The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform
Reinoud Gosens - One of the best experts on this subject based on the ideXlab platform.
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acetylcholine beyond Bronchoconstriction roles in inflammation and remodeling
Trends in Pharmacological Sciences, 2015Co-Authors: Loes E M Kistemaker, Reinoud GosensAbstract:Acetylcholine is the primary parasympathetic neurotransmitter in the airways, where it not only induces Bronchoconstriction and mucus secretion, but also regulates airway inflammation and remodeling. In this review, we propose that these effects are all primarily mediated via the muscarinic M 3 receptor. Acetylcholine promotes inflammation and remodeling via direct effects on airway cells, and via mechanical stress applied to the airways sequential to Bronchoconstriction. The effects on inflammation and remodeling are regulated by both neuronal and non-neuronal acetylcholine. Taken together, we believe that the combined effects of anticholinergic therapy on M 3 -mediated Bronchoconstriction, mucus secretion, inflammation, and remodeling may account for the positive outcome of treatment with these drugs for patients with chronic pulmonary obstructive disease (COPD) or asthma.
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Bronchoconstriction induces tgf β release and airway remodelling in guinea pig lung slices
PLOS ONE, 2013Co-Authors: Tjitske A Oenema, Harm Maarsingh, Marieke Smit, Geny M M Groothuis, Herman Meurs, Reinoud GosensAbstract:Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links Bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in Bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β1 augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin) after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced Bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A) or TGF-β receptor kinase (SB431542) prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl) mimicked the effects of methacholine. Collectively, Bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling.
M. Hermel - One of the best experts on this subject based on the ideXlab platform.
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Influence of atrial natriuretic peptide, brain natriuretic peptide and urodilatin on the histamine-induced Bronchoconstriction in the conscious guinea pig
InflammoPharmacology, 1998Co-Authors: M. HermelAbstract:The influence of human atrial natriuretic peptide (ANP) and of two related peptides, human brain natriuretic peptide (BNP) and urodilatin (URO) on the Bronchoconstriction induced by inhalation of histamine in conscious, non-anaesthetized guinea pigs was tested. Changes in lung function were registered using two independent methods, one operating in a closed body-plethysmographic system, the other in an open system based on the time lag of air flow curves. The peptides were infused (0.25 ml/min) into the jugular vein for a period from 10 min before until 15 min after the histamine inhalation. ANP displayed virtually no effect on the Bronchoconstriction. URO showed some inibition at 1280ng kg^−1 min^−1, but not at lower doses. BNP (640ng kg^−1 min^−1) inhibited the Bronchoconstriction markedly for the total registration period. It can be concluded from these results that BNP exerts bronchoprotective effects in the conscious guinea pig, which are superior to those of ANP or URO.
Paul M Obyrne - One of the best experts on this subject based on the ideXlab platform.
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the interaction between Bronchoconstriction and cough in asthma
Thorax, 2017Co-Authors: Imran Satia, Huda Badri, Mark Woodhead, Stephen J. Fowler, Paul M Obyrne, Jaclyn A. SmithAbstract:Variable airflow obstruction is a pathophysiological hallmark of asthma; however, the interactions between acute Bronchoconstriction and the cough reflex are poorly understood. We performed a randomised, single-blind, placebo-controlled, crossover study to investigate the interaction between Bronchoconstriction and cough in asthma. Capsaicin was administered to evoke coughs and methacholine to induce Bronchoconstriction. We demonstrated that acute Bronchoconstriction increased capsaicin-evoked coughs, which improved as airway calibre spontaneously resolved. However, capsaicin-evoked coughing had no impact on methacholine-induced Bronchoconstriction. This study provides evidence that Bronchoconstriction increases the activation of capsaicin-responsive airway nerves, but the precise mechanisms and mediators involved require further evaluation. Trial registration number ISRCTN14900082.
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effect of ciclesonide dose and duration of therapy on exercise induced Bronchoconstriction in patients with asthma
The Journal of Allergy and Clinical Immunology, 2006Co-Authors: Padmaja Subbarao, Mylinh Duong, Ellinor Adelroth, Joceline Otis, G Obminski, Mark D Inman, Soren Pedersen, Paul M ObyrneAbstract:Effect of ciclesonide dose and duration of therapy on exercise-induced Bronchoconstriction in patients with asthma.
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evidence for mast cell activation during exercise induced Bronchoconstriction
European Respiratory Journal, 1998Co-Authors: Siobhan Osullivan, Paul M Obyrne, A Roquet, Barbro Dahlen, F Larsen, Anders Eklund, Maria Kumlin, S E DahlenAbstract:Controversy remains about the causative mediators in the bronchoconstrictive response to exercise in asthma. This study examined whether mast cell activation is a feature of exercise-induced Bronchoconstriction by measuring urinary metabolites of mast cell mediators. Twelve nonsmoking subjects with mild asthma and a history of exercise-induced Bronchoconstriction exercised on a stationary bicycle ergometer for 5 min at 80% maximum work load. Pulmonary function was monitored and urine was collected before and 30 and 90 min after the provocation. The urinary concentrations of the mast cell markers 9alpha,11beta-prostaglandin (PG)F2 and Ntau-methylhistamine, as well as leukotriene E4 (LTE4) were determined by immunoassay. Seven of the 12 subjects (responders) experienced Bronchoconstriction (>15% fall in the forced expiratory volume in one second) following exercise, whereas the pulmonary function of the remaining five subjects (nonresponders) remained stable. The urinary excretion (mean+/-SE) of 9alpha,11beta-PGF2 in the responders increased significantly compared with the nonresponders at 30 (77.1+/-14.4 versus 37.2+/-5.6; p<0.05) and 90 min (79.3+/-8.6 versus 40.4+/-8.5, p<0.05) after exercise challenge. The urinary excretion of Ntau-methylhistamine and LTE4 was not significantly different between the two groups at 30 or 90 min after exercise. The findings represent the first documentation of increased urinary levels of 9alpha,11beta-prostaglandin F2 in adults following exercise challenge and provides clear evidence for mast cell activation during exercise-induced Bronchoconstriction in asthmatics.
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inhibition of exercise induced Bronchoconstriction by mk 571 a potent leukotriene d4 receptor antagonist
The New England Journal of Medicine, 1990Co-Authors: Patrick J Manning, Richard M Watson, Dorothy J Margolskee, Vanessa C Williams, Jules I Schwartz, Paul M ObyrneAbstract:Abstract Background. Exercise is a common stimulus of Bronchoconstriction in subjects with asthma, who also have Bronchoconstriction after inhaling the sulfidopeptide leukotriene D4 (LTD4). The purpose of this study was to investigate the importance of LTD4 as a mediator of exercise-induced Bronchoconstriction. Methods. In a double-blind, randomized, crossover study, 12 subjects with stable asthma were treated intravenously with MK-571 (160 mg), a selective and potent LTD4-receptor antagonist, or placebo, 20 minutes before each of two challenges involving exercise at a level previously demonstrated to cause a fall of at least 20 percent in the forced expiratory volume in one second (FEV1). The two exercise challenges were separated by one week. The results of the challenges were expressed as both the maximal fall in FEV1 after exercise and the time to recovery from Bronchoconstriction. Results. Treatment with MK-571 attenuated exercise-induced Bronchoconstriction in all the subjects. The mean (±SEM) maxim...
Pierangelo Geppetti - One of the best experts on this subject based on the ideXlab platform.
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Bronchoconstriction induced by citric acid inhalation in guinea pigs role of tachykinins bradykinin and nitric oxide
American Journal of Respiratory and Critical Care Medicine, 1999Co-Authors: Fabio Luigi Massimo Ricciardolo, Peter J Sterk, Vanda Rado, Leonardo M Fabbri, Giuseppe U Di, Pierangelo GeppettiAbstract:Gastroesophageal acid reflux into the airways can trigger asthma attacks. Indeed, citric acid inhalation causes Bronchoconstriction in guinea pigs, but the mechanism of this effect has not been fully clarified. We investigated the role of tachykinins, bradykinin, and nitric oxide (NO) on the citric acid‐ induced Bronchoconstriction in anesthetized and artificially ventilated guinea pigs. Citric acid inhalation (2‐20 breaths) caused a dose-dependent increase in total pulmonary resistance (R L ). R L value obtained after 10 breaths of citric acid inhalation was not significantly different from the value obtained after 20 breaths (p 5 0.22). The effect produced by a half-submaximum dose of citric acid (5 breaths) was halved by the bradykinin B 2 receptor antagonist HOE 140 (0.1 m mol ? kg 2 1 , intravenous) and abolished by the tachykinin NK 2 receptor antagonist SR 48968 (0.3 m mol ? kg 2 1 , intravenous). Bronchoconstriction induced by a submaximum dose of citric acid (10 breaths) was partially reduced by the administration of HOE 140, SR 48968, or the NK 1 receptor antagonist CP-99,994 (8 m mol ? kg 2 1 , intravenous) alone and completely abolished by the combination of SR 48968 and CP-99,994. Pretreatment with the NO synthase inhibitor, L -NMMA (1 mM, 10 breaths every 5 min for 30 min) increased in an L -arginine‐dependent manner the effect of citric acid inhalation on R L . HOE 140 and CP99,994 markedly reduced the L -NMMA‐potentiated Bronchoconstriction to inhaled citric acid. We conclude that citric acid‐induced Bronchoconstriction is caused by tachykinin release from sensory nerves, which, in part, is mediated by endogenously released bradykinin. Simultaneous release of NO by citric acid inhalation counteracts tachykinin-mediated Bronchoconstriction. Our study suggests a possible implication of these mechanisms in asthma associated with gastroesophageal acid reflux and a potential therapeutic role of tachykinin and bradykinin antagonists. Ricciardolo FLM, Rado V, Fabbri LM, Sterk PJ, Di Maria GU, Geppetti P. Bronchoconstriction induced by citric acid inhalation in guinea pigs: role of tachykinins, bradykinin, and nitric oxide. AM J RESPIR CRIT CARE MED 1999;159:557‐562. Gastroesophageal acid reflux is more common in patients with asthma than in the general population, with an estimated
Magnus Dahlback - One of the best experts on this subject based on the ideXlab platform.
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regional sensitivity of the respiratory tract to stimuli causing cough and reflex Bronchoconstriction
Respiratory Medicine, 1991Co-Authors: J A Karlsson, Lennart Hansson, Per Wollmer, Magnus DahlbackAbstract:Sensory nerves mediating cough and reflex Bronchoconstriction have a non-uniform distribution in the respiratorytract. Afferent nerves originating in the laryngeal region differ from those of the intrapulmonary airways in their responsiveness to physical events in the breathing cycle and to chemical stimuli. Also, within each site afferents with separate characteristics are present. Studies in animals and human subjects have shown that the larynx and the carina are particularly sensitive to mechanical stimuli, whereas the intrapulmonary airways seem to be more sensitive to mediators and irritants. Based on recent data, the importance of the intrapulmonary airways to mediator/irritant-induced cough and reflex Bronchoconstriction is emphasized. Inferentially, drugs inhibiting afferent neural activity arising in intrapulmonary airways would be a novel possibility in the treatment of cough and reflex Bronchoconstriction.
