity. - Highlights: • The mode of action for lung carcinogenicity of inhaled Ni3S2 was investigated in rats. • Gene expression changes were determined in micro-dissected lung tissue at 1–4 weeks. • A non-genotoxic mode of action (toxicity

  7. Bronchial responsiveness to adenosine 5 '-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV

    NARCIS (Netherlands)

    De Meer, G; Heederik, D; Postma, DS

    2002-01-01

    Bronchial hyperresponsiveness (BHR) and inflammation are central hallmarks of asthma. Studies in patients with asthma suggest that BHR to adenosine 5'-monophosphate (AMP) is a better marker of bronchial inflammation than BHR to methacholine. The association between markers of airway inflammation and

  8. Children developing asthma by school-age display aberrant immune responses to pathogenic airway bacteria as infants

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura; Pedersen, Susanne Brix; Thysen, Anna Hammerich;

    2014-01-01

    Asthma is a highly prevalent chronic lung disease that commonly originates in early childhood. Colonisation of neonatal airways with the pathogenic bacterial strains H. influenzae, M. catarrhalis and S. pneumoniae is associated with increased risk of later childhood asthma. We hypothesized that c...

  9. Glucocorticosteroids and beta(2)-Adrenoceptor Agonists Synergize to Inhibit Airway Smooth Muscle Remodeling

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Pehlic, Adnan; Mariani, Raissa; Bos, I. Sophie T.; Meurs, Herman; Zaagsma, Johan

    2012-01-01

    Airway remodeling, including increased airway smooth muscle (ASM) mass and contractility, contributes to increased airway narrowing in asthma. Increased ASM mass may be caused by exposure to mitogens, including platelet-derived growth factor (PDGF) and collagen type I, which induce a proliferative,

  10. Resonance response of a single-degree-of-freedom nonlinear vibro-impact system to a narrow-band random parametric excitation

    Institute of Scientific and Technical Information of China (English)

    Su Min-Bang; Rong Hai-Wu

    2011-01-01

    The resonant response of a single-degree-of-freedom nonlinear vibro-impact oscillator with a one-sided barrier to a narrow-band random parametric excitation is investigated. The narrow-band random excitation used here is a bounded random noise. The analysis is based on a special Zhuravlev transformation, which reduces the system to one without impacts, thereby permitting the applications of random averaging over "fast" variables. The averaged equations are solved exactly and an algebraic equation of the amplitude of the response is obtained for the case without random disorder. The methods of linearization and moment are used to obtain the formula of the mean-square amplitude approximately for the case with random disorder. The effects of damping, detuning, restitution factor, nonlinear intensity, frequency and magnitude of random excitations are analysed. The theoretical analyses are verified by numerical results. Theoretical analyses and numerical simulations show that the peak response amplitudes will reduce at large damping or large nonlinear intensity and will increase with large amplitude or frequency of the random excitations. The phenomenon of stochastic jump is observed, that is, the steady-state response of the system will jump from a trivial solution to a large non-trivial one when the amplitude of the random excitation exceeds some threshold value,or will jump from a large non-trivial solution to a trivial one when the intensity of the random disorder of the random excitation exceeds some threshold value.

  11. Picornavirus-Induced Airway Mucosa Immune Profile in Asymptomatic Neonates

    DEFF Research Database (Denmark)

    Wolsk, Helene M.; Følsgaard, Nilofar V.; Birch, Sune;

    2016-01-01

    Bacterial airway colonization is known to alter the airway mucosa immune response in neonates whereas the impact of viruses is unknown. The objective was therefore to examine the effect of respiratory viruses on the immune signature in the airways of asymptomatic neonates. Nasal aspirates from 571......-regulating effect. Asymptomatic presence of picornavirus in the neonatal airway is a potent activator of the topical immune response. This is relevant to understanding the immune potentiating effect of early life exposure to viruses....

  12. Studies of human airways in vitro: A review of the methodology

    OpenAIRE

    Hulsmann, Anthon; de Jongste, Johan

    1993-01-01

    textabstractThe pathophysiology of human airway narrowing is only partly understood. In order to gain more insight in the mechanisms of human lung diseases and potential beneficial therapeutic agents, adequate models are needed. Animal airway models are of limited value since lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are unique to humans and because the mechanisms of airway narrowing differ between species. Therefore, it is important to perform studies on h...

  13. Mainstream cigarette smoke exposure attenuates airway immune inflammatory responses to surrogate and common environmental allergens in mice, despite evidence of increased systemic sensitization.

    Science.gov (United States)

    Robbins, Clinton S; Pouladi, Mahmoud A; Fattouh, Ramzi; Dawe, David E; Vujicic, Neda; Richards, Carl D; Jordana, Manel; Inman, Mark D; Stampfli, Martin R

    2005-09-01

    The purpose of this study was to investigate the impact of mainstream cigarette smoke exposure (MTS) on allergic sensitization and the development of allergic inflammatory processes. Using two different experimental murine models of allergic airways inflammation, we present evidence that MTS increased cytokine production by splenocytes in response to OVA and ragweed challenge. Paradoxically, MTS exposure resulted in an overall attenuation of the immune inflammatory response, including a dramatic reduction in the number of eosinophils and activated (CD69+) and Th2-associated (T1ST2+) CD4 T lymphocytes in the lung. Although MTS did not impact circulating levels of OVA-specific IgE and IgG1, we observed a striking reduction in OVA-specific IgG2a production and significantly diminished airway hyperresponsiveness. MTS, therefore, plays a disparate role in the development of allergic responses, inducing a heightened state of allergen-specific sensitization, but dampening local immune inflammatory processes in the lung. PMID:16116169

  14. Airway responses and inflammation in subjects with asthma after four days of repeated high-single-dose allergen challenge

    OpenAIRE

    Schulze Johannes; Voss Sandra; Zissler Ulrich; Rose Markus A; Zielen Stefan; Schubert Ralf

    2012-01-01

    Abstract Background Both standard and low-dose allergen provocations are an established tool in asthma research to improve our understanding of the pathophysiological mechanism of allergic asthma. However, clinical symptoms are less likely to be induced. Therefore, we designed a protocol for repetitive high-dose bronchial allergen challenges to generate clinical symptoms and airway inflammation. Methods A total of 27 patients aged 18 to 40 years with positive skin-prick tests and mild asthma ...

  15. Airway management in trauma

    Directory of Open Access Journals (Sweden)

    Rashid M Khan

    2011-01-01

    Full Text Available Trauma has assumed epidemic proportion. 10% of global road accident deaths occur in India. Hypoxia and airway mismanagement are known to contribute up to 34% of pre-hospital deaths in these patients. A high degree of suspicion for actual or impending airway obstruction should be assumed in all trauma patients. Objective signs of airway compromise include agitation, obtundation, cyanosis, abnormal breath sound and deviated trachea. If time permits, one should carry out a brief airway assessment prior to undertaking definitive airway management in these patients. Simple techniques for establishing and maintaining airway patency include jaw thrust maneuver and/or use of oro- and nas-opharyngeal airways. All attempts must be made to perform definitive airway management whenever airway is compromised that is not amenable to simple strategies. The selection of airway device and route- oral or -nasal, for tracheal intubation should be based on nature of patient injury, experience and skill level.

  16. IFNβ/TNFα synergism induces a non-canonical STAT2/IRF9-dependent pathway triggering a novel DUOX2 NADPH Oxidase-mediated airway antiviral response

    Institute of Scientific and Technical Information of China (English)

    Karin Fink; Lydie Martin; Esperance Mukawera; Stéfany Chartier; Xavier De Deken; Emmanuelle Brochiero; Fran(c)oise Miot

    2013-01-01

    Airway epithelial cells are key initial innate immune responders in the fight against respiratory viruses,primarily via the secretion of antiviral and proinflammatory cytokines that act in an autocrine/paracrine fashion to trigger the establishment of an antiviral state.It is currently thought that the early antiviral state in airway epithelial cells primarily relies on IFNβ secretion and the subsequent activation of the interferon-stimulated gene factor 3 (ISGF3) transcription factor complex,composed of STAT1,STAT2 and IRF9,which regulates the expression of a panoply of interferon-stimulated genes encoding proteins with antiviral activities.However,the specific pathways engaged by the synergistic action of different cytokines during viral infections,and the resulting physiological outcomes are still ill-defined.Here,we unveil a novel delayed antiviral response in the airways,which is initiated by the synergistic autocrine/paracrine action of IFNβ and TNFα,and signals through a non-canonical STAT2-and IRF9-dependent,but STAT1-independent cascade.This pathway ultimately leads to the late induction of the DUOX2 NADPH oxidase expression.Importantly,our study uncovers that the development of the antiviral state relies on DUOX2-dependent H2O2 production.Key antiviral pathways are often targeted by evasion strategies evolved by various pathogenic viruses.In this regard,the importance of the novel DUOX2-dependent antiviral pathway is further underlined by the observation that the human respiratory syncytial virus is able to subvert DUOX2 induction.

  17. Research on airway inflammation: present status in Mainland China

    Institute of Scientific and Technical Information of China (English)

    WANG Zeng-li

    2005-01-01

    @@ Airway inflammation involving activated eosinophils, mast cells and T lymphocytes is an established feature of asthma and has been the key target to treatment. Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling.

  18. Straight but Not Narrow; Within-Gender Variation in the Gender-Specificity of Women’s Sexual Response

    Science.gov (United States)

    Chivers, Meredith L.; Bouchard, Katrina N.; Timmers, Amanda D.

    2015-01-01

    Gender differences in the specificity of sexual response have been a primary focus in sexual psychophysiology research, however, within-gender variability suggests sexual orientation moderates category-specific responding among women; only heterosexual women show gender-nonspecific genital responses to sexual stimuli depicting men and women. But heterosexually-identified or “straight” women are heterogeneous in their sexual attractions and include women who are exclusively androphilic (sexually attracted to men) and women who are predominantly androphilic with concurrent gynephilia (sexually attracted to women). It is therefore unclear if gender-nonspecific responding is found in both exclusively and predominantly androphilic women. The current studies investigated within-gender variability in the gender-specificity of women’s sexual response. Two samples of women reporting concurrent andro/gynephilia viewed (Study 1, n = 29) or listened (Study 2, n = 30) to erotic stimuli varying by gender of sexual partner depicted while their genital and subjective sexual responses were assessed. Data were combined with larger datasets of predominantly gyne- and androphilic women (total N = 78 for both studies). In both studies, women reporting any degree of gynephilia, including those who self-identified as heterosexual, showed significantly greater genital response to female stimuli, similar to predominantly gynephilic women; gender-nonspecific genital response was observed for exclusively androphilic women only. Subjective sexual arousal patterns were more variable with respect to sexual attractions, likely reflecting stimulus intensity effects. Heterosexually-identified women are therefore not a homogenous group with respect to sexual responses to gender cues. Implications for within-gender variation in women’s sexual orientation and sexual responses are discussed. PMID:26629910

  19. Airway vascular damage in elite swimmers.

    Science.gov (United States)

    Moreira, André; Palmares, Carmo; Lopes, Cristina; Delgado, Luís

    2011-11-01

    We postulated that high level swimming can promote airway inflammation and thus asthma by enhancing local vascular permeability. We aimed to test this hypothesis by a cross-sectional study comparing swimmers (n = 13, 17 ± 3 years, competing 7 ± 4 years, training 18 ± 3 h per week), asthmatic-swimmers (n = 6, 17 ± 2 years, competing 8 ± 3 years, training 16 ± 4 h per week), and asthmatics (n = 19, 14 ± 3 years). Subjects performed induced sputum and had exhaled nitric oxide, lung volumes, and airway responsiveness determined. Airway vascular permeability index was defined as the ratio of albumin in sputum and serum. Results from the multiple linear regression showed each unit change in airway vascular permeability index was associated with an increase of 0.97% (95%CI: 0.02 to 1.92; p = 0.047) in sputum eosinophilis, and of 2.64% (95%CI:0.96 to 4.31; p = 0.006) in sputum neutrophils after adjustment for confounders. In a general linear model no significant differences between airway vascular permeability between index study groups existed, after controlling for sputum eosinophilis and neutrophils. In conclusion, competitive swimmers training in chlorine-rich pools have similar levels of airway vascular permeability than asthmatics. Although competitive swimming has been associated with asthma, airway inflammation and airway hyperesponsiveness do not seem to be dependent on increased airway vascular permeability. PMID:21669516

  20. Extra-cellular matrix proteins induce matrix metalloproteinase-1 (MMP-1 activity and increase airway smooth muscle contraction in asthma.

    Directory of Open Access Journals (Sweden)

    Natasha K Rogers

    Full Text Available Airway remodelling describes the histopathological changes leading to fixed airway obstruction in patients with asthma and includes extra-cellular matrix (ECM deposition. Matrix metalloproteinase-1 (MMP-1 is present in remodelled airways but its relationship with ECM proteins and the resulting functional consequences are unknown. We used airway smooth muscle cells (ASM and bronchial biopsies from control donors and patients with asthma to examine the regulation of MMP-1 by ECM in ASM cells and the effect of MMP-1 on ASM contraction. Collagen-I and tenascin-C induced MMP-1 protein expression, which for tenascin-C, was greater in asthma derived ASM cells. Tenascin-C induced MMP-1 expression was dependent on ERK1/2, JNK and p38 MAPK activation and attenuated by function blocking antibodies against the β1 and β3 integrin subunits. Tenascin-C and MMP-1 were not expressed in normal airways but co-localised in the ASM bundles and reticular basement membrane of patients with asthma. Further, ECM from asthma derived ASM cells stimulated MMP-1 expression to a greater degree than ECM from normal ASM. Bradykinin induced contraction of ASM cells seeded in 3D collagen gels was reduced by the MMP inhibitor ilomastat and by siRNA knockdown of MMP-1. In summary, the induction of MMP-1 in ASM cells by tenascin-C occurs in part via integrin mediated MAPK signalling. MMP-1 and tenascin-C are co-localised in the smooth muscle bundles of patients with asthma where this interaction may contribute to enhanced airway contraction. Our findings suggest that ECM changes in airway remodelling via MMP-1 could contribute to an environment promoting greater airway narrowing in response to broncho-constrictor stimuli and worsening asthma symptoms.

  1. Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells

    OpenAIRE

    Deborah H Strickland; Stumbles, Philip A.; Zosky, Graeme R.; Subrata, Lily S.; Thomas, Jenny A.; Turner, Debra J.; Sly, Peter D.; Holt, Patrick G.

    2006-01-01

    An important feature of atopic asthma is the T cell–driven late phase reaction involving transient bronchoconstriction followed by development of airways hyperresponsiveness (AHR). Using a unique rat asthma model we recently showed that the onset and duration of the aeroallergen-induced airway mucosal T cell activation response in sensitized rats is determined by the kinetics of functional maturation of resident airway mucosal dendritic cells (AMDCs) mediated by cognate interactions with CD4+...

  2. (Airway response to short-term inhalation of NO2, O3 and their mixture in healthy men (author's transl))

    Energy Technology Data Exchange (ETDEWEB)

    Toyama, T.; Tsunoda, T.; Nakaza, M.; Higashi, T.; Nakadate, T.

    1981-05-01

    One hour inhalation of 0.7 ppm (1.32 mg/m3) of nitrogen dioxide (NO2), 0.7 ppm (1.4 mg/m3) of ozone (O3), and their mixture, 0.5 ppm (0.9 mg/m3) of NO2 and 0.5 ppm (1.0 mg/m3) of O3, and sham inhalation were conducted in five healthy male volunteers through mouth breathing using a multipurpose inhalation apparatus. Airway response was measured by specific airway conductance (Gaw/Vtg) and maximum expiratory flow rate at 50 and 25 percent forced vital capacity (Vmax50, Vmax25). Evaluations by analysis of variance revealed: no significant effect of inhalation of NO2 alone, slight significant transient decrease of Vmax50 in inhalation of O3 along (0.1 greater than p greater than 0.05), and slight reversible decrease of Gaw/Vtg and Vmax50 in inhalation of NO2 and O3 in combination (0.1 greater than p greater than 0.05). As their variations were within the range of normal diurnal change, these results were considered to be non-adverse effects.

  3. 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

    2013-01-01

    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 remai

  4. Pharmacogenetics, pharmacogenomics and airway disease

    Directory of Open Access Journals (Sweden)

    Hall Ian P

    2001-11-01

    Full Text Available Abstract The availability of a draft sequence for the human genome will revolutionise research into airway disease. This review deals with two of the most important areas impinging on the treatment of patients: pharmacogenetics and pharmacogenomics. Considerable inter-individual variation exists at the DNA level in targets for medication, and variability in response to treatment may, in part, be determined by this genetic variation. Increased knowledge about the human genome might also permit the identification of novel therapeutic targets by expression profiling at the RNA (genomics or protein (proteomics level. This review describes recent advances in pharmacogenetics and pharmacogenomics with regard to airway disease.

  5. 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...

  6. AA Narrow Quadrupole

    CERN Multimedia

    1979-01-01

    The very particular lattice of the AA required 2 types of quadrupoles: narrow ones (QFN, QDN) and wide ones (QFW, QDW). This is the first one of the narrow quadrupoles, delivered by industry early in 1979.

  7. Near-infrared response photovoltaic device based on novel narrow band gap small molecule and PCBM fabricated by solution processing

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Mingliang; Wang, Li; Zhu, Xuhui; Du, Bin; Liu, Ransheng; Yang, Wei; Cao, Yong [Institute of Polymer Optoelectronic Materials and Devices, South China University of Technology, Key Lab of Specially Functional Materials, Ministry of Education, Wushan Road, Guangzhou 510640 (China)

    2007-11-06

    In this paper, we report on synthesis of a novel diphenylaminofluorenyl-capped thiadiazoloquinoxaline (6,7-dimethyl-4,9-di{l_brace}5-[9,9-bis(octyl)-7-diphenylaminofluorene-2-yl]-4-hexylthien-2-yl{r_brace}[1,2,5]-thiadiazolo[3,4-g]quinoxaline (DPAFL-TDOX-DPAFL which is further abbreviated to TDOX), Scheme 1) and its use as donor material for the realization of efficient bulk-heterojunction organic solar cell by spin coating from blend with PCBM as acceptor. TDOX showed very good solution processibility and film uniformity up to weight ratio TDOX:PCBM=1:4. Spectral response was extended to near-infrared region (at around 1000 nm) with energy conversion efficiency (ECE) 0.75% and short-curcuit current density 1.95 mA/cm{sup 2}. (author)

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

    Directory of Open Access Journals (Sweden)

    O'Connor George T

    2011-07-01

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

  9. Experimental determination of the lateral dose response functions of detectors to be applied in the measurement of narrow photon-beam dose profiles

    Science.gov (United States)

    Poppinga, D.; Meyners, J.; Delfs, B.; Muru, A.; Harder, D.; Poppe, B.; Looe, HK

    2015-12-01

    This study aims at the experimental determination of the detector-specific 1D lateral dose response function K(x) and of its associated rotational symmetric counterpart K(r) for a set of high-resolution detectors presently used in narrow-beam photon dosimetry. A combination of slit-beam, radiochromic film, and deconvolution techniques served to accomplish this task for four detectors with diameters of their sensitive volumes ranging from 1 to 2.2 mm. The particular aim of the experiment was to examine the existence of significant negative portions of some of these response functions predicted by a recent Monte-Carlo-simulation (Looe et al 2015 Phys. Med. Biol. 60 6585-607). In a 6 MV photon slit beam formed by the Siemens Artiste collimation system and a 0.5 mm wide slit between 10 cm thick lead blocks serving as the tertiary collimator, the true cross-beam dose profile D(x) at 3 cm depth in a large water phantom was measured with radiochromic film EBT3, and the detector-affected cross-beam signal profiles M(x) were recorded with a silicon diode, a synthetic diamond detector, a miniaturized scintillation detector, and a small ionization chamber. For each detector, the deconvolution of the convolution integral M(x)  =  K(x)  ∗  D(x) served to obtain its specific 1D lateral dose response function K(x), and K(r) was calculated from it. Fourier transformations and back transformations were performed using function approximations by weighted sums of Gaussian functions and their analytical transformation. The 1D lateral dose response functions K(x) of the four types of detectors and their associated rotational symmetric counterparts K(r) were obtained. Significant negative curve portions of K(x) and K(r) were observed in the case of the silicon diode and the diamond detector, confirming the Monte-Carlo-based prediction (Looe et al 2015 Phys. Med. Biol. 60 6585-607). They are typical for the perturbation of the secondary electron field by a detector with

  10. Experimental determination of the lateral dose response functions of detectors to be applied in the measurement of narrow photon-beam dose profiles

    International Nuclear Information System (INIS)

    This study aims at the experimental determination of the detector-specific 1D lateral dose response function K(x) and of its associated rotational symmetric counterpart K(r) for a set of high-resolution detectors presently used in narrow-beam photon dosimetry. A combination of slit-beam, radiochromic film, and deconvolution techniques served to accomplish this task for four detectors with diameters of their sensitive volumes ranging from 1 to 2.2 mm. The particular aim of the experiment was to examine the existence of significant negative portions of some of these response functions predicted by a recent Monte-Carlo-simulation (Looe et al 2015 Phys. Med. Biol. 60 6585–607).In a 6 MV photon slit beam formed by the Siemens Artiste collimation system and a 0.5 mm wide slit between 10 cm thick lead blocks serving as the tertiary collimator, the true cross-beam dose profile D(x) at 3 cm depth in a large water phantom was measured with radiochromic film EBT3, and the detector-affected cross-beam signal profiles M(x) were recorded with a silicon diode, a synthetic diamond detector, a miniaturized scintillation detector, and a small ionization chamber. For each detector, the deconvolution of the convolution integral M(x)  =  K(x)  ∗  D(x) served to obtain its specific 1D lateral dose response function K(x), and K(r) was calculated from it. Fourier transformations and back transformations were performed using function approximations by weighted sums of Gaussian functions and their analytical transformation.The 1D lateral dose response functions K(x) of the four types of detectors and their associated rotational symmetric counterparts K(r) were obtained. Significant negative curve portions of K(x) and K(r) were observed in the case of the silicon diode and the diamond detector, confirming the Monte-Carlo-based prediction (Looe et al 2015 Phys. Med. Biol. 60 6585–607). They are typical for the perturbation of the secondary electron field by a detector

  11. [Modern airway management--current concepts for more patient safety].

    Science.gov (United States)

    Timmermann, Arnd

    2009-04-01

    Effective and safe airway management is one of the core skills among anaesthesiologists and all physicians involved in acute care medicine. However, failure in airway management is still the most frequent single incidence with the highest impact on patient's morbidity and mortality known from closed claims analyses. The anaesthesiologist has to manage the airway in elective patients providing a high level of safety with as little airway injury and interference with the cardio-vascular system as possible. Clinical competence also includes the management of the expected and unexpected difficult airway in different clinical environments. Therefore, it is the anaesthesiologist's responsibility not only to educate and train younger residents, but also all kinds of medical personnel involved in airway management, e.g. emergency physicians, intensive care therapists or paramedics. Modern airway devices, strategies and educational considerations must fulfill these sometimes diverse and large range requirements. Supraglottic airway devices will be used more often in the daily clinical routine. This is not only due the multiple advantages of these devices compared to the tracheal tube, but also because of the new features of some supraglottic airways, which separate the airway from the gastric track and give information of the pharyngeal position. For the event of a difficult airway, new airway devices and concepts should be trained and applied in daily practice.

  12. Quantitative computed tomography imaging of airway remodeling in severe asthma.

    Science.gov (United States)

    Grenier, Philippe A; Fetita, Catalin I; Brillet, Pierre-Yves

    2016-02-01

    Asthma is a heterogeneous condition and approximately 5-10% of asthmatic subjects have severe disease associated with structure changes of the airways (airway remodeling) that may develop over time or shortly after onset of disease. Quantitative computed tomography (QCT) imaging of the tracheobronchial tree and lung parenchyma has improved during the last 10 years, and has enabled investigators to study the large airway architecture in detail and assess indirectly the small airway structure. In severe asthmatics, morphologic changes in large airways, quantitatively assessed using 2D-3D airway registration and recent algorithms, are characterized by airway wall thickening, luminal narrowing and bronchial stenoses. Extent of expiratory gas trapping, quantitatively assessed using lung densitometry, may be used to assess indirectly small airway remodeling. Investigators have used these quantitative imaging techniques in order to attempt severity grading of asthma, and to identify clusters of asthmatic patients that differ in morphologic and functional characteristics. Although standardization of image analysis procedures needs to be improved, the identification of remodeling pattern in various phenotypes of severe asthma and the ability to relate airway structures to important clinical outcomes should help target treatment more effectively. PMID:26981458

  13. Supreme 喉罩与普通型喉罩对侧卧位老年手术患者气道管理和血流动力学的影响%Effects of Laryngeal Mask Airway Supreme and Laryngeal Mask Airway Classic on Airway Management and Hemodynamic Response in Elderly Patients Undergoing Surgery in Lateral Decubitus Position

    Institute of Scientific and Technical Information of China (English)

    张芳; 戴寒英; 戴祺; 雷恩骏

    2016-01-01

    ABSTRACT:Objective To study the effects of laryngeal mask airway(LMA)Supreme and LMA Classic on airway management and hemodynamic response in elderly patients undergoing surgery in lateral decubitus position.Methods Sixty patients scheduled for elective surgery were divided into two groups,with 30 patients in each group.After anesthesia induction,LMA Supreme and LMA Classic insertion were performed in group S and group C,respectively.Intravenous propofol infusion and sevoflurane inhalation were used to maintain the bispectral index(BIS)between 50 and 60.The catheterization time,success rate of LMA insertion,peak airway pressure(Ppeak), end-tidal carbon dioxide partial pressure(PET CO2 ),oropharyngeal leak pressure(OLP),mean arte-rial blood pressure(MAP),heart rate(HR),and incidence of postoperative adverse events(nause-a,vomiting,sore throat,hoarseness)were recorded in both groups.Results Compared with LMA Classic,LMA Supreme shortened catheterization time((23.29±6.52)s vs (32.81±7.36)s),re-duced intraoperative Ppeak in lateral decubitus position,and increased OLP in both lateral decubi-tus and supine position(P < 0.05).Conclusion LMA Supreme can shorten the catheterization time,improve the success rate of LMA insertion and achieve a high airway sealing pressure. Therefore,LMA Supreme is a safer and more effective airway management device than LMA Classic in elderly patients undergoing surgery in lateral decubitus position.%目的:探讨一次性双管喉罩(Supreme 喉罩)与普通型喉罩对侧卧位老年手术患者气道管理和血流动力学的影响。方法将60例择期手术患者按使用不同的喉罩分为 Supreme 喉罩(S)组和普通型喉罩(C)组,每组30例。2组均行麻醉诱导。麻醉诱导后,S 组置入 Supreme 喉罩,C 组置入普通型喉罩,2组均经静脉泵泵注丙泊酚注射液及吸入七氟醚维持麻醉,维持脑电双频指数值50~60。观察2组置管时间、置入喉罩成功率,术中

  14. Heme oxygenase-1 exerts a protective role in ovalbumin-induced neutrophilic airway inflammation by inhibiting Th17 cell-mediated immune response.

    Science.gov (United States)

    Zhang, Yanjie; Zhang, Liya; Wu, Jinhong; Di, Caixia; Xia, Zhenwei

    2013-11-29

    Allergic asthma is conventionally considered as a Th2 immune response characterized by eosinophilic inflammation. Recent investigations revealed that Th17 cells play an important role in the pathogenesis of non-eosinophilic asthma (NEA), resulting in steroid-resistant neutrophilic airway inflammation. Heme oxygenase-1 (HO-1) has anti-inflammation, anti-oxidation, and anti-apoptosis functions. However, its role in NEA is still unclear. Here, we explore the role of HO-1 in a mouse model of NEA. HO-1 inducer hemin or HO-1 inhibitor tin protoporphyrin IX was injected intraperitoneally into ovalbumin-challenged DO11.10 mice. Small interfering RNA (siRNA) was delivered into mice to knock down HO-1 expression. The results show that induction of HO-1 by hemin attenuated airway inflammation and decreased neutrophil infiltration in bronchial alveolar lavage fluid and was accompanied by a lower proportion of Th17 cells in mediastinal lymph nodes and spleen. More importantly, induction of HO-1 down-regulated Th17-related transcription factor retinoic acid-related orphan receptor γt (RORγt) expression and decreased IL-17A levels, all of which correlated with a decrease in phosphorylated STAT3 (p-STAT3) level and inhibition of Th17 cell differentiation. Consistently, the above events could be reversed by tin protoporphyrin IX. Also, HO-1 siRNA transfection abolished the effect of hemin induced HO-1 in vivo. Meanwhile, the hemin treatment promoted the level of Foxp3 expression and enhanced the proportion of regulatory T cells (Tregs). Collectively, our findings indicate that HO-1 exhibits anti-inflammatory activity in the mouse model of NEA via inhibition of the p-STAT3-RORγt pathway, regulating kinetics of RORγt and Foxp3 expression, thus providing a possible novel therapeutic target in asthmatic patients. PMID:24097973

  15. Effects of all-trans retinoic acid on airway responsiveness and airway remodeling in rats with asthma%全反视黄酸对哮喘大鼠气道反应性和气道重塑的影响

    Institute of Scientific and Technical Information of China (English)

    李文开; 李云; 钟礼立

    2011-01-01

    目的 观察全反视黄酸(ATRA)对哮喘大鼠气道反应性、气道重塑和肺组织基质金属蛋白酶-9(MMP-9)表达的影响,方法:40只大鼠随机分为5组,每组8只:盐水组、模型组、ATRA组、棉籽油组和布地奈德(BUD)组.后4组经卵清蛋白(OVA)致敏14 d后激发6周,构建大鼠慢性哮喘模型.ATRA组、棉籽油组和BUD组每次激发前分别给予ATRA 50 μg/kg,棉籽油1 mL和BUD 0.32 mg/kg,5组大鼠行气道反应性检测,并测定肺组织MMP-9表达和气道重塑情况.结果 ATRA干预组的气道反应性与盐水组比较差异无统计学意义(P>0.05),MMP-9表达高于盐水组,差异具有统计学意义(P<0.05).ATRA干预组的气道反应性和MMP-9表达均明显低于模型组,气道重塑改变减轻,差异具有统计学意义(P<0.05).结论 早期预防性ATRA于预通过减少肺组织MMP-9表达,可在一定程度上减轻哮喘大鼠的气道重塑和气道高反应性.%Objective To study the effects of all-trans retinoic acid ( ATRA) on airway responsiveness, airway remodeling and expression of matrix metalloproteinas-9 ( MMP-9 ) protein in rats with asthma. Methods Forty rats were randomly divided into five groups; asthma model, normal saline (control), ATKA treatment, cotton oil treatment and budesonide treatment (n =8 each). Asthma was induced by ovalbumin sensitization and challenge in the asthma model, and the ATRA, cotton oil or budesonide treatment groups. ATRA (50 fig/kg) , cotton oil (1 mL) or budesonide (0.32 mg/kg) was administered before ovalbumin challenge in the three treatment groups. Airway responsiveness was assessed. The lung tissues were sampled to detect airway remodeling and the expression of MMP-9 protein by immunohistochemistry. Results The expression of MMP-9 in lung tissues in the ATRA treatment group was significantly higher than that in the control group, but the airway responsiveness in the ATRA treatment group was not significantly different from that in the control

  16. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota

    NARCIS (Netherlands)

    Larsen, J.M.; Steen-Jensen, D.B.; Laursen, J.M.; Sondergaard, J.N.; Musavian, H.S.; Butt, T.M.; Brix, S.

    2012-01-01

    Recent studies using culture-independent methods have characterized the human airway microbiota and report microbial communities distinct from other body sites. Changes in these airway bacterial communities appear to be associated with inflammatory lung disease, yet the pro-inflammatory properties o

  17. CCL2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration

    OpenAIRE

    S. R. Singh; Sutcliffe, A.; Kaur, D; Gupta, S.; Desai, D; Saunders, R.; Brightling, C E

    2014-01-01

    Background Asthma is characterized by variable airflow obstruction, airway inflammation, airway hyper-responsiveness and airway remodelling. Airway smooth muscle (ASM) hyperplasia is a feature of airway remodelling and contributes to bronchial wall thickening. We sought to investigate the expression levels of chemokines in primary cultures of ASM cells from asthmatics vs healthy controls and to assess whether differentially expressed chemokines (i) promote fibrocyte (FC) migration towards ASM...

  18. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

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

    2013-01-01

    -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 limits were set at

  19. Reproducibility of the airway response to an exercise protocol standardized for intensity, duration, and inspired air conditions, in subjects with symptoms suggestive of asthma

    Directory of Open Access Journals (Sweden)

    Anderson Sandra D

    2010-09-01

    Full Text Available Abstract Background Exercise testing to aid diagnosis of exercise-induced bronchoconstriction (EIB is commonly performed. Reproducibility of the airway response to a standardized exercise protocol has not been reported in subjects being evaluated with mild symptoms suggestive of asthma but without a definite diagnosis. This study examined reproducibility of % fall in FEV1 and area under the FEV1 time curve for 30 minutes in response to two exercise tests performed with the same intensity and duration of exercise, and inspired air conditions. Methods Subjects with mild symptoms of asthma exercised twice within approximately 4 days by running for 8 minutes on a motorized treadmill breathing dry air at an intensity to induce a heart rate between 80-90% predicted maximum; reproducibility of the airway response was expressed as the 95% probability interval. Results Of 373 subjects challenged twice 161 were positive (≥10% fall FEV1 on at least one challenge. The EIB was mild and 77% of subjects had 1 and 19.3% (72 positive on both challenges. The remaining 23.9% of subjects had only one positive test. The 95% probability interval for reproducibility of the % fall in FEV1 and AUC0-30 min was ± 9.7% and ± 251% for all 278 adults and ± 13.4% and ± 279% for all 95 children. The 95% probability interval for reproducibility of % fall in FEV1 and AUC0-30 min for the 72 subjects with two tests ≥10% fall FEV1 was ± 14.6% and ± 373% and for the 34 subjects with two tests ≥15% fall FEV1 it was ± 12.2% and ± 411%. Heart rate and estimated ventilation achieved were not significantly different either on the two test days or when one test result was positive and one was negative. Conclusions Under standardized, well controlled conditions for exercise challenge, the majority of subjects with mild symptoms of asthma demonstrated agreement in test results. Performing two tests may need to be considered when using exercise to exclude or diagnose EIB, when

  20. 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.

  1. Engineering Airway Epithelium

    OpenAIRE

    John P. Soleas; Paz, Ana; Marcus, Paula; McGuigan, Alison; Waddell, Thomas K.

    2012-01-01

    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 fun...

  2. Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies

    International Nuclear Information System (INIS)

    In order to better understand how ambient air particulate matter (PM) affect lung health, the two main airway cell types likely to interact with inhaled particles, alveolar macrophages (AM) and airway epithelial cells have been exposed to particles in vitro and followed for endpoints of inflammation, and oxidant stress. Separation of Chapel Hill PM 10 into fine and coarse size particles revealed that the main proinflammatory response (TNF, IL-6, COX-2) in AM was driven by material present in the coarse PM, containing 90-95% of the stimulatory material in PM10. The particles did not affect expression of hemoxygenase-1 (HO-1), a sensitive marker of oxidant stress. Primary cultures of normal human bronchial epithelial cells (NHBE) also responded to the coarse fraction with higher levels of IL-8 and COX-2, than induced by fine or ultrafine PM. All size PM induced oxidant stress in NHBE, while fine PM induced the highest levels of HO-1 expression. The production of cytokines in AM by both coarse and fine particles was blocked by the toll like receptor 4 (TLR4) antagonist E5531 involved in the recognition of LPS and Gram negative bacteria. The NHBE were found to recognize coarse and fine PM through TLR2, a receptor with preference for recognition of Gram positive bacteria. Compared to ambient PM, diesel PM induced only a minimal cytokine response in both AM and NHBE. Instead, diesel suppressed LPS-induced TNF and IL-8 release in AM. Both coarse and fine ambient air PM were also found to inhibit LPS-induced TNF release while silica, volcanic ash or carbon black had no inhibitory effect. Diesel particles did not affect cytokine mRNA induction nor protein accumulation but interfered with the release of cytokine from the cells. Ambient coarse and fine PM, on the other hand, inhibited both mRNA induction and protein production. Exposure to coarse and fine PM decreased the expression of TLR4 in the macrophages. Particle-induced decrease in TLR4 and hyporesponsiveness to LPS

  3. Interleukin-19: a constituent of the regulome that controls antigen presenting cells in the lungs and airway responses to microbial products.

    Directory of Open Access Journals (Sweden)

    Carol Hoffman

    Full Text Available BACKGROUND: Interleukin (IL-19 has been reported to enhance chronic inflammatory diseases such as asthma but the in vivo mechanism is incompletely understood. Because IL-19 is produced by and regulates cells of the monocyte lineage, our studies focused on in vivo responses of CD11c positive (CD11c+ alveolar macrophages and lung dendritic cells. METHODOLOGY/PRINCIPAL FINDINGS: IL-19-deficient (IL-19-/- mice were studied at baseline (naïve and following intranasal challenge with microbial products, or recombinant cytokines. Naïve IL-19-/- mixed background mice had a decreased percentage of CD11c+ cells in the bronchoalveolar-lavage (BAL due to the deficiency in IL-19 and a trait inherited from the 129-mouse strain. BAL CD11c+ cells from fully backcrossed IL-19-/- BALB/c or C57BL/6 mice expressed significantly less Major Histocompatibility Complex class II (MHCII in response to intranasal administration of lipopolysaccharide, Aspergillus antigen, or IL-13, a pro-allergic cytokine. Neurogenic-locus-notch-homolog-protein-2 (Notch2 expression by lung monocytes, the precursors of BAL CD11c+ cells, was dysregulated: extracellular Notch2 was significantly decreased, transmembrane/intracellular Notch2 was significantly increased in IL-19-/- mice relative to wild type. Instillation of recombinant IL-19 increased extracellular Notch2 expression and dendritic cells cultured from bone marrow cells in the presence of IL-19 showed upregulated extracellular Notch2. The CD205 positive subset among the CD11c+ cells was 3-5-fold decreased in the airways and lungs of naïve IL-19-/- mice relative to wild type. Airway inflammation and histological changes in the lungs were ameliorated in IL-19-/- mice challenged with Aspergillus antigen that induces T lymphocyte-dependent allergic inflammation but not in IL-19-/- mice challenged with lipopolysaccharide or IL-13. CONCLUSIONS/SIGNIFICANCE: Because MHCII is the molecular platform that displays peptides to T

  4. Response to Commentary on "The influence of lung airways branching structure and diffusion time on measurements and models of short-range 3He gas MR diffusion".

    Science.gov (United States)

    Parra-Robles, Juan; Wild, Jim M

    2014-02-01

    Our extensive investigation of the cylinder model theory through numerical modelling and purpose-designed experiments has demonstrated that it does produce inaccurate estimates of airway dimensions at all diffusion times currently used. This is due to a variety of effects: incomplete treatment of non-Gaussian effects, finite airway size, branching geometry, background susceptibility gradients and diffusion time dependence of the (3)He MR diffusion behaviour in acinar airways. The cylinder model is a good starting point for the development of a lung morphometry technique from (3)He diffusion MR but its limitations need to be understood and documented in the interest of reliable clinical interpretation. PMID:24342570

  5. Pneumococcal components induce regulatory T cells that attenuate the development of allergic airways disease by deviating and suppressing the immune response to allergen.

    Science.gov (United States)

    Thorburn, Alison N; Brown, Alexandra C; Nair, Prema M; Chevalier, Nina; Foster, Paul S; Gibson, Peter G; Hansbro, Philip M

    2013-10-15

    The induction of regulatory T cells (Tregs) to suppress aberrant inflammation and immunity has potential as a therapeutic strategy for asthma. Recently, we identified key immunoregulatory components of Streptococcus pneumoniae, type 3 polysaccharide and pneumolysoid (T+P), which suppress allergic airways disease (AAD) in mouse models of asthma. To elucidate the mechanisms of suppression, we have now performed a thorough examination of the role of Tregs. BALB/c mice were sensitized to OVA (day 0) i.p. and challenged intranasal (12-15 d later) to induce AAD. T+P was administered intratracheally at the time of sensitization in three doses (0, 12, and 24 h). T+P treatment induced an early (36 h-4 d) expansion of Tregs in the mediastinal lymph nodes, and later (12-16 d) increases in these cells in the lungs, compared with untreated allergic controls. Anti-CD25 treatment showed that Treg-priming events involving CD25, CCR7, IL-2, and TGF-β were required for the suppression of AAD. During AAD, T+P-induced Tregs in the lungs displayed a highly suppressive phenotype and had an increased functional capacity. T+P also blocked the induction of IL-6 to prevent the Th17 response, attenuated the expression of the costimulatory molecule CD86 on myeloid dendritic cells (DCs), and reduced the number of DCs carrying OVA in the lung and mediastinal lymph nodes. Therefore, bacterial components (T+P) drive the differentiation of highly suppressive Tregs, which suppress the Th2 response, prevent the Th17 response and disable the DC response resulting in the effective suppression of AAD. PMID:24048894

  6. Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen.

    OpenAIRE

    Schwarze, J.; Hamelmann, E; Bradley, K L; Takeda, K.; Gelfand, E. W.

    1997-01-01

    Viral respiratory infections can predispose to the development of asthma by mechanisms that are presently undetermined. Using a murine model of respiratory syncytial virus (RSV) infection, acute infection is associated with airway hyperresponsiveness as well as enhanced responses to subsequent sensitization to allergen. We demonstrate that acute viral infection results in increased airway responsiveness to inhaled methacholine and pulmonary neutrophilic and eosinophilic inflammation. This res...

  7. A multi-scale approach to airway hyperresponsiveness: from molecule to organ

    Directory of Open Access Journals (Sweden)

    Anne-Marie eLauzon

    2012-06-01

    Full Text Available Airway hyperresponsiveness (AHR, a characteristic of asthma that involves an excessive reduction in airway caliber, is a complex mechanism reflecting multiple processes that manifest over a large range of length and time scales. At one extreme, molecular interactions determine the force generated by airway smooth muscle (ASM. At the other, the spatially distributed constriction of the branching airways leads to breathing difficulties. Similarly, asthma therapies act at the molecular scale while clinical outcomes are determined by lung function. These extremes are linked by events operating over intermediate scales of length and time. Thus, AHR is an emergent phenomenon that limits our understanding of asthma and confounds the interpretation of studies that address physiological mechanisms over a limited range of scales. A solution is a modular computational model that integrates experimental and mathematical data from multiple scales. This includes, at the molecular scale, kinetics and force production of actin-myosin contractile proteins during cross-bridge and latch-state cycling; at the cellular scale, Ca2+ signaling mechanisms that regulate ASM force production; at the tissue scale, forces acting between contracting ASM and opposing viscoelastic tissue that determine airway narrowing; at the organ scale, the topographic distribution of ASM contraction dynamics that determine mechanical impedance of the lung. At each scale, models are constructed with iterations between theory and experimentation to identify the parameters that link adjacent scales. This modular model establishes algorithms for modeling over a wide range of scales and provides a frame-work for the inclusion of other responses such as inflammation or therapeutic regimes. The goal is to develop this lung model so that it can make predictions about bronchoconstriction and identify the pathophysiologic mechanisms having the greatest impact on AHR and its therapy.

  8. Comparative assessment of ProSeal™ laryngeal mask airway intervention versus standard technique of endotracheal extubation for attenuation of pressor response in controlled hypertensive patients

    Directory of Open Access Journals (Sweden)

    Raj Pal Singh

    2016-01-01

    Full Text Available Background and Aims: Swapping of the endotracheal tube with laryngeal mask airway (LMA before emergence from anaesthesia is one of the methods employed for attenuation of pressor response at extubation. We decided to compare the placement of ProSeal ™ LMA (PLMA before endotracheal extubation versus conventional endotracheal extubation in controlled hypertensive patients scheduled for elective surgeries under general anaesthesia. Methods: Sixty consenting adult patients were randomly allocated to two groups of thirty each; Group E in whom extubation was performed using standard technique and Group P in whom PLMA was inserted before endotracheal extubation (Bailey manoeuvre. The primary outcome parameter was heart rate (HR. The secondary outcomes were systolic, diastolic and mean blood pressure (MBP, electrocardiogram, oxygen saturation and end-tidal carbon dioxide. Two-tailed paired Student's t-test was used for comparison between the two study groups. The value of P< 0.05 was considered as statistically significant. Results: The patient characteristics, demographic data and surgical procedures were comparable in the two groups. A statistically significant decrease was observed in HR in Group P as compared to Group E. Secondary outcomes such as systolic, diastolic and MBP depicted a statistically insignificant difference. Conclusion: Bailey manoeuvre was not effective method to be completely relied upon during extubation when compared to standard extubation.

  9. Effects of prior treatment with salmeterol and formoterol on airway and systemic beta 2 responses to fenoterol.

    OpenAIRE

    Grove, A.; Lipworth, B J

    1996-01-01

    BACKGROUND: Previous studies have shown that both salmeterol and formoterol act as partial beta 2 receptor agonists in terms of antagonising the extrapulmonary responses to fenoterol in normal subjects. The aim of the present study was to extend previous observations in evaluating the effect of prior treatment with salmeterol and formoterol on bronchodilator responses to fenoterol, a full beta 2 receptor agonist, in patients with asthma. METHODS: Ten stable asthmatic patients of mean (SE) age...

  10. Cleavage of endogenous γENaC and elevated abundance of αENaC are associated with increased Na+ transport in response to apical fluid volume expansion in human H441 airway epithelial cells

    OpenAIRE

    Tan, Chong D.; Selvanathar, Indusha A.; Baines, Deborah L.

    2011-01-01

    Using human H441 airway epithelial cells cultured at air–liquid interface (ALI), we have uniquely correlated the functional response to apical fluid volume expansion with the abundance and cleavage of endogenous α- and γENaC proteins in the apical membrane. Monolayers cultured at ALI rapidly elevated I sc when inserted into fluid-filled Ussing chambers. The increase in I sc was not significantly augmented by the apical addition of trypsin, and elevation was abolished by the protease inhibitor...

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

    Science.gov (United States)

    Bates, Jason H T

    2016-09-01

    Fresh air entering the mouth and nose is brought to the blood-gas barrier in the lungs by a repetitively branching network of airways. Provided the individual airway branches remain patent, this airway tree achieves an enormous amplification in cross-sectional area from the trachea to the terminal bronchioles. Obstructive lung diseases such as asthma occur when airway patency becomes compromised. Understanding the pathophysiology of these obstructive diseases thus begins with a consideration of the factors that determine the caliber of an individual airway, which include the force balance between the inward elastic recoil of the airway wall, the outward tethering forces of its parenchymal attachments, and any additional forces due to contraction of airway smooth muscle. Other factors may also contribute significantly to airway narrowing, such as thickening of the airway wall and accumulation of secretions in the lumen. Airway obstruction becomes particularly severe when these various factors occur in concert. However, the effect of airway abnormalities on lung function cannot be fully understood only in terms of what happens to a single airway because narrowing throughout the airway tree is invariably heterogeneous and interdependent. Obstructive lung pathologies thus manifest as emergent phenomena arising from the way in which the airway tree behaves a system. These emergent phenomena are studied with clinical measurements of lung function made by spirometry and by mechanical impedance measured with the forced oscillation technique. Anatomically based computational models are linking these measurements to underlying anatomic structure in systems physiology terms. WIREs Syst Biol Med 2016, 8:423-437. doi: 10.1002/wsbm.1347 For further resources related to this article, please visit the WIREs website. PMID:27340818

  12. Narrow trachea in mucopolysaccharidoses

    International Nuclear Information System (INIS)

    Nine of 56 patients with mucopolysaccharidosis (MPS) showed small tracheal diamters on the frontal chest radiographs. Autopsy of an MPS I-H (Hurler disease) patient demonstrated that the small calibre was secondary to deposition of glycosaminoglycan (mucopolysaccharide). Autopsies of two patients with other storage diseases, one with geleophysic dysplasia and one with mucolipidosis II, also exhibited compromise of their airways because of storage material accumulation. (orig.)

  13. The relationship between eosinophilia and airway remodelling in mild asthma

    OpenAIRE

    Wilson, S J; Rigden, H.M.; Ward, J. A.; Laviolette, M.; Jarjour, N N; Djukanović, R.

    2013-01-01

    Background Eosinophilia is a marker of corticosteroid responsiveness and risk of exacerbation in asthma; although it has been linked to submucosal matrix deposition, its relationship with other features of airway remodelling is less clear. Objective The aim of this study was to investigate the relationship between airway eosinophilia and airway remodelling. Methods Bronchial biopsies from subjects (n = 20 in each group) with mild steroid-naïve asthma, with either low (0–0....

  14. Airway Smooth Muscle in Asthma: Just a Target for Bronchodilation?

    OpenAIRE

    Black, Judith L; Reynold A Panettieri; Banerjee, Audreesh; Berger, Patrick

    2012-01-01

    Airway smooth muscle (ASM) has long been recognized as the main cell type responsible for bronchial hyperresponsiveness. It has thus been considered as a target for bronchodilation. In asthma however, there is a complex relationship between ASM and inflammatory cells such as mast cells and T lymphocytes. Moreover, the increased ASM mass in the asthmatic airways is one of the key features of airway remodeling. This article aims to review the main concepts about the three possible roles of ASM ...

  15. Polarized secretion of interleukin (IL-6 and IL-8 by human airway epithelia 16HBE14o- cells in response to cationic polypeptide challenge.

    Directory of Open Access Journals (Sweden)

    Alison Wai-ming Chow

    Full Text Available BACKGROUND: The airway epithelium participates in asthmatic inflammation in many ways. Target cells of the epithelium can respond to a variety of inflammatory mediators and cytokines. Damage to the surface epithelium occurs following the secretion of eosinophil-derived, highly toxic cationic proteins. Moreover, the surface epithelium itself is responsible for the synthesis and release of cytokines that cause the selective recruitment, retention, and accumulation of various inflammatory cells. To mimic the damage seen during asthmatic inflammation, the bronchial epithelium can be challenged with highly charged cationic polypeptides such as poly-L-arginine. METHODOLOGY/PRINCIPAL FINDINGS: In this study, human bronchial epithelial cells, 16HBE14o- cells, were "chemically injured" by exposing them to poly-l-arginine as a surrogate of the eosinophil cationic protein. Cytokine antibody array data showed that seven inflammatory mediators were elevated out of the 40 tested, including marked elevation in interleukin (IL-6 and IL-8 secretion. IL-6 and IL-8 mRNA expression levels were elevated as measured with real-time PCR. Cell culture supernatants from apical and basolateral compartments were collected, and the IL-6 and IL-8 production was quantified with ELISA. IL-6 and IL-8 secretion by 16HBE14o- epithelia into the apical compartment was significantly higher than that from the basolateral compartment. Using specific inhibitors, the production of IL-6 and IL-8 was found to be dependent on p38 MAPK, ERK1/2 MAPK, and NF-kappaB pathways. CONCLUSIONS/SIGNIFICANCE: The results clearly demonstrate that damage to the bronchial epithelia by poly-L-arginine stimulates polarized IL-6 and IL-8 secretion. This apically directed secretion of cytokines may play an important role in orchestrating epithelial cell responses to inflammation.

  16. Matrix metalloprotease 9 mediates neutrophil migration into the airways in response to influenza virus-induced toll-like receptor signaling.

    Directory of Open Access Journals (Sweden)

    Linda M Bradley

    Full Text Available The early inflammatory response to influenza virus infection contributes to severe lung disease and continues to pose a serious threat to human health. The mechanisms by which neutrophils gain entry to the respiratory tract and their role during pathogenesis remain unclear. Here, we report that neutrophils significantly contributed to morbidity in a pathological mouse model of influenza virus infection. Using extensive immunohistochemistry, bone marrow transfers, and depletion studies, we identified neutrophils as the predominant pulmonary cellular source of the gelatinase matrix metalloprotease (MMP 9, which is capable of digesting the extracellular matrix. Furthermore, infection of MMP9-deficient mice showed that MMP9 was functionally required for neutrophil migration and control of viral replication in the respiratory tract. Although MMP9 release was toll-like receptor (TLR signaling-dependent, MyD88-mediated signals in non-hematopoietic cells, rather than neutrophil TLRs themselves, were important for neutrophil migration. These results were extended using multiplex analyses of inflammatory mediators to show that neutrophil chemotactic factor, CCL3, and TNFα were reduced in the Myd88⁻/⁻ airways. Furthermore, TNFα induced MMP9 secretion by neutrophils and blocking TNFα in vivo reduced neutrophil recruitment after infection. Innate recognition of influenza virus therefore provides the mechanisms to induce recruitment of neutrophils through chemokines and to enable their motility within the tissue via MMP9-mediated cleavage of the basement membrane. Our results demonstrate a previously unknown contribution of MMP9 to influenza virus pathogenesis by mediating excessive neutrophil migration into the respiratory tract in response to viral replication that could be exploited for therapeutic purposes.

  17. Use of the i-gel™ supraglottic airway device in a patient with subglottic stenosis -a case report-.

    Science.gov (United States)

    Lee, Ki Hwa; Kang, Eun Su; Jung, Jae Wook; Park, Jae Hong; Choi, Young Gyun

    2013-09-01

    The airway management of patients with subglottic stenosis poses many challenges for the anesthesiologists. Many anesthesiologists use a narrow endotracheal tube for airway control. This, however, can lead to complications such as tracheal mucosal trauma, tracheal perforation or bleeding. The ASA difficult airway algorithm recommends the use of supraglottic airway devices in a failed intubation/ventilation scenario. In this report, we present a case of failed intubation in a patient with subglottic stenosis successfully managed during an i-gel™ supraglottic airway device. The device provided a good seal, and allowed for controlled mechanical ventilation with acceptable peak pressures while the patient was in the beach-chair position.

  18. Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells

    OpenAIRE

    Emily F A van 't Wout; Annemarie van Schadewijk; Ria van Boxtel; Dalton, Lucy E.; Clarke, Hanna J.; Jan Tommassen; Marciniak, Stefan J; Hiemstra, Pieter S.

    2015-01-01

    Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA). Efficient functioning of the endoplasmic reticulum (ER) is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded pr...

  19. Jihadism, Narrow and Wide

    DEFF Research Database (Denmark)

    Sedgwick, Mark

    2015-01-01

    The term “jihadism” is popular, but difficult. It has narrow senses, which are generally valuable, and wide senses, which may be misleading. This article looks at the derivation and use of “jihadism” and of related terms, at definitions provided by a number of leading scholars, and at media usage....... It distinguishes two main groups of scholarly definitions, some careful and narrow, and some appearing to match loose media usage. However, it shows that even these scholarly definitions actually make important distinctions between jihadism and associated political and theological ideology. The article closes...

  20. Blockage of upper airway

    Science.gov (United States)

    ... is made through the neck into the airway ( tracheostomy or cricothyrotomy). If the obstruction is due to ... team. Related MedlinePlus Health Topics Choking Throat Disorders Tracheal Disorders Browse the Encyclopedia A.D.A.M., Inc. ...

  1. Equine recurrent airway obstruction

    OpenAIRE

    Artur Niedźwiedź

    2014-01-01

    Equine Recurrent Airway Obstruction (RAO), also known as heaves or broken wind, is one of the most common disease in middle-aged horses. Inflammation of the airway is inducted by organic dust exposure. This disease is characterized by neutrophilic inflammation, bronchospasm, excessive mucus production and pathologic changes in the bronchiolar walls. Clinical signs are resolved in 3-4 weeks after environmental changes. Horses suffering from RAO are susceptible to allergens throughout their liv...

  2. Correlates of Narrow Bracketing

    DEFF Research Database (Denmark)

    Koch, Alexander; Nafziger, Julia

    We examine whether different phenomena of narrow bracketing can be traced back to some common characteristic and whether and how different phenomena are related. We find that making dominated lottery choices or ignoring the endowment when making risky choices are related phenomena and are both...

  3. Macrophage adaptation in airway inflammatory resolution

    Directory of Open Access Journals (Sweden)

    Manminder Kaur

    2015-09-01

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

  4. Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control

    OpenAIRE

    Bessac, Bret F.; Jordt, Sven-Eric

    2008-01-01

    New studies have revealed an essential role for TRPA1, a sensory neuronal TRP ion channel, in airway chemosensation and inflammation. TRPA1 is activated by chlorine, reactive oxygen species and noxious constituents of smoke and smog, initiating irritation and airway reflex responses. Together with TRPV1, the capsaicin receptor, TRPA1 may contribute to chemical hypersensitivity, chronic cough and airway inflammation in asthma, COPD and reactive airway dysfunction syndrome.

  5. Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control.

    Science.gov (United States)

    Bessac, Bret F; Jordt, Sven-Eric

    2008-12-01

    New studies have revealed an essential role for TRPA1, a sensory neuronal TRP ion channel, in airway chemosensation and inflammation. TRPA1 is activated by chlorine, reactive oxygen species, and noxious constituents of smoke and smog, initiating irritation and airway reflex responses. Together with TRPV1, the capsaicin receptor, TRPA1 may contribute to chemical hypersensitivity, chronic cough, and airway inflammation in asthma, COPD, and reactive airway dysfunction syndrome. PMID:19074743

  6. Size-partitioning of an urban aerosol to identify particle determinants involved in the proinflammatory response induced in airway epithelial cells

    Directory of Open Access Journals (Sweden)

    Martinon Laurent

    2009-03-01

    Full Text Available Abstract Background The contribution of air particles in human cardio-respiratory diseases has been enlightened by several epidemiological studies. However the respective involvement of coarse, fine and ultrafine particles in health effects is still unclear. The aim of the present study is to determine which size fraction from a chemically characterized background aerosol has the most important short term biological effect and to decipher the determinants of such a behaviour. Results Ambient aerosols were collected at an urban background site in Paris using four 13-stage low pressure cascade impactors running in parallel (winter and summer 2005 in order to separate four size-classes (PM0.03–0.17 (defined here as ultrafine particles, PM0.17–1 (fine, PM1–2.5(intermediate and PM2.5–10 (coarse. Accordingly, their chemical composition and their pro-inflammatory potential on human airway epithelial cells were investigated. Considering isomass exposures (same particle concentrations for each size fractions the pro-inflammatory response characterized by Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF release was found to decrease with aerosol size with no seasonal dependency. When cells were exposed to isovolume of particle suspensions in order to respect the particle proportions observed in ambient air, the GM-CSF release was maximal with the fine fraction. In presence of a recombinant endotoxin neutralizing protein, the GM-CSF release induced by particles is reduced for all size-fractions, with exception of the ultra-fine fraction which response is not modified. The different aerosol size-fractions were found to display important chemical differences related to the various contributing primary and secondary sources and aerosol age. The GM-CSF release was correlated to the organic component of the aerosols and especially its water soluble fraction. Finally, Cytochrome P450 1A1 activity that reflects PAH bioavailability varied as a

  7. Upper airway pressure-flow relationships and pharyngeal constrictor EMG activity during prolonged expiration in awake goats

    OpenAIRE

    O'Halloran, K. D.; Bisgard, G. E.

    2008-01-01

    We undertook the present investigation to establish whether narrowing/closure of the upper airway occurs during spontaneous and provoked respiratory rhythm disturbances and whether pharyngeal constrictor muscle recruitment occurs coincident with upper airway occlusion during prolonged expiratory periods. Upper airway pressure-flow relationships and middle pharyngeal constrictor (mPC) EMG activities were recorded in 11 adult female goats during spontaneous and provoked prolongations in expirat...

  8. Role of upper airway ultrasound in airway management.

    Science.gov (United States)

    Osman, Adi; Sum, Kok Meng

    2016-01-01

    Upper airway ultrasound is a valuable, non-invasive, simple, and portable point of care ultrasound (POCUS) for evaluation of airway management even in anatomy distorted by pathology or trauma. Ultrasound enables us to identify important sonoanatomy of the upper airway such as thyroid cartilage, epiglottis, cricoid cartilage, cricothyroid membrane, tracheal cartilages, and esophagus. Understanding this applied sonoanatomy facilitates clinician to use ultrasound in assessment of airway anatomy for difficult intubation, ETT and LMA placement and depth, assessment of airway size, ultrasound-guided invasive procedures such as percutaneous needle cricothyroidotomy and tracheostomy, prediction of postextubation stridor and left double-lumen bronchial tube size, and detecting upper airway pathologies. Widespread POCUS awareness, better technological advancements, portability, and availability of ultrasound in most critical areas facilitate upper airway ultrasound to become the potential first-line non-invasive airway assessment tool in the future. PMID:27529028

  9. Silibinin attenuates allergic airway inflammation in mice

    International Nuclear Information System (INIS)

    Highlights: ► Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. ► Silibinin reduces the levels of various cytokines into the lung of allergic mice. ► Silibinin prevents the development of airway hyperresponsiveness in allergic mice. ► Silibinin suppresses NF-κB 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-κB) pathway. Because NF-κB 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-κB activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-κB activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  10. 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.

  11. 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.

    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 ad

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

    DEFF Research Database (Denmark)

    Bousquet, J; Addis, A; Adcock, I;

    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...

  13. Thermopower and specific heat of the organic molecular salt (TMTSF)(2)ClO(4): observation of the narrow band response.

    Science.gov (United States)

    Sun, Cheng-Hai; Yang, Hong-Shun; Liu, Jian; Gao, Hui-Xian; Wang, Jian-Bin; Cheng, Lu; Cao, Lie-Zhao; Lasjaunias, J C

    2008-06-11

    Measurements of thermopower S(a)(T) along the highly conducting a axis and specific heat of the Bechgaard salts (TMTSF)(2)ClO(4) for various cooling rates through the anion ordering temperature T(a) = 24 K were carried out. Sign reversal in S(a)(T) is found below T(a) and it decreases with increasing cooling rate, which is attributed to the change of a narrow band filling level as the temperature and the cooling rates change. The crossover from 2D to 3D in S(a)(T) is observed around 15 K. The onset temperature of anion ordering in S(a)(T) decreases from 29.8 to 24.2 K as the cooling rate increases. Meanwhile, the electronic specific heat coefficient γ has a pronounced change within this temperature region, giving strong evidence for a narrow band contribution. The difference in the specific heat between the quenched and relaxed states follows a T-cubic law from 5 to 24 K, implying a lattice distortion by the ordered anion only. The entropy estimated from the specific heat peak between 28 and 15 K is Rln (4/3) lower than the value Rln2, consistent with the thermopower result that some anions have been ordered far above T(a) for the relaxed state. PMID:21694314

  14. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura; Steen-Jensen, Daniel Bisgaard; Laursen, Janne Marie;

    2012-01-01

    of individual bacterial species are unknown. In this study, we compared the immune stimulatory capacity on human monocyte-derived dendritic cells (DCs) of selected airway commensal and pathogenic bacteria predominantly associated with lungs of asthma or COPD patients (pathogenic Haemophillus spp. and Moraxella...... spp.), healthy lungs (commensal Prevotella spp.) or both (commensal Veillonella spp. and Actinomyces spp.). All bacteria were found to induce activation of DCs as demonstrated by similar induction of CD83, CD40 and CD86 surface expression. However, asthma and COPD-associated pathogenic bacteria...... provoked a 3-5 fold higher production of IL-23, IL-12p70 and IL-10 cytokines compared to the commensal bacteria. Based on the differential cytokine production profiles, the studied airway bacteria could be segregated into three groups (Haemophilus spp. and Moraxella spp. vs. Prevotella spp. and Veillonella...

  15. Airway reconstruction in children

    Directory of Open Access Journals (Sweden)

    Rao Sanjay

    2009-01-01

    Full Text Available Aim/Background : Airway anomalies are infrequent but potentially life threatening in children. A program to care for these difficult children was set up at our institution, and this paper summarizes our experience. Methods: A total of 34 children were enrolled in the program over a period of three years. These children were evaluated as per the standard protocols. Treatment was individualized. Results: Of these 34 children, 28 had their airways restored and are doing well. Four children continue to remain on tracheostomy and two will require long term tracheostomy. There were two deaths. All children are under surveillance as there is a risk of recurrence. Conclusions: Airway anomalies are complex problems with significant morbidity and mortality. Current therapeutic modalities allow for good results. Most children were successfully decannulated and did well.

  16. Behavioral Inhibition in Rhesus Monkeys (Macaca mulatta) Is Related to the Airways Response, but Not Immune Measures, Commonly Associated with Asthma

    OpenAIRE

    Katie Chun; Lisa A Miller; Schelegle, Edward S.; Hyde, Dallas M.; Capitanio, John P.

    2013-01-01

    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 beha...

  17. Airway statuses and nasopharyngeal airway use for airway obstruction in syndromic craniosynostosis.

    Science.gov (United States)

    Kouga, Takeshi; Tanoue, Koji; Matsui, Kiyoshi

    2014-05-01

    Syndromic craniosynostosis is associated with a high rate of respiratory difficulty, due mainly to midfacial hypoplasia. Nasopharyngeal airway establishment has been reported as the first-line approach to airway obstruction and may obviate the need for a highly invasive tracheotomy. No previous studies have compared airway obstruction status in syndromic craniosynostosis between cases requiring and not requiring airway managements. We focus on nasopharyngeal airway use and airway status outcomes to assess respiratory difficulty in patients with syndromic craniosynostosis. A retrospective data analysis of 51 cases with syndromic craniosynostosis was carried out. We divided 30 of the 51 cases with lateral pharyngeal x-rays taken before operations affecting airway diameters into 2 groups, one with neither nasopharyngeal airway insertion nor tracheotomy and the other with one or both of these interventions, and the mean diameters for 8 indices related to the pharyngeal space were compared. Cases with respiratory difficulty due to nasopharyngeal stenosis and requiring airway managements comprised a significantly higher proportion of those with Pfeiffer syndrome than patients with Crouzon or Apert syndrome. Comparative examination of lateral x-ray cephalometry between cases with neither nasopharyngeal airway insertion nor tracheotomy and cases with one or both revealed oropharyngeal diameters tended to be smaller in those with interventions. Cases requiring nasopharyngeal airway insertion were able to continue nasopharyngeal airway use for more than 1 year and a considerable number avoided tracheotomy. It may be worth considering an oropharyngeal-bypass nasopharyngeal airway before performing a tracheotomy. PMID:24820706

  18. 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. PMID:26317666

  19. 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.

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

    NARCIS (Netherlands)

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

    2013-01-01

    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 (myo)fibro

  1. Issues of critical airway management (Which anesthesia; which surgical airway?

    Directory of Open Access Journals (Sweden)

    Fabrizio Giuseppe Bonanno

    2012-01-01

    Full Text Available Which anesthesia for patients with critical airway? Safe and effective analgesia and anesthesia in critical airway is a skilled task especially after severe maxillofacial injury combined with head injury and hemorrhagic shock. If on one side sedation is wanted, on the other hand it may worsen the airway and hemodynamic situation to a point where hypoventilation and decrease of blood pressure, common side-effect of many opioids, may prejudice the patient′s level of consciousness and hemodynamic compensation, compounding an already critical situation. What to do when endotracheal intubation fails and blood is trickling down the airways in an unconscious patient or when a conscious patient has to sit up to breathe? Which surgical airway in critical airway? Comparative studies among the various methods of emergency surgical airway would be unethical; furthermore, operator′s training and experience is relevant for indications and performance.

  2. Issues of critical airway management (Which anesthesia; which surgical airway?).

    Science.gov (United States)

    Bonanno, Fabrizio Giuseppe

    2012-10-01

    Which anesthesia for patients with critical airway? Safe and effective analgesia and anesthesia in critical airway is a skilled task especially after severe maxillofacial injury combined with head injury and hemorrhagic shock. If on one side sedation is wanted, on the other hand it may worsen the airway and hemodynamic situation to a point where hypoventilation and decrease of blood pressure, common side-effect of many opioids, may prejudice the patient's level of consciousness and hemodynamic compensation, compounding an already critical situation. What to do when endotracheal intubation fails and blood is trickling down the airways in an unconscious patient or when a conscious patient has to sit up to breathe? Which surgical airway in critical airway? Comparative studies among the various methods of emergency surgical airway would be unethical; furthermore, operator's training and experience is relevant for indications and performance. PMID:23248494

  3. Mechanical ventilation causes airway distension with proinflammatory sequelae in mice.

    Science.gov (United States)

    Nickles, Hannah T; Sumkauskaite, Migle; Wang, Xin; Wegner, Ingmar; Puderbach, Michael; Kuebler, Wolfgang M

    2014-07-01

    The pathogenesis of ventilator-induced lung injury has predominantly been attributed to overdistension or mechanical opening and collapse of alveoli, whereas mechanical strain on the airways is rarely taken into consideration. Here, we hypothesized that mechanical ventilation may cause significant airway distension, which may contribute to the pathological features of ventilator-induced lung injury. C57BL/6J mice were anesthetized and mechanically ventilated at tidal volumes of 6, 10, or 15 ml/kg body wt. Mice were imaged by flat-panel volume computer tomography, and central airways were segmented and rendered in 3D for quantitative assessment of airway distension. Alveolar distension was imaged by intravital microscopy. Functional dead space was analyzed in vivo, and proinflammatory cytokine release was analyzed in isolated, ventilated tracheae. CT scans revealed a reversible, up to 2.5-fold increase in upper airway volume during mechanical ventilation compared with spontaneous breathing. Airway distension was most pronounced in main bronchi, which showed the largest volumes at tidal volumes of 10 ml/kg body wt. Conversely, airway distension in segmental bronchi and functional dead space increased almost linearly, and alveolar distension increased even disproportionately with higher tidal volumes. In isolated tracheae, mechanical ventilation stimulated the release of the early-response cytokines TNF-α and IL-1β. Mechanical ventilation causes a rapid, pronounced, and reversible distension of upper airways in mice that is associated with an increase in functional dead space. Upper airway distension is most pronounced at moderate tidal volumes, whereas higher tidal volumes redistribute preferentially to the alveolar compartment. Airway distension triggers proinflammatory responses and may thus contribute relevantly to ventilator-induced pathologies. PMID:24816486

  4. Stress and strain in the contractile and cytoskeletal filaments of airway smooth muscle.

    Science.gov (United States)

    Deng, Linhong; Bosse, Ynuk; Brown, Nathan; Chin, Leslie Y M; Connolly, Sarah C; Fairbank, Nigel J; King, Greg G; Maksym, Geoffrey N; Paré, Peter D; Seow, Chun Y; Stephen, Newman L

    2009-10-01

    Stress and strain are omnipresent in the lung due to constant lung volume fluctuation associated with respiration, and they modulate the phenotype and function of all cells residing in the airways including the airway smooth muscle (ASM) cell. There is ample evidence that the ASM cell is very sensitive to its physical environment, and can alter its structure and/or function accordingly, resulting in either desired or undesired consequences. The forces that are either conferred to the ASM cell due to external stretching or generated inside the cell must be borne and transmitted inside the cytoskeleton (CSK). Thus, maintaining appropriate levels of stress and strain within the CSK is essential for maintaining normal function. Despite the importance, the mechanisms regulating/dysregulating ASM cytoskeletal filaments in response to stress and strain remained poorly understood until only recently. For example, it is now understood that ASM length and force are dynamically regulated, and both can adapt over a wide range of length, rendering ASM one of the most malleable living tissues. The malleability reflects the CSK's dynamic mechanical properties and plasticity, both of which strongly interact with the loading on the CSK, and all together ultimately determines airway narrowing in pathology. Here we review the latest advances in our understanding of stress and strain in ASM cells, including the organization of contractile and cytoskeletal filaments, range and adaptation of functional length, structural and functional changes of the cell in response to mechanical perturbation, ASM tone as a mediator of strain-induced responses, and the novel glassy dynamic behaviors of the CSK in relation to asthma pathophysiology.

  5. 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...

  6. Potential of Helper-Dependent Adenoviral Vectors in Modulating Airway Innate Immunity

    Institute of Scientific and Technical Information of China (English)

    Rahul Kushwah; Huibi Cao; Jim Hu

    2007-01-01

    Innate immune responses form the first line of defense against foreign insults and recently significant advances have been made in our understanding of the initiation of innate immune response along with its ability to modulate inflammation. In airway diseases such as asthma, COPD and cystic fibrosis, over reacting of the airway innate immune responses leads to cytokine imbalance and airway remodeling or damage. Helper-dependent adenoviral vectors have the potential to deliver genes to modulate airway innate immune responses and have many advantages over its predecessors. However, there still are a few limitations that need to be addressed prior to their use in clinical applications.

  7. Supraglottic airway devices in children

    Science.gov (United States)

    Ramesh, S; Jayanthi, R

    2011-01-01

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

  8. 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

  9. Effect of the Velvet Antler of Formosan Sambar Deer (Cervus unicolor swinhoei on the Prevention of an Allergic Airway Response in Mice

    Directory of Open Access Journals (Sweden)

    Ching-Yun Kuo

    2012-01-01

    Full Text Available Two mouse models were used to assay the antiallergic effects of the velvet antler (VA of Formosan sambar deer (Cervus unicolor swinhoei in this study. The results using the ovalbumin- (OVA- sensitized mouse model showed that the levels of total IgE and OVA-specific IgE were reduced after VA powder was administrated for 4 weeks. In addition, the ex vivo results indicated that the secretion of T helper cell 1 (Th1, regulatory T (Treg, and Th17 cytokines by splenocytes was significantly increased (P<0.05 when VA powder was administered to the mice. Furthermore, OVA-allergic asthma mice that have been orally administrated with VA powder showed a strong inhibition of Th2 cytokine and proinflammatory cytokine production in bronchoalveolar fluid compared to control mice. An increase in the regulatory T-cell population of splenocytes in the allergic asthma mice after oral administration of VA was also observed. All the features of the asthmatic phenotype, including airway inflammation and the development of airway hyperresponsiveness, were reduced by treatment with VA. These findings support the hypothesis that oral feeding of VA may be an effective way of alleviating asthmatic symptoms in humans.

  10. The effect of rapid maxillary expansion on nasal airway resistance.

    Science.gov (United States)

    White, B C; Woodside, D G; Cole, P

    1989-06-01

    The purpose of this investigation was to provide quantitative data describing the effects of rapid palatal expansion on nasal airway resistance. Rapid palatal expansion is an orthodontic procedure which is commonly used to widen the maxilla to correct maxillary narrowing resulting in the orthodontic abnormality of crossbite and to provide more space for alignment of crowded teeth. Recordings of nasal airway resistance were taken prior to expansion, immediately after expansion (approximately one month), after a retention period of approximately 4 months and approximately one year after initiation of treatment. Findings indicate an average reduction in nasal airway resistance of 48.7 per cent which was statistically significant at the 0.005 level. The reduction also appeared stable throughout the post treatment observation period (maximum one year) as each series of readings was statistically significantly lower than the initial reading, but not significantly different from each other. Reduction of nasal airway resistance was highly correlated to the initial nasal resistance level prior to rapid maxillary expansion. Those individuals with the greater initial resistance tended to have greater reductions in airway resistance following the expansion.

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

    OpenAIRE

    Siddiqui Salman; Brightling Christopher E

    2007-01-01

    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: ...

  12. Issues of critical airway management (Which anesthesia; which surgical airway?)

    OpenAIRE

    Fabrizio Giuseppe Bonanno

    2012-01-01

    Which anesthesia for patients with critical airway? Safe and effective analgesia and anesthesia in critical airway is a skilled task especially after severe maxillofacial injury combined with head injury and hemorrhagic shock. If on one side sedation is wanted, on the other hand it may worsen the airway and hemodynamic situation to a point where hypoventilation and decrease of blood pressure, common side-effect of many opioids, may prejudice the patient′s level of consciousness and hemodynami...

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

    Science.gov (United States)

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

    2005-04-01

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

  14. Managing upper airway obstruction.

    Science.gov (United States)

    Innes, M H

    A complete respiratory obstruction can lead to death in 3 minutes. The first and constant duty of the nurse aider is to check that the person is breathing by looking, listening and feeling. Partial obstruction is no less serious than complete obstruction. The nurse aider, in any situation, should assess the problem and attempt to overcome the airway obstruction using the measures described. PMID:1490067

  15. Upper airway resistance syndrome.

    Science.gov (United States)

    Hasan, N; Fletcher, E C

    1998-07-01

    Many clinicians are familiar with the clinical symptoms and signs of obstructive sleep apnea (OSA). In its most blatant form, OSA is complete airway obstruction with repetitive, prolonged pauses in breathing, arterial oxyhemoglobin desaturation; followed by arousal with resumption of breathing. Daytime symptoms of this disorder include excessive daytime somnolence, intellectual dysfunction, and cardiovascular effects such as systemic hypertension, angina, myocardial infarction, and stroke. It has been recently recognized that increased pharyngeal resistance with incomplete obstruction can lead to a constellation of symptoms identical to OSA called "upper airway resistance syndrome" (UARS). The typical findings of UARS on sleep study are: (1) repetitive arousals from EEG sleep coinciding with a (2) waxing and waning of the respiratory airflow pattern and (3) increased respiratory effort as measured by esophageal pressure monitoring. There may be few, if any, obvious apneas or hypopneas with desaturation, but snoring may be a very prominent finding. Treatment with nasal positive airway pressure (NCPAP) eliminates the symptoms and confirms the diagnosis. Herein we describe two typical cases of UARS. PMID:9676067

  16. Lipids in airway secretions

    International Nuclear Information System (INIS)

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO2, (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors 14C acetate and 14C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway. (author)

  17. Lipids in airway secretions

    Energy Technology Data Exchange (ETDEWEB)

    Bhaskar, K.R.; DeFeudis O' Sullivan, D.; Opaskar-Hincman, H.; Reid, L.M.

    1987-01-01

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO/sub 2/, (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors /sup 14/C acetate and /sup 14/C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway.

  18. Effects of hyperosmolarity on human isolated central airways.

    OpenAIRE

    Jongejan, R. C.; de Jongste, J. C.; Raatgeep, R. C.; Stijnen, T; Bonta, I.L.; Kerrebijn, K. F.

    1991-01-01

    1. We studied the effect of hyperosmolarity on human isolated airways because a better understanding of the effect of hyperosmolarity on the human airway wall may improve insight into the pathophysiology of hyperosmolarity-induced bronchoconstriction in asthma. 2. In cartilaginous bronchial rings dissected from fresh human lung tissue, hyperosmolar krebs-Henseleit buffer (450 mosM, extra sodium chloride added) evoked a biphasic response: a rapid relaxation phase (peak after 5.0 +/- 0.3 min) f...

  19. Biomechanics of liquid-epithelium interactions in pulmonary airways

    OpenAIRE

    Ghadiali, Samir N.; Gaver, Donald P.

    2008-01-01

    The delicate structure of the lung epithelium makes it susceptible to surface tension induced injury. For example, the cyclic reopening of collapsed and/or fluid-filled airways during the ventilation of injured lungs generates hydrodynamic forces that further damage the epithelium and exacerbate lung injury. The interactions responsible for epithelial injury during airway reopening are fundamentally multiscale, since air-liquid interfacial dynamics affect global lung mechanics, while surface ...

  20. LIGHT is a crucial mediator of airway remodeling.

    Science.gov (United States)

    Hung, Jen-Yu; Chiang, Shyh-Ren; Tsai, Ming-Ju; Tsai, Ying-Ming; Chong, Inn-Wen; Shieh, Jiunn-Min; Hsu, Ya-Ling

    2015-05-01

    Chronic inflammatory airway diseases like asthma and chronic obstructive pulmonary disease are major health problems globally. Airway epithelial cells play important role in airway remodeling, which is a critical process in the pathogenesis of diseases. This study aimed to demonstrate that LIGHT, an inflammatory factor secreted by T cells after allergen exposure, is responsible for promoting airway remodeling. LIGHT increased primary human bronchial epithelial cells (HBECs) undergoing epithelial-mesenchymal transition (EMT) and expressing MMP-9. The induction of EMT was associated with increased NF-κB activation and p300/NF-κB association. The interaction of NF-κB with p300 facilitated NF-κB acetylation, which in turn, was bound to the promoter of ZEB1, resulting in E-cadherin downregulation. LIGHT also stimulated HBECs to produce numerous cytokines/chemokines that could worsen airway inflammation. Furthermore, LIGHT enhanced HBECs to secrete activin A, which increased bronchial smooth muscle cell (BSMC) migration. In contrast, depletion of activin A decreased such migration. The findings suggest a new molecular determinant of LIGHT-mediated pathogenic changes in HBECs and that the LIGHT-related vicious cycle involving HBECs and BSMCs may be a potential target for the treatment of chronic inflammation airway diseases with airway remodeling. PMID:25251281

  1. Increased expression of senescence markers in cystic fibrosis airways.

    Science.gov (United States)

    Fischer, Bernard M; Wong, Jessica K; Degan, Simone; Kummarapurugu, Apparao B; Zheng, Shuo; Haridass, Prashamsha; Voynow, Judith A

    2013-03-15

    Cystic Fibrosis (CF) is a chronic lung disease characterized by chronic neutrophilic airway inflammation and increased levels of neutrophil elastase (NE) in the airways. We have previously reported that NE treatment triggers cell cycle arrest. Cell cycle arrest can lead to senescence, a complete loss of replicative capacity. Importantly, senescent cells can be proinflammatory and would perpetuate CF chronic inflammation. By immunohistochemistry, we evaluated whether airway sections from CF and control subjects expressed markers of senescence, including p16(INK4a) (p16), a cyclin-dependent kinase inhibitor, phospho-Histone H2A.X (γH2A.X), and phospho-checkpoint 2 kinase (phospho-Chk2), which are also DNA damage response markers. Compared with airway epithelium from control subjects, CF airway epithelium had increased levels of expression of all three senescence markers. We hypothesized that the high load of NE in the CF airway triggers epithelial senescence by upregulating expression of p16, which inhibits cyclin-dependent kinase 4 (CDK4). Normal human bronchial epithelial (NHBE) cells, cultured in air-liquid interface were treated with NE (0, 200, and 500 nM) to induce visible injury. Total cell lysates were collected and evaluated by Western analysis for p16 protein expression and CDK4 kinase activity. NE significantly increased p16 expression and decreased CDK4 kinase activity in NHBE cells. These results support the concept that NE triggers expression of senescence markers in CF airway epithelial cells. PMID:23316069

  2. Motorcycle exhaust particles induce airway inflammation and airway hyperresponsiveness in BALB/C mice.

    Science.gov (United States)

    Lee, Chen-Chen; Liao, Jiunn-Wang; Kang, Jaw-Jou

    2004-06-01

    A number of large studies have reported that environmental pollutants from fossil fuel combustion can cause deleterious effects to the immune system, resulting in an allergic reaction leading to respiratory tract damage. In this study, we investigated the effect of motorcycle exhaust particles (MEP), a major pollutant in the Taiwan urban area, on airway inflammation and airway hyperresponsiveness in laboratory animals. BALB/c mice were instilled intratracheally (i.t.) with 1.2 mg/kg and 12 mg/kg of MEP, which was collected from two-stroke motorcycle engines. The mice were exposed 3 times i.t. with MEP, and various parameters for airway inflammation and hyperresponsiveness were sequentially analyzed. We found that MEP would induce airway and pulmonary inflammation characterized by infiltration of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid (BALF) and inflammatory cell infiltration in lung. In addition, MEP treatment enhanced BALF interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) cytokine levels and serum IgE production. Bronchial response measured by unrestrained plethysmography with methacholine challenge showed that MEP treatment induced airway hyperresponsiveness (AHR) in BALB/c mice. The chemical components in MEP were further fractionated with organic solvents, and we found that the benzene-extracted fraction exerts a similar biological effect as seen with MEP, including airway inflammation, increased BALF IL-4, serum IgE production, and induction of AHR. In conclusion, we present evidence showing that the filter-trapped particles emitted from the unleaded-gasoline-fueled two-stroke motorcycle engine may induce proinflammatory and proallergic response profiles in the absence of exposure to allergen.

  3. 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.

  4. Narrow, duplicated internal auditory canal

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, T. [Servico de Neurorradiologia, Hospital Garcia de Orta, Avenida Torrado da Silva, 2801-951, Almada (Portugal); Shayestehfar, B. [Department of Radiology, UCLA Oliveview School of Medicine, Los Angeles, California (United States); Lufkin, R. [Department of Radiology, UCLA School of Medicine, Los Angeles, California (United States)

    2003-05-01

    A narrow internal auditory canal (IAC) constitutes a relative contraindication to cochlear implantation because it is associated with aplasia or hypoplasia of the vestibulocochlear nerve or its cochlear branch. We report an unusual case of a narrow, duplicated IAC, divided by a bony septum into a superior relatively large portion and an inferior stenotic portion, in which we could identify only the facial nerve. This case adds support to the association between a narrow IAC and aplasia or hypoplasia of the vestibulocochlear nerve. The normal facial nerve argues against the hypothesis that the narrow IAC is the result of a primary bony defect which inhibits the growth of the vestibulocochlear nerve. (orig.)

  5. Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13

    Directory of Open Access Journals (Sweden)

    Siddiqui Salman

    2010-07-01

    Full Text Available Abstract Background During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs function in the presence and absence of IL-13 and TNFα, cytokines known to be important in asthma. Method Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL samples from healthy subjects and those with asthma. Results PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL-13 and tumor necrosis factor (TNFα stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFα had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL fluid derived from healthy subjects as well as from those with asthma. Conclusion Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a

  6. A new compound, 1H,8H-pyrano[3,4-c]pyran-1,8-dione, suppresses airway epithelial cell inflammatory responses in a murine model of asthma.

    Science.gov (United States)

    Lee, H; Han, A R; Kim, Y; Choi, S H; Ko, E; Lee, N Y; Jeong, J H; Kim, S H; Bae, H

    2009-01-01

    Clinical and experimental studies have established eosinophilia as a sign of allergic disorders. Activation of eosinophils in the airways is believed to cause epithelial tissue injury, contraction of airway smooth muscle and increased bronchial responsiveness. As part of the search for new antiasthmatic agents produced by medicinal plants, the effects of 270 standardized medicinal plant extracts on cytokine-activated A549 human lung epithelial cells were evaluated. After several rounds of activity-guided screening, the new natural compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione (PPY), was isolated from Vitex rotundifolia L. To elucidate the mechanism by which the anti-asthmatic responses of PPY occurred in vitro, lung epithelial cells (A549 cell) were stimulated with TNF-alpha, IL-4 and IL-1beta to induce the expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. PPY treatments reduced the expression of eotaxin, IL-8, IL-16 and VCAM-1 mRNA significantly. Additionally, PPY reduced eotaxin secretion in a dose-dependent manner and significantly inhibited eosinophil migration toward A549 medium. In addition, PPY treatment suppressed the phosphorylation of p65 and ERK1/2, suggesting that it can inhibit the MAPK/NF-KB pathway. To clarify the anti-inflammatory and antiasthmatic effects of PPY in vivo, we examined the influence of PPY on the development of pulmonary eosinophilic inflammation in a murine model of asthma. To accomplish this, mice were sensitized and challenged with ovalbumin (OVA) and then examined for the following typical asthmatic reactions: an increase in the number of eosinophils in BALF; the presence of Th2 cytokines such as IL-4 and IL-5 in the BALF; the presence of allergen-specific IgE in the serum; and a marked influx of inflammatory cells into the lung. Taken together, our results revealed that PPY exerts profound inhibitory effects on the accumulation of eosinophils into the airways while reducing the levels of IL-4, IL-5

  7. Research Upregulation of CD23 (FcεRII Expression in Human Airway Smooth Muscle Cells (huASMC in Response to IL-4, GM-CSF, and IL-4/GM-CSF

    Directory of Open Access Journals (Sweden)

    Lew D Betty

    2005-05-01

    Full Text Available Abstract Background Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE. Methods Serum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence. Results The CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF. The percentage of cells with increased fluorescence intensity above the control was 25.1 ± 4.2% (IL-4, 15.6 ± 2.7% (GM-CSF and 32.9 ± 13.9% (IL-4/GMCSF combination(n = 3. The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Rα and a low level expression of IL-2Rγc in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rγc. Conclusion CD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in huASMC and may provide an avenue

  8. Research Upregulation of CD23 (FcεRII) Expression in Human Airway Smooth Muscle Cells (huASMC) in Response to IL-4, GM-CSF, and IL-4/GM-CSF

    Science.gov (United States)

    Belleau, Joseph T; Gandhi, Radha K; McPherson, Holly M; Lew, D Betty

    2005-01-01

    Background Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE. Methods Serum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence. Results The CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF. The percentage of cells with increased fluorescence intensity above the control was 25.1 ± 4.2% (IL-4), 15.6 ± 2.7% (GM-CSF) and 32.9 ± 13.9% (IL-4/GMCSF combination)(n = 3). The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Rα and a low level expression of IL-2Rγc in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rγc. Conclusion CD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in huASMC and may provide an avenue for new therapeutic options

  9. Predictors of Airway Hyperresponsiveness in Elite Athletes

    DEFF Research Database (Denmark)

    Toennesen, Louise L; Porsbjerg, Celeste; Pedersen, Lars;

    2015-01-01

    INTRODUCTION: Elite athletes frequently experience asthma and airway hyperresponsiveness (AHR). We aimed to investigate predictors of airway pathophysiology in a group of unselected elite summer-sport athletes, training for the summer 2008 Olympic Games, including markers of airway inflammation...

  10. Cholinergic regulation of airway inflammation and remodelling

    NARCIS (Netherlands)

    Kolahian, Saeed; Gosens, Reinoud

    2012-01-01

    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 disease

  11. [Effects of once-daily low-dose administration of sustained-release theophylline on airway inflammation and airway hyperresponsiveness in patients with asthma].

    Science.gov (United States)

    Terao, Ichiro

    2002-04-01

    Bronchial asthma is eosinophilic airway inflammation with enhanced airway responsiveness induced by eosinophilic granule proteins such as eosinophilic cationic protein (ECP) that are released from eosinophils. In the present study using 30 outpatients with mild to moderate asthma who had no history of treatment with steroid inhalation, we examined the effects of 4-week low-dose (200 mg/day) treatment with Uniphyl Tablets, a sustained-release theophylline formulated for once-daily dosing, on airway inflammation and airway hyperresponsiveness, as well as on respiratory function. Uniphyl Tablets significantly (p statistically significant (p V50 also showed statistically significant (p < 0.05) improvement. Mean blood theophylline concentration at the time the improvements were seen was 3.95 mg/mL. These results suggest that low-dose administration of Uniphyl Tablets has anti-airway inflammatory and anti-airway hyperresponsiveness effects in mild to moderate asthmatic patients.

  12. 哮喘豚鼠气道重塑与气道反应性 的图像分析%Image analysis of airway remodeling and responsiveness in asthmatic guinea pig

    Institute of Scientific and Technical Information of China (English)

    章晓初; 姚婉贞; 赵鸣武; 何其华; 陈月

    2001-01-01

    目的研究哮喘豚鼠气道重塑的机制及气道反应性的变化。方法实验分二组:对照组(20只)和哮喘组(20只),取双肺与不同刺激因素作用后作组织切片、HE染色,通过图像分析仪测定支气管内周长、管壁厚度、外周长,并计算平滑肌收缩百分比(PMS)。结果(1)哮喘组支气管壁厚度(WA/Pi)为(10.0±2.0)μm2/μm,支气管壁平滑肌厚度(平滑肌的面积/Pi)为(4.8±1.5)μm2/μm,对照组WA/Pi为(7.9±2.1)μm2/μm,平滑肌的面积/Pi为(3.1±2.0)μm2/μm,两组比较差异均有显著性(P<0.01),支气管壁平滑肌细胞核数量(N/Pi)哮喘组为(0.012 3±0.002 7)个/μm,对照组为(0.010±0.003)个/μm,两组比较差异有显著性(P<0.05)。(2)哮喘组气道平滑肌对腺苷的反应性(以PMS表示)为0.34±0.07,对照组为0.29±0.08,两组比较差异有显著性(P<0.05),联用氨茶碱和腺苷后,哮喘组PMS为0.26±0.07,与单用腺苷组(0.34±0.07)比较差异有显著性(P<0.01)。(3)在Ach作用下哮喘组的PMS为0.24±0.04,对照组为0.19±0.06,两组比较差异有显著性(P<0.05),联用肝素和Ach后,哮喘组PMS为0.20±0.04,与单用Ach组(0.24±0.04)比较差异有显著性(P<0.05)。结论哮喘气道平滑肌增生是气道重塑的主要原因,氨茶碱和肝素可以抑制气道对腺苷和乙酰胆碱的反应性。%Objective To observe the mechanism of airway remodeling and changes of airway responsiveness in guinea pig model of asthma. Methods 40 guinea pigs were randomly divided into two groups: control (20)and asthmatic group (20). After incubating with different stimulus, bilateral lung tissue section were stained with HE. Using image analysis system to measure the airway internal perimeter, wall area, external perimeter, etc. and calculate percentage of muscle shortening (PMS) according to formula

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

    Directory of Open Access Journals (Sweden)

    Morgan Carrie I

    2011-12-01

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

  14. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation

    DEFF Research Database (Denmark)

    Nassini, Romina; Pedretti, Pamela; Moretto, Nadia;

    2012-01-01

    inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express...... activation orchestrates an additional inflammatory response which is not neurogenic. This finding suggests that non-neuronal TRPA1 in the airways is functional and potentially capable of contributing to inflammatory airway diseases....... functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells...

  15. Airway emergencies in cancer

    Directory of Open Access Journals (Sweden)

    Patil Vijaya

    2007-01-01

    Full Text Available Management of airway obstruction is always challenging but more so in cancer setting, as obstruction can lie at any level right from pyriform fossa to low down in medistinum. Morbidity is significant but if not managed properly leads to frightful death by suffocation. These cases need to be evaluated, diagnosed and managed with care, skill, speed and appropriate intervention. With the advent of technology, it has become much easier to manage such situations with a team of specialists involving anesthetist, thoracic surgeon and intensivist.

  16. Dose-response met-RANTES treatment of experimental periodontitis: a narrow edge between the disease severity attenuation and infection control.

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Repeke

    Full Text Available Chemokines and chemokine receptors have been implicated in the selective migration of leukocyte subsets to periodontal tissues, which consequently influences the disease outcome. Among these chemoattractants, the chemokines CCL3, CCL4 and CCL5 and its receptors, CCR1 and CCR5, have been associated with increased disease severity in mice and humans. Therefore, in this study we investigated the modulation of experimental periodontitis outcome by the treatment with a specific antagonist of CCR1 and 5 receptors, called met-RANTES. C57Bl/6 mice was orally infected with Aggregatibacter actinomycetemcomitans and treated with 0.05, 0.1, 0.5, 1.5 and 5 mg doses of met-RANTES on alternate days, and evaluated by morphometric, cellular, enzymatic and molecular methods. At 0.5 mg up to 5 mg doses, a strong reduction in the alveolar bone loss and inflammatory cell migration were observed. Interestingly, 5 mg dose treatment resulted in the maximum inhibition of inflammatory cell migration, but resulted in a similar inhibition of bone loss when compared with the lower doses, and also resulted in increased bacterial load and CRP response. When 0.5 and 5 mg therapy regimens were compared it was observed that both therapeutic protocols were able to downregulate the levels of pro-inflammatory, Th1-type and osteoclastogenic cytokines, and CD3+ and F4/80+ cells migration to periodontal tissues, but the high dose modulates host response in a more pronounced and unspecific and excessive way, interfering also with the production of antimicrobial mediators such as MPO, iNOS and IgG, and with GR1+ and CD19+ cells migration. Our results demonstrate a thin line between beneficial immunoregulation and impaired host defense during experimental periodontitis, and the determination of the exact equilibrium point is mandatory for the improvement of immune-targeted therapy of periodontitis.

  17. Paediatric airway management: basic aspects

    DEFF Research Database (Denmark)

    Holm-Knudsen, R J; Rasmussen, L S

    2009-01-01

    children. This paper aims at providing the non-paediatric anaesthesiologist with a set of safe and simple principles for basic paediatric airway management. In contrast to adults, most children with difficult airways are recognised before induction of anaesthesia but problems may arise in all children...

  18. Clinical surveys on the incidence of asthma and airway hyper responsiveness in allergic rhinitis%变应性鼻炎患者潜在哮喘和下气道高反应的筛查研究

    Institute of Scientific and Technical Information of China (English)

    刘晓芳; 王向东; 王杨; 赵岩; 孙永昌; 张罗

    2012-01-01

    OBJECTIVE Allergic rhinitis and its impact on asthma (ARIA) questionnaire combined with indices in spirometric test may facilitate early diagnosis for asthma complicating in allergic rhinitis (AR) and for airway hyperresponsiveness (AHR) . METHODS A total of 306 AR patients without diagnosis of asthma received ARIA questionnaire, spirometric test and methacholine challenge test (MCT) to determine the incidence of asthma or AHR. The values corresponding to FEVi% and FEF25-75% were compared and ROC curves were plotted. RESULTS There were 127 cases with more than one positive response in the questionnaire, of which 24 cases showed positive response in pulmonary function diastole test, and 32 cases positive response in MCT. The omission diagnose rate of asthma was 18%, and the incidence of asthma in the cases with positive response was 44.1%. There were 179 cases with no positive response in the questionnaire, of which 41 cases were diagnosed as AHR with the incidence of 13%. The values of FEV1% and FEF25-75% in the different groups with MCT positive responses were significantly lower than those in the group with negative responses. Moreover, the ROC curves demonstrated the diagnostic accuracy of FEF25-75% was slightly higher than that of FEVi% for asthma or AHR. CONCLUSION ARIA questionnaire may help screen the combined asthma in AR. Some AR patients affiliated AHR. Damage in small airway function may prompt occurrence of asthma or AHR, and the related cases should receive MCT.%目的 探讨问卷调查结合肺功能发现变应性鼻炎(AR)合并哮喘和气道高反应性(airway hyperresponsiveness,AHR)的意义.方法 306例无哮喘的AR患者行问卷调查、肺功能乙酰甲胆碱激发试验(methacholine challenge test,MCT),诊断哮喘或AHR.比较第一秒用力呼气容积占预计值的百分比(FEV1%)和用力呼气中段流速(FEF25-75%)值,绘制ROC曲线.结果 127例有哮喘症状,24例肺功能舒张试验阳性,32

  19. Airway hyperresponsiveness in asthma: Mechanisms, Clinical Significance and Treatment

    Directory of Open Access Journals (Sweden)

    John Daniel Brannan

    2012-12-01

    Full Text Available Airway hyperresponsiveness (AHR and airway inflammation are key pathophysiological features of asthma. Bronchial provocation tests (BPTs are objective tests for AHR that are clinically useful to aid in the diagnosis of asthma. BPTs can be either ‘direct’ or ‘indirect’, referring to the mechanism by which a stimulus mediates bronchoconstriction. Direct BPTs refer to the administration of pharmacological agonist (e.g., methacholine or histamine that act on specific receptors on the airway smooth muscle. Airway inflammation and/or airway remodeling may be key determinants of the response to direct stimuli. Indirect BPTs are those in which the stimulus causes the release of mediators of bronchoconstriction from inflammatory cells (e.g., exercise, allergen, mannitol. Airway sensitivity to indirect stimuli is dependent upon the presence of inflammation (e.g., mast cells, eosinophils, which responds to treatment with inhaled corticosteroids (ICS. Thus, there is a stronger relationship between indices of steroid-sensitive inflammation (e.g., sputum eosinophils, fraction of exhaled nitric oxide and airway sensitivity to indirect compared to direct stimuli. Regular treatment with ICS does not result in the complete inhibition of responsiveness to direct stimuli. AHR to indirect stimuli identifies individuals that are highly likely to have a clinical improvement with ICS therapy in association with an inhibition of airway sensitivity following weeks to months of treatment with ICS. To comprehend the clinical utility of direct or indirect stimuli in either diagnosis of asthma or monitoring of therapeutic intervention requires an understanding of the underlying pathophysiology of AHR and mechanisms of action of both stimuli.

  20. Prostaglandin I2 enhances cough reflex sensitivity to capsaicin in the asthmatic airway

    OpenAIRE

    Ishiura, Yoshihisa; Fujimura, Masaki; Nobata, Kouichi; Oribe, Yoshitaka; Abo, Miki; Myou, Shigeharu

    2007-01-01

    Inflammatory mediators are involved in the pathogenesis of airway inflammation, but the role of prostaglandin I2 (PGI2) remains obscure. This study was designed to investigate the role of PGI2 in cough reflex sensitivity of the asthmatic airway, which is characterized by chronic eosinophilic airway inflammation. The effect of beraprost, a chemically and biologically stable analogue of PGI2, on cough response to inhaled capsaicin was examined in 21 patients with stable asthma in a randomized, ...

  1. Cryogenic Detectors (Narrow Field Instruments)

    Science.gov (United States)

    Hoevers, H.; Verhoeve, P.

    basic elements of the NFI 1 detector array. With a DROID-based array of 48 times 10 elements covering the NFI 1 field of view of 0.5 arcmin, the number of signal wires would already be reduced by a factor 2.4 compared to a 48 times 48 array of single pixels. While the present prototype DROIDS are still covered with a 480 nm thick SiOx insulation layer, this layer could easily be reduced in thickness or omitted. The detection efficiency of such a device with a 500 nm thick Ta absorber would be >80% in the energy range of 100-3000eV, without any disturbing contributions from other layers as in single STJs. Further developments involve devices of lower Tc-superconductors for better energy resolution and faster diffusion (e.g. Mo). The narrow field imager 2 The NFI 2 will consist of an array of 32 times 32 detector pixels. Each detector is a microcalorimeter which consists of a a superconducting to normal phase transition edge thermometer (transition edge sensor, TES) with an operating temperature of 100 mK, and an absorber which allows a detection efficiency of >90% and a filling factor of the focal plane in excess of 90%. Single pixel microcalorimeters with a Ti/Au TES have already shown an energy resolution of 3.9 eV at 5.89 keV in combination with a thermal response time of 100 mus. These results imply that they the high-energy requirement for XEUS can be met, in terms of energy resolution and response time. It has been demonstrated that bismuth can be applied as absorber material without impeding on the detector performance. Bi increases the stopping power in excess of 90 % and allows for a high filling factor since the absorber is can be modeled in the shape of a mushroom, allowing that the wiring to the detector and the thermal support structure are placed under the hat of the mushroom. In order to realize the NFI 2 detector array, there are two major development areas. Firstly, there is the development of micromachined Si and SiN structures that will provide proper

  2. Highly Visible Light Responsive, Narrow Band gap TiO2 Nanoparticles Modified by Elemental Red Phosphorus for Photocatalysis and Photoelectrochemical Applications

    Science.gov (United States)

    Ansari, Sajid Ali; Cho, Moo Hwan

    2016-05-01

    This paper reports that the introduction of elemental red phosphorus (RP) into TiO2 can shift the light absorption ability from the UV to the visible region, and confirmed that the optimal RP loading and milling time can effectively improve the visible light driven-photocatalytic activity of TiO2. The resulting RP-TiO2 nanohybrids were characterized systematically by a range of techniques and the photocatalytic ability of the RP-TiO2 photocatalysts was assessed further by the photodegradation of a model Rhodamine B pollutant under visible light irradiation. The results suggest that the RP-TiO2 has superior photodegradation ability for model contaminant decomposition compared to other well-known photocatalysts, such as TiO2 and other reference materials. Furthermore, as a photoelectrode, electrochemical impedance spectroscopy, differential pulse voltammetry, and linear scan voltammetry were also performed in the dark and under visible light irradiation. These photoelectrochemical performances of RP-TiO2 under visible light irradiation revealed more efficient photoexcited electron-hole separation and rapid charge transfer than under the dark condition, and thus improved photocatalytic activity. These findings show that the use of earth abundant and inexpensive red phosphorus instead of expensive plasmonic metals for inducing visible light responsive characteristics in TiO2 is an effective strategy for the efficient energy conversion of visible light.

  3. Fungal colonization with Pneumocystis correlates to increasing chloride channel accessory 1 (hCLCA1 suggesting a pathway for up-regulation of airway mucus responses, in infant lungs

    Directory of Open Access Journals (Sweden)

    Francisco J. Pérez

    2014-01-01

    Full Text Available Fungal colonization with Pneumocystis is associated with increased airway mucus in infants during their primary Pneumocystis infection, and to severity of COPD in adults. The pathogenic mechanisms are under investigation. Interestingly, increased levels of hCLCA1 – a member of the calcium-sensitive chloride conductance family of proteins that drives mucus hypersecretion – have been associated with increased mucus production in patients diagnosed with COPD and in immunocompetent rodents with Pneumocystis infection. Pneumocystis is highly prevalent in infants; therefore, the contribution of Pneumocystis to hCLCA1 expression was examined in autopsied infant lungs. Respiratory viruses that may potentially increase mucus, were also examined. hCLCA1 expression was measured using actin-normalized Western-blot, and the burden of Pneumocystis organisms was quantified by qPCR in 55 autopsied lungs from apparently healthy infants who died in the community. Respiratory viruses were diagnosed using RT-PCR for RSV, metapneumovirus, influenza, and parainfluenza viruses; and by PCR for adenovirus. hCLCA1 levels in virus positive samples were comparable to those in virus-negative samples. An association between Pneumocystis and increased hCLCA1 expression was documented (P=0.028. Additionally, increasing Pneumocystis burden correlated with increasing hCLCA1 protein expression levels (P=0.017. Results strengthen the evidence of Pneumocystis-associated up-regulation of mucus-related airway responses in infant lungs. Further characterization of this immunocompetent host-Pneumocystis-interaction, including assessment of potential clinical significance, is warranted.

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

    OpenAIRE

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

    2009-01-01

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

  5. Compliance Measurements of the Upper Airway in Pediatric Down Syndrome Sleep Apnea Patients.

    Science.gov (United States)

    Subramaniam, Dhananjay Radhakrishnan; Mylavarapu, Goutham; McConnell, Keith; Fleck, Robert J; Shott, Sally R; Amin, Raouf S; Gutmark, Ephraim J

    2016-04-01

    Compliance of soft tissue and muscle supporting the upper airway are two of several factors contributing to pharyngeal airway collapse. We present a novel, minimally invasive method of estimating regional variations in pharyngeal elasticity. Magnetic resonance images for pediatric sleep apnea patients with Down syndrome [9.5 ± 4.3 years (mean age ± standard deviation)] were analyzed to segment airways corresponding to baseline (no mask pressure) and two positive pressures. A three dimensional map was created to evaluate axial and circumferential variation in radial displacements of the airway, dilated by the positive pressures. The displacements were then normalized with respect to the appropriate transmural pressure and radius of an equivalent circle to obtain a measure of airway compliance. The resulting elasticity maps indicated the least and most compliant regions of the pharynx. Airway stiffness of the most compliant region [403 ± 204 (mean ± standard deviation) Pa] decreased with severity of obstructive sleep apnea. The non-linear response of the airway wall to continuous positive airway pressure was patient specific and varied between anatomical locations. We identified two distinct elasticity phenotypes. Patient phenotyping based on airway elasticity can potentially assist clinical practitioners in decision making on the treatments needed to improve airway patency.

  6. Increased Th2 cytokine secretion, eosinophilic airway inflammation, and airway hyperresponsiveness in neurturin-deficient mice.

    Science.gov (United States)

    Michel, Tatiana; Thérésine, Maud; Poli, Aurélie; Domingues, Olivia; Ammerlaan, Wim; Brons, Nicolaas H C; Hentges, François; Zimmer, Jacques

    2011-06-01

    Neurotrophins such as nerve growth factor and brain-derived neurotrophic factor have been described to be involved in the pathogenesis of asthma. Neurturin (NTN), another neurotrophin from the glial cell line-derived neurotrophic factor family, was shown to be produced by human immune cells: monocytes, B cells, and T cells. Furthermore, it was previously described that the secretion of inflammatory cytokines was dramatically stimulated in NTN knockout (NTN(-/-)) mice. NTN is structurally similar to TGF-β, a protective cytokine in airway inflammation. This study investigates the implication of NTN in a model of allergic airway inflammation using NTN(-/-) mice. The bronchial inflammatory response of OVA-sensitized NTN(-/-) mice was compared with wild-type mice. Airway inflammation, Th2 cytokines, and airway hyperresponsiveness (AHR) were examined. NTN(-/-) mice showed an increase of OVA-specific serum IgE and a pronounced worsening of inflammatory features. Eosinophil number and IL-4 and IL-5 concentration in the bronchoalveolar lavage fluid and lung tissue were increased. In parallel, Th2 cytokine secretion of lung draining lymph node cells was also augmented when stimulated by OVA in vitro. Furthermore, AHR was markedly enhanced in NTN(-/-) mice after sensitization and challenge when compared with wild-type mice. Administration of NTN before challenge with OVA partially rescues the phenotype of NTN(-/-) mice. These findings provide evidence for a dampening role of NTN on allergic inflammation and AHR in a murine model of asthma. PMID:21508262

  7. Narrow-Band Microwave Filters

    Directory of Open Access Journals (Sweden)

    A.V. Strizhachenko

    2010-01-01

    Full Text Available Original design of the narrow-band compact filters based on the high-quality waveguide-dielectric resonator with anisotropic materials has been presented in this work. Designed filters satisfy the contradictory requirements: they provide the narrow frequency band (0.05 ÷ 0.1 % of the main frequency f0 and the low initial losses α0 ≤ 1 dB.

  8. Vessel-guided Airway Tree Segmentation

    DEFF Research Database (Denmark)

    Lo, P.; Sporring, J.; Ashraf, H.;

    2010-01-01

    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. 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...

  9. Possible role of differential growth in airway wall remodeling in asthma

    KAUST Repository

    Moulton, D. E.

    2011-01-20

    Possible role of differential growth in airway wall remodeling in asthma. J Appl Physiol 110: 1003-1012, 2011. First published January 20, 2011; doi:10.1152/japplphysiol.00991.2010.- Airway remodeling in patients with chronic asthma is characterized by a thickening of the airway walls. It has been demonstrated in previous theoretical models that this change in thickness can have an important mechanical effect on the properties of the wall, in particular on the phenomenon of mucosal folding induced by smooth muscle contraction. In this paper, we present a model for mucosal folding of the airway in the context of growth. The airway is modeled as a bilayered cylindrical tube, with both geometric and material nonlinearities accounted for via the theory of finite elasticity. Growth is incorporated into the model through the theory of morphoelasticity. We explore a range of growth possibilities, allowing for anisotropic growth as well as different growth rates in each layer. Such nonuniform growth, referred to as differential growth, can change the properties of the material beyond geometrical changes through the generation of residual stresses. We demonstrate that differential growth can have a dramatic impact on mucosal folding, in particular on the critical pressure needed to induce folding, the buckling pattern, as well as airway narrowing. We conclude that growth may be an important component in airway remodeling. Copyright © 2011 the American Physiological Society.

  10. Rare Upper Airway Anomalies.

    Science.gov (United States)

    Windsor, Alanna; Clemmens, Clarice; Jacobs, Ian N

    2016-01-01

    A broad spectrum of congenital upper airway anomalies can occur as a result of errors during embryologic development. In this review, we will describe the clinical presentation, diagnosis, and management strategies for a few select, rare congenital malformations of this system. The diagnostic tools used in workup of these disorders range from prenatal tests to radiological imaging, swallowing evaluations, indirect or direct laryngoscopy, and rigid bronchoscopy. While these congenital defects can occur in isolation, they are often associated with disorders of other organ systems or may present as part of a syndrome. Therefore workup and treatment planning for patients with these disorders often involves a team of multiple specialists, including paediatricians, otolaryngologists, pulmonologists, speech pathologists, gastroenterologists, and geneticists. PMID:26277452

  11. 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 that is trai......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...... that is trained to differentiate between airway and non-airway voxels. Vessel and airway orientation information are used in the form of a vessel orientation similarity measure, which indicates how similar the orientation of the an airway candidate is to the orientation of the neighboring vessel. The method...

  12. Airway vascular reactivity and vascularisation in human chronic airway disease

    NARCIS (Netherlands)

    Bailey, Simon R; Boustany, Sarah; Burgess, Janette K; Hirst, Stuart J; Sharma, Hari S; Simcock, David E; Suravaram, Padmini R; Weckmann, Markus

    2009-01-01

    Altered bronchial vascular reactivity and remodelling including angiogenesis are documented features of asthma and other chronic inflammatory airway diseases. Expansion of the bronchial vasculature under these conditions involves both functional (vasodilation, hyperperfusion, increased microvascular

  13. Airway Smooth Muscle Hypercontractility in Asthma

    Directory of Open Access Journals (Sweden)

    Rachid Berair

    2013-01-01

    Full Text Available In recent years, asthma has been defined primarily as an inflammatory disorder with emphasis on inflammation being the principle underlying pathophysiological characteristic driving airway obstruction and remodelling. Morphological abnormalities of asthmatic airway smooth muscle (ASM, the primary structure responsible for airway obstruction seen in asthma, have long been described, but surprisingly, until recently, relatively small number of studies investigated whether asthmatic ASM was also fundamentally different in its functional properties. Evidence from recent studies done on single ASM cells and on ASM-impregnated gel cultures have shown that asthmatic ASM is intrinsically hypercontractile. Several elements of the ASM contraction apparatus in asthmatics and in animal models of asthma have been found to be different from nonasthmatics. These differences include some regulatory contractile proteins and also some components of both the calcium-dependent and calcium-independent contraction signalling pathways. Furthermore, oxidative stress was also found to be heightened in asthmatic ASM and contributes to hypercontractility. Understanding the abnormalities and mechanisms driving asthmatic ASM hypercontractility provides a great potential for the development of new targeted drugs, other than the conventional current anti-inflammatory and bronchodilator therapies, to address the desperate unmet need especially in patients with severe and persistent asthma.

  14. Lentiviral vector gene transfer to porcine airways.

    Science.gov (United States)

    Sinn, Patrick L; Cooney, Ashley L; Oakland, Mayumi; Dylla, Douglas E; Wallen, Tanner J; Pezzulo, Alejandro A; Chang, Eugene H; McCray, Paul B

    2012-01-01

    In this study, we investigated lentiviral vector development and transduction efficiencies in well-differentiated primary cultures of pig airway epithelia (PAE) and wild-type pigs in vivo. We noted gene transfer efficiencies similar to that observed for human airway epithelia (HAE). Interestingly, feline immunodeficiency virus (FIV)-based vectors transduced immortalized pig cells as well as pig primary cells more efficiently than HIV-1-based vectors. PAE express TRIM5α, a well-characterized species-specific lentiviral restriction factor. We contrasted the restrictive properties of porcine TRIM5α against FIV- and HIV-based vectors using gain and loss of function approaches. We observed no effect on HIV-1 or FIV conferred transgene expression in response to porcine TRIM5α overexpression or knockdown. To evaluate the ability of GP64-FIV to transduce porcine airways in vivo, we delivered vector expressing mCherry to the tracheal lobe of the lung and the ethmoid sinus of 4-week-old pigs. One week later, epithelial cells expressing mCherry were readily detected. Our findings indicate that pseudotyped FIV vectors confer similar tropisms in porcine epithelia as observed in human HAE and provide further support for the selection of GP64 as an appropriate envelope pseudotype for future preclinical gene therapy studies in the porcine model of cystic fibrosis (CF).Molecular Therapy - Nucleic Acids (2012) 1, e56; doi:10.1038/mtna.2012.47; published online 27 November 2012. PMID:23187455

  15. Regulation of actin dynamics by WNT-5A: implications for human airway smooth muscle contraction

    NARCIS (Netherlands)

    Koopmans, Tim; Kumawat, Kuldeep; Halayko, Andrew J; Gosens, Reinoud

    2016-01-01

    A defining feature of asthma is airway hyperresponsiveness (AHR), which underlies the exaggerated bronchoconstriction response of asthmatics. The role of the airway smooth muscle (ASM) in AHR has garnered increasing interest over the years, but how asthmatic ASM differs from healthy ASM is still an

  16. WNT-5A and WNT-5B modulate calcium homeostasis in airway smooth muscle

    NARCIS (Netherlands)

    Koopmans, Tim; Kumawat, Kudleer; Van Den Berge, Maarten; Hoffmann, Roland; Halayko, Andrew J.; Gosens, Reinoud

    2014-01-01

    Rationale Airway hyperresponsiveness is a common feature of asthma explained in part by an excessive contractile response of the airway smooth muscle (ASM). The underlying mechanisms are complex and in need of study. WNT-5A and WNT-5B, two members of the WNT signaling pathway, may be of significance

  17. CORRELATES BETWEEN HUMAN LUNG INJURY AFTER PARTICLE EXPOSURE AND RECURRENT AIRWAY OBSTRUCTION IN THE HORSE

    Science.gov (United States)

    Characteristics of the clinical presentation, physiologic changes, and pathology of the human response to particulate matter (PM) are comparable to inflammatory airway disease (lAD) and recurrent airway obstruction (RAO)lheaves in the horse. Both present with symptoms of cough,...

  18. AIRWAY HYPERRESPONSIVENESS AND THE PREVALENCE OF WORK-RELATED SYMPTOMS IN WORKERS EXPOSED TO IRRITANTS

    NARCIS (Netherlands)

    KREMER, AM; PAL, TM; BOLEIJ, JSM; SCHOUTEN, JP; RIJCKEN, B

    1994-01-01

    The association between exposure to airway irritants and the presence of work-related symptoms and whether this association was modified by airway hyper-responsiveness, smoking, and allergy by history was studied in 668 workers of synthetic fiber plants. A Dutch version of the British Medical Resear

  19. Effects of a mandibular advancement device on the upper airway morphology : a cephalometric analysis

    NARCIS (Netherlands)

    Doff, M. H. J.; Hoekema, A.; Pruim, G. J.; van der Hoeven, J. H.; de Bont, L. G. M.; Stegenga, B.

    2009-01-01

    The aims of this study were to assess changes in the upper airway morphology associated with an oral appliance in situ in patients suffering from the obstructive sleep apnoea-hypopnoea syndrome and to relate these changes to treatment response. Changes in upper airway morphology as a result of an or

  20. Structural and functional localization of airway effects from episodic exposure of infant monkeys to allergen and/or ozone

    International Nuclear Information System (INIS)

    Both allergen and ozone exposure increase asthma symptoms and airway responsiveness in children. Little is known about how these inhalants may differentially modify airway responsiveness in large proximal as compared to small distal airways. We evaluated whether bronchi and respiratory bronchioles from infant monkeys exposed episodically to allergen and/or ozone differentially develop intrinsic hyperresponsiveness to methacholine and whether eosinophils and/or pulmonary neuroendocrine cells play a role. Infant monkeys were exposed episodically for 5 months to: (1) filtered air, (2) aerosolized house dust mite allergen, (3) ozone 0.5 ppm, or (4) house dust mite allergen + ozone. Studying the function/structure relationship of the same lung slices, we evaluated methacholine airway responsiveness and histology of bronchi and respiratory bronchioles. In bronchi, intrinsic responsiveness was increased by allergen exposure, an effect reduced by bombesin antagonist. In respiratory bronchioles, intrinsic airway responsiveness was increased by allergen + ozone exposure. Eosinophils were increased by allergen and allergen + ozone exposure in bronchi and by allergen exposure in respiratory bronchioles. In both airways, exposure to allergen + ozone resulted in fewer tissue eosinophils than did allergen exposure alone. In bronchi, but not in respiratory bronchioles, the number of eosinophils and neuroendocrine cells correlated with airway responsiveness. We conclude that episodically exposing infant monkeys to house dust mite allergen with or without ozone increased intrinsic airway responsiveness to methacholine in bronchi differently than in respiratory bronchioles. In bronchi, eosinophils and neuroendocrine cells may play a role in the development of airway hyperresponsiveness

  1. Research Upregulation of CD23 (FcεRII) Expression in Human Airway Smooth Muscle Cells (huASMC) in Response to IL-4, GM-CSF, and IL-4/GM-CSF

    OpenAIRE

    Lew D Betty; McPherson Holly M; Gandhi Radha K; Belleau Joseph T

    2005-01-01

    Abstract Background Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE. Methods Serum starved huASMC were stimulated with either IL-4, GM...

  2. ISO-1, a Macrophage Migration Inhibitory Factor Antagonist, Inhibits Airway Remodeling in a Murine Model of Chronic Asthma

    OpenAIRE

    Chen, Pei-Fen; Luo, Ya-ling; Wang, Wei; Wang, Jiang-xin; Lai, Wen-yan; Hu, Si-ming; Cheng, Kai Fan; Al-Abed, Yousef

    2010-01-01

    Airway remodeling is the process of airway structural change that occurs in patients with asthma in response to persistent inflammation and leads to increasing disease severity. Drugs that decrease this persistent inflammation play a crucial role in managing asthma episodes. Mice sensitized (by intraperitoneal administration) and then challenged (by inhalation) with ovalbumin (OVA) develop an extensive eosinophilic inflammatory response, goblet cell hyperplasia, collagen deposition, airway sm...

  3. Nucleotide-mediated airway clearance.

    Science.gov (United States)

    Schmid, Andreas; Clunes, Lucy A; Salathe, Mathias; Verdugo, Pedro; Dietl, Paul; Davis, C William; Tarran, Robert

    2011-01-01

    A thin layer of airway surface liquid (ASL) lines the entire surface of the lung and is the first point of contact between the lung and the environment. Surfactants contained within this layer are secreted in the alveolar region and are required to maintain a low surface tension and to prevent alveolar collapse. Mucins are secreted into the ASL throughout the respiratory tract and serve to intercept inhaled pathogens, allergens and toxins. Their removal by mucociliary clearance (MCC) is facilitated by cilia beating and hydration of the ASL by active ion transport. Throughout the lung, secretion, ion transport and cilia beating are under purinergic control. Pulmonary epithelia release ATP into the ASL which acts in an autocrine fashion on P2Y(2) (ATP) receptors. The enzymatic network describes in Chap. 2 then mounts a secondary wave of signaling by surface conversion of ATP into adenosine (ADO), which induces A(2B) (ADO) receptor-mediated responses. This chapter offers a comprehensive description of MCC and the extensive ramifications of the purinergic signaling network on pulmonary surfaces. PMID:21560046

  4. Viral bronchiolitis in young rats causes small airway lesions that correlate with reduced lung function.

    Science.gov (United States)

    Sorkness, Ronald L; Szakaly, Renee J; Rosenthal, Louis A; Sullivan, Ruth; Gern, James E; Lemanske, Robert F; Sun, Xin

    2013-11-01

    Viral illness with wheezing during infancy is associated with the inception of childhood asthma. Small airway dysfunction is a component of childhood asthma, but little is known about how viral illness at an early age may affect the structure and function of small airways. We used a well-characterized rat model of postbronchiolitis chronic airway dysfunction to address how postinfectious small airway lesions affect airway physiological function and if the structure/function correlates persist into maturity. Brown Norway rats were sham- or virus inoculated at 3 to 4 weeks of age and allowed to recover from the acute illness. At 3 to 14 months of age, physiology (respiratory system resistance, Newtonian resistance, tissue damping, and static lung volumes) was assessed in anesthetized, intubated rats. Serial lung sections revealed lesions in the terminal bronchioles that reduced luminal area and interrupted further branching, affecting 26% (range, 13-39%) of the small airways at 3 months of age and 22% (range, 6-40%) at 12 to 14 months of age. At 3 months of age (n = 29 virus; n = 7 sham), small airway lesions correlated with tissue damping (rs = 0.69) but not with Newtonian resistance (rs = 0.23), and Newtonian resistance was not elevated compared with control rats, indicating that distal airways were primarily responsible for the airflow obstruction. Older rats (n = 7 virus; n = 6 sham) had persistent small airway dysfunction and significantly increased Newtonian resistance in the postbronchiolitis group. We conclude that viral airway injury at an early age may induce small airway lesions that are associated quantitatively with small airway physiological dysfunction early on and that these defects persist into maturity.

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

    Science.gov (United States)

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

    2009-06-01

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

  6. 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

    the examination and registration of predictors for difficult mask ventilation with a non-specified clinical airway assessment on prediction of difficult mask ventilation.Method/Design: We cluster-randomized 28 Danish departments of anaesthesia to airway assessment either by the SARI or by usual non......-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...... reduction equalling a number needed to treat of 180. Sample size estimation is adjusted for the study design and based on standards for randomization on cluster-level. With an average cluster size of 2,500 patients, 70,000 patients will be enrolled over a 1-year trial period. The database is programmed so...

  7. Methacholine-Induced Variations in Airway Volume and the Slope of the Alveolar Capnogram Are Distinctly Associated with Airflow Limitation and Airway Closure.

    Science.gov (United States)

    Plantier, Laurent; Marchand-Adam, Sylvain; Boyer, Laurent; Taillé, Camille; Delclaux, Christophe

    2015-01-01

    Mechanisms driving alteration of lung function in response to inhalation of a methacholine aerosol are incompletely understood. To explore to what extent large and small airways contribute to airflow limitation and airway closure in this context, volumetric capnography was performed before (n = 93) and after (n = 78) methacholine provocation in subjects with an intermediate clinical probability of asthma. Anatomical dead space (VDaw), reflecting large airway volume, and the slope of the alveolar capnogram (slope3), an index of ventilation heterogeneity linked to small airway dysfunction, were determined. At baseline, VDaw was positively correlated with lung volumes, FEV1 and peak expiratory flow, while slope3 was not correlated with any lung function index. Variations in VDaw and slope3 following methacholine stimulation were correlated to a small degree (R2 = -0.20). Multivariate regression analysis identified independent associations between variation in FEV1 and variations in both VDaw (Standardized Coefficient-SC = 0.66) and Slope3 (SC = 0.35). By contrast, variation in FVC was strongly associated with variations in VDaw (SC = 0.8) but not Slope3. Thus, alterations in the geometry and/or function of large and small airways were weakly correlated and contributed distinctly to airflow limitation. While both large and small airways contributed to airflow limitation as assessed by FEV1, airway closure as assessed by FVC reduction mostly involved the large airways. PMID:26599006

  8. Methacholine-Induced Variations in Airway Volume and the Slope of the Alveolar Capnogram Are Distinctly Associated with Airflow Limitation and Airway Closure.

    Directory of Open Access Journals (Sweden)

    Laurent Plantier

    Full Text Available Mechanisms driving alteration of lung function in response to inhalation of a methacholine aerosol are incompletely understood. To explore to what extent large and small airways contribute to airflow limitation and airway closure in this context, volumetric capnography was performed before (n = 93 and after (n = 78 methacholine provocation in subjects with an intermediate clinical probability of asthma. Anatomical dead space (VDaw, reflecting large airway volume, and the slope of the alveolar capnogram (slope3, an index of ventilation heterogeneity linked to small airway dysfunction, were determined. At baseline, VDaw was positively correlated with lung volumes, FEV1 and peak expiratory flow, while slope3 was not correlated with any lung function index. Variations in VDaw and slope3 following methacholine stimulation were correlated to a small degree (R2 = -0.20. Multivariate regression analysis identified independent associations between variation in FEV1 and variations in both VDaw (Standardized Coefficient-SC = 0.66 and Slope3 (SC = 0.35. By contrast, variation in FVC was strongly associated with variations in VDaw (SC = 0.8 but not Slope3. Thus, alterations in the geometry and/or function of large and small airways were weakly correlated and contributed distinctly to airflow limitation. While both large and small airways contributed to airflow limitation as assessed by FEV1, airway closure as assessed by FVC reduction mostly involved the large airways.

  9. Upper airway finding on CT scan with and without nasal CPAP in obstructive sleep apnea patients

    International Nuclear Information System (INIS)

    The area of upper airway (from the nasopharynx to the hypopharynx) was measured by means of computed tomography (CT) scan in 15 confirmed cases of obstructive sleep apnea (OSA) and in 4 normal controls while they were awake. The minimum cross-sectional area (MA) of the upper airway was 14.7±20.0 mm2 in OSA patients and 80.0±33.1 mm2 in normal controls and the difference was statistically significant (p2 and lowest SO2. MA was also measured with OSA patients while nasal continuous positive airway pressure (NCPAP) of 10 cmH2O was applied and it was found that MA was significantly widened when NCPAP therapy was performed. We conclude that upper airway narrowing is consistent finding in OSA patients but the degree of narrowing does not correlate with parameters of apnea and gas exchange during sleep, and NCPAP is effective to widen the area of upper airway in OSA patients. (author)

  10. Upper airway finding on CT scan with and without nasal CPAP in obstructive sleep apnea patients

    Energy Technology Data Exchange (ETDEWEB)

    Akashiba, Tsuneto; Sasaki, Iwao; Kurashina, Keiji; Yoshizawa, Takayuki; Otsuka, Kenzo; Horie, Takashi (Nihon Univ., Tokyo (Japan). School of Medicine)

    1991-04-01

    The area of upper airway (from the nasopharynx to the hypopharynx) was measured by means of computed tomography (CT) scan in 15 confirmed cases of obstructive sleep apnea (OSA) and in 4 normal controls while they were awake. The minimum cross-sectional area (MA) of the upper airway was 14.7+-20.0 mm{sup 2} in OSA patients and 80.0+-33.1 mm{sup 2} in normal controls and the difference was statistically significant (p<0.01). In OSA patients, MA did not correlate with age, body weight, apnea index, desaturation index, mean nadir-SO{sub 2} and lowest SO{sub 2}. MA was also measured with OSA patients while nasal continuous positive airway pressure (NCPAP) of 10 cmH{sub 2}O was applied and it was found that MA was significantly widened when NCPAP therapy was performed. We conclude that upper airway narrowing is consistent finding in OSA patients but the degree of narrowing does not correlate with parameters of apnea and gas exchange during sleep, and NCPAP is effective to widen the area of upper airway in OSA patients. (author).

  11. 不同剂量致敏原对小鼠哮喘模型气道反应性的影响%Different doeses of ovalbumin sensitization in airway responsiveness in a murine model of asthma

    Institute of Scientific and Technical Information of China (English)

    唐晓媛; 于化鹏; 邓火金; 陈新; 樊慧珍; 龚雨新; 刘俊芳

    2011-01-01

    目的:探讨不同剂量致敏原鸡卵蛋白(OVA)制备哮喘模型时对哮喘小鼠气道反应性的影响.方法:将30只BALB/c小鼠随机分为哮喘组和正常对照组(C组),哮喘组又分为小剂量OVA致敏组(A组)和大剂量OVA致敏组(B组),每组各10只.A、B组在开始和第14天时给予含OVA的致敏液200 μl(A组含10 μg OVA,B组含2 mg OVA,两者含同样的氢氧化铝及生理盐水),21 d开始雾化吸入OVA,连续雾化6 d,操作时观察小鼠活动及呼吸情况;各组分别于末次雾化激发24 h后测定小鼠的无创肺功能中的增强呼气间歇(Penh)值以评价气道反应性;对支气管肺泡灌洗液(BALF)行细胞总数、嗜酸粒细胞计数;取肺组织作HE染色病理切片;ELISA方法测外周血、BALF上清液中的IgE、IFN-γ含量.结果:哮喘B组在第二次致敏后可见喘息、呼吸困难、口唇和尾巴黏膜发紫表现,并在雾化时出现扭体、燥动、呼吸加快等症状.哮喘A、B组的Penh值明显高于C组(P0.05).结论:哮喘小鼠组模型制备成功.在观察气道高反应方面,较高剂量OVA致敏哮喘模型较低剂量OVA致敏的气道高反应性更敏感.%Objective: To explore the different does of ovalbumin(OVA) sensitization whether have influences on airway hyper responsiveness of mice model of asthma.Methods: The mice were randomly divided into 3 groups,with 10 mice in each group: control group and asthmatic groups( including asthma A group, the does of OVA sensitization was 10 μg every time; and asthma B group,which was 2 rog).The asthmatic A and B group were sensitized on the 0th, 14th day with different does of OVA, then inhaled OVA beginning on the 21st day for 6 days.Meanwhile the breathing and the color of oral and tail mucosa were monitered.The last time OVA stimulated and 24 hours later, Penh were measured to evaluate the airway responsiveness by noninvasive lung functional instrument,bronchoalveolar lavage cytology was performed and lung tissue

  12. Comparison of threshold estimation in infants with hearing loss or normal hearing using auditory steady-state response evoked by narrow band CE-chirps and auditory brainstem response evoked by tone pips

    DEFF Research Database (Denmark)

    Michel, Franck; Jørgensen, Kristoffer Foldager

    2016-01-01

    OBJECTIVE: The objective of this study is to compare air-conduction thresholds obtained with ASSR evoked by narrow band (NB) CE-chirps and ABR evoked by tone pips (tpABR) in infants with various degrees of hearing loss. DESIGN: Thresholds were measured at 500, 1000, 2000 and 4000 Hz. Data on each...... participant were collected at the same day. STUDY SAMPLE: Sixty-seven infants aged 4 d to 22 months (median age = 96 days), resulting in 57, 52, 87 and 56 ears for 500, 1000, 2000 and 4000 Hz, respectively. RESULTS: Statistical analysis was performed for ears with hearing loss (HL) and showed a very strong.......7). Linear regression analysis indicated that the relationship was not influenced by the degree of hearing loss. CONCLUSION: We propose that dB nHL to dB eHL correction values for ASSR evoked by NB CE-chirps should be 5 dB lower than values used for tpABR....

  13. Analysis of airways in computed tomography

    DEFF Research Database (Denmark)

    Petersen, Jens

    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...... of scan on airway dimensions in subjects with and without COPD. The results show measured airway dimensions to be affected by differences in the level of inspiration and this dependency is again influenced by COPD. Inspiration level should therefore be accounted for when measuring airways, and airway...

  14. Role of Small Airways in Asthma.

    Science.gov (United States)

    Finkas, Lindsay K; Martin, Richard

    2016-08-01

    Asthma is an inflammatory condition of both the small and large airways. Recently the small airways have gained attention as studies have shown significant inflammation in the small airways in all severities of asthma. This inflammation has correlated with peripheral airway resistance and as a result, noninvasive methods to reliably measure small airways have been pursued. In addition, recent changes in asthma inhalers have led to alterations in drug formulations and the development of extrafine particle inhalers that improve delivery to the distal airways. PMID:27401620

  15. The effects of emphysema on airway disease: Correlations between multi-detector CT and pulmonary function tests in smokers

    Energy Technology Data Exchange (ETDEWEB)

    Yahaba, Misuzu, E-mail: mis_misuzu@yahoo.co.jp; Kawata, Naoko, E-mail: chumito_03@yahoo.co.jp; Iesato, Ken, E-mail: iesato_k@yahoo.co.jp; Matsuura, Yukiko, E-mail: matsuyuki_future@yahoo.co.jp; Sugiura, Toshihiko, E-mail: sugiura@js3.so-net.ne.jp; Kasai, Hajime, E-mail: daikasai6075@yahoo.co.jp; Sakurai, Yoriko, E-mail: yoliri@nifty.com; Terada, Jiro, E-mail: jirotera@chiba-u.jp; Sakao, Seiichiro, E-mail: sakao@faculty.chiba-u.jp; Tada, Yuji, E-mail: ytada@faculty.chiba-u.jp; Tanabe, Nobuhiro, E-mail: ntanabe@faculty.chiba-u.jp; Tatsumi, Koichiro, E-mail: tatsumi@faculty.chiba-u.jp

    2014-06-15

    Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and small airway narrowing. Quantitative evaluation of airway dimensions by multi-detector computed tomography (MDCT) has revealed a correlation between airway dimension and airflow limitation. However, the effect of emphysema on this correlation is unclear. Objective: The goal of this study was to determine whether emphysematous changes alter the relationships between airflow limitation and airway dimensions as measured by inspiratory and expiratory MDCT. Methods: Ninety-one subjects underwent inspiratory and expiratory MDCT. Images were evaluated for mean airway luminal area (Ai), wall area percentage (WA%) from the third to the fifth generation of three bronchi (B1, B5, B8) in the right lung, and low attenuation volume percent (LAV%). Correlations between each airway index and airflow limitation were determined for each patient and compared between patients with and without evidence of emphysema. Results: In patients without emphysema, Ai and WA% from both the inspiratory and expiratory scans were significantly correlated with FEV{sub 1.} No correlation was detected in patients with emphysema. In addition, emphysematous COPD patients with GOLD stage 1 or 2 disease had significantly lower changes in B8 Ai than non-emphysematous patients. Conclusions: A significant correlation exists between airway parameters and FEV{sub 1} in patients without emphysema. Emphysema may influence airway dimensions even in patients with mild to moderate COPD.

  16. The effects of emphysema on airway disease: Correlations between multi-detector CT and pulmonary function tests in smokers

    International Nuclear Information System (INIS)

    Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and small airway narrowing. Quantitative evaluation of airway dimensions by multi-detector computed tomography (MDCT) has revealed a correlation between airway dimension and airflow limitation. However, the effect of emphysema on this correlation is unclear. Objective: The goal of this study was to determine whether emphysematous changes alter the relationships between airflow limitation and airway dimensions as measured by inspiratory and expiratory MDCT. Methods: Ninety-one subjects underwent inspiratory and expiratory MDCT. Images were evaluated for mean airway luminal area (Ai), wall area percentage (WA%) from the third to the fifth generation of three bronchi (B1, B5, B8) in the right lung, and low attenuation volume percent (LAV%). Correlations between each airway index and airflow limitation were determined for each patient and compared between patients with and without evidence of emphysema. Results: In patients without emphysema, Ai and WA% from both the inspiratory and expiratory scans were significantly correlated with FEV1. No correlation was detected in patients with emphysema. In addition, emphysematous COPD patients with GOLD stage 1 or 2 disease had significantly lower changes in B8 Ai than non-emphysematous patients. Conclusions: A significant correlation exists between airway parameters and FEV1 in patients without emphysema. Emphysema may influence airway dimensions even in patients with mild to moderate COPD

  17. Concomitant exposure to ovalbumin and endotoxin augments airway inflammation but not airway hyperresponsiveness in a murine model of asthma.

    Science.gov (United States)

    Mac Sharry, John; Shalaby, Karim H; Marchica, Cinzia; Farahnak, Soroor; Chieh-Li, Tien; Lapthorne, Susan; Qureshi, Salman T; Shanahan, Fergus; Martin, James G

    2014-01-01

    Varying concentrations of lipopolysaccharide (LPS) in ovalbumin (OVA) may influence the airway response to allergic sensitization and challenge. We assessed the contribution of LPS to allergic airway inflammatory responses following challenge with LPS-rich and LPS-free commercial OVA. BALB/c mice were sensitized with LPS-rich OVA and alum and then underwent challenge with the same OVA (10 µg intranasally) or an LPS-free OVA. Following challenge, bronchoalveolar lavage (BAL), airway responsiveness to methacholine and the lung regulatory T cell population (Treg) were assessed. Both OVA preparations induced BAL eosinophilia but LPS-rich OVA also evoked BAL neutrophilia. LPS-free OVA increased interleukin (IL)-2, IL-4 and IL-5 whereas LPS-rich OVA additionally increased IL-1β, IL-12, IFN-γ, TNF-α and KC. Both OVA-challenged groups developed airway hyperresponsiveness. TLR4-deficient mice challenged with either OVA preparation showed eosinophilia but not neutrophilia and had increased IL-5. Only LPS-rich OVA challenged mice had increased lung Tregs and LPS-rich OVA also induced in vitro Treg differentiation. LPS-rich OVA also induced a Th1 cytokine response in human peripheral blood mononuclear cells.We conclude that LPS-rich OVA evokes mixed Th1, Th2 and innate immune responses through the TLR-4 pathway, whereas LPS-free OVA evokes only a Th2 response. Contaminating LPS is not required for induction of airway hyperresponsiveness but amplifies the Th2 inflammatory response and is a critical mediator of the neutrophil, Th1 and T regulatory cell responses to OVA. PMID:24968337

  18. Concomitant exposure to ovalbumin and endotoxin augments airway inflammation but not airway hyperresponsiveness in a murine model of asthma.

    Directory of Open Access Journals (Sweden)

    John Mac Sharry

    Full Text Available Varying concentrations of lipopolysaccharide (LPS in ovalbumin (OVA may influence the airway response to allergic sensitization and challenge. We assessed the contribution of LPS to allergic airway inflammatory responses following challenge with LPS-rich and LPS-free commercial OVA. BALB/c mice were sensitized with LPS-rich OVA and alum and then underwent challenge with the same OVA (10 µg intranasally or an LPS-free OVA. Following challenge, bronchoalveolar lavage (BAL, airway responsiveness to methacholine and the lung regulatory T cell population (Treg were assessed. Both OVA preparations induced BAL eosinophilia but LPS-rich OVA also evoked BAL neutrophilia. LPS-free OVA increased interleukin (IL-2, IL-4 and IL-5 whereas LPS-rich OVA additionally increased IL-1β, IL-12, IFN-γ, TNF-α and KC. Both OVA-challenged groups developed airway hyperresponsiveness. TLR4-deficient mice challenged with either OVA preparation showed eosinophilia but not neutrophilia and had increased IL-5. Only LPS-rich OVA challenged mice had increased lung Tregs and LPS-rich OVA also induced in vitro Treg differentiation. LPS-rich OVA also induced a Th1 cytokine response in human peripheral blood mononuclear cells.We conclude that LPS-rich OVA evokes mixed Th1, Th2 and innate immune responses through the TLR-4 pathway, whereas LPS-free OVA evokes only a Th2 response. Contaminating LPS is not required for induction of airway hyperresponsiveness but amplifies the Th2 inflammatory response and is a critical mediator of the neutrophil, Th1 and T regulatory cell responses to OVA.

  19. The Airway Microbiome at Birth.

    Science.gov (United States)

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

    2016-01-01

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

  20. The Airway Microbiome at Birth

    Science.gov (United States)

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

    2016-01-01

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

  1. Sarcoidosis with Major Airway, Vascular and Nerve Compromise

    Directory of Open Access Journals (Sweden)

    Hiroshi Sekiguchi

    2013-01-01

    Full Text Available The present report describes a 60-year-old Caucasian woman who presented with progressive dyspnea, cough and wheeze. A computed tomography scan of the chest showed innumerable bilateral inflammatory pulmonary nodules with bronchovascular distribution and a mediastinal and hilar infiltrative process with calcified lymphadenopathy leading to narrowing of lobar bronchi and pulmonary arteries. An echocardiogram revealed pulmonary hypertension. Bronchoscopy showed left vocal cord paralysis and significant narrowing of the bilateral bronchi with mucosal thickening and multiple nodules. Transbronchial biopsy was compatible with sarcoidosis. Despite balloon angioplasty of the left lower lobe and pulmonary artery, and medical therapy with oral corticosteroids, her symptoms did not significantly improve. To the authors’ knowledge, the present report describes the first case of pulmonary sarcoidosis resulting in major airway, vascular and nerve compromise due to compressive lymphadenopathy and suspected concurrent granulomatous infiltration. Its presentation mimicked idiopathic mediastinal fibrosis.

  2. Effects of Flavin7 on allergen induced hyperreactivity of airways

    Directory of Open Access Journals (Sweden)

    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.

  3. Hyaluronan Mediates Ozone-induced Airway Hyperresponsiveness in Mice*

    OpenAIRE

    Garantziotis, Stavros; Li, Zhuowei; Potts, Erin N.; Kimata, Koji; Zhuo, Lisheng; Morgan, Daniel L.; Savani, Rashmin C.; Noble, Paul W.; Foster, W. Michael; Schwartz, David A; John W Hollingsworth

    2009-01-01

    Ozone is a common urban environmental air pollutant and significantly contributes to hospitalizations for respiratory illness. The mechanisms, which regulate ozone-induced bronchoconstriction, remain poorly understood. Hyaluronan was recently shown to play a central role in the response to noninfectious lung injury. Therefore, we hypothesized that hyaluronan contributes to airway hyperreactivity (AHR) after exposure to ambient ozone. Using an established model of ozone...

  4. Phenotype modulation of airway smooth muscle in asthma

    NARCIS (Netherlands)

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

    2013-01-01

    The biological responses of airway smooth muscle (ASM) are diverse, in part due to ASM phenotype plasticity. ASM phenotype plasticity refers to the ability of ASM cells to change the degree of a variety of functions, including contractility, proliferation, migration and secretion of inflammatory med

  5. Hyperpolarized 3He magnetic resonance imaging ventilation defects in asthma: relationship to airway mechanics.

    Science.gov (United States)

    Leary, Del; Svenningsen, Sarah; Guo, Fumin; Bhatawadekar, Swati; Parraga, Grace; Maksym, Geoffrey N

    2016-04-01

    In patients with asthma, magnetic resonance imaging (MRI) provides direct measurements of regional ventilation heterogeneity, the etiology of which is not well-understood, nor is the relationship of ventilation abnormalities with lung mechanics. In addition, respiratory resistance and reactance are often abnormal in asthmatics and the frequency dependence of respiratory resistance is thought to reflect ventilation heterogeneity. We acquiredMRIventilation defect maps, forced expiratory volume in one-second (FEV1), and airways resistance (Raw) measurements, and used a computational airway model to explore the relationship of ventilation defect percent (VDP) with simulated measurements of respiratory system resistance (Rrs) and reactance (Xrs).MRIventilation defect maps were experimentally acquired in 25 asthmatics before, during, and after methacholine challenge and these were nonrigidly coregistered to the airway tree model. Using the model coregistered to ventilation defect maps, we narrowed proximal (9th) and distal (14th) generation airways that were spatially related to theMRIventilation defects. The relationships forVDPwith Raw measured using plethysmography (r = 0.79), and model predictions of Rrs>14(r = 0.91,P 9(r = 0.88,P mechanics measurements were different (P mechanics and ventilation defects, impedance predictions were made using a computational airway tree model with simulated constriction of airways related to ventilation defects measured in mild-moderate asthmatics.

  6. LARYNGEAL CHONDROSARCOMA: SUCCESSFUL USE OF VIDEO LARYNGOSCOPE IN ANTICIPATED DIFFICULT AIRWAY MANAGEMENT.

    Science.gov (United States)

    Dolinaj, Vladimir; Milošev, Sanja; Janjević, Dušanka

    2016-03-01

    Laryngeal chondrosarcoma is a rare mesenchymal tumor, most frequently affecting cricoid cartilage. The objective of this report is to present successful video laryngoscope usage in a patient with anticipated difficult airway who refused awake fiberoptic endotracheal intubation (AFOI). A 59-year-old male patient was admitted in our hospital due to difficulty breathing and swallowing. On clinical examination performed by ENT surgeon, preoperative endoscopic airway examination (PEAE) could not be performed properly due to the patient's uncooperativeness. Computed tomography revealed a spherical tumor that obstructed the subglottic area almost entirely. Due to the narrowed airway, the first choice for the anticipated difficult airway management was AFOI, which the patient refused. Consequently, we decided to perform endotracheal intubation with indirect laryngoscope using a C-MAC video laryngoscope (Karl Storz, Tuttlingen, Germany). Reinforced endotracheal tube (6.0 mm internal diameter) was placed gently between the tumor mass and the posterior wall of the trachea in the first attempt. Confirmation of endotracheal intubation was done by capnography. In a patient with subglottic area chondrosarcoma refusing PEAE and AFOI, video laryngoscope is a particularly helpful device for difficult airway management when difficult airway is anticipated. PMID:27276783

  7. CD69 expression on airway eosinophils and airway inflammation in a murine model of asthma

    Institute of Scientific and Technical Information of China (English)

    WANG Hui-ying; SHEN Hua-hao; James J Lee; Nancy A Lee

    2006-01-01

    Background Asthma is a chronic airway disease with inflammation characterized by physiological changes(airway hyper-responsiveness, AHR) and pathological changes (inflammatory cells infiltration and mucus production). Eosinophils play a key role in the allergic inflammation. But the causative relationship between eosinophils and airway inflammation is hard to prove. One of the reasons is lack of activation marker of murine eosinophils. We investigated the expression of CD69 on murine eosinophils in vitro, the relationship between the expression of CD69 on eosinophils from peripheral blood and bronchoalveolar lavage fluid and on airway inflammation in asthmatic mice.Methods Eosinophils from peripheral blood of IL-5 transgenic mice (NJ.1638) were purified. Mice were divided into five groups: wild type mice sensitized and challenged with saline (WS group), wild type mice sensitized and challenged with ovalbumin (WO group), IL-5-/- mice sensitized and challenged with saline and transferred with purified eosinophils (ISE group), IL-5-/- mice sensitized and challenged with OVA and transferred with purified eosinophils (IOE group), IL-5-/- mice sensitized and challenged with OVA and transferred with purified eosinophils, pretreated with anti CD4 monoclonal antibody (IOE+antiCD4mAb group).IL-5-/- mice were sensitized with OVA at day 0 and day 14, then challenged with OVA aerosol. On days 24, 25, 26and 27 purified eosinophils were transferred intratracheally to IL-5-/- mice. On day 28, blood and BALF were collected and CD69 expression on eosinophils measured by flowcytometry.Results Purified eosinophils did not express CD69. But eosinophils cultured with PMA+MA, IFN- γ, IL-5 or GM-CSF expressed CD69 strongly. Eosinophils from blood of WO, WS group did not express CD69 at all. The numbers of eosinophils in BALF of WO group, IOE group, ISE group and IOE+antiCD4mAb group were significantly higher than in mice of WS group which did not have eosinophils at all. CD69 expression

  8. Recent advances in airway management in children

    OpenAIRE

    Veyckemans, Francis

    2009-01-01

    Recent anatomic findings, technological progress, and both in vitro and in vivo studies of the pressure generated in the cuff of endotracheal tubes and supraglottic airways should lead to modification of the way we control the pediatric upper airway.

  9. Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms

    Directory of Open Access Journals (Sweden)

    Johan Øvrevik

    2015-07-01

    Full Text Available Inflammation is considered to play a central role in a diverse range of disease outcomes associated with exposure to various types of inhalable particulates. The initial mechanisms through which particles trigger cellular responses leading to activation of inflammatory responses are crucial to clarify in order to understand what physico-chemical characteristics govern the inflammogenic activity of particulate matter and why some particles are more harmful than others. Recent research suggests that molecular triggering mechanisms involved in activation of proinflammatory genes and onset of inflammatory reactions by particles or soluble particle components can be categorized into direct formation of reactive oxygen species (ROS with subsequent oxidative stress, interaction with the lipid layer of cellular membranes, activation of cell surface receptors, and direct interactions with intracellular molecular targets. The present review focuses on the immediate effects and responses in cells exposed to particles and central down-stream signaling mechanisms involved in regulation of proinflammatory genes, with special emphasis on the role of oxidant and non-oxidant triggering mechanisms. Importantly, ROS act as a central second-messenger in a variety of signaling pathways. Even non-oxidant mediated triggering mechanisms are therefore also likely to activate downstream redox-regulated events.

  10. Kinetic narrowing of size distribution

    Science.gov (United States)

    Dubrovskii, V. G.

    2016-05-01

    We present a model that reveals an interesting possibility for narrowing the size distribution of nanostructures when the deterministic growth rate changes its sign from positive to negative at a certain stationary size. Such a behavior occurs in self-catalyzed one-dimensional III-V nanowires and more generally whenever a negative "adsorption-desorption" term in the growth rate is compensated by a positive "diffusion flux." By asymptotically solving the Fokker-Planck equation, we derive an explicit representation for the size distribution that describes either Poissonian broadening or self-regulated narrowing depending on the parameters. We show how the fluctuation-induced spreading of the size distribution can be completely suppressed in systems with size self-stabilization. These results can be used for obtaining size-uniform ensembles of different nanostructures.

  11. Kinins, airway obstruction, and anaphylaxis.

    Science.gov (United States)

    Kaplan, Allen P

    2010-01-01

    Anaphylaxis is a term that implies symptoms that are present in many organs, some of which are potentially fatal. The pathogenic process can either be IgE-dependent or non-IgE-dependent; the latter circumstance may be referred to as anaphylactoid. Bradykinin is frequently responsible for the manifestations of IgE-independent reactions. Blood levels may increase because of overproduction; diseases such as the various forms of C1 inhibitor deficiency (hereditary or acquired) or hereditary angioedema with normal C1 inhibitor are examples in this category. Blood levels may also increase because of an abnormality in bradykinin metabolism; the angioedema due to ACE inhibitors is a commonly encountered example. Angioedema due to bradykinin has the potential to cause airway obstruction and asphyxia as well as severe gastrointestinal symptoms simulating an acute abdomen. Formation of bradykinin in plasma is a result of a complex interaction among proteins such as factor XII, prekallikrein, and high molecular weight kininogen (HK) resulting in HK cleavage and liberation of bradykinin. These proteins also assemble along the surface of endothelial cells via zinc-dependent interactions with gC1qR, cytokeratin 1, and u-PAR. Endothelial cell expression (or secretion) of heat-shock protein 90 or prolylcarboxypeptidase can activate the prekallikrein-HK complex to generate bradykinin in the absence of factor XII, however factor XII is then secondarily activated by the kallikrein that results. Bradykinin is destroyed by carboxypeptidase N and angiotensin-converting enzyme. The hypotension associated with IgE-dependent anaphylaxis maybe mediated, in part, by massive proteolytic digestion of HK by kallikreins (tissue or plasma-derived) or other cell-derived kininogenases. PMID:20519882

  12. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation.

    Directory of Open Access Journals (Sweden)

    Romina Nassini

    Full Text Available BACKGROUND: The transient receptor potential ankyrin 1 (TRPA1 channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1. METHODOLOGY/PRINCIPAL FINDINGS: By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells and fibroblasts, acrolein and CS extract evoked IL-8 release, a response selectively reduced by TRPA1 antagonists. Capsaicin, agonist of the transient receptor potential vanilloid 1 (TRPV1, a channel co-expressed with TRPA1 by airway sensory nerves, and acrolein or CS (TRPA1 agonists, or the neuropeptide substance P (SP, which is released from sensory nerve terminals by capsaicin, acrolein or CS, produced neurogenic inflammation in mouse airways. However, only acrolein and CS, but not capsaicin or SP, released the keratinocyte chemoattractant (CXCL-1/KC, IL-8 analogue in bronchoalveolar lavage (BAL fluid of wild-type mice. This effect of TRPA1 agonists was attenuated by TRPA1 antagonism or in TRPA1-deficient mice, but not by pharmacological ablation of sensory nerves. CONCLUSIONS: Our results demonstrate that, although either TRPV1 or TRPA1 activation causes airway neurogenic inflammation, solely TRPA1 activation orchestrates an additional inflammatory response which is not neurogenic. This finding suggests

  13. Bone marrow cell derived arginase I is the major source of allergen-induced lung arginase but is not required for airway hyperresponsiveness, remodeling and lung inflammatory responses in mice

    Directory of Open Access Journals (Sweden)

    Rothenberg Marc E

    2009-06-01

    Full Text Available Abstract Background Arginase is significantly upregulated in the lungs in murine models of asthma, as well as in human asthma, but its role in allergic airway inflammation has not been fully elucidated in mice. Results In order to test the hypothesis that arginase has a role in allergic airway inflammation we generated arginase I-deficient bone marrow (BM chimeric mice. Following transfer of arginase I-deficient BM into irradiated recipient mice, arginase I expression was not required for hematopoietic reconstitution and baseline immunity. Arginase I deficiency in bone marrow-derived cells decreased allergen-induced lung arginase by 85.8 ± 5.6%. In contrast, arginase II-deficient mice had increased lung arginase activity following allergen challenge to a similar level to wild type mice. BM-derived arginase I was not required for allergen-elicited sensitization, recruitment of inflammatory cells in the lung, and proliferation of cells. Furthermore, allergen-induced airway hyperresponsiveness and collagen deposition were similar in arginase-deficient and wild type mice. Additionally, arginase II-deficient mice respond similarly to their control wild type mice with allergen-induced inflammation, airway hyperresponsiveness, proliferation and collagen deposition. Conclusion Bone marrow cell derived arginase I is the predominant source of allergen-induced lung arginase but is not required for allergen-induced inflammation, airway hyperresponsiveness or collagen deposition.

  14. Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases.

    Science.gov (United States)

    Reuter, Sebastian; Beckert, Hendrik; Taube, Christian

    2016-02-01

    Bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases that are associated with inflammation and structural changes in the airways and lungs. Recent findings have implicated Wnt pathways in critically regulating inflammatory responses, especially in asthma. Furthermore, canonical and noncanonical Wnt pathways are involved in structural changes such as airway remodeling, goblet cell metaplasia, and airway smooth muscle (ASM) proliferation. In COPD, Wnt pathways are not only associated with structural changes in the airways but also involved in the development of emphysema. The present review summarizes the role and function of the canonical and noncanonical Wnt pathway with regard to airway inflammation and structural changes in asthma and COPD. Further identification of the role and function of different Wnt molecules and pathways could help to develop novel therapeutic options for these diseases. PMID:26595171

  15. Airway Tree Extraction with Locally Optimal Paths

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

  16. Detonation Nanodiamond Toxicity in Human Airway Epithelial Cells Is Modulated by Air Oxidation

    Science.gov (United States)

    Detonational nanodiamonds (DND), a nanomaterial with an increasing range of industrial and biomedical applications, have previously been shown to induce a pro-inflammatory response in cultured human airway epithelial cells (HAEC). We now show that surface modifications induced by...

  17. A multi-omics approach identifies key hubs associated with cell type-specific responses of airway epithelial cells to staphylococcal alpha-toxin.

    Directory of Open Access Journals (Sweden)

    Erik Richter

    Full Text Available Responsiveness of cells to alpha-toxin (Hla from Staphylococcus aureus appears to occur in a cell-type dependent manner. Here, we compare two human bronchial epithelial cell lines, i.e. Hla-susceptible 16HBE14o- and Hla-resistant S9 cells, by a quantitative multi-omics strategy for a better understanding of Hla-induced cellular programs. Phosphoproteomics revealed a substantial impact on phosphorylation-dependent signaling in both cell models and highlights alterations in signaling pathways associated with cell-cell and cell-matrix contacts as well as the actin cytoskeleton as key features of early rHla-induced effects. Along comparable changes in down-stream activity of major protein kinases significant differences between both models were found upon rHla-treatment including activation of the epidermal growth factor receptor EGFR and mitogen-activated protein kinases MAPK1/3 signaling in S9 and repression in 16HBE14o- cells. System-wide transcript and protein expression profiling indicate induction of an immediate early response in either model. In addition, EGFR and MAPK1/3-mediated changes in gene expression suggest cellular recovery and survival in S9 cells but cell death in 16HBE14o- cells. Strikingly, inhibition of the EGFR sensitized S9 cells to Hla indicating that the cellular capacity of activation of the EGFR is a major protective determinant against Hla-mediated cytotoxic effects.

  18. Blockade of Airway Inflammation by Kaempferol via Disturbing Tyk-STAT Signaling in Airway Epithelial Cells and in Asthmatic Mice

    Directory of Open Access Journals (Sweden)

    Ju-Hyun Gong

    2013-01-01

    Full Text Available Asthma is characterized by bronchial inflammation causing increased airway hyperresponsiveness and eosinophilia. The interaction between airway epithelium and inflammatory mediators plays a key role in the asthmatic pathogenesis. The in vitro study elucidated inhibitory effects of kaempferol, a flavonoid found in apples and many berries, on inflammation in human airway epithelial BEAS-2B cells. Nontoxic kaempferol at ≤20 μM suppressed the LPS-induced IL-8 production through the TLR4 activation, inhibiting eotaxin-1 induction. The in vivo study explored the demoting effects of kaempferol on asthmatic inflammation in BALB/c mice sensitized with ovalbumin (OVA. Mouse macrophage inflammatory protein-2 production and CXCR2 expression were upregulated in OVA-challenged mice, which was attenuated by oral administration of ≥10 mg/kg kaempferol. Kaempferol allayed the airway tissue levels of eotaxin-1 and eotaxin receptor CCR3 enhanced by OVA challenge. This study further explored the blockade of Tyk-STAT signaling by kaempferol in both LPS-stimulated BEAS-2B cells and OVA-challenged mice. LPS activated Tyk2 responsible for eotaxin-1 induction, while kaempferol dose-dependently inhibited LPS- or IL-8-inflamed Tyk2 activation. Similar inhibition of Tyk2 activation by kaempferol was observed in OVA-induced mice. Additionally, LPS stimulated the activation of STAT1/3 signaling concomitant with downregulated expression of Tyk-inhibiting SOCS3. In contrast, kaempferol encumbered STAT1/3 signaling with restoration of SOCS3 expression. Consistently, oral administration of kaempferol blocked STAT3 transactivation elevated by OVA challenge. These results demonstrate that kaempferol alleviated airway inflammation through modulating Tyk2-STAT1/3 signaling responsive to IL-8 in endotoxin-exposed airway epithelium and in asthmatic mice. Therefore, kaempferol may be a therapeutic agent targeting asthmatic diseases.

  19. Epithelium-generated neuropeptide Y induces smooth muscle contraction to promote airway hyperresponsiveness.

    Science.gov (United States)

    Li, Shanru; Koziol-White, Cynthia; Jude, Joseph; Jiang, Meiqi; Zhao, Hengjiang; Cao, Gaoyuan; Yoo, Edwin; Jester, William; Morley, Michael P; Zhou, Su; Wang, Yi; Lu, Min Min; Panettieri, Reynold A; Morrisey, Edward E

    2016-05-01

    Asthma is one of the most common chronic diseases globally and can be divided into presenting with or without an immune response. Current therapies have little effect on nonimmune disease, and the mechanisms that drive this type of asthma are poorly understood. Here, we have shown that loss of the transcription factors forkhead box P1 (Foxp1) and Foxp4, which are critical for lung epithelial development, in the adult airway epithelium evokes a non-Th2 asthma phenotype that is characterized by airway hyperresponsiveness (AHR) without eosinophilic inflammation. Transcriptome analysis revealed that loss of Foxp1 and Foxp4 expression induces ectopic expression of neuropeptide Y (Npy), which has been reported to be present in the airways of asthma patients, but whose importance in disease pathogenesis remains unclear. Treatment of human lung airway explants with recombinant NPY increased airway contractility. Conversely, loss of Npy in Foxp1- and Foxp4-mutant airway epithelium rescued the AHR phenotype. We determined that NPY promotes AHR through the induction of Rho kinase activity and phosphorylation of myosin light chain, which induces airway smooth muscle contraction. Together, these studies highlight the importance of paracrine signals from the airway epithelium to the underlying smooth muscle to induce AHR and suggest that therapies targeting epithelial induction of this phenotype may prove useful in treatment of noneosinophilic asthma. PMID:27088802

  20. Distinct Tlr4-expressing cell compartments control neutrophilic and eosinophilic airway inflammation

    OpenAIRE

    McAlees, Jaclyn W.; Whitehead, Gregory S.; Harley, Isaac T. W.; Cappelletti, Monica; Rewerts, Cheryl L.; Holdcroft, A. Maria; Divanovic, Senad; Wills-Karp, Marsha; Finkelman, Fred D.; Karp, Christopher L.; Cook, Donald N.

    2014-01-01

    Allergic asthma is a chronic, inflammatory lung disease. Some forms of allergic asthma are characterized by Th2-driven eosinophilia while others are distinguished by Th17-driven neutrophilia. Stimulation of Toll-like receptor 4 (TLR4) on hematopoietic and airway epithelial cells (AECs) contributes to the inflammatory response to lipopolysaccharide (LPS) and allergens, but the specific contribution of TLR4 in these cell compartments to airway inflammatory responses remains poorly understood. W...

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

    Directory of Open Access Journals (Sweden)

    Mi Kyung Park

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

  2. Vitamin D deficiency causes airway hyperresponsiveness, increases airway smooth muscle mass, and reduces TGF‐β expression in the lungs of female BALB/c mice

    OpenAIRE

    Rachel E Foong; Shaw, Nicole C.; Berry, Luke J.; Hart, Prue H.; Gorman, Shelley; Zosky, Graeme R.

    2014-01-01

    Abstract Vitamin D deficiency is associated with disease severity in asthma. We tested whether there is a causal association between vitamin D deficiency, airway smooth muscle (ASM) mass, and the development of airway hyperresponsiveness (AHR). A physiologically relevant mouse model of vitamin D deficiency was developed by raising BALB/c mice on vitamin D‐deficient or ‐replete diets. AHR was assessed by measuring lung function responses to increasing doses of inhaled methacholine. Five‐micron...

  3. [Airway equipment and its maintenance for a non difficult adult airway management (endotracheal intubation and its alternative: face mask, laryngeal mask airway, laryngeal tube)].

    Science.gov (United States)

    Francon, D; Estèbe, J P; Ecoffey, C

    2003-08-01

    The airway equipment for a non difficult adult airway management are described: endotracheal tubes with a specific discussion on how to inflate the balloon, laryngoscopes and blades, stylets and intubation guides, oral airways, face masks, laryngeal mask airways and laryngeal tubes. Cleaning and disinfections with the maintenance are also discussed for each type of airway management. PMID:12943860

  4. Multislice helical CT analysis of small-sized airway wall thickness in smokers and patients with bronchial asthma

    International Nuclear Information System (INIS)

    There is accumulating evidence that airway remodeling, which contributes to airway narrowing, plays a role in the pathogenesis of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). Development of the multislice helical CT (MSCT) with improved spatial resolution has made it possible to obtain more precise imaging of small-sized airways. Small-sized airway wall-thickness was measured using the MSCT scan to analyze small-sized airways of smokers and BA patients, and examine the effects of a β2 agonists on small-sized airway wall-thickness of BA patients. Thirty-six non-asthmatics who participated in the Health Check Program of Iwate Medical University and 25 patients with asthma were recruited. Amongst the 36 non-asthmatics were 20 healthy never-smokers and 15 smokers. The other 25 asthmatics were recruited from the outpatient clinic at Iwate Medical University. MSCT was performed and the right B10 bronchus was chosen for dimensional analysis. Airway wall thickness was expressed as a percentage of wall area (WA%). WA% of the 7 asthmatics before and 30 mim after procaterol (20μg) inspiration were compared. Small-sized airway wall thickness was significantly increased in smokers and patients with asthma compared to healthy never-smokers, when determined by MSCT. Both %V50 and %V25 had significant negative correlations with WA% among the healthy never-smokers and smoker population. Procaterol inspiration reduced WA% in the small airway of patients with asthma. Increase of small-sized airway thickness measured by MSCT scan may reflect peripheral obstructive lesions of smokers and BA patients. (author)

  5. Pharyngeal airway changes following mandibular setback surgery

    Directory of Open Access Journals (Sweden)

    Babu Ramesh

    2005-01-01

    Full Text Available Treatment of dentofacial deformities with jaw osteotomies has an effect on airway anatomy and therefore mandibular setback surgery has the potential to diminish airway size. The purpose of this study was to evaluate the effect of mandibular setback surgery on airway size. 8 consecutive patients were examined prospectively. All patients underwent mandibular setback surgery. Cephalometric analysis was performed preoperatively and 3 months post operatively with particular attention to pharyngeal airway changes. Pharyngeal airway size decreased considerably in all, patients thus predisposing to development of obstructive sleep apnea. Therefore, large anteroposterior discrepancies should be corrected by combined maxillary and mandibular osteotomies.

  6. Inflammatory bowel disease and airway diseases

    Science.gov (United States)

    Vutcovici, Maria; Brassard, Paul; Bitton, Alain

    2016-01-01

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

  7. Mucus hypersecretion in the airway

    Institute of Scientific and Technical Information of China (English)

    WANG Ke; WEN Fu-qiang; XU Dan

    2008-01-01

    @@ Mucus hypersecretion is a distinguishing feature of Chronic intlammation diseases,such as asthma,1chronic bronchitis.2 bronchiectasis3 and cystic fibrosis.4Mucus hypersecretion leads to impairment of mucociliary clearance,abnormal bacterial plantation,mucus plug in the airway,and dysfunction of gas exchange.5

  8. 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

  9. 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

  10. Potassium permanganate toxicity: A rare case with difficult airway management and hepatic damage

    Directory of Open Access Journals (Sweden)

    Vijay Kumar Agrawal

    2014-01-01

    Full Text Available Potassium permanganate (KMnO 4 is rarely used for suicidal attempt. Its ingestion can lead to local as well as systemic toxicities due to coagulation necrosis and damage, caused by free radicals of permanganate. We recently managed a case of suicidal ingestion of KMnO 4 in a lethal dose. She had significant narrowing of upper airway leading to difficult intubation as well as hepatic dysfunction and coagulopathy as systemic manifestation. We suggest to keep ourselves ready to handle difficult airway with the aid of fiber optic bronchoscope or surgical airway management in such patients. Upper gastrointestinal (GI endoscopy should be done at the earliest to determine the extent of upper GI injury and further nutrition planning.

  11. Multidetector CT evaluation of central airways stenoses: Comparison of virtual bronchoscopy, minimal-intensity projection, and multiplanar reformatted images

    Directory of Open Access Journals (Sweden)

    Dinesh K Sundarakumar

    2011-01-01

    Full Text Available Aims: To evaluate the diagnostic utility of virtual bronchoscopy, multiplanar reformatted images, and minimal-intensity projection in assessing airway stenoses. Settings and Design: It was a prospective study involving 150 patients with symptoms of major airway disease. Materials and Methods: Fifty-six patients were selected for analysis based on the detection of major airway lesions on fiber-optic bronchoscopy (FB or routine axial images. Comparisons were made between axial images, virtual bronchoscopy (VB, minimal-intensity projection (minIP, and multiplanar reformatted (MPR images using FB as the gold standard. Lesions were evaluated in terms of degree of airway narrowing, distance from carina, length of the narrowed segment and visualization of airway distal to the lesion. Results: MPR images had the highest degree of agreement with FB (Κ = 0.76 in the depiction of degree of narrowing. minIP had the least degree of agreement with FB (Κ = 0.51 in this regard. The distal visualization was best on MPR images (84.2%, followed by axial images (80.7%, whereas FB could visualize the lesions only in 45.4% of the cases. VB had the best agreement with FB in assessing the segment length (Κ = 0.62. Overall there were no statistically significant differences in the measurement of the distance from the carina in the axial, minIP, and MPR images. MPR images had the highest overall degree of confidence, namely, 70.17% (n = 40. Conclusion: Three-dimensional reconstruction techniques were found to improve lesion evaluation compared with axial images alone. The technique of MPR images was the most useful for lesion evaluation and provided additional information useful for surgical and airway interventions in tracheobronchial stenosis. minIP was useful in the overall depiction of airway anatomy.

  12. Sarcoidosis of the upper and lower airways.

    Science.gov (United States)

    Morgenthau, Adam S; Teirstein, Alvin S

    2011-12-01

    Sarcoidosis is a systemic granulomatous disease of undetermined etiology characterized by a variable clinical presentation and disease course. Although clinical granulomatous inflammation may occur within any organ system, more than 90% of sarcoidosis patients have lung disease. Sarcoidosis is considered an interstitial lung disease that is frequently characterized by restrictive physiologic dysfunction on pulmonary function tests. However, sarcoidosis also involves the airways (large and small), causing obstructive airways disease. It is one of a few interstitial lung diseases that affects the entire length of the respiratory tract - from the nose to the terminal bronchioles - and causes a broad spectrum of airways dysfunction. This article examines airway dysfunction in sarcoidosis. The anatomical structure of the airways is the organizational framework for our discussion. We discuss sarcoidosis involving the nose, sinuses, nasal passages, larynx, trachea, bronchi and small airways. Common complications of airways disease, such as, atelectasis, fibrosis, bullous leions, bronchiectasis, cavitary lesions and mycetomas, are also reviewed. PMID:22082167

  13. Systems-level airway models of bronchoconstriction.

    Science.gov (United States)

    Donovan, Graham M

    2016-09-01

    Understanding lung and airway behavior presents a number of challenges, both experimental and theoretical, but the potential rewards are great in terms of both potential treatments for disease and interesting biophysical phenomena. This presents an opportunity for modeling to contribute to greater understanding, and here, we focus on modeling efforts that work toward understanding the behavior of airways in vivo, with an emphasis on asthma. We look particularly at those models that address not just isolated airways but many of the important ways in which airways are coupled both with each other and with other structures. This includes both interesting phenomena involving the airways and the layer of airway smooth muscle that surrounds them, and also the emergence of spatial ventilation patterns via dynamic airway interaction. WIREs Syst Biol Med 2016, 8:459-467. doi: 10.1002/wsbm.1349 For further resources related to this article, please visit the WIREs website. PMID:27348217

  14. Tube Law of the Pharyngeal Airway in Sleeping Patients with Obstructive Sleep Apnea

    Science.gov (United States)

    Genta, Pedro R.; Edwards, Bradley A.; Sands, Scott A.; Owens, Robert L.; Butler, James P.; Loring, Stephen H.; White, David P.; Wellman, Andrew

    2016-01-01

    Study Objectives: Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapse during sleep. However, the dynamics of pharyngeal narrowing and re-expansion during flow-limited breathing are not well described. The static pharyngeal tube law (end-expiratory area versus luminal pressure) has demonstrated increasing pharyngeal compliance as luminal pressure decreases, indicating that the airway would be sucked closed with sufficient inspiratory effort. On the contrary, the airway is rarely sucked closed during inspiratory flow limitation, suggesting that the airway is getting stiffer. Therefore, we hypothesized that during inspiratory flow limitation, as opposed to static conditions, the pharynx becomes stiffer as luminal pressure decreases. Methods: Upper airway endoscopy and simultaneous measurements of airflow and epiglottic pressure were performed during natural nonrapid eye movement sleep. Continuous positive (or negative) airway pressure was used to induce flow limitation. Flow-limited breaths were selected for airway cross-sectional area measurements. Relative airway area was quantified as a percentage of end-expiratory area. Inspiratory airway radial compliance was calculated at each quintile of epiglottic pressure versus airway area plot (tube law). Results: Eighteen subjects (14 males) with OSA (apnea-hypopnea index = 57 ± 27 events/h), aged 49 ± 8 y, with a body mass index of 35 ± 6 kg/m2 were studied. A total of 163 flow limited breaths were analyzed (9 ± 3 breaths per subject). Compliances at the fourth (2.0 ± 4.7 % area/cmH2O) and fifth (0.0 ± 1.7 % area/cmH2O) quintiles were significantly lower than the first (12.2 ± 5.5 % area/cmH2O) pressure quintile (P < 0.05). Conclusions: The pharyngeal tube law is concave (airway gets stiffer as luminal pressure decreases) during respiratory cycles under inspiratory flow limitation. Citation: Genta PR, Edwards BA, Sands SA, Owens RL, Butler JP, Loring SH, White DP, Wellman A. Tube law of

  15. The cystic fibrosis lower airways microbial metagenome

    Science.gov (United States)

    Moran Losada, Patricia; Chouvarine, Philippe; Dorda, Marie; Hedtfeld, Silke; Mielke, Samira; Schulz, Angela; Wiehlmann, Lutz

    2016-01-01

    Chronic airway infections determine most morbidity in people with cystic fibrosis (CF). Herein, we present unbiased quantitative data about the frequency and abundance of DNA viruses, archaea, bacteria, moulds and fungi in CF lower airways. Induced sputa were collected on several occasions from children, adolescents and adults with CF. Deep sputum metagenome sequencing identified, on average, approximately 10 DNA viruses or fungi and several hundred bacterial taxa. The metagenome of a CF patient was typically found to be made up of an individual signature of multiple, lowly abundant species superimposed by few disease-associated pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, as major components. The host-associated signatures ranged from inconspicuous polymicrobial communities in healthy subjects to low-complexity microbiomes dominated by the typical CF pathogens in patients with advanced lung disease. The DNA virus community in CF lungs mainly consisted of phages and occasionally of human pathogens, such as adeno- and herpesviruses. The S. aureus and P. aeruginosa populations were composed of one major and numerous minor clone types. The rare clones constitute a low copy genetic resource that could rapidly expand as a response to habitat alterations, such as antimicrobial chemotherapy or invasion of novel microbes. PMID:27730195

  16. The impacts of open-mouth breathing on upper airway space in obstructive sleep apnea: 3-D MDCT analysis.

    Science.gov (United States)

    Kim, Eun Joong; Choi, Ji Ho; Kim, Kang Woo; Kim, Tae Hoon; Lee, Sang Hag; Lee, Heung Man; Shin, Chol; Lee, Ki Yeol; Lee, Seung Hoon

    2011-04-01

    Open-mouth breathing during sleep is a risk factor for obstructive sleep apnea (OSA) and is associated with increased disease severity and upper airway collapsibility. The aim of this study was to investigate the effect of open-mouth breathing on the upper airway space in patients with OSA using three-dimensional multi-detector computed tomography (3-D MDCT). The study design included a case-control study with planned data collection. The study was performed at a tertiary medical center. 3-D MDCT analysis was conducted on 52 patients with OSA under two experimental conditions: mouth closed and mouth open. Under these conditions, we measured the minimal cross-sectional area of the retropalatal and retroglossal regions (mXSA-RP, mXSA-RG), as well as the upper airway length (UAL), defined as the vertical dimension from hard palate to hyoid. We also computed the volume of the upper airway space by 3-D reconstruction of both conditions. When the mouth was open, mXSA-RP and mXSA-RG significantly decreased and the UAL significantly increased, irrespective of the severity of OSA. However, between the closed- and open-mouth states, there was no significant change in upper airway volume at any severity of OSA. Results suggest that the more elongated and narrow upper airway during open-mouth breathing may aggravate the collapsibility of the upper airway and, thus, negatively affect OSA severity.

  17. Spectral Narrowing in Semiconductor Microcavities

    Science.gov (United States)

    La Rocca, G. C.; Bassani, F.; Agranovich, V. M.

    1998-03-01

    The notion of in-plane motional narrowing of cavity polariton (CP) lines has been recently considered ( D.M. Whittaker et al.), Phys. Rev. Lett. 77, 4792 (1996); V. Savona et al.. Phys. Rev. Lett. 78, 4470 (1997). We point out that, in the presence of N>1 resonating quantum wells (QWs), the exciton component in a CP is coherently delocalized over all the individual QWs. Besides the two CP branches, also a dark exciton branch is present given by N-1 states similarly delocalized, but orthogonal to the cavity photon mode. If the QW disorder potential is weak compared to the Rabi splitting, it is seen by a CP as reduced by a factor 1/√N because of averaging along the cavity axis (G.C. La Rocca, F. Bassani, V.M. Agranovich, JOSA B 15), (1998). As for the in-plane motional narrowing, a simple scaling procedure shows that it would imply that the inhomogeneous linewidth of a CP be reduced by about four orders of magnitude compared to a QW exciton, which is incompatible with the experimental observations. The physical reason of such a shortcoming is that the disorder introduces localized exciton states which can resonantly scatter CPs, mixing them with states having a large k vector as well as with dark exciton states.

  18. Available techniques for objective assessment of upper airway narrowing in snoring and sleep apnea

    DEFF Research Database (Denmark)

    Faber, Christian; Grymer, Luisa

    2003-01-01

    A number of techniques are available to determine the level of obstructive predominance in snoring and in the obstructive sleep apnea hypopnea syndrome (OSAHS): lateral cephalography, awake endoscopy, awake endoscopy with the Müller maneuver, endoscopy during sleep, endoscopy with nasal continuous...

  19. Noninvasive clearance of airway secretions.

    Science.gov (United States)

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  20. Comparing three-dimensional volume-rendered CT images with fibreoptic tracheobronchoscopy in the evaluation of airway compression caused by tuberculous lymphadenopathy in children

    Energy Technology Data Exchange (ETDEWEB)

    Plessis, Jaco du; George, Reena [University of Stellenbosch, Department of Radiology, Tygerberg (South Africa); Goussard, Pierre; Gie, Robert [Tygerberg Children' s Hospital, Department of Paediatrics, Cape Town (South Africa); Andronikou, Savvas [University of Cape Town, Department of Radiology, Cape Town (South Africa)

    2009-07-15

    Lymphobronchial tuberculosis (TB) causes airway compression in 38% of patients. The airway obstruction is conventionally assessed with fibreoptic tracheobronchoscopy (FTB). Multidetector-row spiral computed tomography (MDCT) with three-dimensional volume rendering (3-D VR) has significantly improved the imaging of the airways. No previous studies have assessed the accuracy of 3-D VR in determining the degree of airway compression in children due to TB lymphadenopathy. To compare 3-D VR CT to FTB for the assessment of airway compression due to TB lymphadenopathy in children. Included in the study were 26 children presenting with symptoms of airway compression caused by pulmonary TB. MDCT of the chest and FTB were performed in all patients. Retrospective 3-D VR reconstruction of the major airways was performed from the original CT raw data and used to evaluate the tracheobronchial tree for site and degree of airway compression and then compared to the FTB findings. FTB was used as the reference standard By FTB 87 sites of airway compression were identified. Using the 3-D VR technique, 138 sites of airway compression were identified, of which 78 (90%) matched with the sites identified by FTB. The sensitivity and specificity of 3-D VR when compared with that of FTB was 92% and 85%, respectively. In four patients (15%), severe narrowing of the bronchus intermedius made FTB evaluation of the right middle and right lower lobe bronchi impossible. VR demonstrated significant distal obstruction in three of these four patients 3-D VR demonstrates a very good correlation with FTB in determining airway compression caused by TB lymphadenopathy in children. In combination with FTB, 3-D VR adds confidence to the bronchoscopy findings and complements FTB by adding additional information on the status of the airway distal to severe obstructions unreachable by FTB. (orig.)

  1. Potassium permanganate toxicity: A rare case with difficult airway management and hepatic damage

    OpenAIRE

    Vijay Kumar Agrawal; Abhishek Bansal; Ranjeet Kumar; Bhanwar Lal Kumawat; Parul Mahajan

    2014-01-01

    Potassium permanganate (KMnO 4 ) is rarely used for suicidal attempt. Its ingestion can lead to local as well as systemic toxicities due to coagulation necrosis and damage, caused by free radicals of permanganate. We recently managed a case of suicidal ingestion of KMnO 4 in a lethal dose. She had significant narrowing of upper airway leading to difficult intubation as well as hepatic dysfunction and coagulopathy as systemic manifestation. We suggest to keep ourselves ready to handle difficul...

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

    Science.gov (United States)

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

    2014-08-01

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers). PMID:24925919

  3. Paediatric airway management: What is new?

    Directory of Open Access Journals (Sweden)

    S Ramesh

    2012-01-01

    Full Text Available Airway management plays a pivotal role in Paediatric Anaesthesia. Over the last two decades many improvements in this area have helped us to overcome this final frontier. From an era where intubation with a conventional laryngoscope or blind nasal intubation was the only tool for airway management, we have come a long way. Today supraglottic airway devices have pride of place in the Operating Room and are becoming important airway devices used in routine procedures. Direct and indirect fibreoptic laryngoscopes and transtracheal devices help us overcome difficult and previously impossible airway situations. These developments mean that we need to update our knowledge on these devices. Also much of our basic understanding of the physiology and anatomy of the paediatric airway has changed. This article attempts to shed light on some of the most important advances/opinions in paediatric airway management like, cuffed endotracheal tubes, supraglottic airway devices, video laryngoscopes, rapid sequence intubation, the newly proposed algorithm for difficult airway management and the role of Ex Utero Intrapartum Treatment (EXIT procedure in the management of the neonatal airway.

  4. Paediatric airway management: What is new?

    Science.gov (United States)

    Ramesh, S; Jayanthi, R; Archana, SR

    2012-01-01

    Airway management plays a pivotal role in Paediatric Anaesthesia. Over the last two decades many improvements in this area have helped us to overcome this final frontier. From an era where intubation with a conventional laryngoscope or blind nasal intubation was the only tool for airway management, we have come a long way. Today supraglottic airway devices have pride of place in the Operating Room and are becoming important airway devices used in routine procedures. Direct and indirect fibreoptic laryngoscopes and transtracheal devices help us overcome difficult and previously impossible airway situations. These developments mean that we need to update our knowledge on these devices. Also much of our basic understanding of the physiology and anatomy of the paediatric airway has changed. This article attempts to shed light on some of the most important advances/opinions in paediatric airway management like, cuffed endotracheal tubes, supraglottic airway devices, video laryngoscopes, rapid sequence intubation, the newly proposed algorithm for difficult airway management and the role of Ex Utero Intrapartum Treatment (EXIT) procedure in the management of the neonatal airway. PMID:23293383

  5. Broad Diphotons from Narrow States

    CERN Document Server

    An, Haipeng; Zhang, Yue

    2015-01-01

    ATLAS and CMS have each reported a modest diphoton excess consistent with the decay of a broad resonance at ~ 750 GeV. We show how this signal can arise in a weakly coupled theory comprised solely of narrow width particles. In particular, if the decaying particle is produced off-shell, then the associated diphoton resonance will have a broad, adjustable width. We present simplified models which explain the diphoton excess through the three-body decay of a scalar or fermion. Our minimal ultraviolet completion is a weakly coupled and renormalizable theory of a singlet scalar plus a heavy vector-like quark and lepton. The smoking gun of this mechanism is an asymmetric diphoton peak recoiling against missing transverse energy, jets, or leptons.

  6. Aeroallergen-induced eosinophilic inflammation, lung damage, and airways hyperreactivity in mice can occur independently of IL-4 and allergen-specific immunoglobulins.

    OpenAIRE

    Hogan, S P; A. Mould; Kikutani, H; Ramsay, A. J.; Foster, P.S.

    1997-01-01

    In this investigation we have used a mouse model containing certain phenotypic characteristics consistent with asthma and IL-4- and CD40-deficient mice to establish the role of this cytokine and allergen-specific immunoglobulins in the initiation of airways hyperreactivity and morphological changes to the airways in responses to aeroallergen challenge. Sensitization and aerosol challenge of mice with ovalbumin resulted in a severe airways inflammatory response which directly correlated with t...

  7. Small airway obstruction in COPD: new insights based on micro-CT imaging and MRI imaging.

    Science.gov (United States)

    Hogg, James C; McDonough, John E; Suzuki, Masaru

    2013-05-01

    The increase in total cross-sectional area in the distal airways of the human lung enhances the mixing of each tidal breath with end-expiratory gas volume by slowing bulk flow and increasing gas diffusion. However, this transition also favors the deposition of airborne particulates in this region because they diffuse 600 times slower than gases. Furthermore, the persistent deposition of toxic airborne particulates stimulates a chronic inflammatory immune cell infiltration and tissue repair and remodeling process that increases the resistance in airways lumen narrowing because it increases resistance in proportion to the change in lumen radius raised to the fourth power. In contrast, removal of one-half the number of tubes arranged in parallel is required to double their resistance, and approximately 90% need to be removed to explain the increase in resistance measured in COPD. However, recent reexamination of this problem based on micro-CT imaging indicates that terminal bronchioles are both narrowed and reduced to 10% of the control values in the centrilobular and 25% in the panlobular emphysematous phenotype of very severe (GOLD [Global Initiative for Chronic Obstructive Lung Disease] grade IV) COPD. These new data indicate that both narrowing and reduction in numbers of terminal bronchioles contribute to the rapid decline in FEV₁ that leads to severe airway obstruction in COPD. Moreover, the observation that terminal bronchiolar loss precedes the onset of emphysematous destruction suggests this destruction begins in the very early stages of COPD. PMID:23648907

  8. Polyopes affinis alleviates airway inflammation in a murine model of allergic asthma

    Indian Academy of Sciences (India)

    Dae-Sung Lee; Won Sun Park; Soo-Jin Heo; Seon-Heui Cha; Daekyung Kim; You-Jin Jeon; Sae-Gwang Park; Su-Kil Seo; Jung Sik Choi; Sung-Jae Park; Eun Bo Shim; Il-Whan Choi; Won-Kyo Jung

    2011-12-01

    Marine algae have been utilized in food as well as medicine products for a variety of purposes. The purpose of this study was to determine whether an ethanol extract of Polyopes affinis (P.affinis) can inhibit the pathogenesis of T helper 2 (Th2)-mediated allergen-induced airway inflammation in a murine model of asthma. Mice that were sensitized and challenged with ovalbumin (OVA) evidenced typical asthmatic reactions such as the following: an increase in the number of eosinophils in the bronchoalveolar lavage (BAL) fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways as well as the narrowing of the airway luminal; the development of airway hyperresponsiveness (AHR); the presence of pulmonary Th2 cytokines; and the presence of allergen-specific immunoglobulin E (IgE) in the serum. The successive intraperitoneal administration of P. affinis ethanolic extracts before the last airway OVA-challenge resulted in a significant inhibition of all asthmatic reactions. These data suggest that P. affinis ethanolic extracts possess therapeutic potential for the treatment of pulmonary allergic disorders such as allergic asthma.

  9. Simvastatin inhibits TGFβ1-induced fibronectin in human airway fibroblasts

    Directory of Open Access Journals (Sweden)

    Ghavami Saeid

    2011-08-01

    Full Text Available Abstract Background Bronchial fibroblasts contribute to airway remodelling, including airway wall fibrosis. Transforming growth factor (TGF-β1 plays a major role in this process. We previously revealed the importance of the mevalonate cascade in the fibrotic response of human airway smooth muscle cells. We now investigate mevalonate cascade-associated signaling in TGFβ1-induced fibronectin expression by bronchial fibroblasts from non-asthmatic and asthmatic subjects. Methods We used simvastatin (1-15 μM to inhibit 3-hydroxy-3-methlyglutaryl-coenzyme A (HMG-CoA reductase which converts HMG-CoA to mevalonate. Selective inhibitors of geranylgeranyl transferase-1 (GGT1; GGTI-286, 10 μM and farnesyl transferase (FT; FTI-277, 10 μM were used to determine whether GGT1 and FT contribute to TGFβ1-induced fibronectin expression. In addition, we studied the effects of co-incubation with simvastatin and mevalonate (1 mM, geranylgeranylpyrophosphate (30 μM or farnesylpyrophosphate (30 μM. Results Immunoblotting revealed concentration-dependent simvastatin inhibition of TGFβ1 (2.5 ng/ml, 48 h-induced fibronectin. This was prevented by exogenous mevalonate, or isoprenoids (geranylgeranylpyrophosphate or farnesylpyrophosphate. The effects of simvastatin were mimicked by GGTI-286, but not FTI-277, suggesting fundamental involvement of GGT1 in TGFβ1-induced signaling. Asthmatic fibroblasts exhibited greater TGFβ1-induced fibronectin expression compared to non-asthmatic cells; this enhanced response was effectively reduced by simvastatin. Conclusions We conclude that TGFβ1-induced fibronectin expression in airway fibroblasts relies on activity of GGT1 and availability of isoprenoids. Our results suggest that targeting regulators of isoprenoid-dependent signaling holds promise for treating airway wall fibrosis.

  10. Distinct Tlr4-expressing cell compartments control neutrophilic and eosinophilic airway inflammation.

    Science.gov (United States)

    McAlees, J W; Whitehead, G S; Harley, I T W; Cappelletti, M; Rewerts, C L; Holdcroft, A M; Divanovic, S; Wills-Karp, M; Finkelman, F D; Karp, C L; Cook, D N

    2015-07-01

    Allergic asthma is a chronic, inflammatory lung disease. Some forms of allergic asthma are characterized by T helper type 2 (Th2)-driven eosinophilia, whereas others are distinguished by Th17-driven neutrophilia. Stimulation of Toll-like receptor 4 (TLR4) on hematopoietic and airway epithelial cells (AECs) contributes to the inflammatory response to lipopolysaccharide (LPS) and allergens, but the specific contribution of TLR4 in these cell compartments to airway inflammatory responses remains poorly understood. We used novel, conditionally mutant Tlr4(fl/fl) mice to define the relative contributions of AEC and hematopoietic cell Tlr4 expression to LPS- and allergen-induced airway inflammation. We found that Tlr4 expression by hematopoietic cells is critical for neutrophilic airway inflammation following LPS exposure and for Th17-driven neutrophilic responses to the house dust mite (HDM) lysates and ovalbumin (OVA). Conversely, Tlr4 expression by AECs was found to be important for robust eosinophilic airway inflammation following sensitization and challenge with these same allergens. Thus, Tlr4 expression by hematopoietic and airway epithelial cells controls distinct arms of the immune response to inhaled allergens. PMID:25465099

  11. Mechanisms of BDNF regulation in asthmatic airway smooth muscle.

    Science.gov (United States)

    Aravamudan, Bharathi; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S

    2016-08-01

    Brain-derived neurotrophic factor (BDNF), a neurotrophin produced by airway smooth muscle (ASM), enhances inflammation effects on airway contractility, supporting the idea that locally produced growth factors influence airway diseases such as asthma. We endeavored to dissect intrinsic mechanisms regulating endogenous, as well as inflammation (TNF-α)-induced BDNF secretion in ASM of nonasthmatic vs. asthmatic humans. We focused on specific Ca(2+) regulation- and inflammation-related signaling cascades and quantified BDNF secretion. We find that TNF-α enhances BDNF release by ASM cells, via several mechanisms relevant to asthma, including transient receptor potential channels TRPC3 and TRPC6 (but not TRPC1), ERK 1/2, PI3K, PLC, and PKC cascades, Rho kinase, and transcription factors cAMP response element binding protein and nuclear factor of activated T cells. Basal BDNF expression and secretion are elevated in asthmatic ASM and increase further with TNF-α exposure, involving many of these regulatory mechanisms. We conclude that airway BDNF secretion is regulated at multiple levels, providing a basis for autocrine effects of BDNF under conditions of inflammation and disease, with potential downstream influences on contractility and remodeling. PMID:27317689

  12. United airway disease: current perspectives

    OpenAIRE

    Giavina-Bianchi P; Aun MV; Takejima P; Kalil J; Agondi RC

    2016-01-01

    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 str...

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Xu Cang-Bao

    2008-11-01

    Full Text Available 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 every other day or GW5074 intraperitoneally every day for three weeks. The tone of the tracheal ring segments was recorded with a myograph system and concentration-response curves were obtained by cumulative administration of agonists. Histopathology was examined by light microscopy. Results Four weeks of exposure to cigarette smoke significantly increased the mouse airway contractile response to carbachol, endothelin-1 and potassium. Intraperitoneal administration of GW5074 or dexamethasone significantly suppressed the enhanced airway contractile responses, while airway epithelium-dependent relaxation was not affected. In addition, the smoke-induced infiltration of inflammatory cells and mucous gland hypertrophy were attenuated by the administration of GW5074 or dexamethasone. Conclusion Sidestream smoke induces airway contractile hyperresponsiveness. Inhibition of Raf-1 activity and airway inflammation suppresses smoking-associated airway hyperresponsiveness.

  15. 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.

  16. Role of Inhaled Steroids in Vascular Airway Remodelling in Asthma and COPD

    OpenAIRE

    Alfredo Chetta; Dario Olivieri

    2012-01-01

    In chronic obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), changes in bronchial microvasculature are present in response to inflammatory stimuli. Vascular changes may significantly contribute to airway wall remodelling. Angiogenesis and vascular leakage are prevalent in asthma, while vasodilation and vascular leakage dominate in COPD. An endothelial dysfunction may be present both in asthma and in COPD. Vascular changes may occur simultaneously wi...

  17. Haemophilus influenzae Infection Drives IL-17-Mediated Neutrophilic Allergic Airways Disease

    OpenAIRE

    Essilfie, Ama-Tawiah; Simpson, Jodie L.; Horvat, Jay C.; Julie A Preston; Dunkley, Margaret L.; Paul S Foster; Gibson, Peter G; Hansbro, Philip M

    2011-01-01

    A subset of patients with stable asthma has prominent neutrophilic and reduced eosinophilic inflammation, which is associated with attenuated airways hyper-responsiveness (AHR). Haemophilus influenzae has been isolated from the airways of neutrophilic asthmatics; however, the nature of the association between infection and the development of neutrophilic asthma is not understood. Our aim was to investigate the effects of H. influenzae respiratory infection on the development of hallmark featu...

  18. Repeated Nitrogen Dioxide Exposures and Eosinophilic Airway Inflammation in Asthmatics: A Randomized Crossover Study

    OpenAIRE

    Ezratty, Véronique; Guillossou, Gaëlle; Neukirch, Catherine; Dehoux, Monique; Koscielny, Serge; Bonay, Marcel; Cabanes, Pierre-André; Samet, Jonathan M; Mure, Patrick; Ropert, Luc; Tokarek, Sandra; Lambrozo, Jacques; Aubier, Michel

    2014-01-01

    Background: Nitrogen dioxide (NO2), a ubiquitous atmospheric pollutant, may enhance the asthmatic response to allergens through eosinophilic activation in the airways. However, the effect of NO2 on inflammation without allergen exposure is poorly studied. Objectives: We investigated whether repeated peaks of NO2, at various realistic concentrations, induce changes in airway inflammation in asthmatics. Methods: Nineteen nonsmokers with asthma were exposed at rest in a double-blind, crossover s...

  19. Haemophilus influenzae infection drives IL-17-mediated neutrophilic allergic airways disease.

    OpenAIRE

    Ama-Tawiah Essilfie; Simpson, Jodie L.; Horvat, Jay C.; Julie A Preston; Dunkley, Margaret L.; Paul S Foster; Gibson, Peter G; Hansbro, Philip M

    2011-01-01

    A subset of patients with stable asthma has prominent neutrophilic and reduced eosinophilic inflammation, which is associated with attenuated airways hyper-responsiveness (AHR). Haemophilus influenzae has been isolated from the airways of neutrophilic asthmatics; however, the nature of the association between infection and the development of neutrophilic asthma is not understood. Our aim was to investigate the effects of H. influenzae respiratory infection on the development of hallmark featu...

  20. Corticosteroid modulation of Na(+)-K+ pump-mediated relaxation in maturing airway smooth muscle.

    OpenAIRE

    Schramm, C. M.; Grunstein, M. M.

    1996-01-01

    1. The ontogeny of the relaxant influence of the airway electrogenic Na(+)-K+ pump and its potential modulation by corticosteroids were examined in airway smooth muscle (ASM) segments isolated from newborn and adult rabbits. 2. Control and methylprednisolone-treated (MP) ASM segments were half-maximally contracted with methacholine in K(+)-free buffer and the ASM relaxant responses to Na(+)-K+ pump activation were subsequently evaluated. Relative to adult ASM, control newborn ASM showed signi...

  1. Enhancement of Allergen-induced Airway Inflammation by NOX2 Deficiency

    OpenAIRE

    Won, Hee Yeon; Jang, Eun Jung; Min, Hyun Jung; Hwang, Eun Sook

    2011-01-01

    Background NADPH oxidase (NOX) modulates cell proliferation, differentiation and immune response through generation of reactive oxygen species. Particularly, NOX2 is recently reported to be important for regulating Treg cell differentiation of CD4+ T cells. Methods We employed ovalbumin-induced airway inflammation in wild-type and NOX2-deficient mice and analyzed tissue histopathology and cytokine profiles. Results We investigated whether NOX2-deficiency affects T cell-mediated airway inflamm...

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

    OpenAIRE

    2014-01-01

    An acidic microenvironment has been shown to evoke a variety of airway responses, including cough, bronchoconstriction, airway hyperresponsiveness (AHR), infiltration of inflammatory cells in the lung, and stimulation of mucus hyperproduction. Except for the participation of transient receptor potential vanilloid-1 (TRPV1) and acid-sensing ion channels (ASICs) in severe acidic pH (of less than 6.0)-induced cough and bronchoconstriction through sensory neurons, the molecular mechanisms underly...

  3. Sealing of Airway Fistulas for Metallic Covered Z-type Stents

    Directory of Open Access Journals (Sweden)

    Hongwu WANG

    2011-08-01

    Full Text Available Background and objective Treating airway fistulas, including esophagorespiratory fistulas (ERFs, bronchopleural fistulas (BPFs, and tracheomediastinal fistulas (TMFs, is difficult. The aim of this study is to evaluate the safety and clinical efficacy of metallic covered Z-type stents (CZTS for the treatment of airway fistulas through bronchoscopy or fluroscopy. Methods Thirty-eight patients with fistulas between the esophagus, mediastina, and airways (32 ERFs, 5 BPFs, and 1 TMF were retrospectively reviewed after treatment with covered metallic esophageal and airway stents. The fistulas were caused by esophageal (n=26, bronchogenic (n=11, and thyroid (n=1 carcinomas. Results Forty-six fistulas were found in 38 patients. The fistula size ranged from 0.5 cm to 7.0 cm. Forty airway covered metal stents (24 Y-type, 8 L-type, and 8 I-type and 24 esophageal metal stents were placed. Complete responses to the sealing effects of fistulas were noted in 4.3% of all the fistulas, 60.9% showed complete clinical responses, 23.9% showed partial responses, and 10.9% showed no response. An effectivity rate of 89.1% was observed, and the median survival duration of all patients was 5 months. Conclusion The use of CZTS appears to be safe and feasible for the palliative treatment of ERFs, BPFs, and TMFs. Airway stent placement is recommended for patients with ERF. In the event that airway stents fail, esophageal stents should be given. Airway bifurcation stents were observed to be especially suitable for the sealing of fistulas near the trachea carina.

  4. Nrf2 protects against airway disorders

    International Nuclear Information System (INIS)

    Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver, gastrointestinal tract, airway, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2-directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome or lung cancer, which further supports the role for NRF2 in these lung diseases. In the current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies.

  5. 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. PMID:25583659

  6. Nasal and bronchial airway reactivity in allergic and non allergic airway inflammation

    OpenAIRE

    Kölbeck, Karl-Gustav

    2003-01-01

    In allergic or asthmatic airways disease, upper and lower airways show a uniform eosinophilic inflammation of the mucosa, and bronchial hyperreactivity is a common finding. To study the co- variation of mucosal reactivity in upper and lower airways, histamine challenges of both sites were performed in a group of patients with allergic rhinitis during non-season. Upper airways were monitored during challenge by the use of rhinostereometry, an optical technique that non-invasi...

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

    OpenAIRE

    Keglowich, L F; Borger, P

    2015-01-01

    Asthma affects more than 300 million people worldwide and its prevalence is still rising. Acute asthma attacks are characterized by severe symptoms such as breathlessness, wheezing, tightness of the chest, and coughing, which may lead to hospitalization or death. Besides the acute symptoms, asthma is characterized by persistent airway inflammation and airway wall remodeling. The term airway wall remodeling summarizes the structural changes in the airway wall: epithelial cell shedding, goblet ...

  8. The three A's in asthma - airway smooth muscle, airway remodeling & angiogenesis

    OpenAIRE

    Keglowich, L F; Borger, P

    2015-01-01

    Asthma affects more than 300 million people worldwide and its prevalence is still rising. Acute asthma attacks are characterized by severe symptoms such as breathlessness, wheezing, tightness of the chest, and coughing, which may lead to hospitalization or death. Besides the acute symptoms, asthma is characterized by persistent airway inflammation and airway wall remodeling. The term airway wall remodeling summarizes the structural changes in the airway wall: epithelial cell shedding, goblet ...

  9. The airway microvasculature and exercise induced asthma.

    OpenAIRE

    Anderson, S. D.; Daviskas, E

    1992-01-01

    It has been proposed that exercise induced asthma is a result of "rapid expansion of the blood volume of peribronchial plexi" (McFadden ER, Lancet 1990;335:880-3). This hypothesis proposes that the development of exercise induced asthma depends on the thermal gradient in the airways at the end of hyperpnoea. The events that result in exercise induced asthma are vasoconstriction and airway cooling followed by reactive hyperaemia. We agree that the airway microcirculation has the potential for ...

  10. Predominant constitutive CFTR conductance in small airways

    OpenAIRE

    Lytle Christian; Wang Xiaofei; Quinton Paul M

    2005-01-01

    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 ...

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

    Directory of Open Access Journals (Sweden)

    Thomas Trian

    Full Text Available BACKGROUND AND OBJECTIVE: Asthma is associated with airway narrowing in response to bronchoconstricting stimuli and increased airway smooth muscle (ASM mass. In addition, some studies have suggested impaired β-agonist induced ASM relaxation in asthmatics, but the mechanism is not known. OBJECTIVE: To characterize the potential defect in β-agonist induced cAMP in ASM derived from asthmatic in comparison to non-asthmatic subjects and to investigate its mechanism. METHODS: We examined β(2-adrenergic (β(2AR receptor expression and basal β-agonist and forskolin (direct activator of adenylyl cyclase stimulated cAMP production in asthmatic cultured ASM (n = 15 and non-asthmatic ASM (n = 22. Based on these results, PDE activity, PDE4D expression and cell proliferation were determined. RESULTS: In the presence of IBMX, a pan PDE inhibitor, asthmatic ASM had ∼50% lower cAMP production in response to isoproterenol, albuterol, formoterol, and forskolin compared to non-asthmatic ASM. However when PDE4 was specifically inhibited, cAMP production by the agonists and forskolin was normalized in asthmatic ASM. We then measured the amount and activity of PDE4, and found ∼2-fold greater expression and activity in asthmatic ASM compared to non-asthmatic ASM. Furthermore, inhibition of PDE4 reduced asthmatic ASM proliferation but not that of non-asthmatic ASM. CONCLUSION: Decreased β-agonist induced cAMP in ASM from asthmatics results from enhanced degradation due to increased PDE4D expression. Clinical manifestations of this dysregulation would be suboptimal β-agonist-mediated bronchodilation and possibly reduced control over increasing ASM mass. These phenotypes appear to be "hard-wired" into ASM from asthmatics, as they do not require an inflammatory environment in culture to be observed.

  12. 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.

  13. AIRWAY VISUALIZATION: EYES SEE WHAT MIND KNOWS.

    Science.gov (United States)

    Sorbello, Massimiliano; Frova, Giulio; Zdravković, Ivana

    2016-03-01

    Airway management is basic for anesthesia practice, and sometimes it can represent a really dramatic scenario for both the patient and the physicians. Laryngoscopy has been the gold standard of airway visualization for more than 60 years, showing its limitations and failure rates with time. New technology has made available an opportunity to move the physician's eye inside patient airways thanks to video laryngoscopy and video assisted airway management technique. Undoubtedly, we have entered a new era of high resolution airway visualization and different approach in airway instrumentation. Nevertheless, each new technology needs time to be tested and considered reliable, and pitfalls and limitations may come out with careful and long lasting analysis, so it is probably not the right time yet to promote video assisted approach as a new gold standard for airway visualization, despite the fact that it certainly offers some new prospects. In any case, whatever the visualization approach, no patient dies because of missed airway visualization or failed intubation, but due to failed ventilation, which remains without doubt the gold standard of any patient safety goal and airway management technique.

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

    Directory of Open Access Journals (Sweden)

    Umesh C S Yadav

    Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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

  15. Cigarette Smoke and Estrogen Signaling in Human Airway Smooth Muscle

    Directory of Open Access Journals (Sweden)

    Venkatachalem Sathish

    2015-06-01

    Full Text Available Aims: Cigarette smoke (CS in active smokers and second-hand smoke exposure exacerbate respiratory disorders such as asthma and chronic bronchitis. While women are known to experience a more asthmatic response to CS than emphysema in men, there is limited information on the mechanisms of CS-induced airway dysfunction. We hypothesize that CS interferes with a normal (protective bronchodilatory role of estrogens, thus worsening airway contractility. Methods: We tested effects of cigarette smoke extract (CSE on 17β-estradiol (E2 signaling in enzymatically-dissociated bronchial airway smooth muscle (ASM obtained from lung samples of non-smoking female patients undergoing thoracic surgery. Results: In fura-2 loaded ASM cells, CSE increased intracellular calcium ([Ca2+]i responses to 10µM histamine. Acute exposure to physiological concentrations of E2 decreased [Ca2+]i responses. However, in 24h exposed CSE cells, although expression of estrogen receptors was increased, the effect of E2 on [Ca2+]i was blunted. Acute E2 exposure also decreased store-operated Ca2+ entry and inhibited stromal interaction molecule 1 (STIM1 phosphorylation: effects blunted by CSE. Acute exposure to E2 increased cAMP, but less so in 24h CSE-exposed cells. 24h CSE exposure increased S-nitrosylation of ERα. Furthermore, 24h CSE-exposed bronchial rings showed increased bronchoconstrictor agonist responses that were not reduced as effectively by E2 compared to non-CSE controls. Conclusion: These data suggest that CS induces dysregulation of estrogen signaling in ASM, which could contribute to increased airway contractility in women exposed to CS.

  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. Anger perceptually and conceptually narrows cognitive scope.

    Science.gov (United States)

    Gable, Philip A; Poole, Bryan D; Harmon-Jones, Eddie

    2015-07-01

    For the last 50 years, research investigating the effect of emotions on scope of cognitive processing was based on models proposing that affective valence determined cognitive scope. More recently, our motivational intensity model suggests that this past work had confounded valence with motivational intensity. Research derived from this model supports the idea that motivational intensity, rather than affective valence, explains much of the variance emotions have on cognitive scope. However, the motivational intensity model is limited in that the empirical work has examined only positive affects high in approach and negative affects high in avoidance motivation. Thus, perhaps only approach-positive and avoidance-negative states narrow cognitive scope. The present research was designed to clarify these conceptual issues by examining the effect of anger, a negatively valenced approach-motivated state, on cognitive scope. Results revealed that anger narrowed attentional scope relative to a neutral state and that attentional narrowing to anger was similar to the attentional narrowing caused by high approach-motivated positive affects (Study 1). This narrowing of attention was related to trait approach motivation (Studies 2 and Study 3). Anger also narrowed conceptual cognitive categorization (Study 4). Narrowing of categorization related to participants' approach motivation toward anger stimuli. Together, these results suggest that anger, an approach-motivated negative affect, narrows perceptual and conceptual cognitive scope. More broadly, these results support the conceptual model that motivational intensity per se, rather than approach-positive and avoidance-negative states, causes a narrowing of cognitive scope.

  18. IL-13–induced airway mucus production is attenuated by MAPK13 inhibition

    Science.gov (United States)

    Alevy, Yael G.; Patel, Anand C.; Romero, Arthur G.; Patel, Dhara A.; Tucker, Jennifer; Roswit, William T.; Miller, Chantel A.; Heier, Richard F.; Byers, Derek E.; Brett, Tom J.; Holtzman, Michael J.

    2012-01-01

    Increased mucus production is a common cause of morbidity and mortality in inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the precise molecular mechanisms for pathogenic mucus production are largely undetermined. Accordingly, there are no specific and effective anti-mucus therapeutics. Here, we define a signaling pathway from chloride channel calcium-activated 1 (CLCA1) to MAPK13 that is responsible for IL-13–driven mucus production in human airway epithelial cells. The same pathway was also highly activated in the lungs of humans with excess mucus production due to COPD. We further validated the pathway by using structure-based drug design to develop a series of novel MAPK13 inhibitors with nanomolar potency that effectively reduced mucus production in human airway epithelial cells. These results uncover and validate a new pathway for regulating mucus production as well as a corresponding therapeutic approach to mucus overproduction in inflammatory airway diseases. PMID:23187130

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

    Directory of Open Access Journals (Sweden)

    Haruka Aoki

    2014-01-01

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

  20. Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling.

    Science.gov (United States)

    Johnson, Jill R; Wiley, Ryan E; Fattouh, Ramzi; Swirski, Filip K; Gajewska, Beata U; Coyle, Anthony J; Gutierrez-Ramos, José-Carlos; Ellis, Russ; Inman, Mark D; Jordana, Manel

    2004-02-01

    It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4+ lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposed mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly. PMID:14597485

  1. Extraction of Airways from CT (EXACT'09)

    NARCIS (Netherlands)

    Lo, P.; Ginneken, B. van; Reinhardt, J.M.; Tarunashree, Y.; Jong, P.A. de; Irving, B.; Fetita, C.; Ortner, M.; Pinho, R.; Sijbers, J.; Feuerstein, M.; Fabijanska, A.; Bauer, C.; Beichel, R.; Mendoza, C.S.; Wiemker, R.; Lee, J. van der; Reeves, A.P.; Born, S.; Weinheimer, O.; Rikxoort, E.M. van; Tschirren, J.; Mori, K.; Odry, B.; Naidich, D.P.; Hartmann, I.J.; Hoffman, E.A.; Prokop, M.; Pedersen, J.H.; Bruijne, M. de

    2012-01-01

    This paper describes a framework for establishing a reference airway tree segmentation, which was used to quantitatively evaluate fifteen different airway tree extraction algorithms in a standardized manner. Because of the sheer difficulty involved in manually constructing a complete reference stand

  2. Diagnostic tools assessing airway remodelling in asthma.

    Science.gov (United States)

    Manso, L; Reche, M; Padial, M A; Valbuena, T; Pascual, C

    2012-01-01

    Asthma is an inflammatory disease of the lower airways characterised by the presence of airway inflammation, reversible airflow obstruction and airway hyperresponsiveness and alterations on the normal structure of the airways, known as remodelling. Remodelling is characterised by the presence of metaplasia of mucous glands, thickening of the lamina reticularis, increased angiogenesis, subepithelial fibrosis and smooth muscle hypertrophy/hyperplasia. Several techniques are being optimised at present to achieve a suitable diagnosis for remodelling. Diagnostic tools could be divided into two groups, namely invasive and non-invasive methods. Invasive techniques bring us information about bronchial structural alterations, obtaining this information directly from pathological tissue, and permit measure histological modification placed in bronchi layers as well as inflammatory and fibrotic cell infiltration. Non-invasive techniques were developed to reduce invasive methods disadvantages and measure airway remodelling-related markers such as cytokines, inflammatory mediators and others. An exhaustive review of diagnostic tools used to analyse airway remodelling in asthma, including the most useful and usually employed methods, as well as the principal advantages and disadvantages of each of them, bring us concrete and summarised information about all techniques used to evaluate alterations on the structure of the airways. A deep knowledge of these diagnostic tools will make an early diagnosis of airway remodelling possible and, probably, early diagnosis will play an important role in the near future of asthma. PMID:22236733

  3. Extraction of Airways from CT (EXACT’09)

    DEFF Research Database (Denmark)

    Lo, Pechin; 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 standar...

  4. Inhibition of Toll-Like Receptor 2-Mediated Interleukin-8 Production in Cystic Fibrosis Airway Epithelial Cells via the α7-Nicotinic Acetylcholine Receptor

    OpenAIRE

    Shane J. O'Neill; McElvaney, Noel G; Wells, Robert J.; Hugh Ramsay; Greene, Catherine M

    2010-01-01

    Cystic Fibrosis (CF) is an inherited disorder characterised by chronic inflammation of the airways. The lung manifestations of CF include colonization with Pseudomonas aeruginosa and Staphylococcus aureus leading to neutrophil-dominated airway inflammation and tissue damage. Inflammation in the CF lung is initiated by microbial components which activate the innate immune response via Toll-like receptors (TLRs), increasing airway epithelial cell production of proinflammatory mediators such as ...

  5. Spirometric abnormalities associated with chronic bronchitis, asthma, and airway hyperresponsiveness among boilermaker construction workers

    Energy Technology Data Exchange (ETDEWEB)

    Hauser, R.; Eisen, E,A,; Pothier, L,; Lewis, D,; Bledsoe, T,; Christiani, D.C. [Harvard University, Boston, MA (United States). School of Public Health

    2002-06-01

    In a 2-year longitudinal study of boilermaker construction workers, authors found a significant association between working at oil-fired, coal-fired, and gas-fired industries during the past year and reduced lung function. In the present study, authors investigated whether chronic bronchitis, asthma, or baseline methacholine airway responsiveness can explain the heterogeneity in lung function response to boilermaker work. Exposure was assessed with a work history questionnaire. Spirometry was performed annually to assess lung function. A generalized estimating equation approach was used to account for the repeated-measures design. One hundred eighteen boilermakers participated in the study. Self-reported history of chronic bronchitis and asthma were associated with a larger FEV1 reduction in response to workplace exposure at coal-fired and gas-fired industries. Although a high prevalence (39%) of airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEVI of {lt} 8 mg/mL) among boilermakers was found, there was no consistent pattern of effect modification by airway responsiveness. Conclusions: Although chronic bronchitis and asthma were associated with a greater loss in lung function in response to hours worked as a boilermaker, and therefore they acted as effect modifiers of the exposure-lung function relationship, airway hyperresponsiveness did not. However, the high prevalence of airway hyperresponsiveness found in the cohort may be a primary consequence of long-term workplace exposure among boilermakers.

  6. The influence of upper airways diameter on the intensity of obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Jolanta Szymańska

    2014-03-01

    Full Text Available Introduction and Objective. Obstructive sleep apnea (OSA is characterized by at least 5 ten-second-long episodes of apnea or hypopnea, per hour of sleep. This disease may lead to severe, life-threatening complications. Therefore, risk analysis and its influence on disease intensity is crucial for proper implementation of preventive treatments. Objective. To determine the relation between the intensity of OSA expressed in Apnea-Hypopnea Index (AHI, and the anterior-posterior diameter of upper airways at the levels of soft palate and tongue base. Material and Method. Medical records of 41 patients with sleep apnea (AHI>4 diagnosed through polysomnographic examination obstructive were used for the study. The data consisted of: age and gender, polysomnographic examination results (AHI, lateral cephalogram with cephalomertic analysis, together with measurements of the upper and lower pharyngeal depth according to McNamara. Statistical analysis was carried out in accordance with Pearson’s r correlation coefficient test (Statistica 8.0 software package. Results. Analysis of the influence of upper airways diameter on the intensity of OSA showed that the value of upper Airways diameter at the tongue base level had no statistically significant impact on the value of AHI (p=0.795. However, a statistically significant impact of the value of upper airways diameter on the AHI value (p=0.008 at the soft palate level was observed. Patients with OSA have narrowed upper airways diameter. The value of AHI increases with the decrease of upper diameter and is not dependent on a lower diameter value. Patients with a decreased upper airways diameter should be informed about potential breathing disorders during sleep.

  7. Investigating the geometry of pig airways using computed tomography

    Science.gov (United States)

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

    2015-03-01

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

  8. Use of spirometry in detecting airway obstruction in asymptomatic smokers

    International Nuclear Information System (INIS)

    Objectives: To detect spirometric abnormalities in asymptomatic smokers in relation to duration of smoking. Study Design: Cross sectional study. Place and Duration of Study: The study was carried out at PNS Shifa from Oct 2006 to June 2007. Subjects and Methods: Hundred individuals were included in this study who fulfilled the required criteria. Spirometry was done after briefing the patient about the procedure. Smokers were divided into two groups. Group I (5 to 9 pack years) and group II (= 10 pack years). All relevant information were recorded on Performa (Annex-A). The data was analyzed through SPSS-10, in terms of Mean +- SD (Standard Deviation) for numeric response variables and independent sample T test was applied to compare significance of proportion for numeric response variables at p < 0.05. Categorical variables were compared by applying Chi-square test at p < 0.05 level of significance. Results: Significant statistical difference was found between the mean age in the two groups with p-value of 0.011. This may be due to the longer duration of smoking history in Group II. Strong association was found between number of cigarette smoked and the pattern of airway obstruction as significant statistical difference of airway obstruction and early airflow limitation was found between the two groups of smokers at p value of 0.004. Conclusion: There is strong association between duration of smoking and development of airway obstruction even before the smoker become symptomatic. (author)

  9. Inflammatory Signalings Involved in Airway and Pulmonary Diseases

    Directory of Open Access Journals (Sweden)

    I-Ta Lee

    2013-01-01

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

  10. Modular microfluidic system as a model of cystic fibrosis airways

    DEFF Research Database (Denmark)

    Skolimowski, Maciej; Weiss Nielsen, Martin; Abeille, Fabien;

    2012-01-01

    A modular microfluidic airways model system that can simulate the changes in oxygen tension in different compartments of the cystic fibrosis (CF) airways was designed, developed, and tested. The fully reconfigurable system composed of modules with different functionalities: multichannel peristaltic...... pumps, bubble traps, gas exchange chip, and cell culture chambers. We have successfully applied this system for studying the antibiotic therapy of Pseudomonas aeruginosa, the bacteria mainly responsible for morbidity and mortality in cystic fibrosis, in different oxygen environments. Furthermore, we...... have mimicked the bacterial reinoculation of the aerobic compartments (lower respiratory tract) from the anaerobic compartments (cystic fibrosis sinuses) following an antibiotic treatment. This effect is hypothesised as the one on the main reasons for recurrent lung infections in cystic fibrosis...

  11. Narrow-linewidth and tunable fiber lasers

    OpenAIRE

    Morkel, P.R.

    1993-01-01

    1. Introduction 2. Line-narrowed fiber laser devices Integral fiber reflective Bragg grating lasers Intra-cavity etalon laser 3. Tunable, line narrowed fiber laser devices Ring lasers using wavelength selective couplers Tunable lasers using bulk-optic components a) Mechanical tuning b) Electronic tuning 4. Single frequency fiber lasers Integral fiber reflective Bragg grating laser Interferometric cavity laser Injection locked laser Travellin...

  12. Quantitative analysis of dynamic airway changes after methacholine and salbutamol inhalation on xenon-enhanced chest CT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sang Joon; Goo, Jin Mo; Kim, Jong Hyo; Park, Eun-Ah [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Lee, Chang Hyun [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Jung, Jae-Woo; Park, Heung-Woo [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of); Cho, Sang-Heon [Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of)

    2012-11-15

    To investigate the dynamic changes in airways in response to methacholine and salbutamol inhalation and to correlate the xenon ventilation index on xenon-enhanced chest CTs in asthmatics. Thirty-one non-smokers (6 normal, 25 asthmatics) underwent xenon-enhanced chest CT and pulmonary function tests. Images were obtained at three stages (basal state, after methacholine inhalation and after salbutamol inhalation), and the total xenon ventilation index (TXVI) as well as airway values were measured and calculated. The repeated measures ANOVA and Spearman's correlation coefficient were used for statistical analysis. TXVI in the normal group did not significantly change (P > 0.05) with methacholine and salbutamol. For asthmatics, however, the TXVI significantly decreased after methacholine inhalation and increased after salbutamol inhalation (P < 0.05). Of the airway parameters, the airway inner area (IA) significantly increased after salbutamol inhalation in all airways (P < 0.01) in asthmatics. Airway IA, wall thickness and wall area percentage did not significantly decrease after methacholine inhalation (P > 0.05). IA of the large airways was well correlated with basal TXVI, FEV{sub 1} and FVC (P < 0.05). Airway IA is the most reliable parameter for reflecting the dynamic changes after methacholine and salbutamol inhalation, and correlates well with TXVI in asthmatics on xenon-enhanced CT. (orig.)

  13. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations.

    Directory of Open Access Journals (Sweden)

    Edith T Zemanick

    Full Text Available BACKGROUND: Pulmonary exacerbations (PEx, frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF. Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood. OBJECTIVE: To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx. METHODS: Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d. and late treatment (>7d. for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE; and circulating C-reactive protein (CRP were measured. RESULTS: Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA of Pseudomonas (r = -0.67, p<0.001, decreased FEV(1% predicted (r = 0.49, p = 0.03 and increased CRP (r = -0.58, p = 0.01. In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus. CONCLUSIONS: Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.

  14. Lower Corticosteroid Skin Blanching Response Is Associated with Severe COPD

    NARCIS (Netherlands)

    Hoonhorst, Susan J. M.; ten Hacken, Nicolaas; Loi, Adele T. Lo Tam; Koenderman, Leo; Lammers, Jan Willem J.; Telenga, Eef D.; Boezen, Hendrika; van den Berge, Maarten; Postma, Dirkje S.

    2014-01-01

    Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused by ongoing inflammatory and remodeling processes of the airways and lung tissue. Inflammation can be targeted by corticosteroids. However, airway inflammation is generally less responsive t

  15. Prevalence of upper airway obstruction in patients with apparently asymptomatic euthyroid multi nodular goitre

    Directory of Open Access Journals (Sweden)

    Sunil K Menon

    2011-01-01

    Full Text Available Aims: To study the prevalence of upper airway obstruction (UAO in "apparently asymptomatic" patients with euthyroid multinodular goitre (MNG and find correlation between clinical features, UAO on pulmonary function test (PFT and tracheal narrowing on computerised tomography (CT. Materials and Methods: Consecutive patients with apparently asymptomatic euthyroid MNG attending thyroid clinic in a tertiary centre underwent clinical examination to elicit features of UAO, PFT, and CT of neck and chest. Statistical Analysis Used: Statistical analysis was done with SPSS version 11.5 using paired t-test, Chi square test, and Fisher′s exact test. P value of <0.05 was considered to be significant. Results: Fifty-six patients (52 females and four males were studied. The prevalence of UAO (PFT and significant tracheal narrowing (CT was 14.3%. and 9.3%, respectively. Clinical features failed to predict UAO or significant tracheal narrowing. Tracheal narrowing (CT did not correlate with UAO (PFT. Volume of goitre significantly correlated with degree of tracheal narrowing. Conclusions: Clinical features do not predict UAO on PFT or tracheal narrowing on CT in apparently asymptomatic patients with euthyroid MNG.

  16. Biomechanism of airway smooth muscle growth in bronchial asthma%支气管哮喘气道平滑肌生长的生化机制

    Institute of Scientific and Technical Information of China (English)

    刘庆华; 宋泽庆

    2010-01-01

    Airway smooth muscle growth lies in bronchial asthma and leads to narrowing and airflow obstruction of the airway,whose molecular mechanism and functional effeCt of remodeling of airway remains unclear.This review will discuss airway smooth muscle hyperplasia,hypertrophy and biomechanism of them.%支气管哮喘都有气道平滑肌的生长,并引起气道的狭窄和气流阻塞.其分子机制和气道重塑而发生的功能改变仍然不清楚.这篇综述将讨论气道平滑肌增生、肥大以及功能的改变和发生的生化机制.

  17. Comparative evaluation of intraocular pressure changes subsequent to insertion of laryngeal mask airway and endotracheal tube.

    Directory of Open Access Journals (Sweden)

    Ghai B

    2001-07-01

    Full Text Available AIMS: To evaluate the intraocular pressure and haemodynamic changes subsequent to insertion of laryngeal mask airway and endotracheal tube. SUBJECTS AND METHODS: The study was conducted in 50 adult patients. A standard general anaesthesia was administered to all the patients. After 3 minutes of induction of anaesthesia baseline measurements of heart rate, non-invasive blood pressure and intraocular pressure were taken following which patients were divided into two groups: laryngeal mask airway was inserted in group 1 and tracheal tube in group 2. These measurements were repeated at 15-30 second, every minute thereafter up to 5 minutes after airway instrumentation. RESULTS: A statistically significant rise in heart rate, systolic blood pressure, diastolic blood pressure and intraocular pressure was seen in both the groups subsequent to insertion of laryngeal mask airway or endotracheal tube. Mean maximum increase was statistically more after endotracheal intubation than after laryngeal mask airway insertion. The duration of statistically significant pressure responses was also longer after endotracheal intubation. CONCLUSION: Laryngeal mask airway is an acceptable alternative technique for ocular surgeries, offering advantages in terms of intraocular pressure and cardiovascular stability compared to tracheal intubation.

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

    Directory of Open Access Journals (Sweden)

    Claudiney de Freitas Alves

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wei Xu

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

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

    Science.gov (United States)

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

    2012-01-01

    Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4(+)FoxP3(+)) and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma. PMID:22792275

  1. Vitamin D attenuates cytokine-induced remodeling in human fetal airway smooth muscle cells.

    Science.gov (United States)

    Britt, Rodney D; Faksh, Arij; Vogel, Elizabeth R; Thompson, Michael A; Chu, Vivian; Pandya, Hitesh C; Amrani, Yassine; Martin, Richard J; Pabelick, Christina M; Prakash, Y S

    2015-06-01

    Asthma in the pediatric population remains a significant contributor to morbidity and increasing healthcare costs. Vitamin D3 insufficiency and deficiency have been associated with development of asthma. Recent studies in models of adult airway diseases suggest that the bioactive Vitamin D3 metabolite, calcitriol (1,25-dihydroxyvitamin D3 ; 1,25(OH)2 D3 ), modulates responses to inflammation; however, this concept has not been explored in developing airways in the context of pediatric asthma. We used human fetal airway smooth muscle (ASM) cells as a model of the early postnatal airway to explore how calcitriol modulates remodeling induced by pro-inflammatory cytokines. Cells were pre-treated with calcitriol and then exposed to TNFα or TGFβ for up to 72 h. Matrix metalloproteinase (MMP) activity, production of extracellular matrix (ECM), and cell proliferation were assessed. Calcitriol attenuated TNFα enhancement of MMP-9 expression and activity. Additionally, calcitriol attenuated TNFα and TGFβ-induced collagen III expression and deposition, and separately, inhibited proliferation of fetal ASM cells induced by either inflammatory mediator. Analysis of signaling pathways suggested that calcitriol effects in fetal ASM involve ERK signaling, but not other major inflammatory pathways. Overall, our data demonstrate that calcitriol can blunt multiple effects of TNFα and TGFβ in developing airway, and point to a potentially novel approach to alleviating structural changes in inflammatory airway diseases of childhood. PMID:25204635

  2. 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.

  3. 复合异丙酚时瑞芬太尼抑制老年男性患者喉罩置入反应的半数有效效应室浓度%Median effective effect-site concentration of remifentanil inhibiting responses to laryngeal mask airway insertion when combined with propofol in elderly male patients

    Institute of Scientific and Technical Information of China (English)

    孙健; 卢悦淳; 吕国义

    2014-01-01

    目的:确定复合异丙酚时瑞芬太尼抑制老年男性患者喉罩置入反应的半数有效效应室浓度(EC50)。方法择期全麻下拟行经尿道膀胱肿瘤或前列腺电切术男性患者30例,ASA分级Ⅰ或Ⅱ级,体重指数<30 kg/m2,年龄>65岁。采用靶控输注异丙酚诱导,血浆靶浓度设为3μg/ml ,当镇静/警醒评分≤1分时,靶控输注瑞芬太尼,初始靶浓度为4.0 ng/ml。调节异丙酚靶浓度,BIS值55~65时置入喉罩,按改良序贯法进行试验,发生喉罩置入反应,下一例患者升高1个浓度梯度,否则降低1个浓度梯度,相邻浓度比值为1.2。发生喉罩置入反应的标准为:置入过程中或置入后3 min内发生明显咳嗽、喉痉挛和/或体动。计算复合异丙酚时瑞芬太尼抑制老年男性患者喉罩置入反应的EC50及其95%可信区间(95% CI )。结果复合异丙酚时瑞芬太尼抑制老年男性患者喉罩置入反应的EC50及其95% CI为1.86(1.64~2.12) ng/ml。结论复合异丙酚时瑞芬太尼抑制老年男性患者喉罩置入反应的EC50为1.86 ng/ml。%Objective To determine the median effective effect-site concentration (EC50 ) of remifentanil inhibiting responses to laryngeal mask airway insertion when combined with propofol in elderly male patients . Methods Thirty ASA physical status Ⅰ or Ⅱ male patients ,aged 65>yr ,with body mass index <30 kg/m2 , scheduled for elective transurethral resection of bladder tumor or prostate under general anesthesia ,were enrolled in this study .Anesthesia was induced with target-controlled infusion of propofol with a target plasma concentration (Cp) of 3 μg/ml .When Observer′s Assessment of Alertness/Sedation (OAA/S ) score ≤1 ,remifentanil target-controlled infusion was started with the initial target Cp set at 4.0 ng/ml . The concentration of propofol was adjusted until BIS value reached 55-65 ,and then the laryngeal mask airway was inserted

  4. Spontaneous peristaltic airway contractions propel lung liquid through the bronchial tree of intact and fetal lung explants.

    Science.gov (United States)

    Schittny, J C; Miserocchi, G; Sparrow, M P

    2000-07-01

    Spontaneous contractions of the fetal airways are a well recognized but poorly characterized phenomenon. In the present study spontaneous narrowing of the airways was analyzed in freshly isolated lungs from early to late gestation in fetal pigs and rabbits and in cultured fetal mouse lungs. Propagating waves of contraction traveling proximal to distal were observed in fresh lungs throughout gestation which displaced the lung liquid along the lumen. In the pseudoglandular and canalicular stages (fetal pigs) the frequency ranged from 2.3 to 3.3 contractions/min with a 39 to 46% maximum reduction of lumen diameter. In the saccular stage (rabbit) the frequency was 10 to 12/min with a narrowing of approximately 30%. In the organ cultures the waves of narrowing started at the trachea in whole lungs, or at the main bronchus in lobes (5.2 +/- 1.5 contractions/min, 22 +/- 8% reduction of lumen diameter), and as they proceeded distally along the epithelial tubes the luminal liquid was shifted toward the terminal tubules, which expanded the endbuds. As the tubules relaxed the flow of liquid was reversed. Thus the behavior of airway smooth muscle in the fetal lung is phasic in type (like gastrointestinal muscle) in contrast to that in postnatal lung, where it is tonic. An intraluminal positive pressure of 2.33 +/- 0.77 cm H(2)O was recorded in rabbit fetal trachea. It is proposed that the active tone of the smooth muscle maintains the positive intraluminal pressure and acts as a stimulus to lung growth via the force exerted across the airway wall and adjacent parenchyma. The expansion of the compliant endbuds by the fluid shifts at the airway tip may promote their growth into the surrounding mesenchyme.

  5. Vessel-guided airway tree segmentation: A voxel classification approach

    DEFF Research Database (Denmark)

    Ashraf, Haseem; Pedersen, Jesper J H; Lo, Pechin Chien Pau;

    2010-01-01

    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. 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...

  6. 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.......01; n = 94) and the arousal index (Spearman correlation, r = 0.21; p CPAP treatment, the AHI was significantly reduced from 27 ± 3 events · h(-1) to 4 ± 2 events · h(-1) (each n = 29; p

  7. Airways disorders and the swimming pool.

    Science.gov (United States)

    Bougault, Valérie; Boulet, Louis-Philippe

    2013-08-01

    Concerns have been expressed about the possible detrimental effects of chlorine derivatives in indoor swimming pool environments. Indeed, a controversy has arisen regarding the possibility that chlorine commonly used worldwide as a disinfectant favors the development of asthma and allergic diseases. The effects of swimming in indoor chlorinated pools on the airways in recreational and elite swimmers are presented. Recent studies on the influence of swimming on airway inflammation and remodeling in competitive swimmers, and the phenotypic characteristics of asthma in this population are reviewed. Preventative measures that could potentially reduce the untoward effects of pool environment on airways of swimmers are discussed. PMID:23830132

  8. Emergency surgical airway management in Denmark

    DEFF Research Database (Denmark)

    Rosenstock, C V; Kehlet Nørskov, Anders; Wetterslev, J;

    2016-01-01

    general anaesthesia and tracheal intubation from the DAD from June 1, 2008 to March 15, 2014. Difficult airway management involving an ESA was retrieved for analysis and compared with hospitals files. Two independent reviewers evaluated airway management according to the ASAs'2003 practice guideline...... per thousand (95% CI; 1.0-2.4). A Supraglottic Airway Device and/or the administration of a neuromuscular blocking agent before ESA were used as a rescue in 6/27 and 13/27 of the patients, respectively. In 19/27 patients ENT surgeons performed the ESA's and anaesthetists attempted 6/27 of the ESAs...

  9. Leukocyte trafficking in alveoli and airway passages

    Directory of Open Access Journals (Sweden)

    Doerschuk Claire M

    2000-10-01

    Full Text Available Abstract Many pulmonary diseases preferentially affect the large airways or the alveoli. Although the mechanisms are often particular to each disease process, site-specific differences in leukocyte trafficking and the regulation of inflammation also occur. Differences in the process of margination, sequestration, adhesion, and migration occur that can be attributed to differences in anatomy, hemodynamics, and the expression of proteins. The large airways are nourished by the bronchial circulation, whereas the pulmonary circulation feeds the distal lung parenchyma. The presence of different cell types in large airways from those in alveoli might contribute to site-specific differences in the molecular regulation of the inflammatory process.

  10. Contribution of air pollution to COPD and small airway dysfunction.

    Science.gov (United States)

    Berend, Norbert

    2016-02-01

    Although in many Western countries levels of ambient air pollution have been improving with the setting of upper limits and better urban planning, air pollution in developing countries and particularly those with rapid industrialization has become a major global problem. Together with increased motor vehicle ownership and traffic congestion, there is a growing issue with airborne particles of respirable size. These particles are thought responsible for respiratory and cardiovascular effects and have also been implicated in cancer pathogenesis. The pathologic effects in the lung are mediated via inflammatory pathways and involve oxidative stress similar to cigarette smoking. These effects are seen in the peripheral airways where the smaller particle fractions are deposited and lead to airway remodelling. However, emphysema and loss of bronchioles seen with cigarette smoking have not been described with ambient air pollution, and there are few studies specifically looking at peripheral airway function. Definitive evidence of air pollution causing COPD is lacking and a different study design is required to link air pollution and COPD. PMID:26412571

  11. Contribution of air pollution to COPD and small airway dysfunction.

    Science.gov (United States)

    Berend, Norbert

    2016-02-01

    Although in many Western countries levels of ambient air pollution have been improving with the setting of upper limits and better urban planning, air pollution in developing countries and particularly those with rapid industrialization has become a major global problem. Together with increased motor vehicle ownership and traffic congestion, there is a growing issue with airborne particles of respirable size. These particles are thought responsible for respiratory and cardiovascular effects and have also been implicated in cancer pathogenesis. The pathologic effects in the lung are mediated via inflammatory pathways and involve oxidative stress similar to cigarette smoking. These effects are seen in the peripheral airways where the smaller particle fractions are deposited and lead to airway remodelling. However, emphysema and loss of bronchioles seen with cigarette smoking have not been described with ambient air pollution, and there are few studies specifically looking at peripheral airway function. Definitive evidence of air pollution causing COPD is lacking and a different study design is required to link air pollution and COPD.

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

    Science.gov (United States)

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

    2004-04-01

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

  13. Comparison of bougie-guided insertion of Proseal tm laryngeal mask airway with digital technique in adults

    Directory of Open Access Journals (Sweden)

    Anand Kuppusamy

    2010-01-01

    Full Text Available The Proseal TM laryngeal mask airway (PLMA TM , Laryngeal Mask Company, UK was designed to improve ventilatory characteristics and offer protection against regurgitation and gastric insufflation. The PLMA is a modified laryngeal mask airway with large ventral cuff, dorsal cuff and a drain tube. These modifications improve seal around glottis and enable better ventilatory characteristics. The drain tube prevents gastric distension and offers protection against aspiration. There were occasional problems, like failed insertion and inadequate ventilation, in placing PLMA TM using the classical digital technique. To overcome these problems, newer placement techniques like thumb insertion technique, introducer tool placement and gum elastic bougie (GEB-aided placement were devised. We compared classical digital placement of PLMA TM with gum elastic bougie-aided technique in 60 anaesthetised adult patients (with 30 patients in each group with respect to number of attempts to successful placement, effective airway time, airway trauma during insertion, postoperative airway morbidity and haemodynamic response to insertion. The number of attempts to successful placement, airway trauma during insertion and haemodynamic response to insertion were comparable among the two groups, while effective airway time and oropharyngeal leak pressure were significantly higher in bougie- guided insertion of PLMA. Postoperatively, sore throat was more frequent with digital technique while dysphagia was more frequent with bougie-guided technique. Hence gum elastic bougie guided, laryngoscope aided insertion of PLMA is an excellent alternate to classical digital technique.

  14. In vivo role of platelet-derived growth factor-BB in airway smooth muscle proliferation in mouse lung.

    Science.gov (United States)

    Hirota, Jeremy A; Ask, Kjetil; Farkas, Laszlo; Smith, Jane Ann; Ellis, Russ; Rodriguez-Lecompte, Juan Carlos; Kolb, Martin; Inman, Mark D

    2011-09-01

    Airway smooth muscle (ASM) hyperplasia in asthma likely contributes considerably to functional changes. Investigating the mechanisms behind proliferation of these cells may lead to therapeutic benefit. Platelet-derived growth factor (PDGF)-BB is a well known ASM mitogen in vitro but has yet to be directly explored using in vivo mouse models in the context of ASM proliferation and airway responsiveness. To determine the in vivo influence of PDGF-BB on gene transcripts encoding contractile proteins, ASM proliferation, and airway physiology, we used an adenovirus overexpression system and a model of chronic allergen exposure. We used adenovirus technology to selectively overexpress PDGF-BB in the airway epithelium of mice. Outcome measurements, including airway physiology, real time RT-PCR measurements, proliferating cell nuclear antigen staining, and airway smooth muscle quantification, were performed 7 days after exposure. The same outcome measurements were performed 24 hours and 4 weeks after a chronic allergen exposure model. PDGF-BB overexpression resulted in airway hyperresponsiveness, decreased lung compliance, increased airway smooth muscle cell numbers, positive proliferating cell nuclear antigen-stained airway smooth muscle cells, and a reduction in genes encoding contractile proteins. Chronic allergen exposure resulted in elevations in lung lavage PDGF-BB, which were observed in conjunction with changes in gene transcript expression encoding contractile proteins and ASM proliferation. We demonstrate for the first time in vivo that PDGF-BB induces ASM hyperplasia and changes in lung mechanics in mice and that, during periods of allergen exposure changes in lung, PDGF-BB are associated with changes in airway structure and function.

  15. Crouzon syndrome with bony upper airway obstruction: case report and review literature.

    Science.gov (United States)

    Gothwal, Sunil; Nayan, Swati; Kumar, Jagdish

    2014-08-01

    Crouzon syndrome is a rare genetic disorder. It is inherited as an autosomal dominant pattern. Mutations in the FGFR2 gene are known to cause Crouzon syndrome. Craniofacial abnormalities are common at birth and may progress with time. The severity of these signs and symptoms varies among affected children. A full term, large for date, male baby was delivered to a gravida 2 mother by cesarean section having facial dimorphism suggestive of Crouzon syndrome. Genetic team confirmed the diagnosis. Baby had severe respiratory distress. On work up, upper bony airway narrowing was found (diameter 3 mm). Later on, baby was operated for the same. Baby is asymptomatic now and doing well up to 2 months of follow-up. Management of Crouzon disease is multidisciplinary and early diagnosis has prime importance. Follow-up must ensure late features like hearing problems, vision problems, dental problems, intelligence, cranial synostosis, and upper airway problems. PMID:24828762

  16. Device Physics of Narrow Gap Semiconductors

    CERN Document Server

    Chu, Junhao

    2010-01-01

    Narrow gap semiconductors obey the general rules of semiconductor science, but often exhibit extreme features of these rules because of the same properties that produce their narrow gaps. Consequently these materials provide sensitive tests of theory, and the opportunity for the design of innovative devices. Narrow gap semiconductors are the most important materials for the preparation of advanced modern infrared systems. Device Physics of Narrow Gap Semiconductors offers descriptions of the materials science and device physics of these unique materials. Topics covered include impurities and defects, recombination mechanisms, surface and interface properties, and the properties of low dimensional systems for infrared applications. This book will help readers to understand not only the semiconductor physics and materials science, but also how they relate to advanced opto-electronic devices. The last chapter applies the understanding of device physics to photoconductive detectors, photovoltaic infrared detector...

  17. Obstructive airway in Morquio A syndrome, the past, the present and the future.

    Science.gov (United States)

    Tomatsu, Shunji; Averill, Lauren W; Sawamoto, Kazuki; Mackenzie, William G; Bober, Michael B; Pizarro, Christian; Goff, Christopher J; Xie, Li; Orii, Tadao; Theroux, Mary

    2016-02-01

    Patients with severe tracheal obstruction in Morquio A syndrome are at risk of dying of sleep apnea and related complications. Tracheal obstruction also leads to life-threatening complications during anesthesia as a result of the difficulty in managing the upper airway due to factors inherent to the Morquio A syndrome, compounded by the difficulty in intubating the trachea. A detailed description of the obstructive pathology of the trachea is not available in the literature probably due to lack of a homogenous group of Morquio A patients to study at any one particular center. We present a series of cases with significant tracheal obstruction who were unrecognized due to the difficulty in interpreting tracheal narrowing airway symptoms. Our goal is to provide the guidelines in the management of these patients that allow earlier recognition and intervention of tracheal obstruction. Sagittal MRI images of the cervical spine of 28 Morquio A patients (12±8.14years) showed that19/28 (67.9%) patients had at least 25% tracheal narrowing and that narrowing worsened with age (all 8 patients over 15years had greater than 50% narrowing). Eight out of 28 patients were categorized as severe (>75%) tracheal narrowing when images were evaluated in neutral head and neck position. Of the 19 patients with tracheal narrowing, compression by the tortuous brachiocephalic artery was the most common cause (n=15). Evidence of such tracheal narrowing was evident as early as at 2years of age. The etiology of tracheal impingement by the brachiocephalic artery in Morquio A appears to be due to a combination of the narrow thoracic inlet crowding structures and the disproportionate growth of trachea and brachiocephalic artery in relationship to the chest cavity leading to tracheal tortuosity. In conclusion, tracheal narrowing, often due to impression from the crossing tortuous brachiocephalic artery, increases with age in Morquio A patients. Greater attention to the trachea is needed when

  18. Narrow linewidth pulsed optical parametric oscillator

    Indian Academy of Sciences (India)

    S Das

    2010-11-01

    Tunable narrow linewidth radiation by optical parametric oscillation has many applications, particularly in spectroscopic investigation. In this paper, different techniques such as injection seeding, use of spectral selecting element like grating, grating and etalon in combination, grazing angle of incidence, entangled cavity configuration and type-II phase matching have been discussed for generating tunable narrow linewidth radiation by singly resonant optical parametric oscillation process.

  19. Synchronized imaging and acoustic analysis of the upper airway in patients with sleep-disordered breathing

    International Nuclear Information System (INIS)

    Progressive narrowing of the upper airway increases airflow resistance and can produce snoring sounds and apnea/hypopnea events associated with sleep-disordered breathing due to airway collapse. Recent studies have shown that acoustic properties during snoring can be altered with anatomic changes at the site of obstruction. To evaluate the instantaneous association between acoustic features of snoring and the anatomic sites of obstruction, a novel method was developed and applied in nine patients to extract the snoring sounds during sleep while performing dynamic magnetic resonance imaging (MRI). The degree of airway narrowing during the snoring events was then quantified by the collapse index (ratio of airway diameter preceding and during the events) and correlated with the synchronized acoustic features. A total of 201 snoring events (102 pure retropalatal and 99 combined retropalatal and retroglossal events) were recorded, and the collapse index as well as the soft tissue vibration time were significantly different between pure retropalatal (collapse index, 24  ±  11%; vibration time, 0.2  ±  0.3 s) and combined (retropalatal and retroglossal) snores (collapse index, 13  ±  7% [P ≤ 0.0001]; vibration time, 1.2  ±  0.7 s [P ≤ 0.0001]). The synchronized dynamic MRI and acoustic recordings successfully characterized the sites of obstruction and established the dynamic relationship between the anatomic site of obstruction and snoring acoustics. (paper)

  20. Virtual Airway Skills Trainer (VAST) Simulator

    Science.gov (United States)

    DEMIREL, Doga; YU, Alexander; HALIC, Tansel; SANKARANARAYANAN, Ganesh; RYASON, Adam; SPINDLER, David; BUTLER, Kathryn L.; CAO, Caroline; PETRUSA, Emil; MOLINA, Marcos; JONES, Dan; DE, Suvranu; DEMOYA, Marc; JONES, Stephanie

    2016-01-01

    This paper presents a simulation of Virtual Airway Skill Trainer (VAST) tasks. The simulated tasks are a part of two main airway management techniques; Endotracheal Intubation (ETI) and Cricothyroidotomy (CCT). ETI is a simple nonsurgical airway management technique, while CCT is the extreme surgical alternative to secure the airway of a patient. We developed identification of Mallampati class, finding the optimal angle for positioning pharyngeal/mouth axes tasks for ETI and identification of anatomical landmarks and incision tasks for CCT. Both ETI and CCT simulators were used to get physicians’ feedback at Society for Education in Anesthesiology and Association for Surgical Education spring meetings. In this preliminary validation study, total 38 participants for ETI and 48 for CCT performed each simulation task and completed pre and post questionnaires. In this work, we present the details of the simulation for the tasks and also the analysis of the collected data from the validation study. PMID:27046559

  1. Role of platelets in allergic airway inflammation.

    Science.gov (United States)

    Idzko, Marco; Pitchford, Simon; Page, Clive

    2015-06-01

    Increasing evidence suggests an important role for platelets and their products (e.g., platelet factor 4, β-thromboglobulin, RANTES, thromboxane, or serotonin) in the pathogenesis of allergic diseases. A variety of changes in platelet function have been observed in patients with asthma, such as alterations in platelet secretion, expression of surface molecules, aggregation, and adhesion. Moreover, platelets have been found to actively contribute to most of the characteristic features of asthma, including bronchial hyperresponsiveness, bronchoconstriction, airway inflammation, and airway remodeling. This review brings together the current available data from both experimental and clinical studies that have investigated the role of platelets in allergic airway inflammation and asthma. It is anticipated that a better understanding of the role of platelets in the pathogenesis of asthma might lead to novel promising therapeutic approaches in the treatment of allergic airway diseases. PMID:26051948

  2. Lung hyperinflation and its reversibility in patients with airway obstruction of varying severity.

    Science.gov (United States)

    Deesomchok, Athavudh; Webb, Katherine A; Forkert, Lutz; Lam, Yuk-Miu; Ofir, Dror; Jensen, Dennis; O'Donnell, Denis E

    2010-12-01

    The natural history of lung hyperinflation in patients with airway obstruction is unknown. In particular, little information exists about the extent of air trapping and its reversibility to bronchodilator therapy in those with mild airway obstruction. We completed a retrospective analysis of data from individuals with airway obstruction who attended our pulmonary function laboratory and had plethysmographic lung volume measurements pre- and post-bronchodilator (salbutamol). COPD was likely the predominant diagnosis but patients with asthma may have been included. We studied 2,265 subjects (61% male), age 65 ± 9 years (mean ± SD) with a post-bronchodilator FEV(1)/FVC lung hyperinflation, and measured responses to bronchodilation across subgroups stratified by GOLD criteria. In GOLD stage I, vital capacity (VC) and inspiratory capacity (IC) were in the normal range; pre-bronchodilator residual volume (RV), functional residual capacity (FRC) and specific airway resistance were increased to 135%, 119% and 250% of predicted, respectively. For the group as a whole, RV and FRC increased exponentially as FEV(1) decreased, while VC and IC decreased linearly. Regardless of baseline FEV(1), the most consistent improvement following bronchodilation was RV reduction, in terms of magnitude and responder rate. In conclusion, increases (above normal) in airway resistance and plethysmographic lung volumes were found in those with only minor airway obstruction. Indices of lung hyperinflation increased exponentially as airway obstruction worsened. Those with the greatest resting lung hyperinflation showed the largest bronchodilator-induced volume deflation effects. Reduced air trapping was the predominant response to acute bronchodilation across severity subgroups.

  3. Role of cholinergic neural transmission on airway resistance in the dog.

    Science.gov (United States)

    Kondo, T; Kobayashi, I; Hayama, N; Tazaki, G; Ohta, Y

    2000-04-12

    The unique contractile profiles of bronchial smooth muscle (Kondo et al., 1995) and its neural control were investigated by comparing responses of the bronchus and trachea to acute hypercapnia, stimulation of vagus efferent fibers before and after intravenous atropine, and intravenous acetylcholine in decerebrated and paralyzed dogs. During acute hypercapnia, airway resistance represented by peak airway pressure (Pedley et al., 1970) significantly increased as well as tracheal tension (Ttr). During electric stimulation of the vagal efferent fibers, Ttr increased and was sustained throughout the simulation period while the peak airway pressure was not maintained at the peak level. The peak Ttr and the airway resistance (Raw) calculated from ventilatory flow and airway pressure increased with increases in intensity of electric stimulation. Ttr reached its maximal level at an intensity 16 times of the threshold (T), while Raw became maximal at 4T. Although both the Ttr-stimulus intensity and Raw-intensity curves were shifted to the right by administration of intravenous atropine, the Raw curve shifted more to the right than the Ttr curve with the same dose of atropine. When muscular muscarinic receptors were directly stimulated by intravenous acetylcholine, Ttr once increased and then decreased promptly while peak airway pressure remained at a high level for a few minutes. These findings suggested that the bronchus is more sensitive to vagal efferent stimulation and susceptible to competitive antagonist of actylcholine than the trachea. In conclusion, the contractile profiles of the fifth-order bronchus we have reported (Kondo et al., 1995) were reflected in airway resistance, and the neuromuscular junction may be the site of adaptation of bronchoconstrictor response to motor nerve adaptation.

  4. 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

  5. Airway CD8(+) T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection.

    Science.gov (United States)

    Connors, Thomas J; Ravindranath, Thyyar M; Bickham, Kara L; Gordon, Claire L; Zhang, Feifan; Levin, Bruce; Baird, John S; Farber, Donna L

    2016-06-01

    Infants and young children are disproportionately susceptible to severe complications from respiratory viruses, although the underlying mechanisms remain unknown. Recent studies show that the T cell response in the lung is important for protective responses to respiratory infections, although details on the infant/pediatric respiratory immune response remain sparse. The objectives of the present study were to characterize the local versus systemic immune response in infants and young children with respiratory failure from viral respiratory tract infections and its association to disease severity. Daily airway secretions were sampled from infants and children 4 years of age and younger receiving mechanical ventilation owing to respiratory failure from viral infection or noninfectious causes. Samples were examined for immune cell composition and markers of T cell activation. These parameters were then correlated with clinical disease severity. Innate immune cells and total CD3(+) T cells were present in similar proportions in airway aspirates derived from infected and uninfected groups; however, the CD8:CD4 T cell ratio was markedly increased in the airways of patients with viral infection compared with uninfected patients, and specifically in infected infants with acute lung injury. T cells in the airways were phenotypically and functionally distinct from those in blood with activated/memory phenotypes and increased cytotoxic capacity. We identified a significant increase in airway cytotoxic CD8(+) T cells in infants with lung injury from viral respiratory tract infection that was distinct from the T cell profile in circulation and associated with increasing disease severity. Airway sampling could therefore be diagnostically informative for assessing immune responses and lung damage. PMID:26618559

  6. Central airways remodeling in COPD patients

    Directory of Open Access Journals (Sweden)

    Pini L

    2014-09-01

    Full Text Available Laura Pini,1 Valentina Pinelli,2 Denise Modina,1 Michela Bezzi,3 Laura Tiberio,4 Claudio Tantucci1 1Unit of Respiratory Medicine, Department of Clinical and Experimental Sciences, University of Brescia, 2Department of Respiratory Medicine, Spedali Civili di Brescia, 3Department Bronchoscopy, Spedali Civili di Brescia, 4Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Background: The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD patients has been well documented, but less is known about the role played by the large airways. Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients. Objectives: The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM area and the extracellular matrix (ECM protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes. Methods: Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin. ECM protein deposition was measured at both subepithelial, and ASM layers. Results: The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects. An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity. A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls. Conclusion: These findings indicate that airway remodeling also affects

  7. Anaesthesia and airway management in mucopolysaccharidosis

    OpenAIRE

    Walker, Robert; Belani, Kumar G.; Braunlin, Elizabeth A.; Bruce, Iain A.; Hack, Henrik; Harmatz, Paul R.; Jones, Simon; Rowe, Richard; Solanki, Guirish A.; Valdemarsson, Barbara

    2012-01-01

    This paper provides a detailed overview and discussion of anaesthesia in patients with mucopolysaccharidosis (MPS), the evaluation of risk factors in these patients and their anaesthetic management, including emergency airway issues. MPS represents a group of rare lysosomal storage disorders associated with an array of clinical manifestations. The high prevalence of airway obstruction and restrictive pulmonary disease in combination with cardiovascular manifestations poses a high anaesthetic ...

  8. Dynamic Properties of Human Bronchial Airway Tissues

    OpenAIRE

    Wang, Jau-Yi; Mesquida, Patrick; 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 a...

  9. Leukocyte trafficking in alveoli and airway passages

    OpenAIRE

    Doerschuk Claire M

    2000-01-01

    Abstract Many pulmonary diseases preferentially affect the large airways or the alveoli. Although the mechanisms are often particular to each disease process, site-specific differences in leukocyte trafficking and the regulation of inflammation also occur. Differences in the process of margination, sequestration, adhesion, and migration occur that can be attributed to differences in anatomy, hemodynamics, and the expression of proteins. The large airways are nourished by the bronchial circula...

  10. Numerical simulation of airway dimension effects on airflow patterns and odorant deposition patterns in the rat nasal cavity.

    Directory of Open Access Journals (Sweden)

    Zehong Wei

    Full Text Available The sense of smell is largely dependent on the airflow and odorant transport in the nasal cavity, which in turn depends on the anatomical structure of the nose. In order to evaluate the effect of airway dimension on rat nasal airflow patterns and odorant deposition patterns, we constructed two 3-dimensional, anatomically accurate models of the left nasal cavity of a Sprague-Dawley rat: one was based on high-resolution MRI images with relatively narrow airways and the other was based on artificially-widening airways of the MRI images by referencing the section images with relatively wide airways. Airflow and odorant transport, in the two models, were determined using the method of computational fluid dynamics with finite volume method. The results demonstrated that an increase of 34 µm in nasal airway dimension significantly decreased the average velocity in the whole nasal cavity by about 10% and in the olfactory region by about 12% and increased the volumetric flow into the olfactory region by about 3%. Odorant deposition was affected to a larger extent, especially in the olfactory region, where the maximum odorant deposition difference reached one order of magnitude. The results suggest that a more accurate nasal cavity model is necessary in order to more precisely study the olfactory function of the nose when using the rat.

  11. 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

  12. Interleukin-20 promotes airway remodeling in asthma.

    Science.gov (United States)

    Gong, Wenbin; Wang, Xin; Zhang, Yuguo; Hao, Junqing; Xing, Chunyan; Chu, Qi; Wang, Guicheng; Zhao, Jiping; Wang, Junfei; Dong, Qian; Liu, Tian; Zhang, Yuanyuan; Dong, Liang

    2014-12-01

    Previous studies have demonstrated that interleukin-20 (IL-20) is a pro-inflammatory cytokine, and it has been implicated in psoriasis, lupus nephritis, rheumatoid arthritis, atherosclerosis, and ulcerative colitis. Little is known about the effects of IL-20 in airway remodeling in asthma. The aim of our study was to demonstrate the function of IL-20 in airway remodeling in asthma. To identify the expression of IL-20 and its receptor, IL-20R1/IL-20R2, in the airway epithelium in bronchial tissues, bronchial biopsy specimens were collected from patients and mice with asthma and healthy subjects and stained with specific antibodies. To characterize the effects of IL-20 in asthmatic airway remodeling, we silenced and stimulated IL-20 in cell lines isolated from mice by shRNA and recombinant protein approaches, respectively, and detected the expression of α-SMA and FN-1 by Western blot analysis. First, overexpression of IL-20 and its receptor, IL-20R1/IL-20R2, was detected in the airway epithelium collected from patients and mice with asthma. Second, IL-20 increased the expression of fibronectin-1 and α-SMA, and silencing of IL-20 in mouse lung epithelial (MLE)-12 cells decreased the expression of fibronectin-1 and α-SMA. IL-20 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting IL-20 and/or its receptors may be a new therapeutic strategy for asthma. PMID:25028099

  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. Store-operated Ca2+ channels in airway epithelial cell function and implications for asthma.

    Science.gov (United States)

    Samanta, Krishna; Parekh, Anant B

    2016-08-01

    The epithelial cells of the lung are at the interface of a host and its environment and are therefore directly exposed to the inhaled air-borne particles. Rather than serving as a simple physical barrier, airway epithelia detect allergens and other irritants and then help organize the subsequent immune response through release of a plethora of secreted signals. Many of these signals are generated in response to opening of store-operated Ca(2+) channels in the plasma membrane. In this review, we describe the properties of airway store-operated channels and their role in regulating airway epithelial cell function.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377718

  15. Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells.

    Science.gov (United States)

    Shkumatov, Artem; Thompson, Michael; Choi, Kyoung M; Sicard, Delphine; Baek, Kwanghyun; Kim, Dong Hyun; Tschumperlin, Daniel J; Prakash, Y S; Kong, Hyunjoon

    2015-06-01

    Multiple pulmonary conditions are characterized by an abnormal misbalance between various tissue components, for example, an increase in the fibrous connective tissue and loss/increase in extracellular matrix proteins (ECM). Such tissue remodeling may adversely impact physiological function of airway smooth muscle cells (ASMCs) responsible for contraction of airways and release of a variety of bioactive molecules. However, few efforts have been made to understand the potentially significant impact of tissue remodeling on ASMCs. Therefore, this study reports how ASMCs respond to a change in mechanical stiffness of a matrix, to which ASMCs adhere because mechanical stiffness of the remodeled airways is often different from the physiological stiffness. Accordingly, using atomic force microscopy (AFM) measurements, we found that the elastic modulus of the mouse bronchus has an arithmetic mean of 23.1 ± 14 kPa (SD) (median 18.6 kPa). By culturing ASMCs on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we found that gels designed to be softer than average airway tissue significantly increased cellular secretion of vascular endothelial growth factor (VEGF). Conversely, gels stiffer than average airways stimulated cell proliferation, while reducing VEGF secretion and agonist-induced calcium responses of ASMCs. These dependencies of cellular activities on elastic modulus of the gel were correlated with changes in the expression of integrin-β1 and integrin-linked kinase (ILK). Overall, the results of this study demonstrate that changes in matrix mechanics alter cell proliferation, calcium signaling, and proangiogenic functions in ASMCs.

  16. TRPA1 is a major oxidant sensor in murine airway sensory neurons.

    Science.gov (United States)

    Bessac, Bret F; Sivula, Michael; von Hehn, Christian A; Escalera, Jasmine; Cohn, Lauren; Jordt, Sven-Eric

    2008-05-01

    Sensory neurons in the airways are finely tuned to respond to reactive chemicals threatening airway function and integrity. Nasal trigeminal nerve endings are particularly sensitive to oxidants formed in polluted air and during oxidative stress as well as to chlorine, which is frequently released in industrial and domestic accidents. Oxidant activation of airway neurons induces respiratory depression, nasal obstruction, sneezing, cough, and pain. While normally protective, chemosensory airway reflexes can provoke severe complications in patients affected by inflammatory airway conditions like rhinitis and asthma. Here, we showed that both hypochlorite, the oxidizing mediator of chlorine, and hydrogen peroxide, a reactive oxygen species, activated Ca(2+) influx and membrane currents in an oxidant-sensitive subpopulation of chemosensory neurons. These responses were absent in neurons from mice lacking TRPA1, an ion channel of the transient receptor potential (TRP) gene family. TRPA1 channels were strongly activated by hypochlorite and hydrogen peroxide in primary sensory neurons and heterologous cells. In tests of respiratory function, Trpa1(-/-) mice displayed profound deficiencies in hypochlorite- and hydrogen peroxide-induced respiratory depression as well as decreased oxidant-induced pain behavior. Our results indicate that TRPA1 is an oxidant sensor in sensory neurons, initiating neuronal excitation and subsequent physiological responses in vitro and in vivo. PMID:18398506

  17. Protease-activated receptor 2 activation of myeloid dendritic cells regulates allergic airway inflammation

    Directory of Open Access Journals (Sweden)

    Dienger Krista

    2011-09-01

    Full Text Available Abstract Background A common characteristic of allergens is that they contain proteases that can activate protease-activated receptor (PAR-2; however the mechanism by which PAR-2 regulates allergic airway inflammation is unclear. Methods Mice (wild type and PAR-2-deficient were sensitized using German cockroach (GC feces (frass, the isolated protease from GC frass, or through adoptive transfer of GC frass-treated bone marrow-derived dendritic cells (BMDC and measurements of airway inflammation (cellular infiltration, cytokine expression, and mucin production, serum IgE levels and airway hyperresponsiveness (AHR were assessed. BMDC were cultured, treated with GC frass and assessed for cytokine production. PAR-2 expression on pulmonary mDCs was determined by flow cytometry. Results Exposure to GC frass induced AHR and airway inflammation in wild type mice; however PAR-2-deficient mice had significantly attenuated responses. To directly investigate the role of the protease, we isolated the protease from GC frass and administered the endotoxin-free protease into the airways of mice in the presence of OVA. GC frass proteases were sufficient to promote the development of AHR, serum IgE, and Th2 cytokine production. PAR-2 expression on mDC was upregulated following GC frass exposure, but the presence of a functional PAR-2 did not alter antigen uptake. To determine if PAR-2 activation led to differential cytokine production, we cultured BMDC in the presence of GM-CSF and treated these cells ex vivo with GC frass. PAR-2-deficient BMDC released significantly less IL-6, IL-23 and TNFα compared to BMDC from wild type mice, suggesting PAR-2 activation was important in Th2/Th17 skewing cytokine production. To determine the role for PAR-2 on mDCs on the initiation of allergic airway inflammation, BMDCs from wild type and PAR-2-deficient mice were treated in the presence or absence of GC frass and then adoptively transferred into the airway of wild type mice

  18. Origins of increased airway smooth muscle mass in asthma.

    Science.gov (United States)

    Berair, Rachid; Saunders, Ruth; Brightling, Christopher E

    2013-01-01

    Asthma is characterized by both chronic inflammation and airway remodeling. Remodeling--the structural changes seen in asthmatic airways--is pivotal in the pathogenesis of the disease. Although significant advances have been made recently in understanding the different aspects of airway remodeling, the exact biology governing these changes remains poorly understood. There is broad agreement that, in asthma, increased airway smooth muscle mass, in part due to smooth muscle hyperplasia, is a very significant component of airway remodeling. However, significant debate persists on the origins of these airway smooth muscle cells. In this review article we will explore the natural history of airway remodeling in asthma and we will discuss the possible contribution of progenitors, stem cells and epithelial cells in mesenchymal cell changes, namely airway smooth muscle hyperplasia seen in the asthmatic airways. PMID:23742314

  19. Trigger of bronchial hyperresponsiveness development may not always need eosinophilic airway inflammation in very early stage of asthma

    OpenAIRE

    Obase, Yasushi; Shimoda, Terufumi; Kishikawa, Reiko; Kohno, Shigeru; Iwanaga, Tomoaki

    2016-01-01

    Background: Cough variant asthma (CVA), a suggested precursor of standard bronchial asthma (SBA), is characterized by positive bronchial hyperresponsiveness (BHR) and a chronic cough response to bronchodilator that persists for >8 weeks. Objective: Airway inflammation, BHR, and airway obstructive damage were analyzed to assess whether CVA represents early or mild-stage SBA. Methods: Patients with newly diagnosed CVA (n = 72) and SBA (n = 84) naive to oral or inhaled corticosteroids and withou...

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

    OpenAIRE

    Konstantinos Samitas; Vasiliki Delimpoura; Eleftherios Zervas; Mina Gaga

    2015-01-01

    Asthma is a disorder of the airways involving various inflammatory cells and mediators and characterised by bronchial hyperresponsiveness, chronic inflammation and structural alterations in the airways, also known as remodelling. IgE is an important mediator of allergic reactions and has a central role in allergic asthma pathophysiology, as it is implicated in both the early and late phase allergic response. Moreover, clinical and mechanistic evidence has lately emerged, implicating IgE in th...

  1. Recent Advances in Mechanisms and Treatments of Airway Remodeling in Asthma: A Message from the Bench Side to the Clinic

    OpenAIRE

    Cho, Jae Youn

    2011-01-01

    Airway remodeling in asthma is a result of persistent inflammation and epithelial damage in response to repetitive injury. Recent studies have identified several important mediators associated with airway remodeling in asthma, including transforming growth factor-β, interleukin (IL)-5, basic fibroblast growth factor, vascular endothelial growth factor, LIGHT, tumor necrosis factor (TNF)-α, thymic stromal lymphopoietin, IL-33, and IL-25. In addition, the epithelium mesenchymal transformation (...

  2. Pseudomonas aeruginosa pyocyanin modulates mucin glycosylation with sialyl-Lewis(x) to increase binding to airway epithelial cells.

    Science.gov (United States)

    Jeffries, J L; Jia, J; Choi, W; Choe, S; Miao, J; Xu, Y; Powell, R; Lin, J; Kuang, Z; Gaskins, H R; Lau, G W

    2016-07-01

    Cystic fibrosis (CF) patients battle life-long pulmonary infections with the respiratory pathogen Pseudomonas aeruginosa (PA). An overabundance of mucus in CF airways provides a favorable niche for PA growth. When compared with that of non-CF individuals, mucus of CF airways is enriched in sialyl-Lewis(x), a preferred binding receptor for PA. Notably, the levels of sialyl-Lewis(x) directly correlate with infection severity in CF patients. However, the mechanism by which PA causes increased sialylation remains uncharacterized. In this study, we examined the ability of PA virulence factors to modulate sialyl-Lewis(x) modification in airway mucins. We found pyocyanin (PCN) to be a potent inducer of sialyl-Lewis(x) in both mouse airways and in primary and immortalized CF and non-CF human airway epithelial cells. PCN increased the expression of C2/4GnT and ST3Gal-IV, two of the glycosyltransferases responsible for the stepwise biosynthesis of sialyl-Lewis(x), through a tumor necrosis factor (TNF)-α-mediated phosphoinositol-specific phospholipase C (PI-PLC)-dependent pathway. Furthermore, PA bound more efficiently to airway epithelial cells pre-exposed to PCN in a flagellar cap-dependent manner. Importantly, antibodies against sialyl-Lewis(x) and anti-TNF-α attenuated PA binding. These results indicate that PA secretes PCN to induce a favorable environment for chronic colonization of CF lungs by increasing the glycosylation of airway mucins with sialyl-Lewis(x). PMID:26555707

  3. Temporal correlation of optical coherence tomography in-vivo images of rabbit airway for the diagnosis of edema

    Science.gov (United States)

    Kang, DongYel; Wang, Alex; Tjoa, Tjoson; Volgger, Veronika; Hamamoto, Ashley; Su, Erica; Jing, Joseph; Chen, Zhongping; Wong, Brian J. F.

    2014-03-01

    Recently, full-range optical coherence tomography (OCT) systems have been developed to image the human airway. These novel systems utilize a fiber-based OCT probe which acquires three-dimensional (3-D) images with micrometer resolution. Following an airway injury, mucosal edema is the first step in the body's inflammatory response, which occasionally leads to airway stenosis, a life-threatening condition for critically ill newborns. Therefore, early detection of edema is vital for airway management and prevention of stenosis. In order to examine the potential of the full-range OCT to diagnose edema, we investigated temporal correlation of OCT images obtained from the subglottic airway of live rabbits. Temporally correlated OCT images were acquired at fixed locations in the rabbit subglottis of either artificially induced edema or normal tissues. Edematous tissue was experimentally modeled by injecting saline beneath the epithelial layer of the subglottic mucosa. The calculated cross temporal correlations between OCT images of normal airway regions show periodicity that correlates with the respiratory motion of the airway. However, the temporal correlation functions calculated from OCT images of the edematous regions show randomness without the periodic characteristic. These in-vivo experimental results of temporal correlations between OCT images show the potential of a computer-based or -aided diagnosis of edema in the human respiratory mucosa with a full-range OCT system.

  4. Lipocalin2 protects against airway inflammation and hyperresponsiveness in a murine model of allergic airway disease

    DEFF Research Database (Denmark)

    Dittrich, A M; Krokowski, M; Meyer, H-A;

    2010-01-01

    Allergen-induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering different inflammatory pathways.......Allergen-induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering different inflammatory pathways....

  5. 75 FR 13079 - Action Affecting Export Privileges; MAHAN AIRWAYS; Mahan Airways, Mahan Tower, No. 21, Azadegan...

    Science.gov (United States)

    2010-03-18

    ... Secretary Jackson issued an Order adding Blue Airways FZE and Blue Airways, both of Dubai, United Arab... conduct illustrates its refusal to comply with the TDO or U.S. export control laws.\\6\\ \\6\\ My findings are... full written statement in support of the appeal with the Office of the Administrative Law Judge,...

  6. Full Airway Drainage by Fiber Bronchoscopy Through Artificial Airway in the Treatment of Occult Traumatic Atelectasis.

    Science.gov (United States)

    Zhao, Xue Hong; Zhang, Yun; Liang, Zhong Yan; Zhang, Shao Yang; Yu, Wen Qiao; Huang, Fang-Fang

    2015-12-01

    The objective of this study is to investigate the effects of full airway drainage by fiber bronchoscopy through artificial airway in the treatment of traumatic atelectasis with occult manifestations. From May 2006 to May 2011, 40 cases of occult traumatic atelectasis were enrolled into our prospective study. Group A (n = 18) received drainage by nasal bronchoscope; group B underwent airway drainage by fiber bronchoscopy through artificial airway (n = 22). The effects of treatment were evaluated by the incidence of adult respiratory distress syndrome (ARDS), lung abscess, and the average length of hospital stay. Compared with nasal fiber-optic treatment, airway drainage by fiber bronchoscopy through artificial airway reduced the incidence of ARDS (p = 0.013) and lung abscess (p = 0.062) and shortened the mean length of stay (p = 0.018). Making the decision to create an artificial airway timely and carry out lung lavage by fiber bronchoscopy through artificial airway played a significant role in the treatment of occult traumatic atelectasis.

  7. Cystic fibrosis airway epithelial Ca2+ i signaling: the mechanism for the larger agonist-mediated Ca2+ i signals in human cystic fibrosis airway epithelia.

    Science.gov (United States)

    Ribeiro, Carla M Pedrosa; Paradiso, Anthony M; Carew, Mark A; Shears, Stephen B; Boucher, Richard C

    2005-03-18

    In cystic fibrosis (CF) airways, abnormal epithelial ion transport likely initiates mucus stasis, resulting in persistent airway infections and chronic inflammation. Mucus clearance is regulated, in part, by activation of apical membrane receptors coupled to intracellular calcium (Ca(2+)(i)) mobilization. We have shown that Ca(2+)(i) signals resulting from apical purinoceptor (P2Y(2)-R) activation are increased in CF compared with normal human airway epithelia. The present study addressed the mechanism for the larger apical P2Y(2)-R-dependent Ca(2+)(i) signals in CF human airway epithelia. We show that the increased Ca(2+)(i) mobilization in CF was not specific to P2Y(2)-Rs because it was mimicked by apical bradykinin receptor activation, and it did not result from a greater number of P2Y(2)-R or a more efficient coupling between P2Y(2)-Rs and phospholipase C-generated inositol 1,4,5-trisphosphate. Rather, the larger apical P2Y(2)-R activation-promoted Ca(2+)(i) signals in CF epithelia resulted from an increased density and Ca(2+) storage capacity of apically confined endoplasmic reticulum (ER) Ca(2+) stores. To address whether the ER up-regulation resulted from ER retention of misfolded DeltaF508 CFTR or was an acquired response to chronic luminal airway infection/inflammation, three approaches were used. First, ER density was studied in normal and CF sweat duct human epithelia expressing high levels of DeltaF508 CFTR, and it was found to be the same in normal and CF epithelia. Second, apical ER density was morphometrically analyzed in airway epithelia from normal subjects, DeltaF508 homozygous CF patients, and a disease control, primary ciliary dyskinesia; it was found to be greater in both CF and primary ciliary dyskinesia. Third, apical ER density and P2Y(2)-R activation-mobilized Ca(2+)(i), which were investigated in airway epithelia in a long term culture in the absence of luminal infection, were similar in normal and CF epithelia. To directly test whether

  8. Predictors of neutrophilic airway inflammation in young smokers with asthma

    DEFF Research Database (Denmark)

    Westergaard, Christian Grabow; Munck, Christian; Helby, Jens;

    2014-01-01

    . The investigation also included analysis for effect of pack years, current tobacco consumption, body mass index, lung function, FeNO; methacholine and mannitol responsiveness, atopy, gender, asthma history and presence of bacteria. The most common potentially pathogenic bacteria found were Streptococcus spp......Introduction: Asthma is one of the most widespread chronic diseases worldwide. In spite of numerous detrimental effects on asthma, smoking is common among asthma patients. These smoking-induced aggravations of asthma may be attributed to changes in airway inflammation, which is characterized...... smokers, neutrophilia may be induced when a certain threshold of tobacco consumption is reached....

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

    Directory of Open Access Journals (Sweden)

    Arizmendi Narcy G

    2011-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Kenneth R Eyring

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

  11. Pore Narrowing of Mesoporous Silica Materials

    Directory of Open Access Journals (Sweden)

    Christophe Detavernier

    2013-02-01

    Full Text Available To use mesoporous silicas as low-k materials, the pore entrances must be really small to avoid diffusion of metals that can increase the dielectric constant of the low-k dielectric. In this paper we present a new method to narrow the pores of mesoporous materials through grafting of a cyclic-bridged organosilane precursor. As mesoporous material, the well-studied MCM-41 powder was selected to allow an easy characterization of the grafting reactions. Firstly, the successful grafting of the cyclic-bridged organosilane precursor on MCM-41 is presented. Secondly, it is demonstrated that pore narrowing can be obtained without losing porosity by removing the porogen template after grafting. The remaining silanols in the pores can then be end-capped with hexamethyl disilazane (HMDS to make the material completely hydrophobic. Finally, we applied the pore narrowing method on organosilica films to prove that this method is also successful on existing low-k materials.

  12. Numerical simulation for the upper airway flow characteristics of Chinese patients with OSAHS using CFD models.

    Science.gov (United States)

    Tan, Jie; Huang, Jianmin; Yang, Jianguo; Wang, Desheng; Liu, Jianzhi; Liu, Jingbo; Lin, Shuchun; Li, Chen; Lai, Haichun; Zhu, Hongyu; Hu, Xiaohua; Chen, Dongxu; Zheng, Longxiang

    2013-03-01

    OSAHS is a common disease with many factors related to the etiology. Airflow plays an important role in the pathogenesis of OSAHS. Previous research has not yielded a sufficient understanding of the relationship between airflow in upper airway and the pathophysiology of OSAHS. Therefore, a better understanding of the flow inside the upper airway in an OSAHS patient is necessary. In this study, ten Chinese adults with OSAHS were recruited. We used the software MIMICS 13.1 to construct 3-dimensional (3-D) models based on the computer tomography scans of them. The numerical simulations were carried out using the software ANSYS 12.0. We found that during the inhalation phase, the vortices and turbulences were located in both the anterior part of the cavity and nasopharynx. But there is no vortex in the whole nasal cavity during the expiratory phase. The airflow velocity is much higher than that of the normal models. The distributions of pressure and wall shear stress are different in two phases. The maximum velocity, pressure and wall shear stress (WSS) are located in velopharynx. It is notable that a strong negative pressure region is found in pharyngeal airway. The maximum velocity is 19.26 ± 12.4 and 19.46 ± 13.1 m/s; the average pressure drop is 222.71 ± 208.84 and 238.5 ± 218.56 Pa and the maximum average WSS is 0.72 ± 0.58 and 1.01 ± 0.61 Pa in inspiratory and expiratory, respectively. The changes of airflow due to the structure changes play an important role in the occurrence of collapse and obstruction of the upper airway, especially, the abnormal pressure changes in velopharyngeal during both inspiratory and expiratory phases. We can say that the airway narrowing in the pharynx may be one of the most important factors driving airway collapse. In addition, the most collapsible region of the pharyngeal airway of the patient with OSAHS may be the velopharynx and oropharynx. In spite of limitations, our results can provide a basis for the further research

  13. Safety And Efficacy Of Proseal Laryngeal Mask Airway Versus Classic Laryngeal Mask Airway And Endo Tracheal Tube During Elective surgery

    Directory of Open Access Journals (Sweden)

    Soad A. Mansour , Wafaa G.Ahmed , Kawthar A. Azzam ,Tarek M. EL said

    2005-12-01

    Full Text Available The present study was performed to compare safety , efficacy of Proseal Laryngeal Mask Airway (PLMA, classic Laryngeal mask airway (LMA and cuffed Endo Tracheal Tube (ETT as a ventilatory device during controlled positive pressure ventilation and airway management , Haemodynamic response to insertion and removal, gastric tube insertion through either device, air leak detection and assessment of position by fiberoptic bronchoscope . Forty five ASA I or II patients aged between 18-55 years old , were divided equally into three groups of fifteen patients each , and airway management either through PLMA(groupI,classic LMA (groupIIand ETT (group III . All patients were premedicated by zantac hydrochloride 150 mg orally at mid night and two hours before the operation ­ Anaesthesia was induced with fentanyl 2 ug/kg and propofol 2.5 mg /kg and maintenance was with a mixture of 50% N2O , 50% O2 and isoflurane 1 - 1.5 % and rocuronium 0.5 mg /kg followed by continous infusion of rocuronium 0.3-0.6 mg/kg/hr A proper size PLMA , classic LMA or ETT was selected oxygenation and ventilation were optimal in 100% in group I and III while in group II 80% optimal and suboptimal in 13.3% and failed in 6.7 % . Haemodynamic parameters showed that significantly increase in HR and MAP in the three studied groups especially at insertion and removal of the airway device with statisticaly significant difference between group I,II in comparison to group III, comparison of gastric tube insertion showed that positive insertion was 86.7% in group I and in 46.7% in group II, while in group III positive insertion was 100% air leak was detected by epigastric auscultation which signified lower leakage in PLMA group than LMA group . Position assessment by fiberoptic bronchoscope in PLMA group was grade 4 in 5 patients , grade 3 in 5 patients , grade2 in 4 patients and grade 1 in 1 patient while in LMA group it was grade 4 in 7 patients , grade 3 in 6 patients , grade 2 in 2

  14. Pulmonary CD103 expression regulates airway inflammation in asthma.

    Science.gov (United States)

    Bernatchez, Emilie; Gold, Matthew J; Langlois, Anick; Lemay, Anne-Marie; Brassard, Julyanne; Flamand, Nicolas; Marsolais, David; McNagny, Kelly M; Blanchet, Marie-Renee

    2015-04-15

    Although CD103(+) cells recently emerged as key regulatory cells in the gut, the role of CD103 ubiquitous expression in the lung and development of allergic airway disease has never been studied. To answer this important question, we evaluated the response of Cd103(-/-) mice in two separate well-described mouse models of asthma (ovalbumin and house dust mite extract). Pulmonary inflammation was assessed by analysis of bronchoalveolar lavage content, histology, and cytokine response. CD103 expression was analyzed on lung dendritic cells and T cell subsets by flow cytometry. Cd103(-/-) mice exposed to antigens developed exacerbated lung inflammation, characterized by increased eosinophilic infiltration, severe tissue inflammation, and altered cytokine response. In wild-type mice exposed to house dust mite, CD103(+) dendritic cells are increased in the lung and an important subset of CD4(+) T cells, CD8(+) T cells, and T regulatory cells express CD103. Importantly, Cd103(-/-) mice presented a deficiency in the resolution phase of inflammation, which supports an important role for this molecule in the control of inflammation severity. These results suggest an important role for CD103 in the control of airway inflammation in asthma. PMID:25681437

  15. Heat transfer models in narrow gap

    International Nuclear Information System (INIS)

    For severe accident assessment in a light water reactor (LWR), heat transfer models in a narrow annular gap between the overheated core debris and the reactor pressure vessel (RPV) are important to evaluate the integrity of RPV and emergency procedures. Some heat transfer models have been proposed as gap cooling CHF (critical heat flux) but the effects of superheat on the heat transfer surface were not taken into account. This paper presents the effects of superheat based on existing data and heat transfer models in a narrow gap. (author)

  16. Left mainstem bronchial narrowing: a vascular compression syndrome? Evaluation by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hungate, R.G.; Newman, B.; Meza, M.P. [Department of Radiology, Children`s Hospital of Pittsburgh and University of Pittsburgh Medical Center, 3705 Fifth Avenue, Pittsburgh, PA 15213 (United States)

    1998-07-01

    Background and objective. Vascular compression of the left mainstem bronchus (LMSB) between the descending aorta (DA) and pulmonary artery (PA) has been suggested as a cause for LMSB narrowing in children. These anatomic relationships have not been compared with those in children with a normal LMSB. Materials and methods. We undertook a retrospective review of the medical and radiologic records of 10 symptomatic young children (1-19 months, 5 boys, 5 girls) with MR demonstration of LMSB narrowing and compared them to 40 young children without great vessel or bronchial abnormality on MR (1 week-19 months, 28 boys, 12 girls). Chest MR evaluation included assessment of airway and great vessel anatomy with specific attention to the course of the LMSB and its relationship to the adjacent DA and PA. The position of the DA in relation to the spine was carefully evaluated. Results. Five children had focal and five had diffuse LMSB narrowing. DA position at the level of the crossing LMSB: in 40 % of symptomatic children the DA was located in front of the adjacent vertebral body; in 40 %, {sup 1}/{sub 2}-{sup 3}/{sub 4} and in 20 % {sup 1}/{sub 4}-{sup 1}/{sub 2} of the circumference of the DA was located anterior to the spine. In the control group, the DA was prespinal in 10 %, with a trend toward a more paraspinal location of the DA. The trend toward a difference in position of the DA between symptomatic and control patients was statistically significant (P < 0.05). DA position was not related to age (up to 19 months). At the level where the LMSB crossed the DA, a segment of the PA was located anterior to the LMSB, more often the right PA (RPA) or pulmonary bifurcation in symptomatic children and the left PA (LPA) in controls. No correlation was apparent between length of LMSB narrowing and DA or PA position. Chest radiographic abnormalities, when present, were subtle. Excellent MR/bronchoscopic correlation of LMSB narrowing was found in nine of the ten symptomatic

  17. Bioelectric and Morphological Response of Liquid-Covered Human Airway Epithelial Calu-3 Cell Monolayer to Periodic Deposition of Colloidal 3-Mercaptopropionic-Acid Coated CdSe-CdS/ZnS Core-Multishell Quantum Dots.

    Directory of Open Access Journals (Sweden)

    Aizat Turdalieva

    Full Text Available Lung epithelial cells are extensively exposed to nanoparticles present in the modern urban environment. Nanoparticles, including colloidal quantum dots (QDs, are also considered to be potentially useful carriers for the delivery of drugs into the body. It is therefore important to understand the ways of distribution and the effects of the various types of nanoparticles in the lung epithelium. We use a model system of liquid-covered human airway epithelial Calu-3 cell cultures to study the immediate and long-term effects of repeated deposition of colloidal 3-mercaptopropionic-acid coated CdSe-CdS/ZnS core-multishell QDs on the lung epithelial cell surface. By live confocal microscope imaging and by QD fluorescence measurements we show that the QD permeation through the mature epithelial monolayers is very limited. At the time of QD deposition, the transepithelial electrical resistance (TEER of the epithelial monolayers transiently decreased, with the decrement being proportional to the QD dose. Repeated QD deposition, once every six days for two months, lead to accumulation of only small amounts of the QDs in the cell monolayer. However, it did not induce any noticeable changes in the long-term TEER and the molecular morphology of the cells. The colloidal 3-mercaptopropionic-acid coated CdSe-CdS/ZnS core-multishell QDs could therefore be potentially used for the delivery of drugs intended for the surface of the lung epithelia during limited treatment periods.

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

    Science.gov (United States)

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

    2016-01-01

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

  19. In vivo deposition of ultrafine aerosols in human nasal and oral airways

    International Nuclear Information System (INIS)

    The extrathoracic airways, including the nasal passage, oral passage, pharynx, and larynx, are the first targets for inhaled particles and provide an important defense for the lung. Understanding the deposition efficiency of the nasal and oral passages is therefore crucial for assessing doses of inhaled particles to the extrathoracic airways and the lung. Significant inter-subject variability in nasal deposition has been shown in recent studies by Rasmussen, T.R. et al, using 2.6 μm particles in 10 human subjects and in our preliminary studies using 0.004-0.15 μm particles in four adult volunteers. No oral deposition was reported in either of these studies. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. The aims of the present study were to measure in vivo the nasal airway dimensions and the deposition of ultrafine aerosols in both the nasal and oral passages, and to determine the relationship between nasal airway dimensions and aerosol deposition. A statistical procedure incorporated with the diffusion theory was used to model the dimensional features of the nasal airways which may be responsible for the biological variability in particle deposition. In summary, we have correlated deposition of particles in the size range of 0.004 to 0.15 μm with the nasal dimensions of each subject

  20. In vivo deposition of ultrafine aerosols in human nasal and oral airways

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Hsu-Chi; Swift, D.L. [John Hopkins Univ., Baltimore, MD (United States); Simpson, S.Q. [Univ. of New Mexico, Albuquerque, NM (United States)] [and others

    1995-12-01

    The extrathoracic airways, including the nasal passage, oral passage, pharynx, and larynx, are the first targets for inhaled particles and provide an important defense for the lung. Understanding the deposition efficiency of the nasal and oral passages is therefore crucial for assessing doses of inhaled particles to the extrathoracic airways and the lung. Significant inter-subject variability in nasal deposition has been shown in recent studies by Rasmussen, T.R. et al, using 2.6 {mu}m particles in 10 human subjects and in our preliminary studies using 0.004-0.15 {mu}m particles in four adult volunteers. No oral deposition was reported in either of these studies. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. The aims of the present study were to measure in vivo the nasal airway dimensions and the deposition of ultrafine aerosols in both the nasal and oral passages, and to determine the relationship between nasal airway dimensions and aerosol deposition. A statistical procedure incorporated with the diffusion theory was used to model the dimensional features of the nasal airways which may be responsible for the biological variability in particle deposition. In summary, we have correlated deposition of particles in the size range of 0.004 to 0.15 {mu}m with the nasal dimensions of each subject.

  1. Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium.

    Science.gov (United States)

    Chen, Zhi-Hua; Wu, Yin-Fang; Wang, Ping-Li; Wu, Yan-Ping; Li, Zhou-Yang; Zhao, Yun; Zhou, Jie-Sen; Zhu, Chen; Cao, Chao; Mao, Yuan-Yuan; Xu, Feng; Wang, Bei-Bei; Cormier, Stephania A; Ying, Song-Min; Li, Wen; Shen, Hua-Hao

    2016-01-01

    Environmental ultrafine particulate matter (PM) is capable of inducing airway injury, while the detailed molecular mechanisms remain largely unclear. Here, we demonstrate pivotal roles of autophagy in regulation of inflammation and mucus hyperproduction induced by PM containing environmentally persistent free radicals in human bronchial epithelial (HBE) cells and in mouse airways. PM was endocytosed by HBE cells and simultaneously triggered autophagosomes, which then engulfed the invading particles to form amphisomes and subsequent autolysosomes. Genetic blockage of autophagy markedly reduced PM-induced expression of inflammatory cytokines, e.g. IL8 and IL6, and MUC5AC in HBE cells. Mice with impaired autophagy due to knockdown of autophagy-related gene Becn1 or Lc3b displayed significantly reduced airway inflammation and mucus hyperproduction in response to PM exposure in vivo. Interference of the autophagic flux by lysosomal inhibition resulted in accumulated autophagosomes/amphisomes, and intriguingly, this process significantly aggravated the IL8 production through NFKB1, and markedly attenuated MUC5AC expression via activator protein 1. These data indicate that autophagy is required for PM-induced airway epithelial injury, and that inhibition of autophagy exerts therapeutic benefits for PM-induced airway inflammation and mucus hyperproduction, although they are differentially orchestrated by the autophagic flux.

  2. Suppression of allergic airway inflammation in a mouse model of asthma by exogenous mesenchymal stem cells.

    Science.gov (United States)

    Ou-Yang, Hai-Feng; Huang, Yun; Hu, Xing-Bin; Wu, Chang-Gui

    2011-12-01

    Mesenchymal stem cells (MSCs) have significant immunomodulatory effects in the development of acute lung inflammation and fibrosis. However, it is still unclear as to whether MSCs could attenuate allergic airway inflammation in a mouse model of asthma. We firstly investigated whether exogenous MSCs can relocate to lung tissues in asthmatic mice and analyzed the chemotactic mechanism. Then, we evaluated the in vivo immunomodulatory effect of exogenous MSCs in asthma. MSCs (2 × 10(6)) were administered through the tail vein to mice one day before the first airway challenge. Migration of MSCs was evaluated by flow cytometry. The immunomodulatory effect of MSCs was evaluated by cell counting in bronchoalveolar lavage fluid (BALF), histology, mast cell degranulation, airway hyperreactivity and cytokine profile in BALF. Exogenous MSCs can migrate to sites of inflammation in asthmatic mice through a stromal cell-derived factor-1α/CXCR4-dependent mechanism. MSCs can protect mice against a range of allergic airway inflammatory pathologies, including the infiltration of inflammatory cells, mast cell degranulation and airway hyperreactivity partly via shifting to a T-helper 1 (Th1) from a Th2 immune response to allergens. So, immunotherapy based on MSCs may be a feasible, efficient therapy for asthma. PMID:22114062

  3. Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway inflammation in mice

    NARCIS (Netherlands)

    Pouwels, Simon D; 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

    2015-01-01

    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 COPD. DAMPs can activate pattern recognition receptors (PRRs), triggering innate immune responses. We hypothes

  4. Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective

    DEFF Research Database (Denmark)

    Folkesson, Anders; Jelsbak, Lars; Yang, Lei;

    2012-01-01

    The airways of patients with cystic fibrosis (CF) are nearly always infected with many different microorganisms. This environment offers warm, humid and nutrient-rich conditions, but is also stressful owing to frequent antibiotic therapy and the host immune response. Pseudomonas aeruginosa...

  5. Comparison of gel contraction mediated by airway smooth muscle cells from patients with and without asthma

    NARCIS (Netherlands)

    Matsumoto, Hisako; Moir, Lyn M; Oliver, Brian G G; Burgess, Janette K; Roth, Michael; Black, Judith L; McParland, Brent E

    2007-01-01

    BACKGROUND: Exaggerated bronchial constriction is the most significant and life threatening response of patients with asthma to inhaled stimuli. However, few studies have investigated the contractility of airway smooth muscle (ASM) from these patients. The purpose of this study was to establish a me

  6. The involvement of glycosaminoglycans in airway disease associated with cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2012-02-01

    Individuals with cystic fibrosis (CF) present with severe airway destruction and extensive bronchiectasis. It has been assumed that these structural airway changes have occurred secondary to infection and inflammation, but recent studies suggest that glycosaminoglycan (GAG) remodelling may be an important independent parallel process. Evidence is accumulating that not only the concentration, but also sulphation of GAGs is markedly increased in CF bronchial cells and tissues. Increased expression of GAGs and, in particular, heparan sulphate, has been linked to a sustained inflammatory response and neutrophil recruitment to the CF airways. This present review discusses the biological role of GAGs in the lung, as well as their involvement in CF respiratory disease, and their potential as therapeutic targets.

  7. Hereditary and microbiological factors influencing the airway immunological profile of neonates

    DEFF Research Database (Denmark)

    Følsgaard, Nilofar

    2012-01-01

    Asthma and wheezing together with the other atopic disorders; allergy, eczema and rhinitis are the most common chronic diseases in children with major impact on quality of life for patients and significant socioeconomic costs due to health care utilization. The airway mucosa is constantly exposed...... the penetration and impact of the exposome. The ability to mediate a balanced and appropriate immune response is fundamental for managing healthy airways while inappropriate release of inflammatory mediators may have unfavorable long-term consequences such as asthma. Genetic predisposition to atopic diseases...... is well-recognized, with estimated heritability as high as 60% in asthma. Atopic hereditary disease linkage in the offspring seems stronger for maternal than paternal atopic disease. But it is not known how parental atopic disease may affect early immunity in the target organ, the airways. COPSAC has...

  8. Enhanced airway smooth muscle cell thromboxane receptor signaling via activation of JNK MAPK and extracellular calcium influx

    DEFF Research Database (Denmark)

    Lei, Ying; Cao, Yongxiao; Zhang, Yaping;

    2011-01-01

    airway smooth muscle cells by using an organ culture model and a set of selective pharmacological inhibitors for mitogen-activated protein kinase (MAPK) and calcium signal pathways. Western-blot, immunohistochemistry, myograph and a selective TP receptor agonist U46619 were used for examining TP receptor...... signal proteins and function. Organ culture of rat bronchial segments for up to 48 h induces a time-dependently increased airway contractile response to U46619. This indicates that organ culture increases TP receptor signaling in the airway smooth muscle cells. The enhanced bronchial contraction was...... attenuated by the inhibition of c-Jun N-terminal kinase (JNK) MAPK activity, chelation of extracellular calcium and calcium channel blocker nifedipine, suggesting that JNK MAPK activity and elevated intracellular calcium level are required for the TP receptor signaling. In conclusion, airway smooth muscle...

  9. The Three A's in Asthma - Airway Smooth Muscle, Airway Remodeling & Angiogenesis.

    Science.gov (United States)

    Keglowich, L F; Borger, P

    2015-01-01

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

  10. The Effects of Tumstatin on Vascularity, Airway Inflammation and Lung Function in an Experimental Sheep Model of Chronic Asthma.

    Science.gov (United States)

    Van der Velden, Joanne; Harkness, Louise M; Barker, Donna M; Barcham, Garry J; Ugalde, Cathryn L; Koumoundouros, Emmanuel; Bao, Heidi; Organ, Louise A; Tokanovic, Ana; Burgess, Janette K; Snibson, Kenneth J

    2016-01-01

    Tumstatin, a protein fragment of the alpha-3 chain of Collagen IV, is known to be significantly reduced in the airways of asthmatics. Further, there is evidence that suggests a link between the relatively low level of tumstatin and the induction of angiogenesis and inflammation in allergic airway disease. Here, we show that the intra-segmental administration of tumstatin can impede the development of vascular remodelling and allergic inflammatory responses that are induced in a segmental challenge model of experimental asthma in sheep. In particular, the administration of tumstatin to lung segments chronically exposed to house dust mite (HDM) resulted in a significant reduction of airway small blood vessels in the diameter range 10(+)-20 μm compared to controls. In tumstatin treated lung segments after HDM challenge, the number of eosinophils was significantly reduced in parenchymal and airway wall tissues, as well as in the bronchoalveolar lavage fluid. The expression of VEGF in airway smooth muscle was also significantly reduced in tumstatin-treated segments compared to control saline-treated segments. Allergic lung function responses were not attenuated by tumstatin administration in this model. The data are consistent with the concept that tumstatin can act to suppress vascular remodelling and inflammation in allergic airway disease. PMID:27199164

  11. Airway Clearance Devices for Cystic Fibrosis

    Science.gov (United States)

    2009-01-01

    Executive Summary Objective The purpose of this evidence-based analysis is to examine the safety and efficacy of airway clearance devices (ACDs) for cystic fibrosis and attempt to differentiate between devices, where possible, on grounds of clinical efficacy, quality of life, safety and/or patient preference. Background Cystic fibrosis (CF) is a common, inherited, life-limiting disease that affects multiple systems of the human body. Respiratory dysfunction is the primary complication and leading cause of death due to CF. CF causes abnormal mucus secretion in the airways, leading to airway obstruction and mucus plugging, which in turn can lead to bacterial infection and further mucous production. Over time, this almost cyclical process contributes to severe airway damage and loss of respiratory function. Removal of airway secretions, termed airway clearance, is thus an integral component of the management of CF. A variety of methods are available for airway clearance, some requiring mechanical devices, others physical manipulation of the body (e.g. physiotherapy). Conventional chest physiotherapy (CCPT), through the assistance of a caregiver, is the current standard of care for achieving airway clearance, particularly in young patients up to the ages of six or seven. CF patients are, however, living much longer now than in decades past. The median age of survival in Canada has risen to 37.0 years for the period of 1998-2002 (5-year window), up from 22.8 years for the 5-year window ending in 1977. The prevalence has also risen accordingly, last recorded as 3,453 in Canada in 2002, up from 1,630 in 1977. With individuals living longer, there is a greater need for independent methods of airway clearance. Airway Clearance Devices There are at least three classes of airway clearance devices: positive expiratory pressure devices (PEP), airway oscillating devices (AOD; either handheld or stationary) and high frequency chest compression (HFCC)/mechanical percussion (MP

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

    Andrographolide from traditional Chinese herbal medicines previously showed it possesses a strong anti-inflammatory activity. In present study, we investigated whether Andrographolide could inhibit allergen-induced airway inflammation and airways hyper-responsiveness and explored the mechanism of Andrographolide on allergen-induced airway inflammation and airways hyper-responsiveness. After sensitized and challenged by ovalbumin, the BALB/c mice were administered intraperitoneally with Andrographolide. Hyper-responsiveness was recorded. The lung tissues were assessed by histological examinations. NF-κB in lung was determined by immunofluorescence staining and Western blotting. Treatment of mice with Androqrapholide displayed lower Penh in response to asthma group mice. After treatment with Andrographolide, the extent of inflammation and cellular infltrafion in the airway were reduced. Andrographolide interrupted NF-κB to express in cell nucleus. The level of NF-κB expression was inhibited by Andrographolide. The data indicate that Andrographolide from traditional Chinese herbal medicines could inhibit extensive infiltration of inflammatory cells in lung and decrease airway hyperreactivity. Andrographolide could inhibit NF-κB expression in lung and suppress NF-κB expressed in the nucleus of airway epithelial cells. Cellular & Molecular Immunology. 2009;6(5):381-385.

  13. Expression of taste receptors in Solitary Chemosensory Cells of rodent airways

    Directory of Open Access Journals (Sweden)

    Sbarbati Andrea

    2011-01-01

    Full Text Available Abstract Background Chemical irritation of airway mucosa elicits a variety of reflex responses such as coughing, apnea, and laryngeal closure. Inhaled irritants can activate either chemosensitive free nerve endings, laryngeal taste buds or solitary chemosensory cells (SCCs. The SCC population lies in the nasal respiratory epithelium, vomeronasal organ, and larynx, as well as deeper in the airway. The objective of this study is to map the distribution of SCCs within the airways and to determine the elements of the chemosensory transduction cascade expressed in these SCCs. Methods We utilized a combination of immunohistochemistry and molecular techniques (rtPCR and in situ hybridization on rats and transgenic mice where the Tas1R3 or TRPM5 promoter drives expression of green fluorescent protein (GFP. Results Epithelial SCCs specialized for chemoreception are distributed throughout much of the respiratory tree of rodents. These cells express elements of the taste transduction cascade, including Tas1R and Tas2R receptor molecules, α-gustducin, PLCβ2 and TrpM5. The Tas2R bitter taste receptors are present throughout the entire respiratory tract. In contrast, the Tas1R sweet/umami taste receptors are expressed by numerous SCCs in the nasal cavity, but decrease in prevalence in the trachea, and are absent in the lower airways. Conclusions Elements of the taste transduction cascade including taste receptors are expressed by SCCs distributed throughout the airways. In the nasal cavity, SCCs, expressing Tas1R and Tas2R taste receptors, mediate detection of irritants and foreign substances which trigger trigeminally-mediated protective airway reflexes. Lower in the respiratory tract, similar chemosensory cells are not related to the trigeminal nerve but may still trigger local epithelial responses to irritants. In total, SCCs should be considered chemoreceptor cells that help in preventing damage to the respiratory tract caused by inhaled irritants and

  14. Effects of formoterol-budesonide on airway remodeling in patients with moderate asthma

    Institute of Scientific and Technical Information of China (English)

    Ke WANG; Chun-tao LIU; Yong-hong WU; Yu-lin FENG; Hong-li BAI; En-sen MA; Fu-qiang WEN

    2011-01-01

    Aim: To evaluate the effect of inhaled formoterol-budesonide on airway remodeling in adult patients with moderate asthma.Methods: Thirty asthmatic patients and thirty control subjects were enrolled. Asthmatic subjects used inhaled Symbicort 4.5/160μg twice daily for one year. The effect of formoterol-budesonide on airway remodeling was assessed with comparing high-resolution computer tomography (HRCT) images of asthmatic patients and controls,as well as expression levels of cytokines and growth factors,inflammatory cell count in induced sputum,and airway hyper-responsiveness.Results: The differences in age and gender between the two groups were not significant. However,differences in FVC %pred,FEV1%pred,and PC20 between the two groups were significant. After treatment with formoterol-budesonide,the asthma patients' symptoms were relieved,and their lung function was improved. The WT and WA% of HRCT images in patients with asthma was increased,whereas treatment with formoterol-budesonide caused these values to decrease. The expression of MMP-9,TIMP-1,and TGF-β1 in induced sputum samples increased in patients with asthma and decreased dramatically after treatment with formoterol-budesonide.The WT and WA% are correlated with the expression levels of cytokines and growth factors,inflammatory cell count in induced sputum,and airway hyper-responsiveness,while these same values are correlated negatively with FEV1/FVC and FEV1%.Conclusion: Formoterol-budesonide might interfere in chronic inflammation and airway remodeling in asthmatic patients. HRCT can be used to effectively evaluate airway remodeling in asthmatic patients.

  15. Protease-activated receptor 2 mediates mucus secretion in the airway submucosal gland.

    Directory of Open Access Journals (Sweden)

    Hyun Jae Lee

    Full Text Available Protease-activated receptor 2 (PAR2, a G protein-coupled receptor expressed in airway epithelia and smooth muscle, plays an important role in airway inflammation. In this study, we demonstrated that activation of PAR2 induces mucus secretion from the human airway gland and examined the underlying mechanism using the porcine and murine airway glands. The mucosa with underlying submucosal glands were dissected from the cartilage of tissues, pinned with the mucosal side up at the gas/bath solution interface of a physiological chamber, and covered with oil so that secretions from individual glands could be visualized as spherical bubbles in the oil. Secretion rates were determined by optical monitoring of the bubble diameter. The Ca(2+-sensitive dye Fura2-AM was used to determine intracellular Ca(2+ concentration ([Ca(2+](i by means of spectrofluorometry. Stimulation of human tracheal mucosa with PAR2-activating peptide (PAR2-AP elevated intracellular Ca(2+ and induced glandular secretion equal to approximately 30% of the carbachol response in the human airway. Porcine gland tissue was more sensitive to PAR2-AP, and this response was dependent on Ca(2+ and anion secretion. When the mouse trachea were exposed to PAR2-AP, large amounts of secretion were observed in both wild type and ΔF508 cystic fibrosis transmembrane conductance regulator mutant mice but there is no secretion from PAR-2 knock out mice. In conclusion, PAR2-AP is an agonist for mucus secretion from the airway gland that is Ca(2+-dependent and cystic fibrosis transmembrane conductance regulator-independent.

  16. Quantitative computed tomography imaging of airway remodeling in severe asthma

    OpenAIRE

    Grenier, Philippe A.; Fetita, Catalin I.; Brillet, Pierre-Yves

    2016-01-01

    Asthma is a heterogeneous condition and approximately 5–10% of asthmatic subjects have severe disease associated with structure changes of the airways (airway remodeling) that may develop over time or shortly after onset of disease. Quantitative computed tomography (QCT) imaging of the tracheobronchial tree and lung parenchyma has improved during the last 10 years, and has enabled investigators to study the large airway architecture in detail and assess indirectly the small airway structure. ...

  17. Ultrasound: A promising tool for contemporary airway management

    OpenAIRE

    Garg, Rakesh; Gupta, Anju

    2015-01-01

    Airway evaluation and its management remains an ever emerging clinical science. Present airway management tools are static and do not provide dynamic airway management option. Visualized procedures like ultrasound (US) provide point of care real time dynamic views of the airway in perioperative, emergency and critical care settings. US can provide dynamic anatomical assessment which is not possible by clinical examination alone. US aids in detecting gastric contents and the nature of gastric ...

  18. Electrostatic Charge Effects on Pharmaceutical Aerosol Deposition in Human Nasal–Laryngeal Airways

    Directory of Open Access Journals (Sweden)

    Jinxiang Xi

    2014-01-01

    Full Text Available Electrostatic charging occurs in most aerosol generation processes and can significantly influence subsequent particle deposition rates and patterns in the respiratory tract through the image and space forces. The behavior of inhaled aerosols with charge is expected to be most affected in the upper airways, where particles come in close proximity to the narrow turbinate surface, and before charge dissipation occurs as a result of high humidity. The objective of this study was to quantitatively evaluate the deposition of charged aerosols in an MRI-based nasal–laryngeal airway model. Particle sizes of 5 nm–30 µm and charge levels ranging from neutralized to ten times the saturation limit were considered. A well-validated low Reynolds number (LRN k–ω turbulence model and a discrete Lagrangian tracking approach that accounted for electrostatic image force were employed to simulate the nasal airflow and aerosol dynamics. For ultrafine aerosols, electrostatic charge was observed to exert a discernible but insignificant effect. In contrast, remarkably enhanced depositions were observed for micrometer particles with charge, which could be one order of magnitude larger than no-charge depositions. The deposition hot spots shifted towards the anterior part of the upper airway as the charge level increased. Results of this study have important implications for evaluating nasal drug delivery devices and for assessing doses received from pollutants, which often carry a certain level of electric charges.

  19. Impossible Airway Requiring Venovenous Bypass for Tracheostomy

    Directory of Open Access Journals (Sweden)

    Johnathan Gardes

    2012-01-01

    Full Text Available The elective surgical airway is the definitive management for a tracheal stenotic lesion that is not a candidate for tracheal resection, or who has failed multiple-tracheal dilations. This case report details the management of a patient who has failed an elective awake tracheostomy secondary to the inability to be intubated as well as severe scar tissue at the surgical site. A combination of regional anesthesia and venovenous bypass is used to facilitate the surgical airway management of this patient. Cerebral oximetry and a multidisciplinary team approach aid in early detection of an oxygenation issue, as well as the emergent intervention that preserved this patient’s life.

  20. Automatic Airway Deletion in Pulmonary Segmentation

    Institute of Scientific and Technical Information of China (English)

    WANG Ping; ZHUANG Tian-ge

    2005-01-01

    A method of removing the airway from pulmonary segmentation image was proposed. This method firstly segments the image into several separate regions based on the optimum threshold and morphological operator,and then each region is labeled and noted with its mean grayscale. Therefore, most of the non-lung regions can be removed according to the tissue's Hounsfield units (HU) and the imaging modality. Finally, the airway region is recognized and deleted automatically through using the priori information of its HU and size. This proposed method is tested using several clinical images, yielding satisfying results.