WorldWideScience

Sample records for bronchoconstriction

  1. Exercise-Induced Bronchoconstriction

    Science.gov (United States)

    ... Conditions & Treatments ▸ Conditions Dictionary ▸ Exercise-Induced Bronchoconstriction Share | Exercise-Induced Bronchoconstriction (EIB) « Back to A to Z Listing Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced ...

  2. [Tiotropium as a controller of bronchoconstriction].

    Science.gov (United States)

    Lubiński, Wojciech

    2004-05-01

    Cholinergic nerve fibres arise in the nucleus ambiguus and the dorsal motor nucleus of the vagus nerve in the brainstem. They travel down as the vagus nerve to parasympathetic ganglia placed in the walls of the airways. From these ganglia, short postganglionic fibres innervate airway smooth muscle and the submucosal glands in the lung. Activation of vagal nerve releases acetylcholine at the neuroeffector junctions, where it binds to postsynaptic receptors, resulting in bronchoconstrictions. The resting bronchomotor tone in normal airways has a cholinergic component mediated via muscarinic cholinergic receptors. The human airways have five subtypes of muscarinic cholinergic receptors: the M1 and M3 mediate bronchoconstriction and stimulation of mucus secretion, while M2 control the release of acetylcholine from M1 and M3 receptors through a negative-feedback mechanism. Anticholinergic bronchodilators act by blocking muscarinic receptors. Tiotropium bromide is cutting age anticholinergic bronchodilator. It dissociates more slowly from M1 and M3 than from M2 receptors and subsequently has a long and safety duration of action. In COPD patients tiotropium comparing to placebo, ipratropium and long acting beta agonists significantly improves lung function. It is an effective bronchodilator that reduces dyspnea, COPD exacerbations frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic pulmonary disease therapy. PMID:15524023

  3. Asthma Bronchiale and Exercise-Induced Bronchoconstriction.

    Science.gov (United States)

    Jayasinghe, Harshani; Kopsaftis, Zoe; Carson, Kristin

    2015-01-01

    Exercising regularly has a wide range of beneficial health effects; in particular, it has been well documented to help in the management of chronic illnesses including asthma. However, in some individuals, exertion can also trigger an exacerbation of asthmatic episodes and subsequent acute attacks of breathlessness, coughing, tightness of the chest and wheezing. This physiological process is called exercise-induced bronchoconstriction (EIB) whereby post-exercise forced expiratory volume in 1 s is reduced by 10-15% from baseline. While EIB is highly prevalent in asthmatics and presents with similar respiratory symptoms, asthma and EIB are not mutually exclusive. The aim of this review is to present a broad overview of both conditions in order to enhance the understanding of the similarities and differences distinguishing them as two separate entities. The pathophysiology and mechanisms underlying asthma are well described with research now focussing on defining phenotypes for targeted management strategies. Conversely, the mechanistic understanding of EIB remains largely under-described. Diagnostic pathways for both are established and similar, as are pharmacologic and non-pharmacologic treatments and management approaches, which have enhanced success with early detection. Given the potential for exacerbation of asthma, exercise avoidance is common but counterproductive as current evidence indicates that it is well tolerated and improves quality of life. Literature supporting the benefit of exercise for EIB sufferers is at present favourable, yet extremely limited; therefore, future research should be directed in this area as well as towards further developing the understanding of the pathophysiology and mechanisms underpinning both EIB and asthma.

  4. Bronchoconstriction and airway biology : potential impact and therapeutic opportunities

    NARCIS (Netherlands)

    Gosens, Reinoud; Grainge, Chris

    2015-01-01

    Recent work has demonstrated that mechanical forces occurring in the airway as a consequence of bronchoconstriction are sufficient to not only induce symptoms but also influence airway biology. Animal and human in vitro and in vivo work demonstrates that the airways are structurally and functionally

  5. Regional deposition of particles in human lung after induced bronchoconstriction.

    Science.gov (United States)

    Svartengren, M; Philipson, K; Linnman, L; Camner, P

    1986-01-01

    The percentage 24-hr lung retention (Ret24), a measure of penetration to the aveoli, of 4 micron monodispersed Teflon particles, aerodynamic diameter 6 micron, was studied in 8 healthy nonsmokers. The particles were inhaled at 0.2 1/sec with maximally deep breaths. Bronchoconstriction was induced by inhalation of a methacholinebromide aerosol for one exposure before and for one exposure after inhalation of the Teflon particles. Airway resistance (Raw) was measured using a whole body pletysmograph before and after the induction of bronchoconstriction and increased on an average by a factor 2-3. Ret24 was significantly lower when the Teflon particles were inhaled during bronchoconstriction than when bronchoconstriction was induced after inhalation of the Teflon particles, 26 +/- 12% and 48 +/- 6% (mean +/- SD), respectively. These experimental data agree fairly well with data on deposition due to impaction and sedimentation using a lung model where the diameters of the airways were varied so that an increase in airway resistance occurs similar to that produced in our experimental subjects. However, the experimental data tended to be lower than the theoretical ones when the particles were inhaled during the induced bronchoconstriction. In this study, where the mucociliary transport system was stimulated by methacholinebromide, the percentage 3-hr retention (Ret3) was highly correlated with Ret24, r = 0.97, i.e., Ret3 can be used instead of the Ret24. This implies that radionuclides with shorter half-lives which give lower radiation doses, can be used, and that subjects can be studied within shorter periods of time. PMID:3516667

  6. Plasma catecholamines during exercise-induced bronchoconstriction in bronchial asthma.

    OpenAIRE

    Zieliński, J; Chodosowska, E; Radomyski, A; Araszkiewicz, Z; Kozlowski, S

    1980-01-01

    Plasma levels of adrenaline and noradrenaline during and after submaximal exercise in patients with bronchial asthma were investigated. Three groups were studied comprising 10 patients with exercise-induced bronchoconstriction (EIB), 10 asthmatic patients without EIB and four normal control subjects. Plasma catecholamines were measured at rest, at the end of exercise, and five and 15 minutes after exercise. Changes in airway resistance were assessed by measuring peak expiratory flow rate. Sig...

  7. The inflammatory basis of exercise-induced bronchoconstriction.

    Science.gov (United States)

    Brannan, John D; Turton, James A

    2010-12-01

    Exercise-induced bronchoconstriction (EIB) is common in individuals with asthma, and may be observed even in the absence of a clinical diagnosis of asthma. Exercise-induced bronchoconstriction can be diagnosed via standardized exercise protocols, and anti-inflammatory therapy with inhaled corticosteroids (ICS) is often warranted. Exercise-related symptoms are commonly reported in primary care; however, access to standardized exercise protocols to assess EIB are often restricted because of the need for specialized equipment, as well as time constraints. Symptoms and lung function remain the most accessible indicators of EIB, yet these are poor predictors of its presence and severity. Evidence suggests that exercise causes the airways to narrow as a result of the osmotic and thermal consequences of respiratory water loss. The increase in airway osmolarity leads to the release of bronchoconstricting mediators (eg, histamine, prostaglandins, leukotrienes) from inflammatory cells (eg, mast cells and eosinophils). The objective assessment of EIB suggests the presence of airway inflammation, which is sensitive to ICS in association with a responsive airway smooth muscle. Surrogate tests for EIB, such as eucapnic voluntary hyperpnea or the osmotic challenge tests, cause airway narrowing via a similar mechanism, and a response indicates likely benefit from ICS therapy. The complete inhibition of EIB with ICS therapy in individuals with asthma may be a useful marker of control of airway pathology. Furthermore, inhibition of EIB provides additional, useful information regarding the identification of clinical control based on symptoms and lung function. This article explores the inflammatory basis of EIB in asthma as well as the effect of ICS on the pathophysiology of EIB.

  8. Bronchoconstrictive effect of ultrasonic nebulized distilled water on asthmatic children.

    Science.gov (United States)

    Baba, Y; Hayashida, M; Yasunami, J; Takamatsu, I; Adachi, K; Toyoshima, K

    1989-01-01

    We studied the airway responsiveness of asthmatic and normal children to ultrasonic nebulized distilled water (UNDW inhalation test). It was found that this stimulus induced a fall in FEV1 (forced expiratory volume in 1 s) in asthmatic children, but little fall in normal children. This airway response was shown to be reproducible at about 2-week intervals. The more severe the asthma, the higher the percentage of the responders to the UNDW inhalation test, and the greater the fall in FEV1. The results of the UNDW inhalation test did not correlate with that of acetylcholine inhalation test or of exercise-induced asthma (EIA). UNDW-induced bronchoconstriction was inhibited by premedication with disodium cromoglycate (DSCG) (20 mg) or inhaled ipratropium bromide (40 micrograms). Jet-nebulized distilled water induced little fall in FEV1 in asthmatic children. These data suggest that UNDW-induced bronchoconstriction may involve the release of chemical mediators from the mast cells and cholinergic pathways. We conclude that UNDW inhalation test is a safe, less burdensome, and rather convenient method to evaluate clinically nonspecific airway hyperresponsiveness in asthmatic children. PMID:2534983

  9. Pathophysiology of Bronchoconstriction: Role of Oxidatively Damaged DNA Repair

    Science.gov (United States)

    Bacsi, Attila; Pan, Lang; Ba, Xueqing; Boldogh, Istvan

    2016-01-01

    Purpose of review To provide an overview on the present understanding of roles of oxidative DNA damage repair in cell signaling underlying bronchoconstriction common to, but not restricted to various forms of asthma and chronic obstructive pulmonary disease Recent findings Bronchoconstriction is a tightening of smooth muscle surrounding the bronchi and bronchioles with consequent wheezing and shortness of breath. Key stimuli include air pollutants, viral infections, allergens, thermal and osmotic changes, and shear stress of mucosal epithelium, triggering a wide range of cellular, vascular and neural events. Although activation of nerve fibers, the role of G-proteins, protein kinases and Ca++, and molecular interaction within contracting filaments of muscle are well defined, the overarching mechanisms by which a wide range of stimuli initiate these events are not fully understood. Many, if not all, stimuli increase levels of reactive oxygen species (ROS), which are signaling and oxidatively modifying macromolecules, including DNA. The primary ROS target in DNA is guanine, and 8-oxoguanine is one of the most abundant base lesions. It is repaired by 8-oxoguanine DNA glycosylase1 (OGG1) during base excision repair processes. The product, free 8-oxoG base, is bound by OGG1 with high affinity, and the complex then functions as an activator of small GTPases, triggering pathways for inducing gene expression and contraction of intracellular filaments in mast and smooth muscle cells. Summary Oxidative DNA damage repair-mediated cell activation signaling result in gene expression that “primes” the mucosal epithelium and submucosal tissues to generate mediators of airway smooth muscle contractions. PMID:26694039

  10. Expression of CysLT2 receptors in asthma lung, and their possible role in bronchoconstriction

    Directory of Open Access Journals (Sweden)

    Tomohiko Sekioka

    2015-10-01

    Conclusions: CysLT2 receptors were expressed in lung specimens isolated from asthma subjects. Activation of CysLT2 receptors may contribute to antigen-induced bronchoconstriction in certain asthma population.

  11. Regional Pulmonary Perfusion, Inflation, and Ventilation Defects in Bronchoconstricted Patients with Asthma

    OpenAIRE

    Harris, R. Scott; Winkler, Tilo; Tgavalekos, Nora; Musch, Guido; Melo, Marcos F. Vidal; Schroeder, Tobias; Chang, Yuchiao; Venegas, José G.

    2006-01-01

    Rationale: Bronchoconstriction in asthma leads to heterogeneous ventilation and the formation of large and contiguous ventilation defects in the lungs. However, the regional adaptations of pulmonary perfusion (Q̇) to such ventilation defects have not been well studied.

  12. Inhibition of methoxamine-induced bronchoconstriction by ipratropium bromide and disodium cromoglycate in asthmatic subjects.

    OpenAIRE

    Black, J.; Vincenc, K; Salome, C.

    1985-01-01

    We compared the effects of pretreatment with saline, ipratropium bromide, and disodium cromoglycate (DSCG) on bronchoconstriction induced by methoxamine--an alpha-adrenoceptor agonist, in asthmatic subjects. All 12 patients bronchoconstricted in response to methoxamine after saline. The PD20 (the dose of methoxamine causing a 20% fall in forced expiratory volume in 1 s [FEV1]) ranged from 0.3-18 mumol. Ipratropium bromide (200 micrograms administered by aerosol) significantly inhibited (P les...

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

    Directory of Open Access Journals (Sweden)

    Tjitske A Oenema

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

  14. Effects of lung inflation on airway heterogeneity during histaminergic bronchoconstriction.

    Science.gov (United States)

    Kaczka, David W; Mitzner, Wayne; Brown, Robert H

    2013-09-01

    Lung inflation has been shown to dilate airways by altering the mechanical equilibrium between opposing airway and parenchymal forces. However, it is not known how heterogeneously such dilation occurs throughout the airway tree. In six anesthetized dogs, we measured the diameters of five to six central airway segments using high-resolution computed tomography, along with respiratory input impedance (Zrs) during generalized aerosol histamine challenge, and local histamine challenge in which the agonist was instilled directly onto the epithelia of the imaged central airways. Airway diameters and Zrs were measured at 12 and 25 cmH2O. The Zrs spectra were fitted with a model that incorporated continuous distributions of airway resistances. Airway heterogeneity was quantified using the coefficient of variation for predefined airway distribution functions. Significant reductions in average central airway diameter were observed at 12 cmH2O for both aerosolized and local challenges, along with significant increases upon inflation to 25 cmH2O. No significant differences were observed for the coefficient of variation of airway diameters under any condition. Significant increases in effective airway resistance as measured by Zrs were observed only for the aerosolized challenge at 12 cmH2O, which was completely reversed upon inflation. We conclude that the lung periphery may be the most dominant contributor to increases in airway resistance and tissue elastance during bronchoconstriction induced by aerosolized histamine. However, isolated constriction of only a few central airway segments may also affect tissue stiffness via interdependence with their surrounding parenchyma. PMID:23813528

  15. Air quality and temperature effects on exercise-induced bronchoconstriction.

    Science.gov (United States)

    Rundell, Kenneth W; Anderson, Sandra D; Sue-Chu, Malcolm; Bougault, Valerie; Boulet, Louis-Philippe

    2015-04-01

    Exercise-induced bronchoconstriction (EIB) is exaggerated constriction of the airways usually soon after cessation of exercise. This is most often a response to airway dehydration in the presence of airway inflammation in a person with a responsive bronchial smooth muscle. Severity is related to water content of inspired air and level of ventilation achieved and sustained. Repetitive hyperpnea of dry air during training is associated with airway inflammatory changes and remodeling. A response during exercise that is related to pollution or allergen is considered EIB. Ozone and particulate matter are the most widespread pollutants of concern for the exercising population; chronic exposure can lead to new-onset asthma and EIB. Freshly generated emissions particulate matter less than 100 nm is most harmful. Evidence for acute and long-term effects from exercise while inhaling high levels of ozone and/or particulate matter exists. Much evidence supports a relationship between development of airway disorders and exercise in the chlorinated pool. Swimmers typically do not respond in the pool; however, a large percentage responds to a dry air exercise challenge. Studies support oxidative stress mediated pathology for pollutants and a more severe acute response occurs in the asthmatic. Winter sport athletes and swimmers have a higher prevalence of EIB, asthma and airway remodeling than other athletes and the general population. Because of fossil fuel powered ice resurfacers in ice rinks, ice rink athletes have shown high rates of EIB and asthma. For the athlete training in the urban environment, training during low traffic hours and in low traffic areas is suggested. PMID:25880506

  16. Bronchoconstriction following instillation of phenylephrine eye drops in premature infants with bronchopulmonary dysplasia: two cases report.

    Science.gov (United States)

    Kim, Hyun Jee; Choi, Jin Guk; Kwak, Kyung-Hwa

    2015-12-01

    Premature infants requiring an ophthalmic examination or even surgery for retinopathy of prematurity (ROP) have a high prevalence of co-existing bronchopulmonary dysplasia (BPD). Reactive airway is one of the clinical presentations of BPD. We report two cases of bronchoconstriction following instillation of mydriatic eye drops. One occurred during induction of anesthesia for laser photocoagulation and the other before screening of ROP. The most likely cause in each case was phenylephrine eye drops. We recommend that the minimal dosage of phenylephrine needed to attain proper mydriasis should be instilled to infant patients, and the possibility of bronchoconstriction occurrence kept in mind, especially for infants with low body weight with BPD. PMID:26634087

  17. Assessment of Exercise-Induced Bronchoconstriction in Adolescents and Young Children

    NARCIS (Netherlands)

    van Leeuwen, Janneke C.; Driessen, Jean M. M.; Kersten, Elin T. G.; Thio, Bernard J.

    2013-01-01

    Recent research shows important differences in exercise-induced bronchoconstriction (EIB) between children and adults, suggesting a different pathophysiology of EIB in children. Although exercise can trigger classic symptoms of asthma, in children symptoms can be subtle and nonspecific; parents, chi

  18. Effects of Dietary Induced Weight Loss on Exercise-Induced Bronchoconstriction in Overweight and Obese Children

    NARCIS (Netherlands)

    van Leeuwen, Janneke C.; Hoogstrate, Mira; Duiverman, Eric J.; Thio, Boony J.

    2014-01-01

    RationalePrevious studies showed that obesity in asthmatic children is associated with more severe exercise-induced bronchoconstriction (EIB), compared with non-obese asthmatic children. This study investigates the effect of weight loss on EIB in overweight and obese asthmatic children. MethodsIn th

  19. Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and elimination in a piglet model.

    Science.gov (United States)

    Kretzschmar, Moritz; Kozian, Alf; Baumgardner, James E; Schreiber, Jens; Hedenstierna, Göran; Larsson, Anders; Hachenberg, Thomas; Schilling, Thomas

    2016-01-01

    Bronchoconstriction is a hallmark of asthma and impairs gas exchange. We hypothesized that pharmacokinetics of volatile anesthetics would be affected by bronchoconstriction. Ventilation/perfusion (VA/Q) ratios and pharmacokinetics of desflurane in both healthy state and during inhalational administration of methacholine (MCh) to double peak airway pressure were studied in a piglet model. In piglets, MCh administration by inhalation (100 μg/ml, n=6) increased respiratory resistance, impaired VA/Q distribution, increased shunt, and decreased paO2 in all animals. The uptake and elimination of desflurane in arterial blood was delayed by nebulization of MCh, as determined by Micropore Membrane Inlet Mass Spectrometry (wash-in time to P50, healthy vs. inhalation: 0.5 min vs. 1.1 min, to P90: 4.0 min vs. 14.8 min). Volatile elimination was accordingly delayed. Inhaled methacholine induced severe bronchoconstriction and marked inhomogeneous VA/Q distribution in pigs, which is similar to findings in human asthma exacerbation. Furthermore, MCh-induced bronchoconstriction delayed both uptake and elimination of desflurane. These findings might be considered when administering inhalational anesthesia to asthmatic patients. PMID:26440992

  20. Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children

    NARCIS (Netherlands)

    Kersten, Elin T. G.; van Leeuwen, Janneke C.; Brand, Paul L. P.; Duiverman, Eric J.; de Jongh, Frans H. C.; Thio, Bernard J.; Driessen, Jean M. M.

    2012-01-01

    Rationale Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children. Methods: This was a double-blind,

  1. Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse

    Directory of Open Access Journals (Sweden)

    Koepsell Hermann

    2006-04-01

    Full Text Available Abstract Background It has been proposed that serotonin (5-HT-mediated constriction of the murine trachea is largely dependent on acetylcholine (ACh released from the epithelium. We recently demonstrated that ACh can be released from non-neuronal cells by corticosteroid-sensitive polyspecific organic cation transporters (OCTs, which are also expressed by airway epithelial cells. Hence, the hypothesis emerged that 5-HT evokes bronchoconstriction by inducing release of ACh from epithelial cells via OCTs. Methods We tested this hypothesis by analysing bronchoconstriction in precision-cut murine lung slices using OCT and muscarinic ACh receptor knockout mouse strains. Epithelial ACh content was measured by HPLC, and the tissue distribution of OCT isoforms was determined by immunohistochemistry. Results Epithelial ACh content was significantly higher in OCT1/2 double-knockout mice (42 ± 10 % of the content of the epithelium-denuded trachea, n = 9 than in wild-type mice (16.8 ± 3.6 %, n = 11. In wild-type mice, 5-HT (1 μM caused a bronchoconstriction that slightly exceeded that evoked by muscarine (1 μM in intact bronchi but amounted to only 66% of the response to muscarine after epithelium removal. 5-HT-induced bronchoconstriction was undiminished in M2/M3 muscarinic ACh receptor double-knockout mice which were entirely unresponsive to muscarine. Corticosterone (1 μM significantly reduced 5-HT-induced bronchoconstriction in wild-type and OCT1/2 double-knockout mice, but not in OCT3 knockout mice. This effect persisted after removal of the bronchial epithelium. Immunohistochemistry localized OCT3 to the bronchial smooth muscle. Conclusion The doubling of airway epithelial ACh content in OCT1/2-/- mice is consistent with the concept that OCT1 and/or 2 mediate ACh release from the respiratory epithelium. This effect, however, does not contribute to 5-HT-induced constriction of murine intrapulmonary bronchi. Instead, this activity involves 1 a non

  2. Pulmonary gas exchange during histamine-induced bronchoconstriction in asthmatic subjects.

    Science.gov (United States)

    Burke, T V; Küng, M; Burki, N K

    1989-10-01

    Bronchial provocation for testing airway hyperreactivity is now well-established. However, the effects of histamine-induced bronchoconstriction on pulmonary gas exchange in man have not been systematically studied. We empirically noted marked decreases in PaO2 in some asthmatic subjects following induced bronchoconstriction. Nine subjects with mild, stable asthma were studied, each on two separate days. The first determined the dose of inhaled histamine necessary to decrease FEV1 by 20 percent and the relationship to lung volume and to pulmonary resistance by the interrupter technique (Rint). On the second day arterial blood gases, ventilation, Rint, and the anatomic (VDan) and physiologic (VDphys) dead spaces were measured simultaneously. There was a significant (p less than 0.05), profound fall in PaO2 (mean, -21.8 mm Hg) and in P(A-a)O2 (mean +14.7 mm Hg) within 5 min after bronchoconstriction, associated with a significant (p less than 0.05) increase in respiratory frequency (mean +5.1 min-1); and decrease in tidal volume (mean, -0.3 L). The ratio VDphys/VT increased significantly (p less than 0.05; mean change, +0.08) even though VDan and VDphys did not. Bronchoconstriction induced the broadening of ventilation (V)/perfusion (Q) ratios, with, most likely, an increase in areas of high V/Q. Histamine-induced bronchoconstriction in mild asthma results in a marked fall in PaO2 due to induced V/Q inequality. Therefore, histamine airway challenge should be used with caution in patients with any preexisting hypoxemia. PMID:2791669

  3. Acute relief of exercise-induced bronchoconstriction by inhaled formoterol in children with persistent asthma

    DEFF Research Database (Denmark)

    Hermansen, Mette Northman; Nielsen, Kim Gjerum; Buchvald, Frederik;

    2006-01-01

    -controlled, crossover study of the immediate effect of formoterol, 9 microg, vs terbutaline, 0.5 mg, and placebo administered as dry powder at different study days. Exercise challenge test was used as a model of acute bronchoconstriction. PATIENTS: Twenty-four 7- to 15-year-old children with persistent asthma......STUDY OBJECTIVE: To compare the acute bronchodilatory effect of the long-acting beta2-agonist formoterol against the short-acting beta2-agonist (SABA) terbutaline during exercise-induced bronchoconstriction (EIB) in children with asthma. DESIGN: A randomized, double-blind, placebo...... dose. RESULTS: Formoterol and terbutaline offered a significant acute bronchodilatory effect from 3 min after dose compared with placebo (p

  4. Endothelin-1 in exhaled breath condensate of allergic asthma patients with exercise-induced bronchoconstriction

    OpenAIRE

    Tomasiak Maria M; Skiepko Roman; Zietkowski Ziemowit; Bodzenta-Lukaszyk Anna

    2007-01-01

    Abstract Background Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition, whose pathophysiology is not well understood. Endothelins are proinflammatory, profibrotic, broncho- and vasoconstrictive peptides which play an important role in the development of airway inflammation and remodeling in asthma. The aim of the study was to evaluate the changes in endothelin-1 levels in exhaled breath condensate following intensive exercise in asthmatic patients. Methods The study wa...

  5. Role of leukotrienes in exercise-induced bronchoconstriction before and after a pilot rehabilitation training program

    OpenAIRE

    El-Akkary IM; El-Khouly ZA; El-Seweify ME; El-Batouti GA; Abdel Aziz E; Adam AI

    2013-01-01

    Ibrahim M El-Akkary,1 Zeinat Abdel-Fatah El-Khouly,2 Mervat El-Sayed El-Seweify,1 Gihan A El-Batouti,3 Ekhlas Abdel Aziz,2 Abdelnasser I Adam1 1Department of Human Physiology, 2Department of Applied Medical Chemistry, Medical Research Institute, Alexandria University, 3Department of Microbiology and Immunology, Faculty of Pharmacy, Pharos University, Alexandria, Egypt Background: Whatever the initial stimulus for the exercise-induced bronchoconstriction (EIB) observed in asthmatic patients a...

  6. Bronchoconstriction following instillation of phenylephrine eye drops in premature infants with bronchopulmonary dysplasia: two cases report

    OpenAIRE

    Kim, Hyun Jee; Choi, Jin Guk; Kwak, Kyung-Hwa

    2015-01-01

    Premature infants requiring an ophthalmic examination or even surgery for retinopathy of prematurity (ROP) have a high prevalence of co-existing bronchopulmonary dysplasia (BPD). Reactive airway is one of the clinical presentations of BPD. We report two cases of bronchoconstriction following instillation of mydriatic eye drops. One occurred during induction of anesthesia for laser photocoagulation and the other before screening of ROP. The most likely cause in each case was phenylephrine eye ...

  7. Effects of swimming training on aerobic capacity and exercise induced bronchoconstriction in children with bronchial asthma

    OpenAIRE

    Matsumoto, I.; Araki, H; Tsuda, K; Odajima, H; Nishima, S; Higaki, Y.; Tanaka, H.; Tanaka, M.; Shindo, M

    1999-01-01

    BACKGROUND—A study was undertaken to determine whether swimming training improved aerobic capacity, exercise induced bronchoconstriction (EIB), and bronchial responsiveness to inhaled histamine in children with asthma.
METHODS—Eight children with mild or moderate asthma participated in swimming training every day for six weeks. The intensity of training was individually determined and set at 125% of the child's lactate threshold (LT), measured using a swimming ergometer. ...

  8. Exercise-induced bronchoconstriction: The effects of montelukast, a leukotriene receptor antagonist

    OpenAIRE

    James P Kemp

    2009-01-01

    James P KempClinical Professor of Pediatrics, Division of Immunology and Allergy, University of California School of Medicine, San Diego, CA, USAAbstract: Exercise-induced bronchoconstriction (EIB) is very common in both patients with asthma and those who are otherwise thought to be normal. The intensity of exercise as well as the type of exercise is important in producing symptoms. This may make some types of exercise such as swimming more suitable and extended running more difficult for pat...

  9. Effect of formoterol, a long-lasting beta 2-adrenoceptor agonist, against methacholine-induced bronchoconstriction.

    OpenAIRE

    Nix, A; Nichol, G M; Robson, A; Barnes, P.J.; Chung, K F

    1990-01-01

    1. The effects of a new long-acting inhaled beta 2-adrenoceptor agonist aerosol formoterol (12 micrograms), on FEV1, and on methacholine-induced bronchoconstriction, were compared with those of terbutaline (250 micrograms) and placebo in 12 midly asthmatic subjects. 2. PC20, the concentration of methacholine needed to cause a 20% fall in baseline FEV1, was determined 2 and 5 h after formoterol, terbutaline and placebo on separate days. Baseline PC20 was determined on a different day. 3. Compa...

  10. Lack of paradoxical bronchoconstriction after administration of tiotropium via Respimat® Soft Mist™ Inhaler in COPD

    Directory of Open Access Journals (Sweden)

    Hodder R

    2011-04-01

    Full Text Available Rick Hodder1, Demetri Pavia2, Angela Lee2, Eric Bateman31Divisions of Pulmonary and Critical Care, University of Ottawa, Ottawa, ON, Canada; 2Boehringer Ingelheim Limited, Bracknell, England, UK; 3Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South AfricaAbstract: Bronchoconstriction has been reported in asthma and chronic obstructive pulmonary disease (COPD patients after administration of some aqueous inhalation solutions. We investigated the incidence of this event during long-term clinical trials of tiotropium delivered via Respimat® Soft Mist™ Inhaler (SMI. We retrospectively analyzed pooled data from two identical Phase III clinical trials, in which 1990 patients with COPD received 48 weeks' treatment with once-daily tiotropium (5 or 10 µg or placebo inhaled via Respimat® SMI. We recorded the incidence of bronchospasm and of a range of respiratory events that could suggest bronchoconstriction during the first 30 minutes after inhalation of study treatment on each of the eight test days. No patients reported bronchospasm. Six patients (0.3% reported a combination of at least two events suggestive of bronchoconstriction, and 21 (1.1% reported either rescue medication use or a respiratory adverse event. Asymptomatic falls in forced expiratory volume in one second (FEV1 of ≥15% were recorded on all test days, with no change in incidence over time, and affected 8.2% of those in the tiotropium groups and 14.5% of those on placebo. In COPD patients receiving long-term treatment with tiotropium 5 or 10 µg via Respimat® SMI, no bronchospasm was recorded, and the number of events possibly indicative of paradoxical bronchoconstriction was very low.Keywords: inhalation device, bronchoconstriction, COPD, tiotropium

  11. Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma

    DEFF Research Database (Denmark)

    Duong, MyLinh; Subbarao, Padmaja; Adelroth, Ellinor;

    2008-01-01

    BACKGROUND: The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined. METHODS: Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double...... and sputum analysis were performed. RESULTS: Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated...... eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of eosinophilic groups in the magnitude of improvement in EIB was evident after the first...

  12. Endothelin-1 in exhaled breath condensate of allergic asthma patients with exercise-induced bronchoconstriction

    Directory of Open Access Journals (Sweden)

    Tomasiak Maria M

    2007-10-01

    Full Text Available Abstract Background Exercise-induced bronchoconstriction (EIB is a highly prevalent condition, whose pathophysiology is not well understood. Endothelins are proinflammatory, profibrotic, broncho- and vasoconstrictive peptides which play an important role in the development of airway inflammation and remodeling in asthma. The aim of the study was to evaluate the changes in endothelin-1 levels in exhaled breath condensate following intensive exercise in asthmatic patients. Methods The study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without EIB and 7 healthy volunteers. Changes induced by intensive exercise in the concentrations of endothelin-1 (ET-1 in exhaled breath condensate (EBC during 24 hours after an exercise challenge test were determined. Moreover, the possible correlations of these measurements with the results of other tests commonly associated with asthma and with the changes of airway inflammation after exercise were observed. Results In asthmatic patients with EIB a statistically significant increase in the concentration of ET-1 in EBC collected between 10 minutes and 6 hours after an exercise test was observed. The concentration of ET-1 had returned to its initial level 24 hours after exercise. No effects of the exercise test on changes in the concentrations of ET-1 in EBC in either asthmatic patients without EIB or healthy volunteers were observed. A statistically significant correlation between the maximum increase in ET-1 concentrations in EBC after exercise and either baseline FENO and the increase in FENO or BHR to histamine 24 hours after exercise in the groups of asthmatics with EIB was revealed. Conclusion The release of ET-1 from bronchial epithelium through the influence of many inflammatory cells essential in asthma and interactions with other cytokines, may play an important role in increase of airway inflammation which was observed after postexercise bronchoconstriction in asthmatic patients.

  13. Effects of oral cetirizine, a selective H1 antagonist, on allergen- and exercise-induced bronchoconstriction in subjects with asthma.

    LENUS (Irish Health Repository)

    Gong, H

    1990-03-01

    The protective efficacy of oral cetirizine, a selective and potent H1-receptor antagonist, against the immediate bronchoconstrictive response to allergen inhalation and exercise challenge was evaluated in 16 subjects with stable, predominantly mild asthma. The subjects underwent double-blind, crossover pretreatments in randomized order in two separate protocols with (1) three daily oral doses of 20 mg of cetirizine and placebo, followed by allergen inhalation, and (2) single oral doses of cetirizine (5, 10, and 20 mg), albuterol (4 mg), and placebo, followed by exercise with cold-air inhalation. Cetirizine failed to decrease bronchial sensitivity to inhaled allergen in eight of 10 subjects. Neither cetirizine nor albuterol uniformly inhibited exercise-induced bronchoconstriction. Serum concentrations of cetirizine were consistent with systemic H1-blocking activity. Modest bronchodilation occurred after administration of cetirizine and albuterol before exercise but not after the third dose of cetirizine in the allergen protocol. One subject developed moderate drowsiness during multiple dosing with cetirizine. Thus, cetirizine, in the doses studied, is not uniformly effective in preventing allergen- or exercise-induced bronchoconstriction. Histamine is one of many mediators participating in immediate asthmatic responses, and selective H1 antagonists do not completely block these airway events. However, cetirizine may still clinically benefit some patients with asthma, such as patients with allergic rhinitis or urticaria.

  14. Exercise-induced bronchoconstriction: The effects of montelukast, a leukotriene receptor antagonist

    Directory of Open Access Journals (Sweden)

    James P Kemp

    2009-11-01

    Full Text Available James P KempClinical Professor of Pediatrics, Division of Immunology and Allergy, University of California School of Medicine, San Diego, CA, USAAbstract: Exercise-induced bronchoconstriction (EIB is very common in both patients with asthma and those who are otherwise thought to be normal. The intensity of exercise as well as the type of exercise is important in producing symptoms. This may make some types of exercise such as swimming more suitable and extended running more difficult for patients with this condition. A better understanding of EIB will allow the physician to direct the patient towards a type of exercise and medications that can result in a more active lifestyle without the same concern for resulting symptoms. This is especially important for schoolchildren who are usually enrolled in physical education classes and elite athletes who may desire to participate in competitive sports. Fortunately several medications (short- and long-acting β2-agonists, cromolyn, nedocromil, inhaled corticosteroids, and more recently leukotriene modifiers have been shown to be effective in preventing or attenuating the effects of exercise in many patients. In addition, inhaled β2-agonists have been shown to quickly reverse the airway obstruction that develops in patients and continue to be the reliever medications of choice. Inhaled corticosteroids are increasingly being recommended as regular therapy now that the role of inflammation and airway injury has been identified in EIB. With the discovery that there is a release of mediators such as histamine and leukotrienes from cells in the airway following exercise with resulting airway obstruction in susceptible individuals, interest has turned to attenuating their effects with mediator antagonists especially those that block the effects of leukotrienes. Studies with an oral leukotriene antagonist, montelukast, have shown beneficial effects in adults and children aged as young as 6 years with EIB

  15. A prebiotic galactooligosaccharide mixture reduces severity of hyperpnoea-induced bronchoconstriction and markers of airway inflammation.

    Science.gov (United States)

    Williams, Neil C; Johnson, Michael A; Shaw, Dominick E; Spendlove, Ian; Vulevic, Jelena; Sharpe, Graham R; Hunter, Kirsty A

    2016-09-01

    Gut microbes have a substantial influence on systemic immune function and allergic sensitisation. Manipulation of the gut microbiome through prebiotics may provide a potential strategy to influence the immunopathology of asthma. This study investigated the effects of prebiotic Bimuno-galactooligosaccharide (B-GOS) supplementation on hyperpnoea-induced bronchoconstriction (HIB), a surrogate for exercise-induced bronchoconstriction, and airway inflammation. A total of ten adults with asthma and HIB and eight controls without asthma were randomised to receive 5·5 g/d of either B-GOS or placebo for 3 weeks separated by a 2-week washout period. The peak fall in forced expiratory volume in 1 s (FEV1) following eucapnic voluntary hyperpnoea (EVH) defined HIB severity. Markers of airway inflammation were measured at baseline and after EVH. Pulmonary function remained unchanged in the control group. In the HIB group, the peak post-EVH fall in FEV1 at day 0 (-880 (sd 480) ml) was unchanged after placebo, but was attenuated by 40 % (-940 (sd 460) v. -570 (sd 310) ml, P=0·004) after B-GOS. In the HIB group, B-GOS reduced baseline chemokine CC ligand 17 (399 (sd 140) v. 323 (sd 144) pg/ml, P=0·005) and TNF-α (2·68 (sd 0·98) v. 2·18 (sd 0·59) pg/ml, P=0·040) and abolished the EVH-induced 29 % increase in TNF-α. Baseline C-reactive protein was reduced following B-GOS in HIB (2·46 (sd 1·14) v. 1·44 (sd 0·41) mg/l, P=0·015) and control (2·16 (sd 1·02) v. 1·47 (sd 0·33) mg/l, P=0·050) groups. Chemokine CC ligand 11 and fraction of exhaled nitric oxide remained unchanged. B-GOS supplementation attenuated airway hyper-responsiveness with concomitant reductions in markers of airway inflammation associated with HIB. PMID:27523186

  16. Bronchodilator response following methacholine-induced bronchoconstriction predicts acute asthma exacerbations.

    Science.gov (United States)

    Park, Heung-Woo; Song, Woo-Jung; Chang, Yoon-Suk; Cho, Sang-Heon; Datta, Soma; Weiss, Scott T; Tantisira, Kelan G

    2016-07-01

    Methacholine bronchial provocation test provides the concentration of methacholine causing a 20% decrease in forced expiratory volume in 1 s (FEV1) from baseline (PC20). The dose-response slope (DRS), and other continuous indices of responsiveness (CIR; the percentage decline from the post-diluent baseline FEV1 after the last dose of methacholine), and per cent recovery index (PRI; the percentage increase from the maximally reduced FEV1 after bronchodilator inhalation) are alternative measures. The clinical relevance of these indices in predicting acute asthma exacerbations has not been fully evaluated.In two prospective cohorts of childhood and elderly asthmatics, baseline PC20, DRS, CIR and PRI were measured and evaluated as predictors of acute asthma exacerbations.We found that PRI was significantly related to the presence of asthma exacerbations during the first year of follow-up in both cohorts of childhood (p=0.025) and elderly asthmatics (p=0.003). In addition, PRI showed a significant association with the total number of steroid bursts during 4.3 years of follow-up in the cohort of childhood asthmatics (p=0.04).We demonstrated that PRI, an index of reversibility following methacholine-induced bronchoconstriction, was a good clinical predictor of acute exacerbations of asthma in both childhood and elderly asthmatics. PMID:27076579

  17. A computed tomographic scan assessment of endotracheal suctioning-induced bronchoconstriction in ventilated sheep.

    Science.gov (United States)

    Lu, Q; Capderou, A; Cluzel, P; Mourgeon, E; Abdennour, L; Law-Koune, J D; Straus, C; Grenier, P; Zelter, M; Rouby, J J

    2000-11-01

    This study was directed at assessing changes in bronchial cross-sectional surface areas (BCSA) and in respiratory resistance induced by endotracheal suctioning in nine anesthetized sheep. Cardiorespiratory parameters (Swan-Ganz catheter), respiratory resistance (inspiratory occlusion technique), BCSA, and lung aeration (computed tomography) were studied at baseline, during endotracheal suctioning, and after 20 consecutive hyperinflations. Measurements performed initially at an inspired oxygen fraction (FI(O(2))) of 0.3 were repeated at an FI(O(2)) of 1.0. At an FI(O(2)) of 0.3, endotracheal suctioning resulted in atelectasis, a reduction in BCSA of 29 +/- 23% (mean +/- SD), a decrease in arterial oxygen saturation from 95 +/- 3% to 87 +/- 12% (p = 0.02), an increase in venous admixture from 19 +/- 10% to 31 +/- 19% (p = 0. 006), and an increase in lung tissue resistance (DR(rs)) (p = 0. 0003). At an FI(O(2)) of 1.0, despite an extension of atelectasis and an increase in pulmonary shunt from 19 +/- 5% to 36 +/- 2% (p sheep, the endotracheal suctioning-induced reduction of BCSA was entirely prevented. These data suggest that the endotracheal suctioning-induced decrease in BCSA is related to atelectasis and bronchoconstriction. Both effects can be reversed by hyperoxygenation maneuver before suctioning in combination with recruitment maneuver after suctioning.

  18. EFFECT OF FK224 ON THE BRONCHOCONSTRICTION INDUCED BY ISOCAPNIC HYPERPNEA IN GUINEA PIGS

    Institute of Scientific and Technical Information of China (English)

    陶梦非; 梁永杰

    2005-01-01

    Objective To evaluate effect of Neurokinin receptor antagonist on the prevention from hyperpnea-induced bronchoconstriction using a dual Neurokinin receptor antagonist FK224. Methods 12 pathogenfree Hartley guinea pigs were divided into two groups randomly: Dimethyl sulfoxide (DMSO) control group (n =6)and FK224 group (n =6). Guinea pigs were anesthetized with pentobarbital sodium. A cervical tracheostomy was performed and a polyethylene tube was inserted into the trachea. After measuring baseline value of the lung resistance (RL) and dynamic compliance of respiratory system (Cdyn) , DMSO (0. 3ml/kg) and FK224 ( 1mg/kg) were administered by injection through jugular vein respectively. A rodent respirator with dry 5% CO2-95% O2 mixture at room temperature provided mechanical ventilation ( VT 8ml/animal, 100breaths/min ) for 5min. RL and Cdyn of 2groups were measured after isocapnic hyperpnea challenge. Results In DMSO control group, isocapnic hyperpnea of dry gas elicited a marked increase in RL and decrease in Cdyn. RL and Cdyn of FK224 group did not change significantly. Conclusion FK224 can inhibit the increase in RL and decrease in Cdyn caused by isocapnic hyperpnea in guinea pigs. And antagonists of tachykinins receptors might have effect on prophylaxis and treatment in exercise-induced asthma.

  19. Improving screening and diagnosis of exercise-induced bronchoconstriction: a call to action.

    Science.gov (United States)

    Weiler, John M; Hallstrand, Teal S; Parsons, Jonathan P; Randolph, Christopher; Silvers, William S; Storms, William W; Bronstone, Amy

    2014-01-01

    This article summarizes the findings of an expert panel of nationally recognized allergists and pulmonologists who met to discuss how to improve detection and diagnosis of exercise-induced bronchoconstriction (EIB), a transient airway narrowing that occurs during and most often after exercise in people with and without underlying asthma. EIB is both commonly underdiagnosed and overdiagnosed. EIB underdiagnosis may result in habitual avoidance of sports and physical activity, chronic deconditioning, weight gain, poor asthma control, low self-esteem, and reduced quality of life. Routine use of a reliable and valid self-administered EIB screening questionnaire by professionals best positioned to screen large numbers of people could substantially improve the detection of EIB. The authors conducted a systematic review of the literature that evaluated the accuracy of EIB screening questionnaires that might be adopted for widespread EIB screening in the general population. Results of this review indicated that no existing EIB screening questionnaire had adequate sensitivity and specificity for this purpose. The authors present a call to action to develop a new EIB screening questionnaire, and discuss the rigorous qualitative and quantitative research necessary to develop and validate such an instrument, including key methodological pitfalls that must be avoided.

  20. Regional bronchoconstriction in asthma. 133Xenon washout scans following parenteral methacholine

    International Nuclear Information System (INIS)

    To determine the influence of bronchoconstriction on the distribution of ventilation during an asthma attack, pulmonary clearance of 133 xenon was evaluated in four normal and eight asthmatic subjects within three to five minutes after intramuscular injection of methacholine. In asthmatics, administration of 4-10 mg methacholine resulted in a decrease of forced vital capacity of 28.5 +- 5.1 (SE) percent and a decrease in expiratory flow at 60 percent vital capacity of 44.2 +- 6.9 percent (P less than 0.001). The cumulative ventilation required to reach 50 percent of the pre-washout radioactivity increased from 3.6 +- 0.8 to 9.9 +- 1.6 L after administration of the drug (P less than 0.05). The normal subjects showed no ventilatory effects after receiving 10 mg methacholine. Comparison of clearance of 133 xenon from ten areas of lung (each representing approximately 6 percent of the surface area of one lung) showed that all areas were affected to approximately the same extent during drug-induced asthma. These findings suggest that parenteral methacholine is an effective way to demonstrate airway hyperreactivity and that the airway response to methacholine in asthmatics is relatively generalized throughout the lung

  1. Improving screening and diagnosis of exercise-induced bronchoconstriction: a call to action.

    Science.gov (United States)

    Weiler, John M; Hallstrand, Teal S; Parsons, Jonathan P; Randolph, Christopher; Silvers, William S; Storms, William W; Bronstone, Amy

    2014-01-01

    This article summarizes the findings of an expert panel of nationally recognized allergists and pulmonologists who met to discuss how to improve detection and diagnosis of exercise-induced bronchoconstriction (EIB), a transient airway narrowing that occurs during and most often after exercise in people with and without underlying asthma. EIB is both commonly underdiagnosed and overdiagnosed. EIB underdiagnosis may result in habitual avoidance of sports and physical activity, chronic deconditioning, weight gain, poor asthma control, low self-esteem, and reduced quality of life. Routine use of a reliable and valid self-administered EIB screening questionnaire by professionals best positioned to screen large numbers of people could substantially improve the detection of EIB. The authors conducted a systematic review of the literature that evaluated the accuracy of EIB screening questionnaires that might be adopted for widespread EIB screening in the general population. Results of this review indicated that no existing EIB screening questionnaire had adequate sensitivity and specificity for this purpose. The authors present a call to action to develop a new EIB screening questionnaire, and discuss the rigorous qualitative and quantitative research necessary to develop and validate such an instrument, including key methodological pitfalls that must be avoided. PMID:24811017

  2. Simulation of Forced Expiration in a Biophysical Model, With Homogeneous and Clustered Bronchoconstriction.

    Science.gov (United States)

    Hedges, Kerry L; Tawhai, Merryn H

    2016-06-01

    One limitation of forced spirometry is that it integrates the contribution of the complex and dynamic behavior of all of the airways and tissue of the lung into a single exhaling unit, hence, it is not clear how spirometric measures are affected by local changes to the airways or tissue such as the presence of "ventilation defects." Here, we adapt a wave-speed limitation model to a spatially distributed and anatomically based airway tree that is embedded within a deformable parenchyma, to simulate forced expiration in 1 s (FEV1). This provides a model that can be used to assess the consequence of imposed constrictions on FEV1. We first show how the model can be parameterized to represent imaging and forced spirometry data from nonasthmatic healthy young adults. We then compare the effect of homogeneous and clustered bronchoconstriction on FEV1 in six subject-specific models (three male and three female). The model highlights potential sources of normal subject variability in response to agonist challenge, including the interaction between sites of airway constriction and sites of flow limitation at baseline. The results support earlier studies which proposed that the significant constriction of nondefect airways must be present in order to match to clinical measurements of lung function. PMID:27109169

  3. Randomized controlled trial of fish oil and montelukast and their combination on airway inflammation and hyperpnea-induced bronchoconstriction.

    Directory of Open Access Journals (Sweden)

    Sandra Tecklenburg-Lund

    Full Text Available Both fish oil and montelukast have been shown to reduce the severity of exercise-induced bronchoconstriction (EIB. The purpose of this study was to compare the effects of fish oil and montelukast, alone and in combination, on airway inflammation and bronchoconstriction induced by eucapnic voluntary hyperpnea (EVH in asthmatics.In this model of EIB, twenty asthmatic subjects with documented hyperpnea-induced bronchoconstriction (HIB entered a randomized double-blind trial. All subjects entered on their usual diet (pre-treatment, n = 20 and then were randomly assigned to receive either one active 10 mg montelukast tablet and 10 placebo fish oil capsules (n = 10 or one placebo montelukast tablet and 10 active fish oil capsules totaling 3.2 g EPA and 2.0 g DHA (n = 10 taken daily for 3-wk. Thereafter, all subjects (combination treatment; n = 20 underwent another 3-wk treatment period consisting of a 10 mg active montelukast tablet or 10 active fish oil capsules taken daily.While HIB was significantly inhibited (p0.017 between treatment groups; percent fall in forced expiratory volume in 1-sec was -18.4 ± 2.1%, -9.3±2.8%, -11.6 ± 2.8% and -10.8 ± 1.7% on usual diet (pre-treatment, fish oil, montelukast and combination treatment respectively. All three treatments were associated with a significant reduction (p0.017 in these biomarkers between treatments.While fish oil and montelukast are both effective in attenuating airway inflammation and HIB, combining fish oil with montelukast did not confer a greater protective effect than either intervention alone. Fish oil supplementation should be considered as an alternative treatment for EIB.ClinicalTrials.gov NCT00676468.

  4. Exertional-induced bronchoconstriction: Comparison between cardiopulmonary exercise test and methacholine challenging test

    Directory of Open Access Journals (Sweden)

    Mostafa Ghanei

    2015-01-01

    Full Text Available Introduction: Exertional-induced bronchoconstriction is a condition in which the physical activity causes constriction of airways in patients with airway hyper- responsiveness. In this study, we tried to study and evaluate any relationship between the findings of cardiopulmonary exercise testing (CPET and the response to methacholine challenge test (MCT in patients with dyspnea after activity. Materials and Methods: Thirty patients with complaints of dyspnea following activity referred to "Lung Clinic" of Baqiyatallah Hospital but not suffering from asthma were entered into the study. The subjects were excluded from the study if: Suffering from any other pulmonary diseases, smoking more than 1 cigarette a week in the last year, having a history of smoking more than 10 packets of cigarettes/year, having respiratory infection in the past 4 weeks, having abnormal chest X-ray or electrocardiogram, and cannot discontinue the use of medicines interfering with bronchial provocation. Baseline spirometry was performed for all the patients, and the values of forced expiratory volume in 1 second (FEV1, forced vital capacity (FVC, and FEV/FVC were recorded. The MCT and then the CPET were performed on all patients. Results: The mean VO 2 (volume oxygen in patients with positive methacholine test (20.45 mL/kg/min was significantly lower than patients with negative MCT (28.69 mL/kg/min (P = 0.000. Respiratory rates per minute (RR and minute ventilation in the group with positive MCT (38.85 and 1.636 L were significantly lower than the group with negative methacholine test (46.78 and 2.114 L (P < 0.05. Also, the O 2 pulse rate in the group with negative methacholine test (116.27 mL/beat was significantly higher than the group with positive methacholine test (84.26 mL/beat (P < 0.001. Conclusion: Pulmonary response to exercise in patients with positive methacholine test is insufficient. The dead space ventilation in these patients has increased. Also, dynamic

  5. A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: Effects of epinephrine and oxygen therapies

    International Nuclear Information System (INIS)

    Sarin is an organophosphate nerve agent that is among the most lethal chemical toxins known to mankind. Because of its vaporization properties and ease and low cost of production, sarin is the nerve agent with a strong potential for use by terrorists and rouge nations. The primary route of sarin exposure is through inhalation and, depending on the dose, sarin leads to acute respiratory failure and death. The mechanism(s) of sarin-induced respiratory failure is poorly understood. Sarin irreversibly inhibits acetylcholine esterase, leading to excessive synaptic levels of acetylcholine and, we have previously shown that sarin causes marked ventilatory changes including weakened response to hypoxia. We now show that LD50 sarin inhalation causes severe bronchoconstriction in rats, leading to airway resistance, increased hypoxia-induced factor-1α, and severe lung epithelium injury. Transferring animals into 60% oxygen chambers after sarin exposure improved the survival from about 50% to 75% at 24 h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD50 sarin-exposed animals were administered the bronchodilator epinephrine, > 90% of the animals survived. Moreover, while both epinephrine and oxygen treatments moderated cardiorespiratory parameters, the proinflammatory cytokine surge, and elevated expression of hypoxia-induced factor-1α, only epinephrine consistently reduced the sarin-induced bronchoconstriction. These data suggest that severe bronchoconstriction is a critical factor in the mortality induced by LD50 sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin. - Highlights: • Inhalation exposure of rats to LD50 sarin causes death through respiratory failure. • Severe bronchoconstriction is the major cause of sarin-induced respiratory failure. • Transfer of sarin exposed rats to 60% oxygen improves the mortality temporarily. • Epinephrine improves

  6. A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: Effects of epinephrine and oxygen therapies

    Energy Technology Data Exchange (ETDEWEB)

    Gundavarapu, Sravanthi; Zhuang, Jianguo; Barrett, Edward G.; Xu, Fadi; Russell, Robert G.; Sopori, Mohan L., E-mail: msopori@lrri.org

    2014-01-15

    Sarin is an organophosphate nerve agent that is among the most lethal chemical toxins known to mankind. Because of its vaporization properties and ease and low cost of production, sarin is the nerve agent with a strong potential for use by terrorists and rouge nations. The primary route of sarin exposure is through inhalation and, depending on the dose, sarin leads to acute respiratory failure and death. The mechanism(s) of sarin-induced respiratory failure is poorly understood. Sarin irreversibly inhibits acetylcholine esterase, leading to excessive synaptic levels of acetylcholine and, we have previously shown that sarin causes marked ventilatory changes including weakened response to hypoxia. We now show that LD{sub 50} sarin inhalation causes severe bronchoconstriction in rats, leading to airway resistance, increased hypoxia-induced factor-1α, and severe lung epithelium injury. Transferring animals into 60% oxygen chambers after sarin exposure improved the survival from about 50% to 75% at 24 h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD{sub 50} sarin-exposed animals were administered the bronchodilator epinephrine, > 90% of the animals survived. Moreover, while both epinephrine and oxygen treatments moderated cardiorespiratory parameters, the proinflammatory cytokine surge, and elevated expression of hypoxia-induced factor-1α, only epinephrine consistently reduced the sarin-induced bronchoconstriction. These data suggest that severe bronchoconstriction is a critical factor in the mortality induced by LD{sub 50} sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin. - Highlights: • Inhalation exposure of rats to LD{sub 50} sarin causes death through respiratory failure. • Severe bronchoconstriction is the major cause of sarin-induced respiratory failure. • Transfer of sarin exposed rats to 60% oxygen improves the mortality temporarily.

  7. Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma

    Directory of Open Access Journals (Sweden)

    Spector Sheldon L

    2009-01-01

    Full Text Available Abstract Background Asthma can be difficult to diagnose, but bronchial provocation with methacholine, exercise or mannitol is helpful when used to identify bronchial hyperresponsiveness (BHR, a key feature of the disease. The utility of these tests in subjects with signs and symptoms of asthma but without a clear diagnosis has not been investigated. We investigated the sensitivity and specificity of mannitol to identify exercise-induced bronchoconstriction (EIB as a manifestation of BHR; compared this with methacholine; and compared the sensitivity and specificity of mannitol and methacholine for a clinician diagnosis of asthma. Methods 509 people (6–50 yr were enrolled, 78% were atopic, median FEV1 92.5% predicted, and a low NAEPPII asthma score of 1.2. Subjects with symptoms of seasonal allergy were excluded. BHR to exercise was defined as a ≥ 10% fall in FEV1 on at least one of two tests, to methacholine a PC20 ≤ 16 mg/ml and to mannitol a 15% fall in FEV1 at ≤ 635 mg or a 10% fall between doses. The clinician diagnosis of asthma was made on examination, history, skin tests, questionnaire and response to exercise but they were blind to the mannitol and methacholine results. Results Mannitol and methacholine were therapeutically equivalent to identify EIB, a clinician diagnosis of asthma, and prevalence of BHR. The sensitivity/specificity of mannitol to identify EIB was 59%/65% and for methacholine it was 56%/69%. The BHR was mild. Mean EIB % fall in FEV1 in subjects positive to exercise was 19%, (SD 9.2, mannitol PD15 158 (CI:129,193 mg, and methacholine PC20 2.1(CI:1.7, 2.6mg/ml. The prevalence of BHR was the same: for exercise (43.5%, mannitol (44.8%, and methacholine (41.6% with a test agreement between 62 & 69%. The sensitivity and specificity for a clinician diagnosis of asthma was 56%/73% for mannitol and 51%/75% for methacholine. The sensitivity increased to 73% and 72% for mannitol and methacholine when two exercise tests were

  8. Eficácia do formoterol na reversão imediata do broncoespasmo Efficacy of inhaled formoterol in reversing bronchoconstriction

    Directory of Open Access Journals (Sweden)

    Adalberto Sperb Rubin

    2006-06-01

    Full Text Available OBJETIVO: Avaliar efetividade e rapidez de ação do formoterol liberado através de inalador para pó seco na reversão de broncoespasmo induzido pela metacolina. MÉTODOS: Avaliaram-se prospectivamente 84 pacientes com queda do volume expiratório forçado no primeiro segundo 20% após inalação de metacolina. Todos estavam sob investigação de sintomas respiratórios de etiologia não definida. Foram randomizados 41 pacientes para receber 200 mcg de fenoterol spray e 43 para receber 12 mcg de formoterol sob a forma de inalador de pó seco para reversão imediata do broncoespasmo. Avaliaram-se a queda no volume expiratório forçado no primeiro segundo inicial, dose provocadora de queda de 20% do volume expiratório forçado no primeiro segundo inicial, e volume expiratório forçado no primeiro segundo após cinco e dez minutos da administração dos fármacos. RESULTADOS: Não houve diferença significativa entre os grupos em relação ao sexo, idade, peso, altura, dose provocadora de queda de 20% do volume expiratório forçado no primeiro segundo, volume expiratório forçado no primeiro segundo inicial e pós-metacolina. A melhora do volume expiratório forçado no primeiro segundo após uso do broncodilatador foi de 34% (cinco minutos e 50,1% (dez minutos no primeiro grupo, e 46,5% (cinco minutos e 53,2% (dez minutos no segundo. CONCLUSÃO: O efeito broncodilatador do formoterol após cinco e dez minutos da indução de broncoespasmo pela metacolina foi similar ao do fenoterol. O formoterol, além de ser um broncodilatador de longa duração, tem também rápido início de ação, sugerindo que possa ser empregado como medicação de resgate nas crises de broncoespasmo.OBJECTIVE: To evaluate the effectiveness and onset of action of formoterol delivered by dry-powder inhaler in reversing methacholine-induced bronchoconstriction. METHODS: Patients presenting a drop in forced expiratory volume in one second > 20% after methacholine

  9. Efeito do salbutamol liberado através de inalador de pó seco sobre o broncoespasmo induzido por metacolina Effects of salbutamol delivered by dry-powder inhaler on methacholine-induced bronchoconstriction

    Directory of Open Access Journals (Sweden)

    Adalberto Sperb Rubin

    2004-06-01

    (MDIs are the drugs usually used for the reversal of methacholine-induced bronchoconstriction. The b2 agonists that are delivered by dry-powder inhaler (DPI can be an efficacious option. OBJECTIVE: To evaluate the effectiveness and speed of action of salbutamol delivered by DPI (Pulvinal; Butovent®, in comparison to salbutamol delivered by MDI, in reversing methacholine-induced bronchoconstriction. METHOD: Sixty successive methacholine-induced bronchoconstriction patients who presented a decrease of at least 20% in forced expiratory volume (FEV1 were evaluated prospectively. Of these 60 patients, we randomized 30 (first group to receive 200 mcg of salbutamol by MDI and 30 (second group to receive 200 mcg of salbutamol by DPI (Pulvinal. Both drugs were administered with the objective of reversing bronchoconstriction during the final phase of a bronchoprovocation test. The FEV1 values obtained at 1 and 5 minutes after bronchodilator administration were evaluated. RESULTS: The groups were comparable in gender distribution, age, weight, dose level provoking a 20% drop in FEV1 (first group: 1.3 mg; second group: 1.19 mg; p = 0.79 and post-methacholine FEV1 (first group: 2.03 l; second group: 1.99 l; p = 0.87, with no statistically significant differences between the two groups. In the first group (MDI, the mean increase in FEV1 was 16.2% (at 1 minute and 22.2% (at 5 minutes, and in the second group (DPI it was 17% (at 1 minute and 23.6% (at 5 minutes. There was no statistically significant difference between the groups (p = 0.8. CONCLUSION: The beta2-agonists delivered by DPI (Pulvinal present the same bronchodilator efficacy and speed of action as do those delivered by the more traditional MDI method.

  10. Onset of relief of dyspnoea with budesonide/formoterol or salbutamol following methacholine-induced severe bronchoconstriction in adults with asthma: a double-blind, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Bantje Theo A

    2006-12-01

    Full Text Available Abstract Background The long-acting β2-agonist (LABA formoterol has an onset of effect comparable to that of salbutamol. Consequently, the combination of formoterol and budesonide in one inhaler, approved for maintenance use, can potentially be used for reliever therapy. This study compared the onset of relief from induced bronchospasm with a single dose of budesonide/formoterol versus standard salbutamol therapy in patients with asthma. Methods In this randomised, double-blind, placebo-controlled, cross-over study, 32 patients with asthma underwent a methacholine provocation test leading to a fall in forced expiratory volume in 1 second (FEV1 of ≥30% at enrolment (Visit 1 and three subsequent study visits (Visits 2–4. Immediately after each provocation at Visits 2–4, patients received one of three test treatments: one inhalation of budesonide/formoterol 160/4.5 μg (via Turbuhaler®, two inhalations of salbutamol 100 μg (via a pressurised metered-dose inhaler [pMDI] or placebo. All patients received each of the test treatments in a randomised order, after separate methacholine provocations. The effect of treatment on FEV1 and breathlessness (using the Borg scale was measured at 1, 3, 5, 10, 15, 20, 25 and 30 minutes after test treatment. Results Following methacholine provocation, Borg score increased from a baseline value of below 0.5 to 3.03, 3.31 and 3.50 before treatment with budesonide/formoterol, salbutamol and placebo, respectively. Budesonide/formoterol and salbutamol reversed methacholine-induced dyspnoea (breathlessness rapidly. At 1 minute after inhalation, statistically significant decreases in Borg score were observed for budesonide/formoterol and salbutamol (p = 0.0233 and p 1 (both active treatments p Conclusion Single doses of budesonide/formoterol and salbutamol both provided rapid relief of dyspnoea and reversal of severe airway obstruction in patients with asthma with experimentally induced bronchoconstriction. The

  11. 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

  12. Treatment of exercise-induced bronchoconstriction

    DEFF Research Database (Denmark)

    Backer, Vibeke; Sverrild, Asger; Porsbjerg, Celeste

    2013-01-01

    impairment of performance to severe bronchospasm and a large reduction in FEV1. Treatment of EIB varies from daily to less frequent therapy, depending on the level of activity. In this article, the authors evaluate the treatment possibilities before, during, and after exercise. They also review medications...

  13. Exercise-induced bronchoconstriction : clinical studies in childhood asthma

    NARCIS (Netherlands)

    W.B. Hofstra (Winfried)

    1997-01-01

    textabstractAt present, astluna is regarded as a chronic inflammatory disorder of the airways, In susceptible individuals, asthma causes symptoms, that are usually associated with variable, but often reversible airflow obstmction. Astlulla is the most conunon lung disease in childhood, with a sympto

  14. Air quality and exercise-induced bronchoconstriction in elite athletes.

    Science.gov (United States)

    Rundell, Kenneth W; Sue-Chu, Malcolm

    2013-08-01

    A higher prevalence of airway hyperresponsiveness, airway remodeling, and asthma has been identified among athletes who compete and train in environmental conditions of cold dry air and/or high air pollution. Repeated long-duration exposure to cold/dry air at high minute ventilation rates can cause airway damage. Competition or training at venues close to busy roadways, or in indoor ice arenas or chlorinated swimming pools, harbors a risk for acute and chronic airway disorders from high pollutant exposure. This article discusses the effects of these harsh environments on the airways, and summarizes potential mechanisms and prevalence of airway disorders in elite athletes. PMID:23830133

  15. Air quality and exercise-induced bronchoconstriction in elite athletes.

    Science.gov (United States)

    Rundell, Kenneth W; Sue-Chu, Malcolm

    2013-08-01

    A higher prevalence of airway hyperresponsiveness, airway remodeling, and asthma has been identified among athletes who compete and train in environmental conditions of cold dry air and/or high air pollution. Repeated long-duration exposure to cold/dry air at high minute ventilation rates can cause airway damage. Competition or training at venues close to busy roadways, or in indoor ice arenas or chlorinated swimming pools, harbors a risk for acute and chronic airway disorders from high pollutant exposure. This article discusses the effects of these harsh environments on the airways, and summarizes potential mechanisms and prevalence of airway disorders in elite athletes.

  16. The impact of exercise-induced bronchoconstriction on athletic performance

    DEFF Research Database (Denmark)

    Price, Oliver J; Hull, James H; Backer, Vibeke;

    2014-01-01

    of this review is to provide a systematic appraisal of the current status of knowledge regarding EIB and exercise performance and to highlight potential mechanisms by which performance may be compromised by EIB. DATA SOURCES AND STUDY SELECTION: PubMed/Medline and EBSCO databases were searched up to May 2014...

  17. Desempenho de uma escala analógica visual legendada na determinação do grau de dispneia durante teste de broncoespasmo induzido por exercício em crianças e adolescentes asmáticos Performance of a word labeled visual analog scale in determining the degree of dyspnea during exercise-induced bronchoconstriction in children and adolescents with asthma

    Directory of Open Access Journals (Sweden)

    Patrícia Bueno Lima

    2010-10-01

    labeled visual analog dyspnea scale with a 0-3 score has been widely used for the assessment of the degree of bronchoconstriction, although the perception of such obstruction varies considerably. The objective of this study was to determine whether children and adolescents are able to perceive acute exercise-induced bronchoconstriction (EIB, as well as to measure the discriminatory power of a word labeled visual analog dyspnea scale in relation to the intensity of the EIB. METHODS: A cross-sectional study involving 134 children and adolescents with asthma and submitted to a six-minute steady-state exercise test on a cycle ergometer. The intensity of dyspnea was determined using a word labeled visual analog dyspnea scale prior to each determination of FEV1. The scale is scored from 0 to 3, with a logical sequence of pictures, ranging from "no symptoms" to "severe dyspnea". Variables were determined at baseline, as well as at 5, 10, and 20 min after the exercise test. The accuracy of the dyspnea scale in identifying the degree of EIB was determined by means of ROC curves for the post-exercise fall in FEV1, using cut-off points of 10%, 20%, 30%, and 40%. RESULTS: Of the patients selected, 111 finished the study, and 52 (46.8% presented with EIB. The area under the ROC curve increased in direct proportion to increases in the degree of bronchoconstriction. CONCLUSIONS: Among children and adolescents with asthma, the accuracy of this dyspnea scale improves as the post-exercise percentage fall in FEV1 increases. However, the predictive value of the scale is suboptimal when the percentage fall in FEV1 is lower.

  18. 321 Clinical Analysis of Salbutamol Responsiveness after Acetylcholine-induced Bronchoconstriction in Childhood Asthma

    OpenAIRE

    Kondo, Tomio; Nakashima, Yoshiki; Shikano, Hiroaki

    2012-01-01

    Background The bronchodilator is usually inhaled after the acethylcholine (Ach) inhalation test for asthmatic patients. We investigated clinical characteristics of asthma about the response to a inhalation of salbutamol after the Ach provocation test. Methods Asthmatic patients from 6 to 18 years old were examined. They inhaled aerosol with increased concentration of Ach to produce 20% or more decrease in FEV1.0 (RT-Ach point). After then they inhaled salbutamol, and respiratory function was ...

  19. Effect of bronchoconstrictive aerosols on pulmonary gas trapping in the A/J mouse.

    Science.gov (United States)

    Yiamouyiannis, C A; Stengel, P W; Cockerham, S L; Silbaugh, S A

    1995-10-01

    We exposed A/J mice to several challenge aerosols and measured gas trapped within excised lungs by quantitating their buoyancy in saline (Archimedes' principle). The temporal stability of the excised lung gas volume (ELGV) measurement was also examined. ELGV increased in a dose proportional manner with increasing concentrations of methacholine and reached a maximum of 338 +/- 33% above vehicle-exposed controls. The A/J mice were 100 times more responsive to aerosol methacholine compared to hyporesponsive C3H/HeJ mice. Aerosol challenges of U-46619, a thromboxane A2 mimetic, and serotonin resulted in a 40% and 135% increase in ELGV's versus their controls, respectively. ELGV's were not increased after aerosols of leukotriene C4, histamine, substance P, N-formyl-methionyl-leucyl-phenyl-alanine and platelet activating factor. Both normal (filtered air-exposed) and hyperinflated (methacholine-exposed) excised lungs lost about 10% of their initial volume by 30 min and 40-65% of initial volume by 4 h. Occlusion of the trachea in either group did not affect the total gas lost, suggesting that majority of the gas loss was via transpleural diffusion. We conclude that determination of ELGV in mice, when performed soon after challenge testing, is a simple, rapid and reliable estimate of airway obstruction. PMID:8610213

  20. Exhaled nitric oxide predicts exercise-induced bronchoconstriction in asthmatic school children

    DEFF Research Database (Denmark)

    Buchvald, Frederik; Hermansen, Mette N; Nielsen, Kim G;

    2005-01-01

    used in routine monitoring of pediatric asthma control. The fractional concentration of exhaled nitric oxide (FeNO) also reflects uncontrolled asthma. We hypothesized that FeNO may be used for prescreening of asthmatic children to exclude those with good asthma control unlikely to have EIB, thereby...

  1. S-nitrosoglutathione supplementation to ovalbumin-sensitized and -challenged mice ameliorates methacholine-induced bronchoconstriction

    OpenAIRE

    Foster, Matthew W.; Yang, Zhonghui; Potts, Erin N.; W Michael Foster; Que, Loretta G.

    2011-01-01

    S-nitrosoglutathione (GSNO) is an endogenous bronchodilator present in micromolar concentrations in airway lining fluid. Airway GSNO levels decrease in severe respiratory failure and asthma, which is attributable to increased metabolism by GSNO reductase (GSNOR). Indeed, we have found that GSNOR expression and activity correlate inversely with lung S-nitrosothiol (SNO) content and airway hyperresponsiveness (AHR) to methacholine (MCh) challenge in humans with asthmatic phenotypes (Que LG, Yan...

  2. Exercise-induced bronchoconstriction and non-specific airway hyperreactivity in patients suffering from bronchial asthma

    Directory of Open Access Journals (Sweden)

    Novković Dobrivoje

    2014-01-01

    Full Text Available Background/Aim. Physical activity is a common stimulus of asthmatic symptoms manifestation. Airway hyperreactivity is a predisposing cause of exercise induced bronchial obstruction, diagnosed by histamine inhalation. The aim of this study was to determine the relation between the amounts of histamine needed to induce non-specific airway hyperreactivity and exercise-induced bronchial obstruction. Methods. This randomized cross-over study included 160 male patients (age 19-27 years suffering from bronchial asthma who showed positive results as the reaction after the histamine bronchial provocation test. Histamine concentrations were in a range of 0.03 to 4 mg/mL. Each patient participated in the exercise stress test conducted on a conveyor belt. The results of the exercise stress test were considered positive if the FEV1 level dropped by at least 15% from its initial value, 5-10 minutes after the test. Results. All the patients showed positive results as the reaction after the histamine bronchial provocation test, while 50 of them showed positive results after the exercise-induced stress test. There was a statistically highly significant difference in administrated histamine concentrations between the group of patients that had positive results on exercise stress test and those who did not (1mg/mL vs 0.5mg/mL; U = 1678; p < 0.01. Also, there was a statistically significant difference concerning the frequency of the positive results regarding histamine concentration after induced stress test (χ2 = 10.885; p = 0.001. Among the patients with positive results, there was a statistically highly significant number of patients with bronchial obstruction induced by less than 2 mg/mL of histamine (p < 0.01. A statistically significant relation between the amount of histamine needed to induce bronchial obstruction and the results of the exercise stress test (p < 0.01 was also observed after the testing. Conclusion. In the group of patients with positive results after the exercise-induced stress test, there were significantly more patients with positive results to non-specific bronchial provocation test with lower histamine concentrations. Histamine concentrations needed to induce non-specific hyperreactivity of asthmatic airway were shown to be related to the reactivity to physical effort.

  3. Relief of dyspnoea by beta(2)-agonists after methacholine-induced bronchoconstriction

    NARCIS (Netherlands)

    van der Woude, HJ; Postma, DS; Politiek, MJ; Winter, TH; Aalbers, R

    2004-01-01

    Virtually all asthma patients use bronchodilators. Formoterol and salbutamol have a rapid onset of bronchodilating effect, whereas salmeterol acts slower. We studied the onset of improvement of dyspnoea sensation after inhalation with these bronchodilators and placebo to reverse a methacholine-induc

  4. Analysis of tidal expiratory flow pattern in the assessment of histamine-induced bronchoconstriction.

    OpenAIRE

    Morris, M. J.; Madgwick, R. G.; Lane, D. J.

    1995-01-01

    BACKGROUND--There are times in clinical practice when it would be useful to be able to assess the severity of airways obstruction from tidal breathing. Three indices of airways obstruction derived from analysis of resting tidal expiratory flow have previously been described: (1) Tme/TE = time to reach maximum expiratory flow/expiratory time; (2) Krs = decay constant of exponential fitted to tidal expiratory flow versus time curve; and (3) EV = extrapolated volume--that is, area under the curv...

  5. The effect of climatic conditions on exercise-induced bronchoconstriction in 10-12 year old students.

    Science.gov (United States)

    Marefati, Hamid; Vizvari, Exir; Esmaeilizadeh, Mahdi; Boskabady, Mohammad Hossein

    2016-07-01

    Exercise-induced asthma is seen following vigorous or prolonged exercise or physical exertion. It has been suggested that climatic conditions have an influence on exercise-induced asthma. Therefore, the aim of the present study was to examine the effect of two climatic conditions on exercise-induced deterioration of pulmonary function tests in 10-12 year old students. Two hundred and fifty six students were randomly chosen from two cities namely Kerman and Gorgan (128 subjects in each who were equally from both cities) including 62 girls and 66 boys of 10-12 years old. A questionnaire was used to obtain demographic information and to identify the prevalence of asthma symptoms. Each subject performed a seven-minute free run exercise with maximum effort and sufficient motivation until they reached 70-75% heart rate. Pulmonary function tests (PFT) including, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and maximum expiratory flow at 50% of vital capacity (MEF50) were measured before, at the beginning, and 7 and 20 min after physical activity. The prevalence of both asthma (28.12%) and exercise-induced asthma (20.31%) in Kerman students was higher than those of Gorgan students (21.09% and 17%, respectively). All PFT values declined 7 and 20 min post-exercise in both groups. Although all baselines PFT in Kerman students were higher than those of Gorgan students, the decline in PFT values in Kerman students was greater than those of Gorgan students. At 20 min post exercise, the decline in FEV1, PEF and MEF50 in Kerman students was significantly higher than those of Gorgan students (p exercise-induced asthma in a city with dry and cool climate such as Kerman was higher than in a city with humid climate such as Gorgan. In addition, the results showed that in a humid climate, post-exercise decline in PFT values was less than in a dry climate. PMID:27634077

  6. Differential expression of monocyte CD163 in single- and dual-asthmatic responders during allergen-induced bronchoconstriction

    DEFF Research Database (Denmark)

    Kowal, K; Møller, H J; Dubuske, L M;

    2006-01-01

    ) unchanged sCD163 and (3) increased eNO in DR was contrasted by a pattern of (1) increased CD163 expression, (2) increased sCD163 and (3) unchanged eNO in SR. During allergen challenge, the changes in monocyte CD163 expression and sCD163 inversely correlated with the changes in eNO. CONCLUSION: Both pro...

  7. Comparing the effects of two inhaled glucocorticoids on allergen-induced bronchoconstriction and markers of systemic effects, a randomised cross-over double-blind study

    Directory of Open Access Journals (Sweden)

    Lötvall Jan

    2011-10-01

    Full Text Available Abstract Background Inhaled glucocorticoids are efficient in protecting against asthma exacerbations, but methods to compare their efficacy vs systemic effects have only been attempted in larger multi-centre studies. The aim of the current study was therefore to directly compare the effects of two separate inhaled glucocorticoids, mometasone and budesonide, to compare the effects on the early and late asthmatic responses to inhaled allergen in patients with mild allergic asthma, and sputum eosinophils, and to relate the clinical positive effects to any systemic effects observed. Methods Twelve patients with documented early and late asthmatic responses (EAR and LAR to inhaled allergen at a screening visit were randomized in a double-blind fashion to treatment with mometasone (200 μg × 2 or 400 μg × 2, budesonide (400 μg × 2 or placebo in a double-blind crossover fashion for a period of seven days. Challenge with the total allergen dose causing both an EAR and LAR was given on the last day of treatment taken in the morning. Lung function was assessed using FEV1, and systemic glucocorticoid activity was quantified using 24 h urinary cortisol. Results Mometasone and budesonide attenuate both EAR and LAR to allergen to a similar degree. No significant dose-related effects on the lung function parameters were observed. Both treatments reduced the relative amount of sputum eosinophils (% after allergen. At the dose of 800 μg daily, mometasone reduced 24 h urinary cortisol by approximately 35%. Both drugs were well tolerated. Conclusions Mometasone and budesonide are equieffective in reducing early and late asthmatic responses induced by inhaled allergen challenge. Mometasone 800 μg given for seven days partially affects the HPA axis.

  8. Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma

    NARCIS (Netherlands)

    Hofstra, WB; Neijens, HJ; Duiverman, EJ; Kouwenberg, JM; Mulder, PGH; Kuethe, MC; Sterk, PJ

    2000-01-01

    When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent

  9. Rapid effects of extrafine beclomethasone dipropionate/formoterol fixed combination inhaler on airway inflammation and bronchoconstriction in asthma: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    O'Connor Brian J

    2011-12-01

    Full Text Available Abstract Background The dose-dependent anti-inflammatory effects of a recent fixed combination of extrafine beclomethasone dipropionate/formoterol (BDP/F were investigated using non-invasive markers of inflammation, exhaled nitric oxide (NO and adenosine monophosphate (AMP provocative challenge. The aim was to assess the onset of the anti-inflammatory action of low and high doses and evaluate the suitability of non-invasive assessments to demonstrate dose response. Methods Steroid naïve adult out-patients with mild asthma, sensitive to AMP with baseline exhaled NO > 25 parts per billion entered a double-blind, placebo-controlled, 3-way, cross-over study. Patients were randomised to low dose (1 actuation or high dose (4 actuations extrafine BDP/F 100/6 μg, or placebo administered twice daily on Days 1 and 2 and once in the morning on Day 3 of each period. Exhaled NO was measured pre-dose on Day 1, then 2 and 4 hours post-administration on Day 3. The AMP challenge was performed 4 hours post-administration on Day 3 and forced expiratory volume in 1 second (FEV1, L was measured from 0 to 4 hours post-dose on Day 1. Endpoints were NO at 2 and 4 hours, AMP challenge at 4 hours after the fifth dose on Day 3 and FEV1 area under the curve from 0 to 4 h post-dose on Day 1. Analysis of covariance was performed for NO and FEV1 and analysis of variance for AMP challenge. Results Eighteen patients were randomised and completed the study. Exhaled NO was significantly lower for both doses of extrafine BDP/F versus placebo at 2 and 4 hours (high dose LS mean difference: -22.5 ppb, p 1 was significantly improved versus placebo for both doses (high dose LS mean difference: 0.2 L, p = 0.0001; low dose: 0.2 L p = 0.0001, but without a significant dose response. Conclusions The fixed combination inhaler of extrafine BDP/F has early dose-dependent anti-inflammatory effects with a rapid onset of bronchodilatation in mild asthmatic patients. Trial Registration ClinicalTrials.gov: NCT01343745

  10. Onset of relief of dyspnoea with budesonide/formoterol or salbutamol following methacholine-induced severe bronchoconstriction in adults with asthma: a double-blind, placebo-controlled study

    OpenAIRE

    Bantje Theo A; Jonkers René E; Aalbers René

    2006-01-01

    Abstract Background The long-acting β2-agonist (LABA) formoterol has an onset of effect comparable to that of salbutamol. Consequently, the combination of formoterol and budesonide in one inhaler, approved for maintenance use, can potentially be used for reliever therapy. This study compared the onset of relief from induced bronchospasm with a single dose of budesonide/formoterol versus standard salbutamol therapy in patients with asthma. Methods In this randomised, double-blind, placebo-cont...

  11. Onset of relief of dyspnoea with budesonide/formoterol or salbutamol following methacholine-induced severe bronchoconstriction in adults with asthma: a double-blind, placebo-controlled study

    NARCIS (Netherlands)

    R.E. Jonkers; T.A. Bantje; R. Aalbers

    2006-01-01

    Background: The long-acting beta(2)-agonist ( LABA) formoterol has an onset of effect comparable to that of salbutamol. Consequently, the combination of formoterol and budesonide in one inhaler, approved for maintenance use, can potentially be used for reliever therapy. This study compared the onset

  12. Optimizing inhalation therapy in childhood asthma

    OpenAIRE

    Visser, Reina

    2016-01-01

    Childhood asthma is a common chronic disease, featured by inflammation of the airways and episodic bronchoconstriction. Exercise is an important trigger for bronchoconstriction in asthmatic children. They experience this symptom, limiting participation in play and sports, as the most bothersome aspect of their asthma. Symptoms of exercise induced bronchoconstriction (EIB) can be subtle and stay unrecognized by caregivers and parents, compromising social and motor development. Asthmatic childr...

  13. Optimizing inhalation therapy in childhood asthma

    NARCIS (Netherlands)

    Visser, Reina

    2016-01-01

    Childhood asthma is a common chronic disease, featured by inflammation of the airways and episodic bronchoconstriction. Exercise is an important trigger for bronchoconstriction in asthmatic children. They experience this symptom, limiting participation in play and sports, as the most bothersome aspe

  14. Dicty_cDB: SHE502 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available on, kit and method for treating respiratory tract disorder related to bronchoconstriction, pneumonia, allerg... 71 unordered pieces. 40 0.009 2 BD323302 |BD323302.1 Low-adenosine antisense oligonucleotide, its compositi

  15. Dicty_cDB: FC-IC0700 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ating respiratory tract disorder related to bronchoconstriction, pneumonia, allergy...09 5 BD322951 |BD322951.1 Low-adenosine antisense oligonucleotide, its composition, kit and method for tre

  16. 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

  17. 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...

  18. Exercise and asthma: an overview

    OpenAIRE

    Giacco, Stefano R. Del; Firinu, Davide; Bjermer, Leif; Carlsen, Kai-Håkon

    2015-01-01

    The terms ‘exercise-induced asthma’ (EIA) and ‘exercise-induced bronchoconstriction’ (EIB) are often used interchangeably to describe symptoms of asthma such as cough, wheeze, or dyspnoea provoked by vigorous physical activity. In this review, we refer to EIB as the bronchoconstrictive response and to EIA when bronchoconstriction is associated with asthma symptoms. EIB is a common occurrence for most of the asthmatic patients, but it also affects more than 10% of otherwise healthy individuals...

  19. Effects of methacholine infusion on desflurane pharmacokinetics in piglets

    OpenAIRE

    Alf Kozian; Moritz Kretzschmar; Baumgardner, James E; Jens Schreiber; Göran Hedenstierna; Anders Larsson; Thomas Hachenberg; Thomas Schilling

    2015-01-01

    The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas El...

  20. 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.

  1. Airway resistance and deposition of particles in the lung.

    Science.gov (United States)

    Svartengren, M; Philipson, K; Linnman, L; Camner, P

    1984-01-01

    The percentage 24-h lung retention of 4-micrometers monodispersed Teflon particles, aerodynamic diameter about 6 micrometers, was studied twice in 8 healthy nonsmokers. The particles were inhaled at 0.5 liter/sec with maximally deep breaths. Bronchoconstriction was induced by inhalation of a methacholine-bromide aerosol for one exposure before and for the other 20-30 min after the inhalation of the Teflon particles. For both exposures, airway resistance (Raw) was measured with a whole body plethysmograph before and after the induction of the bronchoconstriction and was found on an average to increase with a factor of 2-3. For the exposure when bronchoconstriction was induced after the inhalation of the Teflon particles, Raw and 24-h lung retention correlated significantly. Retention at 24 h was markedly lower when bronchoconstriction was induced before inhalation of the Teflon particles than when bronchoconstriction was induced after, the ranges being 13-24% and 38-68%, respectively. The experimental data agreed well with theoretical data from a lung model wherein the diameters of the airways were varied. The results indicate that the magnitude of bronchoconstriction occurring in real life can protect the alveolar part of the lung by reducing the amount of inhaled particles that deposit there. PMID:6525990

  2. Desempenho de uma escala analógica visual legendada na determinação do grau de dispneia durante teste de broncoespasmo induzido por exercício em crianças e adolescentes asmáticos Performance of a word labeled visual analog scale in determining the degree of dyspnea during exercise-induced bronchoconstriction in children and adolescents with asthma

    OpenAIRE

    Patrícia Bueno Lima; Ilka Lopes Santoro; Lilian Ballini Caetano; Anna Lúcia de Barros Cabral; Ana Luisa Godoy Fernandes

    2010-01-01

    OBJETIVO: Existe uma relação indireta entre a obstrução das vias aéreas em asma e a intensidade de falta de ar (dispneia). Uma escala visual analógica legendada de dispneia com escore de 0-3 pontos tem sido amplamente utilizada na avaliação da broncoconstrição, embora a percepção de tal obstrução seja muito variável. O objetivo deste estudo foi determinar se crianças e adolescentes são capazes de perceber a broncoconstrição aguda induzida por exercício (BAIE), bem como medir o poder discrimin...

  3. Toll-like receptor and tumour necrosis factor dependent endotoxin-induced acute lung injury

    Science.gov (United States)

    Togbe, Dieudonnée; Schnyder-Candrian, Silvia; Schnyder, Bruno; Doz, Emilie; Noulin, Nicolas; Janot, Laure; Secher, Thomas; Gasse, Pamela; Lima, Carla; Coelho, Fernando Rodrigues; Vasseur, Virginie; Erard, François; Ryffel, Bernhard; Couillin, Isabelle; Moser, Rene

    2007-01-01

    Recent studies on endotoxin/lipopolysaccharide (LPS)-induced acute inflammatory response in the lung are reviewed. The acute airway inflammatory response to inhaled endotoxin is mediated through Toll-like receptor 4 (TLR4) and CD14 signalling as mice deficient for TLR4 or CD14 are unresponsive to endotoxin. Acute bronchoconstriction, tumour necrosis factor (TNF), interleukin (IL)-12 and keratinocyte-derived chemokine (KC) production, protein leak and neutrophil recruitment in the lung are abrogated in mice deficient for the adaptor molecules myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adaptor protein (TIRAP), but independent of TIR-domain-containing adaptor-inducing interferon-beta (TRIF). In particular, LPS-induced TNF is required for bronchoconstriction, but dispensable for inflammatory cell recruitment. Lipopolysaccharide induces activation of the p38 mitogen-activated protein kinase (MAPK). Inhibition of pulmonary MAPK activity abrogates LPS-induced TNF production, bronchoconstriction, neutrophil recruitment into the lungs and broncho-alveolar space. In conclusion, TLR4-mediated, bronchoconstriction and acute inflammatory lung pathology to inhaled endotoxin are dependent on TLR4/CD14/MD2 expression using the adapter proteins TIRAP and MyD88, while TRIF, IL-1R1 or IL-18R signalling pathways are dispensable. Further downstream in this axis of signalling, TNF blockade reduces only acute bronchoconstriction, while MAPK inhibition abrogates completely endotoxin-induced inflammation. PMID:18039275

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

    Science.gov (United States)

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

    1994-04-01

    The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release.

  5. 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

  6. Regulation of actin dynamics by wnt-5a : Implications for human airway smooth muscle contraction

    NARCIS (Netherlands)

    Koopmans, Tim; Kumawat, Kuldeep; Menzen, Mark; Halayko, Andrew; Gosens, Reinoud

    2016-01-01

    An important pathophysiological feature of asthma is airway hyperresponsiveness (AHR), characterized by exaggerated bronchoconstriction in which the airway smooth muscle (ASM) is fundamentally involved. How the ASM in asthmatics differs from that in non-asthmatics is a current focus for research. We

  7. Exercise for Asthma Patients. Little Risk, Big Rewards.

    Science.gov (United States)

    Disabella, Vincent; Sherman, Carl

    1998-01-01

    Asthma patients can benefit from 20 to 30 minutes of exercise at 60 to 85% of maximum heart rate several times a week. Improved fitness can reduce airway reactivity and medication use. The capacity to exercise requires good general control of asthma. Patients must learn to prevent exercise-induced bronchoconstriction by using inhaled medications…

  8. 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...

  9. 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...

  10. Chest physical therapy in acute viral bronchiolitis: an updated review.

    Science.gov (United States)

    Postiaux, Guy; Zwaenepoel, Bruno; Louis, Jacques

    2013-09-01

    We describe the various therapies for infant acute viral bronchiolitis and the contradictory results obtained with chest physical therapy. The treatment target is bronchial obstruction, which is a multifactorial phenomenon that includes edema, bronchoconstriction, and increased mucus production, with a clinical grading defined as severe, moderate, or mild. Chest physical therapy is revisited in its various modalities, according to preliminary scoring of the disease.

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

    Science.gov (United States)

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

    1994-04-01

    The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release. PMID:10184318

  12. Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children

    OpenAIRE

    Kidon Mona; Kang Liew; Chin Chiang; Hoon Lim; Hugo,, Argentiniensis, (ca. 1210-ca. 1270)

    2007-01-01

    Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA)-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction af...

  13. A new perspective on muscarinic receptor antagonism in obstructive airways diseases

    NARCIS (Netherlands)

    Meurs, Herman; Oenema, Tjitske A.; Kistemaker, Loes E. M.; Gosens, Reinoud

    2013-01-01

    Acetylcholine has traditionally only been regarded as a neurotransmitter of the parasympathetic nervous system, causing bronchoconstriction and mucus secretion in asthma and COPD by muscarinic receptor activation on airway smooth muscle and mucus-producing cells. Recent studies in experimental model

  14. Rho-kinase as a drug target for the treatment of airway hyperresponsiveness in asthma

    NARCIS (Netherlands)

    Gosens, R; Schaafsma, D; Nelemans, SA; Halayko, AJ

    2006-01-01

    In asthma, inflammatory and structural cells contribute to increased bronchoconstriction acutely and more chronically to airway remodelling. Current asthma therapy doesn't inhibit these features satisfactorily. This review discusses Rho-kinase as a potential drug target, since increasing evidence su

  15. Asthma in elite athletes: pathogenesis, diagnosis, differential diagnoses, and treatment

    DEFF Research Database (Denmark)

    Pedersen, Lars; Elers, Jimmi; Backer, Vibeke

    2011-01-01

    Elite athletes have a high prevalence of asthma and exercise-induced bronchoconstriction. Although respiratory symptoms can be suggestive of asthma, the diagnosis of asthma in elite athletes cannot be based solely on the presence or absence of symptoms; diagnosis should be based on objective meas...... athletes with asthma, anti-doping regulations, and differential diagnoses such as exercise-induced laryngomalacia are discussed....

  16. Effect of an intranasal conrticosteroid on exercide induced bronchocostriction in asthmatic children

    NARCIS (Netherlands)

    Kersten, E.T.; Leeuwen, J.C. van; Brand, P.L.; Duiverman, E.J.; Jongh, de F.H.C.; Thio, B.J.; Driessen, J.M.

    2012-01-01

    Rationale: Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children. Methods: This was a double-blin

  17. Precipitating factors of asthma.

    Science.gov (United States)

    Lee, T H

    1992-01-01

    Asthma is characterised by bronchial hyperresponsiveness. This feature of the asthmatic diathesis predisposes patients to wheezing in response to a number of different factors. These precipitating factors include specific allergen acting via sensitised mediator cells through an IgE-dependent mechanism. There are irritants which may work through a non-specific manner, or stimuli such as exercise and hyperventilation, which probably also act through mediator release via a non-IgE-dependent manner. The mechanism whereby physical stimuli such as exercise induce bronchoconstriction is of interest, because it increases the context in which the mast cell may participate in acute asthmatic bronchoconstriction. Respiratory infections also commonly provoke asthma, especially in infants and may, indeed, precipitate the asthmatic state itself. Finally, drugs can often trigger asthma attacks and the mechanisms of asthma precipitated by non-steroidal anti-inflammatory drugs such as aspirin have been the subject of recent research.

  18. 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...

  19. Utilization of pressure-volume curves in the pediatric patient.

    Science.gov (United States)

    Bone, R C; Jantzen, D; Heithold, R

    1978-04-01

    Seven patients treated with continuous mechanical ventialtion were monitored with static and dynamic pressure-volume curves. Three patients developed no pulmonary complications, and mechanical ventilation was discontinued within 96 hr. In four patients, pressure-volume curves were used as a diagnostic aid in the detection of the physiologic defect resulting from bronchoconstriction, atelectasis, loculated pleural fluid, pulmonary edema, and mucous plugging. These measurements were also utilized to evaluate the effectivess of therapeutic modalities such as treatment of bronchoconstriction with bronchodilators, mucous plugging with adequate suctioning, and drainage of loculated pleural effusion. Pressure-v-lume measurements are simple, noninvasive, and require the smae equipment used in continuous mechanical ventilation. Pressure-volume monitoring of pediatric patients with curves warrants further investigation to evaluate its value.

  20. 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

  1. Eosinophils and their Interactions with Respiratory Virus Pathogens

    OpenAIRE

    Rosenberg, Helene F; Dyer, Kimberly D.; Domachowske, Joseph B.

    2009-01-01

    Eosinophils are implicated in the pathophysiology of respiratory virus infection, most typically in negative roles, such as promoting wheezing and bronchoconstriction in conjunction with virus-induced exacerbations of reactive airways disease and in association with aberrant hypersensitivity responses to antiviral vaccines. However, experiments carried out in vitro and in vivo suggest positive roles for eosinophils, as they have been shown to reduce virus infectivity in tissue culture and pro...

  2. Studies on neuroimmune interactions in allergic inflammation with focus on neurotrophins

    OpenAIRE

    Kemi, Cecilia

    2006-01-01

    Allergic asthma is a chronic airway disease characterized by an eosinophilic inflammation, bronchoconstriction, increased mucus production and bronchial hyperreactivity. The disease involves several mediators and cell types and is associated with a Th2-mediated immune response. Stress is a factor reported to deteriorate the allergic inflammation. Stress can influence the immune system by activating the HPA axis, resulting in release of glucocorticoids which could effects...

  3. The association of forced expiratory volume in one second and forced expiratory flow at 50% of the vital capacity, peak expiratory flow parameters, and blood eosinophil counts in exercise-induced bronchospasm in children with mild asthma

    OpenAIRE

    Akar, H. Haluk; Tahan, Fulya; Gungor, Hatice Eke

    2015-01-01

    Background Exercise-induced bronchoconstriction (EIB), which describes acute airway narrowing that occurs as a result of exercise, is associated with eosinophilic airway inflammation, bronchial hyperresponsiveness. The forced expiratory volume in one second (FEV1) is the most commonly used spirometric test in the diagnosis of EIB in exercise challenge in asthma. Other parameters such as forced expiratory flow at 50% of the vital capacity (FEF50%) and peak expiratory flow (PEF) are used less o...

  4. The efficacy of a comprehensive lifestyle modification programme based on yoga in the management of bronchial asthma: a randomized controlled trial

    OpenAIRE

    Bijlani Ramesh; Vempati Ramaprabhu; Deepak Kishore

    2009-01-01

    Abstract Background There is a substantial body of evidence on the efficacy of yoga in the management of bronchial asthma. Many studies have reported, as the effects of yoga on bronchial asthma, significant improvements in pulmonary functions, quality of life and reduction in airway hyper-reactivity, frequency of attacks and medication use. In addition, a few studies have attempted to understand the effects of yoga on exercise-induced bronchoconstriction (EIB) or exercise tolerance capacity. ...

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

    OpenAIRE

    JohnDanielBrannan; M. DianeLougheed

    2012-01-01

    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 sm...

  6. 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...

  7. Effects of dynamic compression on lentiviral transduction in an in vitro airway wall model

    OpenAIRE

    Tomei, A. A.; Choe, M. M.; Swartz, M. A.

    2008-01-01

    Asthmatic patients are more susceptible to viral infection, and we asked whether dynamic strain on the airway wall (such as that associated with bronchoconstriction) would influence the rate of viral infection of the epithelial and subepithelial cells. To address this, we characterized the barrier function of a three-dimensional culture model of the bronchial airway wall mucosa, modified the culture conditions for optimization of ciliogenesis, and compared epithelial and subepithelial green f...

  8. Special considerations for adolescent athletic and asthmatic patients

    OpenAIRE

    Wuestenfeld JC; Wolfarth B

    2013-01-01

    Jan C Wuestenfeld,1,2 Bernd Wolfarth1,21Department of Preventive and Rehabilitative Sports Medicine, Technical University Munich (TUM), Munich, Germany; 2Institute for Applied Training Science (IAT), Leipzig, GermanyAbstract: Asthma is defined as a chronic inflammatory disorder of the airways with bronchial hyperresponsiveness and variable bronchoconstriction, and is one of the most common diseases in childhood and adolescence. Exercise-induced asthma-like symptoms and asthma are also frequen...

  9. Relationship between surfactant alterations and severity of disease in horses with recurrent airway obstruction (RAO).

    OpenAIRE

    Christmann, Undine

    2008-01-01

    Pulmonary surfactant is synthesized in the alveoli and lines the respiratory epithelium of the airways. Phospholipids, the main component of surfactant, confer it its ability to lower surface tension and to prevent alveolar collapse. Airway surfactant helps maintain smaller airway patency, improves muco-ciliary clearance, decreases bronchoconstriction, and modulates pulmonary immunity. Surfactant alterations in human asthma are therefore believed to contribute to the severity of airway obstr...

  10. Anstrengelsesutløst astma hos barn og ungdom : En oversiktsartikkel

    OpenAIRE

    2012-01-01

    This review concerns the challenge of growing prevalence of exercise-induced asthma (EIA) in physically active children and adolescents. The article will encompass both mechanisms for developing exercise-induced asthma and bronchoconstriction in children and young athletes and how to manage these symptoms, as well as the epidemiology, diagnosis and treatment. EIA occurs in up to 70-80% percent of asthmatics and 8,6% of Norwegian 10-year-olds in the general population. The severity of th...

  11. Relation between the bronchial obstructive response to inhaled lipopolysaccharide and bronchial responsiveness to histamine.

    OpenAIRE

    Michel, O; Ginanni, R; Sergysels, R

    1992-01-01

    BACKGROUND: Bronchoconstriction has developed after inhalation of lipopolysaccharide in a dose of 20 micrograms in asthmatic patients and of 200 micrograms in normal subjects. This study set out to determine whether the bronchial response to lipopolysaccharide was related to non-specific bronchial responsiveness and atopy. METHODS: Sixteen subjects with a fall in specific airway conductance of 40% (PD40sGaw) after inhaling up to 900 micrograms histamine inhaled 20 micrograms lipopolysaccharid...

  12. Perception of bronchial obstruction in asthmatic patients. Relationship with bronchial eosinophilic inflammation and epithelial damage and effect of corticosteroid treatment.

    OpenAIRE

    Roisman, G L; Peiffer, C; Lacronique, J. G.; Le Cae, A; Dusser, D J

    1995-01-01

    We studied the perception of bronchoconstriction in asthmatic subjects who were randomly treated with inhaled beta 2 agonist given either alone (n = 9) or associated with inhaled corticosteroids (n = 9). Methacholine and bradykinin challenges, bronchoalveolar lavage, and bronchial biopsies were performed in all subjects. After each dose of agonist, breathlessness was assessed using a visual analog scale (VAS) and the forced expiratory volume in 1 s (FEV1) was measured. The relationship betwee...

  13. H2-receptor blockade and exercise-induced asthma.

    OpenAIRE

    Nogrady, S G; Hahn, A G

    1984-01-01

    While in vitro studies suggest that H2-receptor blockade enhances mediator release from bronchial mast cells and leads to bronchoconstriction, in vivo studies have given conflicting results. Eight asthmatic subjects were given cimetidine 800 mg and placebo double-blind on different days. Baseline values of forced expiratory volume in one second (FEV1) were obtained before an 8 min standardized exercise test using a bicycle ergometer. Subjects inhaled cold, dry air and exercise on cimetidine a...

  14. β2 agonists in athletes. An ergogenic aid? = β2 agonistas en deportistas. ¿Una ayuda ergogénica?

    OpenAIRE

    Ospina Uribe, Carlos Fernando

    2013-01-01

    Asthma is a chronic disorder of the airways with bronchial hyperresponsiveness and bronchoconstriction. Exercise can trigger asthma symptoms; this condition is known as exerciseinduced bronchospasm (EIB). Asthma is common in Olympic athletes who therefore use β2 agonists to prevent and treat its episodes. These drugs are preferably supplied by inhalation. In sports, the use of β2 agonists is restricted by anti-doping regulation, arguing that these drugs have the potential to improve physical ...

  15. Effects of dexmedetomidine on oxygenation and lung mechanics in patients with moderate chronic obstructive pulmonary disease undergoing lung cancer surgery

    OpenAIRE

    Lee, Su Hyun; Kim, Namo; Lee, Chang Yeong; Ban, Min Gi; Oh, Young Jun

    2015-01-01

    BACKGROUND Chronic obstructive pulmonary disease (COPD) is a risk factor that increases the incidence of postoperative cardiopulmonary morbidity and mortality after lung resection. Dexmedetomidine, a selective α2-adrenoreceptor agonist, has been reported previously to attenuate intrapulmonary shunt during one-lung ventilation (OLV) and to alleviate bronchoconstriction. OBJECTIVE The objective is to determine whether dexmedetomidine improves oxygenation and lung mechanics in patients with mode...

  16. Initial Evaluation of the Effects of Aerosolized Florida Red Tide Toxins (Brevetoxins) in Persons with Asthma

    OpenAIRE

    Fleming, Lora E.; Kirkpatrick, Barbara; Backer, Lorraine C.; Bean, Judy A.; Wanner, Adam; Dalpra, Dana; Tamer, Robert; Zaias, Julia; Cheng, Yung Sung; Pierce, Richard; Naar, Jerome; Abraham, William; Clark, Richard; Zhou, Yue; Henry, Michael S.

    2005-01-01

    Florida red tides annually occur in the Gulf of Mexico, resulting from blooms of the marine dinoflagellate Karenia brevis. K. brevis produces highly potent natural polyether toxins, known as brevetoxins, that activate voltage-sensitive sodium channels. In experimental animals, brevetoxins cause significant bronchoconstriction. A study of persons who visited the beach recreationally found a significant increase in self-reported respiratory symptoms after exposure to aerosolized Florida red tid...

  17. Improvement of ventilatory function by spa therapy in patients with intractable asthma.

    OpenAIRE

    Tanizaki,Yoshiro

    1986-01-01

    Twenty-five patients with intractable asthma had swimming training in a hot spring pool for 3 months. The subjects were divided into three groups according to their clinical symptoms and ages. Changes of ventilatory function during swimming training were observed in in each group. The ventilatory function test revealed that free swimming training in a hot spring pool for 30 min did not induce bronchoconstriction in any of the groups. The values of ventilatory parameters such as FEV 1.0%, %PEF...

  18. Airway Hyperresponsiveness in Asthma: Mechanisms, Clinical Significance, and Treatment

    OpenAIRE

    Brannan, John D; Lougheed, M Diane

    2012-01-01

    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 in both adults and children. 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 specifi...

  19. 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+...

  20. Activation of the D prostanoid 1 receptor suppresses asthma by modulation of lung dendritic cell function and induction of regulatory T cells

    OpenAIRE

    Hammad, Hamida; Kool, Mirjam; Soullié, Thomas; Narumiya, Shuh; Trottein, François; Hoogsteden, Henk C.; Lambrecht, Bart N.

    2007-01-01

    Prostaglandins (PGs) can enhance or suppress inflammation by acting on different receptors expressed by hematopoietic and nonhematopoietic cells. Prostaglandin D2 binds to the D prostanoid (DP)1 and DP2 receptor and is seen as a critical mediator of asthma causing vasodilation, bronchoconstriction, and inflammatory cell influx. Here we show that inhalation of a selective DP1 agonist suppresses the cardinal features of asthma by targeting the function of lung dendritic cells (DCs). In mice tre...

  1. A novel model of IgE-mediated passive pulmonary anaphylaxis in rats.

    Science.gov (United States)

    Wex, Eva; Thaler, Eva; Blum, Sylvia; Lamb, David

    2014-01-01

    Mast cells are central effector cells in allergic asthma and are augmented in the airways of asthma patients. Attenuating mast cell degranulation and with it the early asthmatic response is an important intervention point to inhibit bronchoconstriction, plasma exudation and tissue oedema formation. To validate the efficacy of novel pharmacological interventions, appropriate and practicable in vivo models reflecting mast cell-dependent mechanisms in the lung, are missing. Thus, we developed a novel model of passive pulmonary anaphylaxis in rats. Rats were passively sensitized by concurrent intratracheal and intradermal (ear) application of an anti-DNP IgE antibody. Intravenous application of the antigen, DNP-BSA in combination with Evans blue dye, led to mast cell degranulation in both tissues. Quantification of mast cell degranulation in the lung was determined by (1) mediator release into bronchoalveolar lavage, (2) extravasation of Evans blue dye into tracheal and bronchial lung tissue and (3) invasive measurement of antigen-induced bronchoconstriction. Quantification of mast cell degranulation in the ear was determined by extravasation of Evans blue dye into ear tissue. We pharmacologically validated our model using the SYK inhibitor Fostamatinib, the H1-receptor antagonist Desloratadine, the mast cell stabilizer disodium cromoglycate (DSCG) and the β2-adrenergic receptor agonist Formoterol. Fostamatinib was equally efficacious in lung and ear. Desloratadine effectively inhibited bronchoconstriction and ear vascular leakage, but was less effective against pulmonary vascular leakage, perhaps reflecting the differing roles for histamine receptor sub-types. DSCG attenuated both vascular leakage in the lung and bronchoconstriction, but with a very short duration of action. As an inhaled approach, Formoterol was more effective in the lung than in the ear. This model of passive pulmonary anaphylaxis provides a tissue relevant readout of early mast cell activity and

  2. A Novel Model of IgE-Mediated Passive Pulmonary Anaphylaxis in Rats

    OpenAIRE

    Eva Wex; Eva Thaler; Sylvia Blum; David Lamb

    2014-01-01

    Mast cells are central effector cells in allergic asthma and are augmented in the airways of asthma patients. Attenuating mast cell degranulation and with it the early asthmatic response is an important intervention point to inhibit bronchoconstriction, plasma exudation and tissue oedema formation. To validate the efficacy of novel pharmacological interventions, appropriate and practicable in vivo models reflecting mast cell-dependent mechanisms in the lung, are missing. Thus, we developed a ...

  3. It’s scary, scary, scary …”: the lived experience of asthma.

    OpenAIRE

    Allen-Collinson, Jacquelyn; Owton, Helen; Siriwardena, Aloysius Niroshan

    2015-01-01

    The research presented here contributes to a developing sociological-phenomenological empirical corpus of literature by addressing the lived experience of asthma in non-élite sports participants and committed exercisers. Despite the prevalence of asthma and exercise-induced asthma/bronchoconstriction, there is a distinct lacuna in terms of qualitative research into living with asthma, and specifically in relation to participation in sports and physical cultures. Here we focus upon the aural d...

  4. Effects of inhaled acid aerosols on lung mechanics: an analysis of human exposure studies.

    OpenAIRE

    Utell, M J

    1985-01-01

    There exist significant gaps in our understanding of human health effects from inhalation of pollutants associated with acid precipitation. Controlled clinical studies examine effects of criteria pollutants almost exclusively by assessing changes in lung mechanics. One constituent of acid precipitation, sulfuric acid aerosols, has been shown to induce bronchoconstriction in exercising extrinsic asthmatics at near ambient levels. These asthmatics may be an order of magnitude more sensitive to ...

  5. A novel model of IgE-mediated passive pulmonary anaphylaxis in rats.

    Science.gov (United States)

    Wex, Eva; Thaler, Eva; Blum, Sylvia; Lamb, David

    2014-01-01

    Mast cells are central effector cells in allergic asthma and are augmented in the airways of asthma patients. Attenuating mast cell degranulation and with it the early asthmatic response is an important intervention point to inhibit bronchoconstriction, plasma exudation and tissue oedema formation. To validate the efficacy of novel pharmacological interventions, appropriate and practicable in vivo models reflecting mast cell-dependent mechanisms in the lung, are missing. Thus, we developed a novel model of passive pulmonary anaphylaxis in rats. Rats were passively sensitized by concurrent intratracheal and intradermal (ear) application of an anti-DNP IgE antibody. Intravenous application of the antigen, DNP-BSA in combination with Evans blue dye, led to mast cell degranulation in both tissues. Quantification of mast cell degranulation in the lung was determined by (1) mediator release into bronchoalveolar lavage, (2) extravasation of Evans blue dye into tracheal and bronchial lung tissue and (3) invasive measurement of antigen-induced bronchoconstriction. Quantification of mast cell degranulation in the ear was determined by extravasation of Evans blue dye into ear tissue. We pharmacologically validated our model using the SYK inhibitor Fostamatinib, the H1-receptor antagonist Desloratadine, the mast cell stabilizer disodium cromoglycate (DSCG) and the β2-adrenergic receptor agonist Formoterol. Fostamatinib was equally efficacious in lung and ear. Desloratadine effectively inhibited bronchoconstriction and ear vascular leakage, but was less effective against pulmonary vascular leakage, perhaps reflecting the differing roles for histamine receptor sub-types. DSCG attenuated both vascular leakage in the lung and bronchoconstriction, but with a very short duration of action. As an inhaled approach, Formoterol was more effective in the lung than in the ear. This model of passive pulmonary anaphylaxis provides a tissue relevant readout of early mast cell activity and

  6. A novel model of IgE-mediated passive pulmonary anaphylaxis in rats.

    Directory of Open Access Journals (Sweden)

    Eva Wex

    Full Text Available Mast cells are central effector cells in allergic asthma and are augmented in the airways of asthma patients. Attenuating mast cell degranulation and with it the early asthmatic response is an important intervention point to inhibit bronchoconstriction, plasma exudation and tissue oedema formation. To validate the efficacy of novel pharmacological interventions, appropriate and practicable in vivo models reflecting mast cell-dependent mechanisms in the lung, are missing. Thus, we developed a novel model of passive pulmonary anaphylaxis in rats. Rats were passively sensitized by concurrent intratracheal and intradermal (ear application of an anti-DNP IgE antibody. Intravenous application of the antigen, DNP-BSA in combination with Evans blue dye, led to mast cell degranulation in both tissues. Quantification of mast cell degranulation in the lung was determined by (1 mediator release into bronchoalveolar lavage, (2 extravasation of Evans blue dye into tracheal and bronchial lung tissue and (3 invasive measurement of antigen-induced bronchoconstriction. Quantification of mast cell degranulation in the ear was determined by extravasation of Evans blue dye into ear tissue. We pharmacologically validated our model using the SYK inhibitor Fostamatinib, the H1-receptor antagonist Desloratadine, the mast cell stabilizer disodium cromoglycate (DSCG and the β2-adrenergic receptor agonist Formoterol. Fostamatinib was equally efficacious in lung and ear. Desloratadine effectively inhibited bronchoconstriction and ear vascular leakage, but was less effective against pulmonary vascular leakage, perhaps reflecting the differing roles for histamine receptor sub-types. DSCG attenuated both vascular leakage in the lung and bronchoconstriction, but with a very short duration of action. As an inhaled approach, Formoterol was more effective in the lung than in the ear. This model of passive pulmonary anaphylaxis provides a tissue relevant readout of early mast cell

  7. The ventilatory effect of external oscillation.

    Science.gov (United States)

    Isabey, D; Piquet, J

    1989-01-01

    High frequency ventilation (HFV) may be achieved by external oscillation (external HFV) applied around the chest wall (HFCWO) in large animals and humans, or over the entire body (HFBSO) in small animals, instead of being applied via the trachea (internal HFV). We present a synthesis of the results obtained with external HFV in both normal and bronchoconstricted subjects. Whereas external and internal HFV were found to be equivalent in terms of gas exchange in normal rats, external HFV was found to have a beneficial effect in bronchoconstricted rabbits, but internal HFV did not. From the frequency-oscillatory tidal volume relationship determined in normocapnic rabbits, HFBSO at 5 Hz was found to be the optimal frequency at which to ventilate with tidal volumes close to the dead space volume, and which was also shown to be the optimal volume to obtain normocapnia. Moreover, 5 Hz oscillations (HFCWO) at 20 ml and 40 ml superimposed on tidal breathing accelerated nitrogen washout, i.e., gas exchange in normal humans. Unfortunately, only oscillations with much smaller volumes (5-10 ml) were obtainable in COPD patients. Nevertheless, they produced a clear change in breathing pattern associated with a slight improvement in gas exchange and a potentially positive effect on inspiratory muscle fatigue. These results support the concept that non-invasive external HFV technique may be of use in assisting ventilation in bronchoconstricted subjects and may possibly replace conventional controlled ventilation, at least in subjects with high lung compliance, such as babies, neonates and normal adults.

  8. Structure Activity Relationship of Brevenal Hydrazide Derivatives

    Directory of Open Access Journals (Sweden)

    Allan Goodman

    2014-03-01

    Full Text Available Brevenal is a ladder frame polyether produced by the dinoflagellate Karenia brevis. This organism is also responsible for the production of the neurotoxic compounds known as brevetoxins. Ingestion or inhalation of the brevetoxins leads to adverse effects such as gastrointestinal maladies and bronchoconstriction. Brevenal shows antagonistic behavior to the brevetoxins and shows beneficial attributes when administered alone. For example, in an asthmatic sheep model, brevenal has been shown to increase tracheal mucosal velocity, an attribute which has led to its development as a potential treatment for Cystic Fibrosis. The mechanism of action of brevenal is poorly understood and the exact binding site has not been elucidated. In an attempt to further understand the mechanism of action of brevenal and potentially develop a second generation drug candidate, a series of brevenal derivatives were prepared through modification of the aldehyde moiety. These derivatives include aliphatic, aromatic and heteroaromatic hydrazide derivatives. The brevenal derivatives were tested using in vitro synaptosome binding assays to determine the ability of the compounds to displace brevetoxin and brevenal from their native receptors. A sheep inhalation model was used to determine if instillation of the brevenal derivatives resulted in bronchoconstriction. Only small modifications were tolerated, with larger moieties leading to loss of affinity for the brevenal receptor and bronchoconstriction in the sheep model.

  9. Gender and perception of dyspnea: The role of the variation in the forced expiratory volume in one second

    Directory of Open Access Journals (Sweden)

    Carlos A. Nigro

    2010-08-01

    Full Text Available During bronchoconstriction women perceive more breathlessness than men. The aims of study were 1 to evaluate if quality of dyspnea in bronchoconstriction was different in women and men 2 to assess if gender difference in the perception of dyspnea could be related to the level of bronchoconstriction. 457 subjects (257 women inhaled methacholine to a 20% decrease in FEV1, or 32 mg/ml. Dyspnea was evaluated using the modified Borg scale and a list of expressions of dyspnea. Borg scores were recorded immediately before the challenge test baseline and at the maximum FEV1 decrease. The prevalence of descriptors of dyspnea reported by women and men was similar. Dyspnea was related to the level of FEV1 (ΔFEV1: OR 1.05, 95%CI 1.01-1.09, p 0.0095, females (OR 2.90, 95%CI 1.33-6.33, p 0.0072, younger subjects (OR 0.93, 95%CI 0.89- 0.97, p 0.0013 and body mass index (BMI (OR 1.11, 95%CI 1.01-1.23, p 0.023. As the FEV1 fell less than 20% from baseline, only the ΔFEV1 was significantly associated with dyspnea (ΔFEV1:OR 1.15, 95%CI 1.07- 1.24, p 0.0002. Instead, if the FEV1 fell higher ≥ 20%, the presence of dyspnea was related to the degree of bronchoconstriction (ΔFEV1: OR 1.04, 95%CI 1.01-1.09, p 0.0187, females (OR 3.02, 95%CI 1.36-6.72, p 0.0067, younger subjects (OR 0.92, 95%CI 0.88-0.96, p 0.0007 and BMI (OR 1.12, 95%CI 1.01-1.23, p 0.023. The quality of dyspnea during the bronchoconstriction was similar in women and men; women showed a higher perception of dyspnea than men only when the FEV1 fell more than 20% from baseline.

  10. Effect of inhaled furosemide and torasemide on bronchial response to ultrasonically nebulized distilled water in asthmatic subjects.

    Science.gov (United States)

    Foresi, A; Pelucchi, A; Mastropasqua, B; Cavigioli, G; Carlesi, R M; Marazzini, L

    1992-08-01

    Inhaled furosemide has been shown to reduce the bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Because the protective effect could be due to the inhibition of the Na(+)-2Cl(-)-K+ cotransport system of bronchial epithelium, we have compared the protective effect of inhaled furosemide with that of inhaled torasemide, a new and more potent loop diuretic, on UNDW-induced bronchoconstriction in a group of 12 asthmatic subjects. UNDW challenge was performed by constructing a stimulus-response curve with five increasing volume outputs of distilled water (from 0.5 to 5.2 ml/min) and the bronchial response expressed as the provocative output causing a 20% fall in FEV1 (PO20UNDW). On different days, each subject inhaled an equal dose (28 mg) of furosemide and torasemide in a randomized, double-blind, placebo-controlled study 5 min prior to an UNDW challenge. Furosemide and torasemide had no significant effect on resting lung function. The geometric mean value of PO20UNDW measured after placebo was 1.73 ml/min. This was significantly lower than that recorded after furosemide (4.25 ml/min; p < 0.025), but not after torasemide (3.05 ml/min; p = 0.07). Inhaled furosemide totally blocked bronchial response to UNDW in five subjects. In two of five subjects the response was also blocked by inhaled torasemide. A remarkable increase in diuresis was noted only after torasemide in most subjects. We conclude that inhaled furosemide has a better protective effect than does inhaled torasemide against UNDW-induced bronchoconstriction. However, the protective effect of furosemide is variable, with some asthmatic patients showing no change in bronchial response to UNDW.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1489126

  11. Exercise and asthma: an overview.

    Science.gov (United States)

    Del Giacco, Stefano R; Firinu, Davide; Bjermer, Leif; Carlsen, Kai-Håkon

    2015-01-01

    The terms 'exercise-induced asthma' (EIA) and 'exercise-induced bronchoconstriction' (EIB) are often used interchangeably to describe symptoms of asthma such as cough, wheeze, or dyspnoea provoked by vigorous physical activity. In this review, we refer to EIB as the bronchoconstrictive response and to EIA when bronchoconstriction is associated with asthma symptoms. EIB is a common occurrence for most of the asthmatic patients, but it also affects more than 10% of otherwise healthy individuals as shown by epidemiological studies. EIA and EIB have a high prevalence also in elite athletes, especially within endurance type of sports, and an athlete's asthma phenotype has been described. However, the occurrence in elite athletes shows that EIA/EIB, if correctly managed, may not impair physical activity and top sports performance. The pathogenic mechanisms of EIA/EIB classically involve both osmolar and vascular changes in the airways in addition to cooling of the airways with parasympathetic stimulation. Airways inflammation plays a fundamental role in EIA/EIB. Diagnosis and pharmacological management must be carefully performed, with particular consideration of current anti-doping regulations, when caring for athletes. Based on the demonstration that the inhaled asthma drugs do not improve performance in healthy athletes, the doping regulations are presently much less strict than previously. Some sports are at a higher asthma risk than others, probably due to a high environmental exposure while performing the sport, with swimming and chlorine exposure during swimming as one example. It is considered very important for the asthmatic child and adolescent to master EIA/EIB to be able to participate in physical activity on an equal level with their peers, and a precise early diagnosis with optimal treatment follow-up is vital in this aspect. In addition, surprising recent preliminary evidences offer new perspectives for moderate exercise as a potential therapeutic tool for

  12. Asthma pharmacotherapy.

    Science.gov (United States)

    Schofield, Minka L

    2014-02-01

    Asthma is a chronic inflammatory disease of the airway that leads to airway obstruction via bronchoconstriction, edema, and mucus hypersecretion. The National Asthma Education and Prevention Program has outlined evidence-based guidelines to standardize asthma therapy and improve outcomes. The initial recommendation of choice for persistent asthmatic patients is an inhaled corticosteroid (ICS). Long-acting beta-2 agonists in combination with ICS, oral corticosteroids, leukotriene modifiers, and anti-IgE therapeutic options can be considered for patients with persistent or worsening symptoms. Many novel therapies are being developed, with an emphasis on anti-inflammatory mechanisms, gene expression, and cytokine modification.

  13. Can resistive breathing injure the lung? Implications for COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Vassilakopoulos T

    2016-09-01

    Full Text Available Theodoros Vassilakopoulos, Dimitrios Toumpanakis Pulmonary and Critical Care Medicine, Medical School, National and Kapodistrian University of Athens, Greece Abstract: In obstructive lung diseases, airway inflammation leads to bronchospasm and thus resistive breathing, especially during exacerbations. This commentary discusses experimental evidence that resistive breathing per se (the mechanical stimulus in the absence of underlying airway inflammation leads to lung injury and inflammation (mechanotransduction. The potential implications of resistive breathing-induced mechanotrasduction in COPD exacerbations are presented along with the available clinical evidence. Keywords: resistive breathing, COPD, mechanotransduction, bronchoconstriction, inflammation

  14. Rosa canina as an adjunctive treatment of asthma: A hypothesis

    OpenAIRE

    Samin Hamidi; Haleh Vaez; Parina Asgharian

    2015-01-01

    Asthma is one of the most common chronic disorders and about 7% of the US population suffers from asthma. Initial response to allergy is associated with mediators like histamine, prostaglandin (PG) D2 and leukotriene (LT) C4. In asthmatic patients, 5-lipo-oxygenase (5-LO) pathway produces more LTC4 than the healthy people. Also, pro-inflammatory factors like interleukin (IL)-1, IL-6 and Tumor Necrosis Factor (TNF)-α play a remarkable role in bronchoconstriction. The common asthma medications ...

  15. Nonsteroidal Anti-Inflammatory Agents in the Treatment of Asthma in Children

    Directory of Open Access Journals (Sweden)

    Pierre Gaudreault

    1995-01-01

    Full Text Available The increasing scientific information clearly demonstrates the important role of inflammation in asthma. This evidence has led physicians to focus their treatment on the elimination of inflammation instead of working solely against bronchoconstriction. Steroids and nonsteroidal agents are currently used to prevent this inflammatory component. This paper focuses only on nonstcroidal anti-inflammatory agents such as sodium cromoglycate, nedocromil sodium and ketotifen and their use in pediatric asthma. The discussion on each medication addresses its mechanism of action, the evidence concerning its efficacy in pediatrics (ie, clinical pharmacology, acute bronchial challenge, late asthmatic response, bronchial hyperrcactivity, clinical efficacy and the pediatric dose.

  16. Quality of Life in Adolescents With Mild Asthma

    OpenAIRE

    Hallstrand, Teal S.; Curtis, J. Randall; Aitken, Moira L.; Sullivan, Sean D.

    2003-01-01

    The majority of individuals with asthma have mild disease, often in conjunction with allergic rhinitis and exercise-induced bronchoconstriction (EIB). Although health-related quality-of-life (HRQoL) is reduced in moderate to severe asthma and allergic rhinitis, little is known about the effect of mild asthma, mild allergic rhinitis, and EIB on HRQoL outcomes. The objective of this study was to determine the effect of mild asthma, allergic rhinitis, and EIB on HRQoL. A cross-sectional study wa...

  17. 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.

  18. Effects of methacholine infusion on desflurane pharmacokinetics in piglets.

    Science.gov (United States)

    Kozian, Alf; Kretzschmar, Moritz; Baumgardner, James E; Schreiber, Jens; Hedenstierna, Göran; Larsson, Anders; Hachenberg, Thomas; Schilling, Thomas

    2015-12-01

    The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets (n=4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO2 of 0.4, tidal volume (V T)=10 ml/kg and PEEP of 5cmH2O using an open system. The determination of V.A/Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30 min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t-test, and by nonparametric Friedman׳s test and Wilcoxon׳s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and

  19. 4-D segmentation and normalization of 3He MR images for intrasubject assessment of ventilated lung volumes

    Science.gov (United States)

    Contrella, Benjamin; Tustison, Nicholas J.; Altes, Talissa A.; Avants, Brian B.; Mugler, John P., III; de Lange, Eduard E.

    2012-03-01

    Although 3He MRI permits compelling visualization of the pulmonary air spaces, quantitation of absolute ventilation is difficult due to confounds such as field inhomogeneity and relative intensity differences between image acquisition; the latter complicating longitudinal investigations of ventilation variation with respiratory alterations. To address these potential difficulties, we present a 4-D segmentation and normalization approach for intra-subject quantitative analysis of lung hyperpolarized 3He MRI. After normalization, which combines bias correction and relative intensity scaling between longitudinal data, partitioning of the lung volume time series is performed by iterating between modeling of the combined intensity histogram as a Gaussian mixture model and modulating the spatial heterogeneity tissue class assignments through Markov random field modeling. Evaluation of the algorithm was retrospectively applied to a cohort of 10 asthmatics between 19-25 years old in which spirometry and 3He MR ventilation images were acquired both before and after respiratory exacerbation by a bronchoconstricting agent (methacholine). Acquisition was repeated under the same conditions from 7 to 467 days (mean +/- standard deviation: 185 +/- 37.2) later. Several techniques were evaluated for matching intensities between the pre and post-methacholine images with the 95th percentile value histogram matching demonstrating superior correlations with spirometry measures. Subsequent analysis evaluated segmentation parameters for assessing ventilation change in this cohort. Current findings also support previous research that areas of poor ventilation in response to bronchoconstriction are relatively consistent over time.

  20. Effect of N-acetylcysteine on gas exchange after methacholine challenge and isoprenaline inhalation in the dog.

    Science.gov (United States)

    Ueno, O; Lee, L N; Wagner, P D

    1989-03-01

    N-acetylcysteine (NAC) has antioxidant and possibly mucolytic properties. To determine whether NAC could be of benefit in acute bronchoconstriction induced by methacholine, 12 of 24 anaesthetized dogs (group 1) received NAC i.v. (loading dose 150 mg.kg-1, then 20 mg.kg-1.hr-1). The other 12 (group 2) received diluent. Nebulized methacholine (1%) was then inhaled until arterial oxygen tension (PaO2) fell to a mean of 5.5 kPa, after which isoprenaline 0.5% was inhaled in six dogs of each group to reverse bronchoconstriction. Over the next 3 h we measured total lung resistance, functional residual capacity (FRC), haemodynamic variables, and pulmonary gas exchange for respiratory and inert gases. After methacholine challenge, lung resistance increased and then fell similarly for both groups, but PaO2 was higher in the NAC group (by 0.6-1.9 kPa) throughout the observation period. The ventilation-perfusion distribution measured by inert gas elimination also showed less abnormality in the NAC treated dogs over this time. Mucus was visible during post-mortem in the large airways in about half of the dogs in both groups, with no significant differences between them. These results show that NAC produces a measurable improvement in gas exchange following methacholine challenge (both with and without subsequent isoprenaline therapy) by mechanisms that remain to be determined.

  1. 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.

  2. Dietary sodium intake and asthma: an epidemiological and clinical review.

    Science.gov (United States)

    Mickleborough, T D; Fogarty, A

    2006-12-01

    The changes in diet associated with the development of a more affluent lifestyle have been considered one of the environmental factors that may have contributed to the rise in the prevalence of asthma over the past few decades, and dietary sodium has been considered to be a dietary constituent which may be implicated in this phenomenon. The data presented in this review demonstrate that adoption of a low sodium diet for a period of 2-5 weeks may improve lung function and decrease bronchial reactivity in adults with asthma, while sodium loading appears to have a detrimental effect. Similarly, a low sodium diet maintained for 1-2 weeks decreases bronchoconstriction in response to exercise in individuals with asthma. There is no data as to the longer-term effect of a low sodium diet on either the prevalence or severity of asthma or on exercise-induced bronchoconstriction. As a low sodium diet has other beneficial health effects, it can be considered as a therapeutic option for adults with asthma, although it should be considered as an adjunctive intervention to supplement optimal pharmacological management of asthma and not as an alternative. If the relationship between higher sodium intake and increased prevalence and severity of asthma is causal, then there are potential population benefits for asthma as well as cardiovascular disease to be derived from public health measures to reduce sodium consumption. PMID:17109669

  3. Australian association for exercise and sports science position statement on exercise and asthma.

    Science.gov (United States)

    Morton, Alan R; Fitch, Kenneth D

    2011-07-01

    Asthma, a chronic inflammatory disorder of the airways is associated with variable obstruction to the airways and is provoked by many triggers including exercise. The management of asthma is primarily pharmacological, but exercise, despite causing bronchoconstriction in almost all asthmatics, is an important adjunct to treatment. With adequate control of the hyperresponsive airways obtained with inhaled corticosteroids (ICS) and inhaled beta 2 agonists (IBA), used as both a pre-exercise preventive agent and a reliever if necessary, all asthmatics should benefit from an exercise program. Some have realised this benefit with such success as to become Olympic and world champions in many sports. Exercise programs should be individually tailored, follow established guidelines and result in similar benefits to those obtained by non-asthmatics. However asthmatics must try to avoid or minimise triggers whenever possible. A specific benefit of a physical training program is that it allows asthmatics to exercise with less bronchoconstriction at the same exercise stress, although it does not abolish or reduce airway hyperresponsiveness (AHR). PMID:21440499

  4. Antagonistic activity of etizolam on platelet-activating factor in vivo experiments.

    Science.gov (United States)

    Terasawa, M; Mikashima, H; Tahara, T; Maruyama, Y

    1987-08-01

    The ability of etizolam, 6-(o-chlorophenyl)-8-ethyl-1-methyl-4H-s-triazolo[3,4-c]thieno[2,3-e] [1,4]diazepine (Y-7131), an anti-anxiety drug, to inhibit platelet-activating factor (PAF)-induced reactions was investigated in experimental animals in vivo. Etizolam (0.01-0.3 mg/kg, i.v.) dose dependently inhibited PAF (0.3 microgram/kg, i.v.)-induced bronchoconstriction (Konzett and Rössler's method) in guinea pigs, but even at doses as large as 3 mg/kg, i.v., it had no effect on bronchoconstriction induced by histamine, serotonin, acetylcholine, arachidonic acid, bradykinin, angiotensin l or leukotriene D4. Etizolam (0.1-1 mg/kg, i.v.) also dose-dependently reversed PAF (1 microgram/kg, i.v.)-induced hypotension in anesthetized rats. Injection of PAF into the tail veins of mice produced lethal shock within 10-30 min. Etizolam (0.1-3 mg/kg, i.v. and 1-10 mg/kg, p.o.) protected against the lethal effect of PAF (75 micrograms/kg, i.v.) in a dose-dependent manner. These results indicate that etizolam specifically inhibits the action of PAF in vivo. PMID:3682404

  5. β2-Adrenoceptor agonist-induced RGS2 expression is a genomic mechanism of bronchoprotection that is enhanced by glucocorticoids.

    Science.gov (United States)

    Holden, Neil S; Bell, Matthew J; Rider, Christopher F; King, Elizabeth M; Gaunt, David D; Leigh, Richard; Johnson, Malcolm; Siderovski, David P; Heximer, Scott P; Giembycz, Mark A; Newton, Robert

    2011-12-01

    In asthma and chronic obstructive pulmonary disease, activation of G(q)-protein-coupled receptors causes bronchoconstriction. In each case, the management of moderate-to-severe disease uses inhaled corticosteroid (glucocorticoid)/long-acting β(2)-adrenoceptor agonist (LABA) combination therapies, which are more efficacious than either monotherapy alone. In primary human airway smooth muscle cells, glucocorticoid/LABA combinations synergistically induce the expression of regulator of G-protein signaling 2 (RGS2), a GTPase-activating protein that attenuates G(q) signaling. Functionally, RGS2 reduced intracellular free calcium flux elicited by histamine, methacholine, leukotrienes, and other spasmogens. Furthermore, protection against spasmogen-increased intracellular free calcium, following treatment for 6 h with LABA plus corticosteroid, was dependent on RGS2. Finally, Rgs2-deficient mice revealed enhanced bronchoconstriction to spasmogens and an absence of LABA-induced bronchoprotection. These data identify RGS2 gene expression as a genomic mechanism of bronchoprotection that is induced by glucocorticoids plus LABAs in human airway smooth muscle and provide a rational explanation for the clinical efficacy of inhaled corticosteroid (glucocorticoid)/LABA combinations in obstructive airways diseases. PMID:22080612

  6. Laboratory studies of biological effects of sulfur oxides

    Energy Technology Data Exchange (ETDEWEB)

    Dalbey, W. E.

    1979-01-01

    Selected results from exposures of laboratory animals to airborne sulfur oxides were briefly summarized. The main observation during acute exposures was reflex bronchoconstriction and a resultant increase in pulmonary resistance. The increase in resistance due to sulfur dioxide (SO/sub 2/) was potentiated by simultaneous exposure to aerosols under conditions which would increase the transfer of sulfur oxides into the respiratory tract and promote transformation to a higher oxidation state, especially one that is acid. Sulfate aerosols, particularly sulfuric acid aerosols, were more potent than SO/sub 2/ in causing bronchoconstriction. Chronic exposure to high concentrations (400 to 650 ppM) of SO/sub 2/ resulted in experimental bronchitis in several species. Longterm exposure to more realistic concentrations of SO/sub 2/ produced little or no changes in respiratory function or morphology. Significant alterations in both pulmonary function and morphology have been reported after chronic exposure to sulfuric acid aerosols. Recent data indicate that changes in the lung may progress after cessation of such exposures.

  7. 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

  8. 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.

  9. Effect of N-acetylcysteine on gas exchange after methacholine challenge and isoprenaline inhalation in the dog.

    Science.gov (United States)

    Ueno, O; Lee, L N; Wagner, P D

    1989-03-01

    N-acetylcysteine (NAC) has antioxidant and possibly mucolytic properties. To determine whether NAC could be of benefit in acute bronchoconstriction induced by methacholine, 12 of 24 anaesthetized dogs (group 1) received NAC i.v. (loading dose 150 mg.kg-1, then 20 mg.kg-1.hr-1). The other 12 (group 2) received diluent. Nebulized methacholine (1%) was then inhaled until arterial oxygen tension (PaO2) fell to a mean of 5.5 kPa, after which isoprenaline 0.5% was inhaled in six dogs of each group to reverse bronchoconstriction. Over the next 3 h we measured total lung resistance, functional residual capacity (FRC), haemodynamic variables, and pulmonary gas exchange for respiratory and inert gases. After methacholine challenge, lung resistance increased and then fell similarly for both groups, but PaO2 was higher in the NAC group (by 0.6-1.9 kPa) throughout the observation period. The ventilation-perfusion distribution measured by inert gas elimination also showed less abnormality in the NAC treated dogs over this time. Mucus was visible during post-mortem in the large airways in about half of the dogs in both groups, with no significant differences between them. These results show that NAC produces a measurable improvement in gas exchange following methacholine challenge (both with and without subsequent isoprenaline therapy) by mechanisms that remain to be determined. PMID:2659384

  10. Protective effect of budesonide/formoterol compared with formoterol, salbutamol and placebo on repeated provocations with inhaled AMP in patients with asthma: a randomised, double-blind, cross-over study

    Directory of Open Access Journals (Sweden)

    van der Woude Hanneke J

    2010-05-01

    Full Text Available Abstract Background The budesonide/formoterol combination is successfully used for fast relief of asthma symptoms in addition to its use as maintenance therapy. The temporarily increased corticosteroid dose during increasing inhaler use for symptom relief is likely to suppress any temporary increase in airway inflammation and may mitigate or prevent asthma exacerbations. The relative contribution of the budesonide and formoterol components to the improved asthma control is unclear. Methods The acute protective effect of inhaled budesonide was tested in a model of temporarily increased airway inflammation with repeated indirect airway challenges, mimicking an acute asthma exacerbation. A randomised, double-blind, cross-over study design was used. Asthmatic patients (n = 17, mean FEV1 95% of predicted who previously demonstrated a ≥30% fall in forced expiratory volume in 1 second (FEV1 after inhaling adenosine 5'-monophosphate (AMP, were challenged on four consecutive test days, with the same dose of AMP (at 09:00, 12:00 and 16:00 hours. Within 1 minute of the maximal AMP-induced bronchoconstriction at 09:00 hours, the patients inhaled one dose of either budesonide/formoterol (160/4.5 μg, formoterol (4.5 μg, salbutamol (2 × 100 μg or placebo. The protective effects of the randomised treatments were assessed by serial lung function measurements over the test day. Results In the AMP provocations at 3 and 7 hours after inhalation, the budesonide/formoterol combination provided a greater protective effect against AMP-induced bronchoconstriction compared with formoterol alone, salbutamol and placebo. In addition all three active treatments significantly increased FEV1 within 3 minutes of administration, at a time when inhaled AMP had induced the 30% fall in FEV1. Conclusions A single dose of budesonide/formoterol provided a greater protective effect against inhaled AMP-induced bronchoconstriction than formoterol alone, both at 3 and at 7 hours

  11. (15S)-15 methyl prostaglandin F2α levels in amniotic fluid and blood in second trimester abortions

    International Nuclear Information System (INIS)

    A single intra-amniotic injection of (15S)-15 methyl prostaglandin F2α (THAM) was used to induce second trimester abortion in five patients. Serial levels of (15S)-15 methyl prostaglandin F2α were subsequently measured in amniotic fluid and plasma by radioimmunoassay. The slow removal of this drug from the amniotic fluid was documented. Plasma levels of (15S)-15 methyl prostaglandin F2α increased fourfold to sevenfold after clinical rupture of the membranes in three patients, supporting the fact that prostaglandins are well absorbed from the vagina. Because this analogue of prostaglandin can cause marked peripheral bronchoconstriction when administered systemically, it is best to avoid its use in patients with a history of asthma

  12. Psychological aspects of asthma.

    Science.gov (United States)

    Lehrer, Paul; Feldman, Jonathan; Giardino, Nicholas; Song, Hye-Sue; Schmaling, Karen

    2002-06-01

    Asthma can be affected by stress, anxiety, sadness, and suggestion, as well as by environmental irritants or allergens, exercise, and infection. It also is associated with an elevated prevalence of anxiety and depressive disorders. Asthma and these psychological states and traits may mutually potentiate each other through direct psychophysiological mediation, nonadherence to medical regimen, exposure to asthma triggers, and inaccuracy of asthma symptom perception. Defensiveness is associated with inaccurate perception of airway resistance and stress-related bronchoconstriction. Asthma education programs that teach about the nature of the disease, medications, and trigger avoidance tend to reduce asthma morbidity. Other promising psychological interventions as adjuncts to medical treatment include training in symptom perception, stress management, hypnosis, yoga, and several biofeedback procedures. PMID:12090377

  13. Role of Asthma Education in the Management of Adult Asthma

    Directory of Open Access Journals (Sweden)

    Johanne Côté

    1995-01-01

    Full Text Available When a patient is newly diagnosed as having asthma, he or she is often prescribed new medication without getting much information on the disease and its treatment. This article emphasizes the need to educate asthmatics. Asthma treatment should begin with a proper adjustment of the medication, allowing asthmatics to lead a normal life. All asthmatics should be shown how to use their inhalation device properly. They should he knowledgeable about the basic aspects of asthma, airway inflammation and bronchoconstriction, use or medication and early symptoms heralding an asthma attack. Environmental factors that may trigger an asthma attack should be explained. Patients should be able to self-monitor asthma using either symptom severity or a peak flow meter. Because asthma is an unpredictable disease, patients should have a self-action plan to implement when their asthma deteriorates.

  14. Postnatal overnutrition in mice leads to impaired pulmonary mechanics in response to salbutamol.

    Science.gov (United States)

    Teixeira, Vanessa P; Cervilha, Daniela A B; Cabral, Layla D M; Oliveira, Luiz M; Incerpi, Erika K; Novaes, Rômulo D; Ionta, Marisa; Soncini, Roseli

    2016-05-01

    Obesity increases the risk of respiratory disease, which is associated with airway hyperresponsiveness. Although the molecular underpinnings of this phenomenon are not well established, lung remodeling is known as an important factor in this process and could potentially explain compromised lung functions. In the present study, the obesity was induced by postnatal overnutrition in Swiss mice and we investigated the pulmonary mechanics after aerosolization of saline, methacholine, and salbutamol. The lungs were prepared for morphometric analysis. Obese animals showed bronchoconstriction in response to methacholine, as evidenced by airway and tissue resistance, tissue elastance, and hysteresivity. Salbutamol was effective at recovering the response only for airway resistance but not for tissue mechanics. We suggest that this impaired response in obese mice is related to collapsed alveolar, to inflammatory cells, and to elevated deposition collagen fibers in parenchymal tissue. PMID:26497334

  15. A systematic review of lung function testing in asthmatic young children.

    Science.gov (United States)

    Ioan, Iulia; Varechova, Silvia; Marchal, François; Pleşca, Doina-Anca

    2015-01-01

    Asthma diagnosis is difficult in young children being mainly based on clinical signs and parents' history, which is sometimes difficult to obtain. Lung function testing may improve asthma diagnosis by objectively assessing its main features, airway obstruction, spontaneously reversible or after use of a bronchodilator drug, ventilation inhomogeneity during an acute bronchoconstriction and airway hyperresponsiveness. In young children that cannot cope with classical tests, it is important to use and develop simple, short lasting methods, made in spontaneous ventilation without active cooperation. Such techniques are a measurement of respiratory resistance by forced oscillations or the interrupter technique, of specific airway resistance by plethysmography and capnography. All these parameters are sensitive to the presence of an airway obstruction and to a bronchodilator or bronchoconstrictor agent, but their cutoff values in differentiating between asthmatic and healthy children as well as their specific indications in asthma management remain to be established. PMID:26506667

  16. 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

  17. Gastro-Oesophageal Reflux in Noncystic Fibrosis Bronchiectasis

    Directory of Open Access Journals (Sweden)

    Annemarie L. Lee

    2011-01-01

    Full Text Available The clinical presentation of noncystic fibrosis bronchiectasis may be complicated by concomitant conditions, including gastro-oesophageal reflux (GOR. Increased acidic GOR is principally caused by gastro-oesophageal junction incompetence and may arise from lower oesophageal sphincter hypotension, including transient relaxations, hiatus hernia, and oesophageal dysmotility. Specific pathophysiological features which are characteristic of respiratory diseases including coughing may further increase the risk of GOR in bronchiectasis. Reflux may impact on lung disease severity by two mechanisms, reflex bronchoconstriction and pulmonary microaspiration. Symptomatic and clinically silent reflux has been detected in bronchiectasis, with the prevalence of 26 to 75%. The cause and effect relationship has not been established, but preliminary reports suggest that GOR may influence the severity of bronchiectasis. Further studies examining the implications of GOR in this condition, including its effect across the disease spectrum using a combination of diagnostic tools, will clarify the clinical significance of this comorbidity.

  18. Improvement of ventilatory function by spa therapy in patients with intractable asthma.

    Directory of Open Access Journals (Sweden)

    Tanizaki,Yoshiro

    1986-02-01

    Full Text Available Twenty-five patients with intractable asthma had swimming training in a hot spring pool for 3 months. The subjects were divided into three groups according to their clinical symptoms and ages. Changes of ventilatory function during swimming training were observed in in each group. The ventilatory function test revealed that free swimming training in a hot spring pool for 30 min did not induce bronchoconstriction in any of the groups. The values of ventilatory parameters such as FEV 1.0%, %PEFR, %V50 and %V25 were improved after the 3-month swimming training. The improvement of ventilatory parameters, especially %MMF, %V50 and %V25, by the training was most remarkable in the type II asthma group. The percent increase in %MMF, %V50 and %V25 was highest in patients more than 61 years of age, and higher in patients aged 40 to 60 years than in younger patients.

  19. Mometasone furoate nasal spray for the treatment of asthma

    DEFF Research Database (Denmark)

    Meteran, Howraman; Backer, Vibeke

    2016-01-01

    INTRODUCTION: Asthma is a common respiratory disease characterized by airway inflammation, bronchoconstriction and airway hyperresponsiveness and symptoms such as coughing, wheezing, shortness of breath and chest tightness. Allergic rhinitis is a common comorbidity in asthma and glucocorticoids are...... associated with an improvement in asthma control. AREAS COVERED: This current paper reviews the current knowledge on the effect of mometasone furoate nasal spray in the treatment of asthma and includes clinical trials in which both subjective and objective outcomes are assessed. EXPERT OPINION: To date, only...... few clinical studies have investigated the effect of nasal steroids in the treatment of asthma. The studies investigating the effect of MFNS report contradicting results, although the most well-designed study to answer this question finds no improvement in asthma control. Thus, it seems unlikely that...

  20. 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...

  1. Inhaled corticosteroids and HPA axis suppression: how important is it and how should it be managed?

    Science.gov (United States)

    Rao Bondugulapati, L N; Rees, D A

    2016-08-01

    Inhaled corticosteroids (ICS) are established as a cornerstone of management for patients with bronchoconstrictive lung disease. However, systemic absorption may lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis in a significant minority of patients. This is more likely in 'higher risk' patients exposed to high cumulative ICS doses, and in those treated with frequent oral corticosteroids or drugs which inhibit cytochrome p450 3A4. Hypothalamic-pituitary-adrenal axis suppression is frequently unrecognized, such that some patients, notably children, only come to light when an adrenal crisis is precipitated by physical stress. To minimize this risk, 'higher risk' patients and those with previously identified suppressed cortisol responses to Synacthen testing should undergo an education programme to inform them about sick day rules. A review of ICS therapy should also be undertaken to ensure that the dose administered is the minimum required to control symptoms. PMID:27038017

  2. Special considerations for adolescent athletic and asthmatic patients

    Directory of Open Access Journals (Sweden)

    Wuestenfeld JC

    2013-01-01

    Full Text Available Jan C Wuestenfeld,1,2 Bernd Wolfarth1,21Department of Preventive and Rehabilitative Sports Medicine, Technical University Munich (TUM, Munich, Germany; 2Institute for Applied Training Science (IAT, Leipzig, GermanyAbstract: Asthma is defined as a chronic inflammatory disorder of the airways with bronchial hyperresponsiveness and variable bronchoconstriction, and is one of the most common diseases in childhood and adolescence. Exercise-induced asthma-like symptoms and asthma are also frequently seen in highly trained athletes. Exercise-induced asthma (EIA and exercise-induced bronchoconstriction (EIB are found in 8%–10% of healthy school-aged children and in 35% of children with asthma. Highly increased ventilation, inhalation of cold, dry air and air pollutants (eg, chlorine are thought to be important triggers for EIA and EIB. EIA is often experienced concurrently with vocal cord dysfunction, which needs to be considered during the differential diagnosis. The pharmacological treatment of EIA is similar to the treatment of asthma in nonexercising adolescents. The therapy is based on anti-inflammatory drugs (eg, inhaled glucocorticosteroids and bronchodilators (eg, β2-agonists. The treatment of EIB is comparable to the treatment of EIA and leukotriene modifiers offer a new and promising treatment option, particularly in EIB. Generally, athletes may not use β2-agonists according to the prohibited list of the World Anti-Doping Agency (WADA. However, the WADA list contains specific β2-agonistic substances that are permitted to be used by inhalation.Keywords: exercise-induced asthma, exercise-induced bronchospasm, adolescents, asthma, athletes

  3. Toxicologic evaluation of pepper spray as a possible weapon for the Dutch police force: risk assessment and efficacy.

    Science.gov (United States)

    Busker, R W; van Helden, H P

    1998-12-01

    The efficacy and possible health risks of pepper spray were evaluated. In a number of countries, pepper spray is being used by police forces to aid in arresting aggressive individuals. Pepper spray is commercially available as a canister filled with Capsicum extract, which contains capsaicin as the active component. When applied in the form of a spray, it causes an acute inflammation, and humans involuntarily close their eyes, experience a burning feeling on the skin, and are usually rapidly incapacitated. Use by the U.S. police was successful in subduing aggressive individuals in 90% of cases, and a reduction of injury to both police and arrested individuals was noted. In general, pepper spray appeared to be a relatively safe weapon with small risk of causing acute physical harm. Despite this evidence, a number of fatalities were reported in the United States following the use of pepper spray. However, it was concluded that it was not the pepper spray but rather other factors such as drugs and hog-tying that contributed to the cause of death. In only 1 case, that of an asthmatic man, was it concluded that the use of pepper spray contributed to the cause of death. Much attention has been paid to possible genotoxic effects of Capsicum extract such as mutagenicity and carcinogenicity. It was concluded that the risk of long-term health effects is negligible. Because pepper spray may induce bronchoconstriction, people suffering from chronic obstructive lung disease may be hypersensitive to it. Although the results of one study indicate that asthmatics do not develop additional bronchoconstriction following inhalation of capsaicin, the number of experimental data are too few to draw sound conclusions. PMID:9885922

  4. Mechanisms of pollution-induced airway disease: in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Peden, D.B. [Univ. of North Carolina School of Medicine, Center for Environmental Medicine and Lung Biology, North Carolina (United States)

    1997-12-31

    Several studies have investigated the effects of ozone, sulphur dioxide (SO{sub 2}), and nitrogen dioxide (NO{sub 2}) on lung function in normal and asthmatic subjects. Decreased lung function has been observed with ozone levels as low as 0.15 ppm - this effect is concentration dependent and is exacerbated by exercise. A number of lines of evidence suggest that the effect on lung function is mediated, at lest in part, by neural mechanisms. In both normals and asthmatics, ozone has been shown to induce neutrophilic inflammation, with increased levels of several inflammatory mediators, including prostaglandin E{sub 2}. However, in normal subjects, none of the markers of inflammation correlate with changes in lung function. The lung function changes in asthmatics may be associated with inflammatory effects; alternatively, ozone may prime the airways for an increased response to subsequently inhaled allergen. Indeed, an influx of both polymorphonucleocytes and eosinophils has been observed in asthmatic patients after ozone exposure. It has been suggested that the effect of ozone on classic allergen-induced bronchoconstriction may be more significant than any direct effect of this pollutant in asthmatics. SO{sub 2} does not appear to affect lung function in normal subjects, but may induce bronchoconstriction in asthmatics. Nasal breathing, which is often impaired in asthmatics, reduces the pulmonary effects of SO{sub 2}, since this water-soluble gas is absorbed by the nasal mucosa. NO{sub 2} may also influence lung function in asthmatics, but further research is warranted. SO{sub 2} and NO{sub 2} alone do not seem to have a priming effect in asthmatics, but a combination of these two gases has resulted in a heightened sensitivity to subsequently inhaled allergen. (au)

  5. 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.

  6. Dyspnea assessment and adverse events during sputum induction in COPD

    Directory of Open Access Journals (Sweden)

    Moschandreas Joanna

    2006-06-01

    Full Text Available Abstract Background The inhalation of normal or hypertonic saline during sputum induction (SI may act as an indirect bronchoconstrictive stimulus leading to dyspnea and lung function deterioration. Our aim was to assess dyspnea and adverse events in COPD patients who undergo SI following a safety protocol. Methods Sputum was induced by normal and hypertonic (4.5% saline solution in 65 patients with COPD of varying severity. In order to minimize saline-induced bronchoconstriction a protocol based on the European Respiratory Society sputum induction Task group report was followed. Dyspnea change was scored using the Borg scale and lung function was assessed by spirometry and oximetry. Results Borg score changes [median(IQR 1.5(0–2] were observed during SI in 40 subjects; 16 patients required temporary discontinuation of the procedure due to dyspnea-general discomfort and 2 did not complete the session due to dyspnea-wheezing. The change in Borg dyspnea score was significantly correlated with oxygen saturation and heart rate changes and with discontinuation of the procedure due to undesired symptoms. 19 subjects presented an hyperresponsive reaction (decline>20% from baseline FEV1. No significant correlation between Borg changes and FEV1decline was found. Patients with advanced COPD presented significantly greater Borg and oxygen saturation changes than patients with less severe disease (p = 0.02 and p = 0.001, respectively. Baseline FEV1, oxygen saturation and 6MWT demonstrated significant diagnostic values in distinguishing subjects who develop an adverse physiologic reaction during the procedure. Conclusion COPD patients undergoing SI following a safety protocol do not experience major adverse events. Dyspnea and oxygen desaturation is more likely to occur in patients with disease in advanced stages, leading to short discontinuation or less frequently to termination of the procedure. Baseline FEV1, oxygen saturation and 6MWT may have a

  7. Protective effects of phosphodiesterase inhibitors on lung function and remodeling in a murine model of chronic asthma

    Directory of Open Access Journals (Sweden)

    H.S. Campos

    2006-02-01

    Full Text Available The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance, histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9, mice were immunized with 10 µg ovalbumin (OVA, ip on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 µg OVA at 3-day intervals. Control mice (N = 8 received saline under the same protocol. In the dexamethasone (N = 8 and LASSBio596 (N = 8 groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76%, respectively compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.

  8. A Halotyrosine Antibody that Detects Increased Protein Modifications in Asthma Patients

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hongjun; Hallstrand, Teal S.; Daly, Don S.; Matzke, Melissa M.; Nair, Parameswaran; Bigelow, Diana J.; Pounds, Joel G.; Zangar, Richard C.

    2014-01-31

    Background-Airway inflammation plays an important pathophysiological role in asthma. Eosinophils produce hypobromite and bromotyrosine while neutrophils produce hypochlorite and chlorotyrosine. Objective-To evaluate halotyrosine modifications of individual airway proteins as a marker of inflammation in asthma using an antibody-based assay. Methods-We developed a novel monoclonal antibody (BTK-94C) that binds halogenated tyrosine residues, and used this antibody in a custom enzyme-linked immunosorbent assay (ELISA) microarray platform to examine halotyrosine levels in 23 proteins in three independent sets of sputum samples (52 samples total). Results-In 15 subjects with either no asthma, or with asthma characterized by high or low sputum eosinophil counts, we found associations between increased halotyrosine levels of at least three proteins and severity of airway hyperresponsiveness (AHR). Treatment with mepolizumab in 17 patients with sputum eosinophilia markedly reduced the sputum eosinophilia and significantly reduced halotyrosine levels in one sputum protein. Further analysis of 10 subjects with neutrophilic asthma and 10 health controls demonstrated a broad increase in halotyrosine in the patients with airway neutrophilia. Conclusions-Significantly higher levels of halotyrosine are associated with asthma in the asthma phenotypes we examined. The halotyrosine levels correlated with indirect AHR in the form of exercise-induced bronchoconstriction. Clinical Implication-An antibody-based assay for tyrosine halogenation in specific proteins may prove useful for assessing airway inflammation in asthma. Capsule Summary-An antibody to measure protein monobrominated tyrosine and other halotyrosine modifications was developed and used to evaluate halogenation in specific proteins in the airways for the first time. Associations were found between levels of halotyrosine and exercise-induced bronchoconstriction, and eosinophil and neutrophil inflammation in sputum from

  9. Regional deposition in human lung of 2.5 microM particles.

    Science.gov (United States)

    Svartengren, M; Linnman, L; Philipson, K; Camner, P

    1987-01-01

    Regional deposition in the lung of 111In-labelled Teflon particles with an aerodynamic diameter of 2.5 micron was studied in eight healthy nonsmokers. The particles were inhaled at 0.5 l/sec with maximally deep breaths. Bronchoconstriction was induced by inhalation of a methacholine bromide aerosol, for one exposure series before (provocation experiment) and for one exposure series after (control experiment) inhalation of the Teflon particles. Airway resistance (Raw) was measured with a whole-body plethysmograph before and after the induction of bronchoconstriction and increased on an average by a factor of 3-4. The total lung deposition, in percent of the inhaled radioactivity, was 83 +/- 6% (mean +/- SD) for the control experiment and 84 +/- 5% for the provocation experiment. Alveolar deposition, estimated as the percentage retention of lung deposition after 24 hrs (Ret24), was significantly lower in the provocation experiment than in the control experiment, 42 +/- 10% and 77 +/- 12%, respectively. Ret24 varied greatly among the subjects in the control experiment; for example, individual tracheobronchial deposition varied by a factor of 5. Ret24 was not related to FEV1, FVC or Raw. The Ret24 values in the two exposure series correlated significantly indicating an individual factor. Retention at 3 and 24 hrs correlated strongly, r = 0.94. This implies that radionuclides with half-lives of a few hours, e.g., 99mTc, can be used in studies of regional lung deposition when mucociliary transport system has been stimulated. PMID:3582281

  10. 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.

  11. Eucapnic voluntary hyperventilation as a bronchoprovocation technique: development of a standarized dosing schedule in asthmatics.

    Science.gov (United States)

    Argyros, G J; Roach, J M; Hurwitz, K M; Eliasson, A H; Phillips, Y Y

    1996-06-01

    A variety of dosing schedules have been reported for the hyperventilation method of broncho-provocation testing. To evaluate the effect of challenge technique on the bronchoconstrictive response, we had 16 subjects perform eucapnic voluntary hyperventilation (EVH) with dry, room temperature gas using four different dosing schedules. The hyperventilation challenge dosages included the following: (1) a target minute ventilation (VE) of 20 x FEV1 for 6 min; (2) a target VE of 15 x FEV1 for 12 min; (3) an interrupted challenge with a target VE of 30 x FEV1 for 2 min repeated 3 times; and (4) a target VE of 30 x FEV1 for 6 min. Challenges 2, 3, and 4 gave identical absolute ventilatory challenges (identical factor FEV1 x minutes) but at different VE dosages or time. Challenges 1 and 4 were of identical length, but different target VE. The mean postchallenge fall in FEV1 was 16.6 +/- 10.9%, 11.0 +/- 8.1%, 19.6 +/- 9.9%, and 26.7 +/- 11.3% for challenges 1, 2, 3, and 4, respectively. The response to an identical EVH challenge (FEV1 x 30 for 6 min) was reproducible when performed on separate days. We conclude that the challenge technique used for hyperventilation testing will have a significant impact on the bronchoconstrictive response and must be taken into account when interpreting study results. Tests may be quantitatively comparable over a narrow range of challenge time and VE. We recommend that a 6-min uninterrupted EVH challenge using dry, room temperature gas at a target VE of 30 x FEV1 be adopted as the "standard" challenge.

  12. Intranasal curcumin and its evaluation in murine model of asthma.

    Science.gov (United States)

    Subhashini; Chauhan, Preeti S; Kumari, Sharda; Kumar, Jarajana Pradeep; Chawla, Ruchi; Dash, D; Singh, Mandavi; Singh, Rashmi

    2013-11-01

    Curcumin, a phytochemical present in turmeric, rhizome of Curcuma longa, has been shown to have a wide variety of pharmacological activities including anti-inflammatory, anti-allergic and anti-asthmatic properties. Curcumin is known for its low systemic bioavailability and rapid metabolization through oral route and has limited its applications. Over the recent decades, the interest in intranasal delivery as a non-invasive route for drugs has increased as target tissue for drug delivery since nasal mucosa offers numerous benefits. In this study, we evaluated intranasal curcumin following its absorption through nasal mucosa by a sensitive and validated high-performance liquid chromatography (HPLC) method for the determination of intranasal curcumin in mouse blood plasma and lung tissue. Intranasal curcumin has been detected in plasma after 15 min to 3 h at pharmacological dose (5 mg/kg, i.n.), which has shown anti-asthmatic potential by inhibiting bronchoconstriction and inflammatory cell recruitment to the lungs. At considerably lower doses has proved better than standard drug disodium cromoglycate (DSCG 50 mg/kg, i.p.) by affecting inflammatory cell infiltration and histamine release in mouse model of asthma. HPLC detection revealed that curcumin absorption in lungs has started after 30 min following intranasal administration and retained till 3h then declines. Present investigations suggest that intranasal curcumin (5.0 mg/kg, i.n.) has effectively being absorbed and detected in plasma and lungs both and suppressed airway inflammations at lower doses than the earlier doses used for detection (100-200 mg/kg, i.p.) for pharmacological studies (10-20 mg/kg, i.p.) in mouse model of asthma. Present study may prove the possibility of curcumin as complementary medication in the development of nasal drops to prevent airway inflammations and bronchoconstrictions in asthma without any side effect. PMID:24021755

  13. Protective effects of phosphodiesterase inhibitors on lung function and remodeling in a murine model of chronic asthma

    Directory of Open Access Journals (Sweden)

    Campos H.S.

    2006-01-01

    Full Text Available The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance, histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9, mice were immunized with 10 µg ovalbumin (OVA, ip on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 µg OVA at 3-day intervals. Control mice (N = 8 received saline under the same protocol. In the dexamethasone (N = 8 and LASSBio596 (N = 8 groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76%, respectively compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.

  14. Gender and perception of dyspnea: The role of the variation in the forced expiratory volume in one second Género y percepción de disnea: el rol de la variación del volumen espiratorio forzado en un segundo

    Directory of Open Access Journals (Sweden)

    Carlos A. Nigro

    2010-08-01

    Full Text Available During bronchoconstriction women perceive more breathlessness than men. The aims of study were 1 to evaluate if quality of dyspnea in bronchoconstriction was different in women and men 2 to assess if gender difference in the perception of dyspnea could be related to the level of bronchoconstriction. 457 subjects (257 women inhaled methacholine to a 20% decrease in FEV1, or 32 mg/ml. Dyspnea was evaluated using the modified Borg scale and a list of expressions of dyspnea. Borg scores were recorded immediately before the challenge test baseline and at the maximum FEV1 decrease. The prevalence of descriptors of dyspnea reported by women and men was similar. Dyspnea was related to the level of FEV1 (ΔFEV1: OR 1.05, 95%CI 1.01-1.09, p 0.0095, females (OR 2.90, 95%CI 1.33-6.33, p 0.0072, younger subjects (OR 0.93, 95%CI 0.89- 0.97, p 0.0013 and body mass index (BMI (OR 1.11, 95%CI 1.01-1.23, p 0.023. As the FEV1 fell less than 20% from baseline, only the ΔFEV1 was significantly associated with dyspnea (ΔFEV1:OR 1.15, 95%CI 1.07- 1.24, p 0.0002. Instead, if the FEV1 fell higher ≥ 20%, the presence of dyspnea was related to the degree of bronchoconstriction (ΔFEV1: OR 1.04, 95%CI 1.01-1.09, p 0.0187, females (OR 3.02, 95%CI 1.36-6.72, p 0.0067, younger subjects (OR 0.92, 95%CI 0.88-0.96, p 0.0007 and BMI (OR 1.12, 95%CI 1.01-1.23, p 0.023. The quality of dyspnea during the bronchoconstriction was similar in women and men; women showed a higher perception of dyspnea than men only when the FEV1 fell more than 20% from baseline.Durante la broncoconstricción las mujeres perciben más disnea que los hombres. Los objetivos del estudio fueron evaluar: 1 si la calidad de la disnea durante la broncoconstricción fue diferente en mujeres y hombres, 2 si la diferencia entre sexos en la percepción de disnea podría relacionarse al nivel de broncoconstricción. 457 sujetos (257 mujeres inhalaron metacolina hasta un descenso del FEV1 ≥ 20% o 32 mg/ml. La

  15. Seasonal variation in bronchial hyperreactivity (BHR) in allergic patients.

    Science.gov (United States)

    Tilles, S A; Bardana, E J

    1997-01-01

    -driven BHR changes involves a type I hypersensitivity late-phase reaction. Characterized by recruitment of eosinophils, lymphocytes, and other cells that are central components of allergic inflammation and are not normally found in the lower airways, this reversible inflammatory process could in turn act, presumably via chemical mediators, on the airway smooth muscle. This may cause bronchoconstriction, but may also increase responsiveness to bronchoconstrictive stimuli independent of bronchoconstriction. This explanation for seasonal BHR changes is supported by findings of blood eosinophil (31,47) and BAL eosinophilic cationic protein (31) level changes that parallel BHR. Prevention of seasonal BHR changes using anti-inflammatory medications (32,33,35) also supports this hypothesis (30) however, and the complex potential interactions between infectious agents and air pollutants on seasonal BHR changes have yet to be studied directly. Therefore, although BHR indeed may predictably vary season to season in allergic individuals, additional investigation is needed to better characterize the reasons for this phenomenon. Further insight in this area may help address the reasons why there are often seasonal epidemics in asthma morbidity and mortality. PMID:9315410

  16. [Pathophysiology, diagnosis and treatment of cough variant asthma].

    Science.gov (United States)

    Fujimura, Masaki

    2014-05-01

    Cough variant asthma (CVA) has been recognized as a precursor of asthma or a pre-asthmatic state because of the mildly heightened bronchial responsiveness and efficacy of bronchodilator therapy. Nevertheless, the accumulating evidence indicates that the pathophysiology is different between CVA and bronchial asthma. The most fundamental physiologic feature is a heightened cough response to methacholine-induced bronchoconstriction in CVA, while this response is rather reduced in bronchial asthma. The sensitivity of cough receptors located in the superficial layer of the airway wall is normal in CVA as well as bronchial asthma, but heightened in atopic cough. The pathologic feature of CVA is eosinophilic inflammation of the central to peripheral airway, reflected by eosinophilia in induced sputum, biopsied bronchial mucosa, and bronchoalveolar lavage fluid. The diagnosis of CVA has been commonly made based on therapeutic diagnostic procedures, while pathophysiologic diagnosis is ideal. The reason is that measurements of the sensitivity of cough receptors to inhaled capsaicin and cough response to induced bronchoconstriction are not possible at most chest clinics in the world. The efficacy of a beta2-agonist for a patient's coughing is evaluated to make a diagnosis of CVA. When the bronchodilator therapy is judged as efficacious, a tentative diagnosis of CVA is made. Then, induction therapy is initiated for resolution of the cough. The induction therapy consists of beta2-agonists, leukotriene receptor antagonists, and inhaled corticosteroids. In some patients whose cough does not subside with the therapy, short-burst oral corticosteroids (1 to 3 weeks) may be added. If the cough still does not subside with the therapy, the patient should be referred to cough specialists. When the cough subsides with the induction therapy, long-term management is recommended using inhaled corticosteroids, because 30% of patients develop typical bronchial asthma within several years

  17. Beta-blockers: friend or foe in asthma?

    Directory of Open Access Journals (Sweden)

    Arboe B

    2013-07-01

    Full Text Available Bente Arboe, Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Hvidovre, DenmarkBackground and aim: Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma.Method: Systematic literature review.Results: No significant increase in the number of patients requiring rescue oral corticosteroid for an exacerbation of asthma has been observed after initiation of β-blocker treatment. Patients with mild to moderate reactive airway disease, probably both asthma and chronic obstructive pulmonary disease, may have a limited fall in forced expiratory volume in 1 second (FEV1 following single-dose administration of β-blocker, whereas no change in FEV1 has been reported following long-term administration. In a murine model of asthma, long-term administration of β-blockers resulted in a decrease in airway hyperresponsiveness, suggesting an anti-inflammatory effect. In keeping with this, long-term administration of a nonselective β-blocker to steroid-naïve asthma patients has shown a dose-dependent improvement in airway hyperresponsiveness, and either an asymptomatic fall in FEV1 or no significant change in FEV1. Furthermore, available studies show that bronchoconstriction induced by inhaled methacholine is reversed by salbutamol in patients on regular therapy with a β-blocker. On the other hand, a recent placebo-controlled trial of propranolol and tiotropium bromide added to inhaled corticosteroids revealed no effect on airway hyperresponsiveness and a small, not statistically significant, fall in FEV1 in patients classified as having mild to moderate asthma.Conclusion: The available, although limited, evidence suggests that a dose-escalating model of β-blocker therapy to patients with asthma is well tolerated, does not

  18. IL-13 Augments Compressive Stress-Induced Tissue Factor Expression in Human Airway Epithelial Cells.

    Science.gov (United States)

    Mitchel, Jennifer A; Antoniak, Silvio; Lee, Joo-Hyeon; Kim, Sae-Hoon; McGill, Maureen; Kasahara, David I; Randell, Scott H; Israel, Elliot; Shore, Stephanie A; Mackman, Nigel; Park, Jin-Ah

    2016-04-01

    Tissue factor (TF) is best known as a cellular initiator of coagulation, but it is also a multifunctional protein that has been implicated in multiple pathophysiologic conditions, including asthma. In the lung, airway epithelial cells express TF, but it is unknown how TF expression is regulated by asthma-associated mediators. We investigated the role of IL-13, a type 2 cytokine, alone and in combination with compressive stress, which mimics asthmatic bronchoconstriction, on TF expression and release of TF-positive extracellular vesicles from primary normal human bronchial epithelial cells. Well-differentiated normal human bronchial epithelial cells were treated with IL-13 and compressive stress, alone and in combination. TF mRNA, protein and activity were measured in the cells and conditioned media. TF was also measured in the bronchoalveolar lavage (BAL) fluid of allergen-challenged mice and patients with asthma. IL-13 and compressive stress increased TF expression, but only compressive stress induced TF-positive extracellular vesicle release. Pretreatment with IL-13 augmented compressive stress-induced TF expression and release. TF protein and activity in BAL fluid were increased in allergen-sensitized and -challenged mice. TF was elevated in the BAL fluid of patients with mild asthma after an allergen challenge. Our in vitro and in vivo data indicate close cooperation between mechanical and inflammatory stimuli on TF expression and release of TF-positive extracellular vesicles in the lungs, which may contribute to pathophysiology of asthma. PMID:26407210

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

    Directory of Open Access Journals (Sweden)

    Groneberg David A

    2008-02-01

    Full Text Available Abstract Background Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity. Methods The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique. Results Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity. Conclusion Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.

  1. Relationship between regional ventilation and aerosol deposition in tidal breathing

    Energy Technology Data Exchange (ETDEWEB)

    Trajan, M.; Logus, J.W.; Enns, E.G.; Man, S.F.

    1984-07-01

    The regional distribution of the deposition of 1.2 micron particles of 99mTc sulfur colloid inhaled by tidal breathing was compared with the distribution of ventilation as measured by a 133Xe washout technique. Twelve subjects were studied, 6 with normal pulmonary function tests, 5 with air-flow limitation, and 1 with unilateral phrenic nerve paralysis. Both xenon and aerosol were inhaled at tidal volume by the subjects while seated upright. A large field gamma camera acquired posterior scans. Thirteen experiments were also done on 7 dogs: 1 with extrathoracic obstruction of the airway to 1 lung, and 12 with bronchoconstriction from the instillation of methacholine chloride into the airways of a lower lobe. Two of these dogs were studied with a gamma camera system, and the others were studied with a Picker multi-probe system. Both in humans and in dogs, an increase in time constant, which indicated a decrease in ventilation, was associated with an increase in peripheral aerosol deposition when normalized for ventilation. It is suggested that the increased residence time is responsible for the increased deposition in regions that received lesser ventilation.

  2. Respiratory toxicity of repeated exposure to particles produced by traffic and sugar cane burning.

    Science.gov (United States)

    Mazzoli-Rocha, Flavia; Carvalho, Giovanna M C; Lanzetti, Manuella; Valença, Samuel S; Silva, Luiz F F; Saldiva, Paulo H N; Zin, Walter A; Faffe, Débora S

    2014-01-15

    We compared the toxicity of subchronic exposure to equivalent masses of particles from sugar cane burning and traffic. BALB/c mice received 3 intranasal instillations/week during 1, 2 or 4 weeks of either distilled water (C1, C2, C4) or particles (15μg) from traffic (UP1, UP2, UP4) or biomass burning (BP1, BP2, BP4). Lung mechanics, histology and oxidative stress were analyzed 24h after the last instillation. In all instances UP and BP groups presented worse pulmonary elastance, airway and tissue resistance, alveolar collapse, bronchoconstriction and macrophage influx into the lungs than controls. UP4, BP2 and BP4 presented more alveolar collapse than UP1 and BP1, respectively. UP and BP had worse bronchial and alveolar lesion scores than their controls; BP4 had greater bronchial lesion scores than UP4. Catalase was higher in UP4 and BP4 than in C4. In conclusion, biomass particles were more toxic than those from traffic after repeated exposures.

  3. Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4.

    Science.gov (United States)

    Lukic, Ana; Ji, Jie; Idborg, Helena; Samuelsson, Bengt; Palmberg, Lena; Gabrielsson, Susanne; Rådmark, Olof

    2016-09-01

    Leukotrienes (LTs) play major roles in lung immune responses, and LTD4 is the most potent agonist for cysteinyl LT1, leading to bronchoconstriction and tissue remodeling. Here, we studied LT crosstalk between myeloid cells and pulmonary epithelial cells. Monocytic cells (Mono Mac 6 cell line, primary dendritic cells) and eosinophils produced primarily LTC4 In coincubations of these myeloid cells and epithelial cells, LTD4 became a prominent product. LTC4 released from the myeloid cells was further transformed by the epithelial cells in a transcellular manner. Formation of LTD4 was rapid when catalyzed by γ-glutamyl transpeptidase (GGT)1 in the A549 epithelial lung cancer cell line, but considerably slower when catalyzed by GGT5 in primary bronchial epithelial cells. When A549 cells were cultured in the presence of IL-1β, GGT1 expression increased about 2-fold. Also exosomes from A549 cells contained GGT1 and augmented LTD4 formation. Serine-borate complex (SBC), an inhibitor of GGT, inhibited conversion of LTC4 to LTD4 Unexpectedly, SBC also upregulated translocation of 5-lipoxygenase (LO) to the nucleus in Mono Mac 6 cells, and 5-LO activity. Our results demonstrate an active role for epithelial cells in biosynthesis of LTD4, which may be of particular relevance in the lung. PMID:27436590

  4. The Quintiles Prize Lecture 2004. The identification of the adenosine A2B receptor as a novel therapeutic target in asthma.

    Science.gov (United States)

    Holgate, Stephen T

    2005-08-01

    Adenosine is a powerful bronchoconstrictor of asthmatic, but not normal, airways. In vitro studies on isolated human mast cells and basophils revealed that adenosine and selective analogues augmented inflammatory mediator release from mast cells by stimulating A(2) receptors. Pharmacological blockade of mast cell mediator release in vivo also attenuated adenosine-induced bronchoconstriction, as did theophylline, by adenosine A(2) receptor antagonism. Further in vitro studies revealed that the asthmatic response to adenosine is likely to be mediated via the A(2B) subtype which is selectively antagonised by enprofylline. Studies in animal models, especially mice, have shown a close synergistic interaction between adenosine, Th2 and airway remodelling responses. The recent description of A(2B) receptors on human airway smooth muscle cells that mediate cytokine and chemokine release and induce differentiation of fibroblasts into myofibroblasts strengthens the view that adenosine maybe more than an inflammatory mediator in asthma but also participates in airway wall remodelling in this disease. These data have provided a firm basis for developing adenosine A(2B) receptor antagonists as a new therapeutic approach to this disease. PMID:15980878

  5. Ambient particulate matter air pollution and cardiopulmonary diseases.

    Science.gov (United States)

    Thurston, George; Lippmann, Morton

    2015-06-01

    Population exposures to ambient outdoor particulate matter (PM) air pollution have been assessed to represent a major burden on global health. Ambient PM is a diverse class of air pollution, with characteristics and health implications that can vary depending on a host of factors, including a particle's original source of emission or formation. The penetration of inhaled particles into the thorax is dependent on their deposition in the upper respiratory tract during inspiration, which varies with particle size, flow rate and tidal volume, and in vivo airway dimensions. All of these factors can be quite variable from person to person, depending on age, transient illness, cigarette smoke and other short-term toxicant exposures that cause transient bronchoconstriction, and occupational history associated with loss of lung function or cumulative injury. The adverse effects of inhaled PM can result from both short-term (acute) and long-term (chronic) exposures to PM, and can range from relatively minor, such as increased symptoms, to very severe effects, including increased risk of premature mortality and decreased life expectancy from long-term exposure. Control of the most toxic PM components can therefore provide major health benefits, and can help guide the selection of the most human health optimal air quality control and climate change mitigation policy measures. As such, a continued improvement in our understanding of the nature and types of PM that are most dangerous to health, and the mechanism(s) of their respective health effects, is an important public health goal.

  6. T(H)2 cytokines modulate the IL-9R expression on human neutrophils.

    Science.gov (United States)

    Dragon, Stéphane; Takhar, Manrit Kaur; Shan, Lianyu; Hayglass, Kent T; Simons, F Estelle; Gounni, Abdelilah S

    2009-06-26

    Interleukin (IL)-9 is associated with key pathological features of asthma such as airway hyperresponsiveness, bronchoconstriction and mucus production. Inflammatory responses mediated by IL-9 rely on the expression of the IL-9R which has been reported on lung epithelial cells, T lymphocytes and recently on airway granulocyte infiltrates. In this study, we assessed the regulatory and constitutive cell surface expression of the IL-9Ralpha in unfractionated and purified human neutrophils from atopic asthmatics, atopic non-asthmatics and healthy normal controls. We demonstrate that T(H)2 cytokines (IL-4 or IL-13) and granulocyte macrophage-colony stimulating factor (GM-CSF) up-regulated mRNA and cell surface expression levels of the IL-9Ralpha in primary human and HL-60 differentiated neutrophils. Pharmacological inhibition of NF-kappaB did not affect T(H)2-mediated IL-9Ralpha expression in human neutrophils although IFN-gamma and IL-10 down-regulated IL-9Ralpha expression when co-incubated with IL-4, IL-13 or GM-CSF. Collectively, our results reveal a regulatory function for IFN-gamma and IL-10 on modulating the inducible IL-9Ralpha expression levels on peripheral blood neutrophils by T(H)2 cytokines.

  7. Diagnostic values of combination of free running asthma screening test and total serum allergen IgE level in children with asthma

    Institute of Scientific and Technical Information of China (English)

    Chen Xin; Li Yong; Zeng Meiying

    2014-01-01

    Background A free running asthma screening test is usually used for screening exercise-induced bronchoconstriction.The total serum allergen IgE level can reveal the patient's atopy characteristics.Our study is to evaluate the diagnostic values of the combination of the two tests in asthmatic children and compare this new diagnostic method with the Intemational Study of Asthma and Allergies in Childhood (ISSAC) questionnaires and the bronchial provocation test,which are popular diagnostic tool for pediatric asthma.Methods A total of 773 school children were recruited in this study.The children's asthma was diagnosed by means of a combination of the free running asthma screening test and total serum allergen IgE level.The new diagnostic method value was assessed using receiver operating characteristic (ROC) curves and compared with other diagnostic tools such as ISSAC questionnaires and the bronchial provocation test.Results The AUC of this new diagnostic method was higher than 0.9.When the cut-off value of total serum allergen IgE level was ≥47 KU/L,the sensitivity and the specificity were 71.4% and 85.1%,respectively,which were better than those of either the ISSAC questionnaires or bronchial provocation test.Conclusion The combination of the free running asthma screening test and total serum allergen IgE level may be an effective diagnostic tool for children's asthma.

  8. β2 agonists in athletes. An ergogenic aid? = β2 agonistas en deportistas. ¿Una ayuda ergogénica?

    Directory of Open Access Journals (Sweden)

    Ospina Uribe, Carlos Fernando

    2013-01-01

    Full Text Available Asthma is a chronic disorder of the airways with bronchial hyperresponsiveness and bronchoconstriction. Exercise can trigger asthma symptoms; this condition is known as exerciseinduced bronchospasm (EIB. Asthma is common in Olympic athletes who therefore use β2 agonists to prevent and treat its episodes. These drugs are preferably supplied by inhalation. In sports, the use of β2 agonists is restricted by anti-doping regulation, arguing that these drugs have the potential to improve physical performance, which can result in a competitive advantage. β2 agonists are prohibited by the WADA (World Anti-Doping Agency, except salbutamol (maximum dose: 1.600 μg over 24 hours and salmeterol. Oral administration of salbutamol can induce ergogenic effects in athletes. It has been documented that when given orally β2 agonists can improve performance in endurance disciplines, increase muscle strength and improve anaerobic power. However, according to scientific evidence, inhaled β2 agonists do not have a relevant performance-enhancing effect in nonasthmatic athletes.

  9. 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

  10. Pharmacogenomics of Prostaglandin and Leukotriene Receptors

    Science.gov (United States)

    Cornejo-García, José A.; Perkins, James R.; Jurado-Escobar, Raquel; García-Martín, Elena; Agúndez, José A.; Viguera, Enrique; Pérez-Sánchez, Natalia; Blanca-López, Natalia

    2016-01-01

    Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs), have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs) and leukotrienes (LTs) are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesized through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2); mast cell maturation, eosinophil recruitment, and allergic responses (PTGD2); vascular and respiratory smooth muscle contraction (PTGF2), and inhibition of platelet aggregation (PTGI2). LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs) (LTC4, LTD4, and LTE4) induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic. PMID:27708579

  11. Leukotriene receptor antagonists--risks and benefits for use in paediatric asthma.

    Science.gov (United States)

    Spahr, Jonathan E; Krawiec, Marzena E

    2004-05-01

    Leukotrienes (LTs) are important mediators of the pathophysiology of asthma, specifically, bronchoconstriction, airway inflammation and oedema and mucus hypersecretion. The LT receptor antagonists (LTRAs) inhibit these potent effects by selectively blocking the cysteinyl LT 1 receptor. These are the first novel therapies for asthma since the introduction of inhaled corticosteroids (ICS) in 1972. Unlike generalised inhibition of airway inflammation by ICS, the LTRAs target inhibition of specific mediators. In general, paediatric data concerning these agents remain quite limited. However, they have demonstrated efficacy against allergen- and exercise-induced bronchospasm in both adults and children. Recently, their potential role for the treatment of viral-induced wheeze in young children has been explored. In multiple, placebo-controlled trials, the LTRAs have demonstrated efficacy for the treatment of mild persistent asthma, additive benefit in the management of symptomatic moderate asthmatics on maintenance ICS and evidence of significant steroid-sparing. Findings from these clinical trials and real-world experience support the use of the LTRAs as controller agents for persistent asthma. Based on their excellent safety profiles, tolerance and ease of administration (including once daily dosing with montelukast), this drug class may offer several important features for use as controller therapy, particularly in asthmatic children as young as 1 year of age, however, this must continue to be reviewed as new paediatric data become available. PMID:15155146

  12. Evidence-based risk assessment and recommendations for physical activity clearance: respiratory disease.

    Science.gov (United States)

    Eves, Neil D; Davidson, Warren J

    2011-07-01

    The 2 most common respiratory diseases are chronic obstructive pulmonary disease (COPD) and asthma. Growing evidence supports the benefits of exercise for all patients with these diseases. Due to the etiology of COPD and the pathophysiology of asthma, there may be some additional risks of exercise for these patients, and hence accurate risk assessment and clearance is needed before patients start exercising. The purpose of this review was to evaluate the available literature regarding the risks of exercise for patients with respiratory disease and provide evidence-based recommendations to guide the screening process. A systematic review of 4 databases was performed. The literature was searched to identify adverse events specific to exercise. For COPD, 102 randomized controlled trials that involved an exercise intervention were included (n = 6938). No study directly assessed the risk of exercise, and only 15 commented on exercise-related adverse events. For asthma, 30 studies of mixed methodologies were included (n = 1278). One study directly assessed the risk of exercise, and 15 commented on exercise-related adverse events. No exercise-related fatalities were reported. The majority of adverse events in COPD patients were musculoskeletal or cardiovascular in nature. In asthma patients, exercise-induced bronchoconstriction and (or) asthma symptoms were the primary adverse events. There is no direct evidence regarding the risk of exercise for patients with COPD or asthma. However, based on the available literature, it would appear that with adequate screening and optimal medical therapy, the risk of exercise for these respiratory patients is low. PMID:21800949

  13. Pathophysiology of the cysteinyl leukotrienes and effects of leukotriene receptor antagonists in asthma.

    Science.gov (United States)

    Bisgaard, H

    2001-01-01

    Cysteinyl leukotrienes, synthesized de novo from cell membrane phospholipids, are proinflammatory mediators that play an important role in the pathophysiology of asthma. These mediators are among the most potent of bronchoconstrictors and cause vasodilation, increased microvascular permeability, exudation of macromolecules and edema. The cysteinyl leukotrienes also have potent chemoattractant properties for eosinophils, causing an influx of eosinophils into the airway mucosa, which further fuels the inflammatory process. In addition, the cysteinyl leukotrienes are potent secretagogues and reduce ciliary motility, which may hinder mucociliary clearance. Asthmatic patients demonstrate increased production of cysteinyl leukotrienes during naturally occurring asthma and acute asthma attacks as well as after allergen and exercise challenge. The leukotriene receptor antagonists montelukast, zafirlukast and pranlukast inhibit bronchoconstriction in asthmatic patients undergoing allergen, exercise, cold air or aspirin challenge. They attenuate the hallmarks of asthmatic inflammation, including eosinophilia in the airway mucosa and peripheral blood. Moreover, exhaled nitric oxide concentrations, another correlate of airway inflammation, are decreased during montelukast treatment in children. Cysteinyl leukotriene synthesis is not blocked by corticosteroid therapy. This important observation suggests that the leukotriene receptor antagonists represent a novel therapeutic approach, one that may provide benefits that are additive with corticosteroid therapy. This supposition is supported by clinical observations that treatment with leukotriene receptor antagonists significantly improve asthma control when added to inhaled corticosteroid therapy. Moreover, the bronchodilator properties of the leukotriene receptor antagonists are additive with those of beta agonists. These data provide strong support for the use of leukotriene receptor antagonists for treating asthma. PMID

  14. Respirable antisense oligonucleotides: a new drug class for respiratory disease

    Directory of Open Access Journals (Sweden)

    Tanaka Makoto

    2000-12-01

    Full Text Available Abstract Respirable antisense oligonucleotides (RASONs, which attenuate specific disease-associated mRNAs, represent a new class of respiratory therapeutics with considerable potential. RASONs overcome previous obstacles that have impeded the development of antisense therapeutics targeting diseases in other organ systems. RASONs are delivered directly to the target tissue via inhalation; their uptake seems to be enhanced by cationic properties inherent in pulmonary surfactant, and, because of the markedly different target properties of mRNA and proteins, they can have very long durations of effect compared with traditional drugs targeting the protein of the same gene. RASONs contain chemical modifications that decrease their degradation by cellular nucleases. However, total insensitivity to nucleases is probably not an optimal design criterion for RASONs, because moderate nuclease sensitivity can prevent their systemic delivery, decreasing the potential for systemic toxicity. EPI-2010 is a 21-mer phosphorothioate RASON that attenuates bronchoconstriction, inflammation and surfactant depletion in preclinical models of human asthma, has a duration of effect of seven days, and seems to undergo minimal systemic delivery.

  15. Regadenoson use in patients with chronic obstructive pulmonary disease: the state of current knowledge

    Directory of Open Access Journals (Sweden)

    Golzar Y

    2014-01-01

    Full Text Available Yasmeen Golzar,1,2 Rami Doukky1,21Division of Adult Cardiology, John H Stroger Jr, Hospital of Cook County, 2Division of Cardiology, Rush University Medical Center, Chicago, IL, USAAbstract: Stress testing is challenging in patients with chronic obstructive pulmonary disease (COPD. Functional capacity is generally decreased in this patient population, limiting patients' ability to achieve physiologic stress through exercise. Additionally, due to emphysematous changes, COPD patients tend to have poor acoustic windows that impair the quality and therefore diagnostic accuracy of stress echocardiography techniques. Pharmacologic stress myocardial perfusion imaging (MPI testing is also problematic, particularly due to the concern for adenosine-induced bronchoconstriction with conventional vasodilator stress agents. Regadenoson, a selective A2A adenosine receptor agonist, has gained popularity due to its ease of administration and improved patient experience in the general population. The literature describing the experience with regadenoson in COPD patients, though limited, is rapidly growing and reassuring. This review summarizes the pharmacology and clinical application of this novel stress agent and presents the available data on the safety and tolerability of its use in COPD patients.Keywords: chronic obstructive pulmonary disease, COPD, regadenoson, myocardial perfusion imaging, safety, tolerability, asthma, emphysema

  16. The Quintiles Prize Lecture 2004: The identification of the adenosine A2B receptor as a novel therapeutic target in asthma

    Science.gov (United States)

    Holgate, Stephen T

    2005-01-01

    Adenosine is a powerful bronchoconstrictor of asthmatic, but not normal, airways. In vitro studies on isolated human mast cells and basophils revealed that adenosine and selective analogues augmented inflammatory mediator release from mast cells by stimulating A2 receptors. Pharmacological blockade of mast cell mediator release in vivo also attenuated adenosine-induced bronchoconstriction, as did theophylline, by adenosine A2 receptor antagonism. Further in vitro studies revealed that the asthmatic response to adenosine is likely to be mediated via the A2B subtype which is selectively antagonised by enprofylline. Studies in animal models, especially mice, have shown a close synergistic interaction between adenosine, Th2 and airway remodelling responses. The recent description of A2B receptors on human airway smooth muscle cells that mediate cytokine and chemokine release and induce differentiation of fibroblasts into myofibroblasts strengthens the view that adenosine maybe more than an inflammatory mediator in asthma but also participates in airway wall remodelling in this disease. These data have provided a firm basis for developing adenosine A2B receptor antagonists as a new therapeutic approach to this disease. PMID:15980878

  17. The Quintiles Prize Lecture 2004. The identification of the adenosine A2B receptor as a novel therapeutic target in asthma.

    Science.gov (United States)

    Holgate, Stephen T

    2005-08-01

    Adenosine is a powerful bronchoconstrictor of asthmatic, but not normal, airways. In vitro studies on isolated human mast cells and basophils revealed that adenosine and selective analogues augmented inflammatory mediator release from mast cells by stimulating A(2) receptors. Pharmacological blockade of mast cell mediator release in vivo also attenuated adenosine-induced bronchoconstriction, as did theophylline, by adenosine A(2) receptor antagonism. Further in vitro studies revealed that the asthmatic response to adenosine is likely to be mediated via the A(2B) subtype which is selectively antagonised by enprofylline. Studies in animal models, especially mice, have shown a close synergistic interaction between adenosine, Th2 and airway remodelling responses. The recent description of A(2B) receptors on human airway smooth muscle cells that mediate cytokine and chemokine release and induce differentiation of fibroblasts into myofibroblasts strengthens the view that adenosine maybe more than an inflammatory mediator in asthma but also participates in airway wall remodelling in this disease. These data have provided a firm basis for developing adenosine A(2B) receptor antagonists as a new therapeutic approach to this disease.

  18. Soft TCPTP Agonism-Novel Target to Rescue Airway Epithelial Integrity by Exogenous Spermidine.

    Science.gov (United States)

    Ghisalberti, Carlo A; Borzì, Rosa M; Cetrullo, Silvia; Flamigni, Flavio; Cairo, Gaetano

    2016-01-01

    A reparative approach of disrupted epithelium in obstructive airway diseases, namely asthma and chronic obstructive pulmonary disease (COPD), may afford protection and long-lasting results compared to conventional therapies, e.g., corticosteroids or immunosuppressant drugs. Here, we propose the polyamine spermidine as a novel therapeutic agent in airways diseases, based on a recently identified mode of action: T-cell protein tyrosine phosphatase (TCPTP) agonism. It may include and surpass single-inhibitors of stress and secondary growth factor pathway signaling, i.e., the new medicinal chemistry in lung diseases. Enhanced polyamine biosynthesis has been charged with aggravating prognosis by competing for L-arginine at detriment of nitric oxide (NO) synthesis with bronchoconstrictive effects. Although excess spermine, a higher polyamine, is harmful to airways physiology, spermidine can pivot the cell homeostasis during stress conditions by the activation of TCPTP. In fact, the dephosphorylating activity of TCPTP inhibits the signaling cascade that leads to the expression of genes involved in detachment and epithelial-to-mesenchymal transition (EMT), and increases the expression of adhesion and tight junction proteins, thereby enhancing the barrier functionality in inflammation-prone tissues. Moreover, a further beneficial effect of spermidine may derive from its ability to promote autophagy, possibly in a TCPTP-dependent way. Since doses of spermidine in the micromolar range are sufficient to activate TCPTP, low amounts of spermidine administered in sustained release modality may provide an optimal pharmacologic profile for the treatment of obstructive airway diseases. PMID:27375482

  19. Life-threatening asthma attack during prolonged fingolimod treatment: case report

    Directory of Open Access Journals (Sweden)

    Zecca C

    2014-07-01

    Full Text Available Chiara Zecca,1,* Matteo Caporro,1,* Sandor Györik,2 Claudio Gobbi11Neurocenter of Southern Switzerland, Department of Neurology, Ospedale Regionale di Lugano, Lugano, Switzerland; 2Department of Internal Medicine, Ospedale Regionale di Bellinzona, Bellinzona, Switzerland*These authors contributed equally to this workBackground: Fingolimod (FTY mediates bronchoconstriction by interacting with sphingosine-1-phosphate receptors. The majority of the reported adverse respiratory events occur during the first weeks of treatment.Case presentation: A 49-year-old woman developed a life-threatening asthma attack after 6 months of continuous FTY treatment. The adverse event required prolonged hospitalization, and the patient recovered without sequelae after FTY interruption. A history of previous airway hyperreactivity and a concurrent viral respiratory infection possibly acted as predisposing factors.Conclusion: This first description of a severe, life-threatening asthma attack during prolonged FTY treatment suggests the need for long-term clinical surveillance, especially in patients with known predisposing factors.Keywords: multiple sclerosis, bronchial hyper-reactivity

  20. Inhalers and nebulizers: which to choose and why.

    Science.gov (United States)

    Pedersen, S

    1996-02-01

    It is obvious that many factors should be considered when an inhaler is prescribed. Based upon the information discussed above, a rational inhaler strategy could be as follows: (1) Children valve system (and a face mask for the children) for the delivery of all drugs. When they are severely obstructed, some may need a nebulizer. If the patient cannot be taught the correct use of a spacer, a nebulizer should be prescribed. (2) Children > or = 5 years and adults are prescribed a spacer or a Turbuhaler for the administration of inhaled corticosteroids and a dry powder inhaler (preferably multiple dose) or a breath-actuated MDI for other drugs. If these alternatives are not available or the patient prefers, a conventional MDI can be used (preferably not for other corticosteroids than fluticasone propionate) provided that careful tuition is given. Fluticasone dipropionate may be given by DPI, Spacer or MDI. (3) Nebulizers are mainly reserved for severe acute attacks of bronchoconstriction. With this approach, most patients can be taught effective inhaler use with a minimum of instructional time. Finally, it must always be remembered to consider the patient's wish, since prescription of an inhaler which the physician likes but the patient does not is likely to reduce compliance.

  1. Acute inhalation of ozone stimulates bronchial C-fibers and rapidly adapting receptors in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Coleridge, J.C.G.; Coleridge, H.M.; Schelegle, E.S.; Green, J.F. (Univ. of California, Davis (United States) Univ. of California, San Francisco (United States))

    1993-05-01

    To identify the afferents responsible for initiating the vagally mediated respiratory changes evoked by acute exposure to ozone, the authors recorded vagal impulses in anesthetized, open-chest, artificially ventilated dogs and examined the pulmonary afferent response to ozone (2--3 ppM in air) delivered to the lower trachea for 20--60 min. Bronchial C-fibers (BrCs) were the lung afferents most susceptible to ozone, the activity of 10 of 11 BrCs increasing from 0.2 [+-] 0.2 to 4.6 [+-] 1.3 impulses/s within 1--7 min of ozone exposure. Ten of 15 rapidly adapting receptors (RARs) were stimulated by ozone, their activity increasing from 1.5 [+-] 0.4 to 4.7 [+-] 0.7 impulses/s. Stimulation of RARs (but not of BrCs) appeared secondary to the ozone-induced reduction of lung compliance because it was abolished by hyperinflation of the lungs. Ozone had little effect on pulmonary C-fibers or slowly adapting pulmonary stretch receptors. The authors' results suggest that both BrCs and RARs contribute to the tachypnea and bronchoconstriction evoked by acute exposure to ozone when vagal conduction is intact and that BrCs alone are responsible for the vagally mediated tachypnea that survives vagal cooling to 7[degrees]C. 23 refs., 5 figs.

  2. Relationship between regional ventilation and aerosol deposition in tidal breathing

    International Nuclear Information System (INIS)

    The regional distribution of the deposition of 1.2 micron particles of 99mTc sulfur colloid inhaled by tidal breathing was compared with the distribution of ventilation as measured by a 133Xe washout technique. Twelve subjects were studied, 6 with normal pulmonary function tests, 5 with air-flow limitation, and 1 with unilateral phrenic nerve paralysis. Both xenon and aerosol were inhaled at tidal volume by the subjects while seated upright. A large field gamma camera acquired posterior scans. Thirteen experiments were also done on 7 dogs: 1 with extrathoracic obstruction of the airway to 1 lung, and 12 with bronchoconstriction from the instillation of methacholine chloride into the airways of a lower lobe. Two of these dogs were studied with a gamma camera system, and the others were studied with a Picker multi-probe system. Both in humans and in dogs, an increase in time constant, which indicated a decrease in ventilation, was associated with an increase in peripheral aerosol deposition when normalized for ventilation. It is suggested that the increased residence time is responsible for the increased deposition in regions that received lesser ventilation

  3. Evidence for homogeneity of thromboxane A2 receptor using structurally different antagonists.

    Science.gov (United States)

    Swayne, G T; Maguire, J; Dolan, J; Raval, P; Dane, G; Greener, M; Owen, D A

    1988-08-01

    Nine structurally dissimilar thromboxane antagonists (SQ 29548, ICI 185282, AH 23848, BM 13505 (Daltroban), BM 13177 (Sulotroban), SK&F 88046, L-636499, L-640035 and a Bayer compound SK&F 47821) were studied for activity as thromboxane A2 receptor antagonists. The assays used were inhibition of responses induced by the thromboxane mimetic, U46619, on human washed platelet aggregation, rabbit platelet aggregation, rabbit aortic strip contraction, anaesthetised guinea-pig bronchoconstriction, and a radio-labelled ligand (125I-PTA-OH) binding assay as a measure of affinity for the human platelet receptor. The results of the present study, with activities spanning at least four orders of magnitude along with statistically significant correlations (at least P less than 0.01), strongly suggests that between assays, antagonists and species a homogenous population of thromboxane A2 receptors exists. This finding is in contrast to those of a close series of 13-azapinane antagonists studied by other workers which have suggested receptor heterogeneity.

  4. Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia and hypoxia in rats

    International Nuclear Information System (INIS)

    Sarin, a highly toxic nerve gas, is believed to cause bronchoconstriction and even death primarily through respiratory failure; however, the mechanism underlying the respiratory failure is not fully understood. The goals of this study were to ascertain whether sarin affects baseline ventilation (VE) and VE chemoreflexes as well as airway resistance and, if so, whether these changes are reversible. Four groups of F344 rats were exposed to vehicle (VEH) or sarin at 2.5, 3.5, and 4.0 mg h m-3 (SL, SM, and SH, respectively). VE and VE responses to hypercapnia (7% CO2) or hypoxia (10% O2) were measured by plethysmography at 2 h and 1, 2, and 5 days after VEH or sarin exposure. Total pulmonary resistance (RL) also was measured in anesthetized VEH- and SH-exposed animals 2 h after exposure. Our results showed that within 2 h after exposure 11% of the SM- and 52% of the SH- exposed groups died. Although the SM and SH significantly decreased hypercapnic and hypoxic VE to similar levels (64 and 69%), SH induced greater respiratory impairment, characterized by lower baseline VE (30%; P E impairment recovered within 1-2 days after sarin exposure; interestingly, SH did not significantly affect baseline RL. Moreover, sarin induced body tremors that were unrelated to the changes in the VE responses. Thus, LC50 sarin causes a reversible impairment of VE that is not dependent on the sarin-induced body tremors and not associated with changes in RL

  5. Aspiration-related pulmonary syndromes.

    Science.gov (United States)

    Hu, Xiaowen; Lee, Joyce S; Pianosi, Paolo T; Ryu, Jay H

    2015-03-01

    Aspiration of foreign matter into the airways and lungs can cause a wide spectrum of pulmonary disorders with various presentations. The type of syndrome resulting from aspiration depends on the quantity and nature of the aspirated material, the chronicity, and the host responses. Aspiration is most likely to occur in subjects with a decreased level of consciousness, compromised airway defense mechanisms, dysphagia, gastroesophageal reflux, and recurrent vomiting. These aspiration-related syndromes can be categorized into airway disorders, including vocal cord dysfunction, large airway obstruction with a foreign body, bronchiectasis, bronchoconstriction, and diffuse aspiration bronchiolitis, or parenchymal disorders, including aspiration pneumonitis, aspiration pneumonia, and exogenous lipoid pneumonia. In idiopathic pulmonary fibrosis, aspiration has been implicated in disease progression and acute exacerbation. Aspiration may increase the risk of bronchiolitis obliterans syndrome in patients who have undergone a lung transplant. Accumulating evidence suggests that a causative role for aspiration is often unsuspected in patients presenting with aspiration-related pulmonary diseases; thus, many cases go undiagnosed. Herein, we discuss the broadening spectrum of these pulmonary syndromes with a focus on presenting features and diagnostic aspects. PMID:25732447

  6. Effects of inspiratory resistance, inhaled beta-agonists and histamine on canine tracheal blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, W.T.; Baile, E.M.; Brancatisano, A.; Pare, P.D.; Engel, L.A. (Dept. of Respiratory Medicine, Westmead Hospital, Westmead, NSW (Australia))

    1992-01-01

    Tracheobronchial blood flow is potentially important in asthma as it could either influence the clearance of mediators form the airways, thus affecting the duration and severity of bronchoispasm, or enhance oedema formation with a resultant increase in airflow obstruction. In anaesthetized dogs, spontaneously breathing via a tracheostomy, we investigated the effects of three interventions which are relevant to acute asthma attacks and could potentially influence blood flow and its distribution to the mucosa and remaining tissues of the trachea: (1) increased negative intrathoracic pressure swings (-25[+-]1 cmH[sub 2]O) induced by an inspiratory resistance; (2) variable inhaled doses of a beta-adrenoceptor-agonist (terbutaline); and (3) aerosolized histamine sufficient to produce a threefold increase in pulmonary resistance. Microspheres labelled with different radioisotopes were used to measure blood flow. Resistive breathing did not influence tracheobronchial blood flow. Following a large dose of terbutaline, mucosal blood flow (Qmb) increased by 50%. After inhaled histamine, Qmb reached 265% of the baseline value. We conclude that, whereas increased negative pressure swings do not influence tracheobronchial blood flow or its distribution, inhalation of aerosolized terbutaline, corresponding to a conventionally nebulized dose, increases mucosal blood flow. Our results also confirm that inhaled histamine, in a dose sufficient to produce moderate bronchoconstriction, increases tracheal mucosal blood flow in the area of deposition. (au).

  7. Fatty acid binding protein 1 is related with development of aspirin-exacerbated respiratory disease.

    Directory of Open Access Journals (Sweden)

    Tae-Hoon Kim

    Full Text Available BACKGROUND: Aspirin-exacerbated respiratory disease (AERD refers to the development of bronchoconstriction in asthmatics following the ingestion of aspirin. Although alterations in eicosanoid metabolites play a role in AERD, other immune or inflammatory mechanisms may be involved. We aimed to identify proteins that were differentially expressed in nasal polyps between patients with AERD and aspirin-tolerant asthma (ATA. METHODOLOGY/PRINCIPAL FINDINGS: Two-dimensional electrophoresis was adopted for differential display proteomics. Proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS. Western blotting and immunohistochemical staining were performed to compare the amount of fatty acid-binding protein 1 (FABP1 in the nasal polyps of patients with AERD and ATA. Fifteen proteins were significantly up- (seven spots or down-regulated in the nasal polyps of patients with AERD (n = 5 compared to those with ATA (n = 8. LC-MS revealed an increase in seven proteins expression and a decrease in eight proteins expression in patients with AERD compared to those with ATA (P = 0.003-0.045. FABP1-expression based on immunoblotting and immunohistochemical analysis was significantly higher in the nasal polyps of patients with AERD compared to that in patients with ATA. FABP1 was observed in epithelial, eosinophils, macrophages, and the smooth-muscle cells of blood vessels in the polyps. CONCLUSIONS/SIGNIFICANCE: Our results indicate that alterations in 15 proteins, including FABP1, may be related to the development of AERD.

  8. Exercise and airway injury in athletes.

    Science.gov (United States)

    Couto, Mariana; Silva, Diana; Delgado, Luis; Moreira, André

    2013-01-01

    Olympic level athletes present an increased risk for asthma and allergy, especially those who take part in endurance sports, such as swimming or running, and in winter sports. Classical postulated mechanisms behind EIA include the osmotic, or airway-drying, hypothesis. Hyperventilation leads to evaporation of water and the airway surface liquid becomes hyperosmolar, providing a stimulus for water to move from any cell nearby, which results in the shrinkage of cells and the consequent release of inflammatory mediators that cause airway smooth muscle contraction. But the exercise-induced asthma/bronchoconstriction explanatory model in athletes probably comprises the interaction between environmental training factors, including allergens and ambient conditions such as temperature, humidity and air quality; and athlete's personal risk factors, such as genetic and neuroimmuneendocrine determinants. After the stress of training and competitions athletes experience higher rate of upper respiratory tract infections (URTI), compared with lesser active individuals. Increasing physical activity in non-athletes is associated with a decreased risk of URTI. Heavy exercise induces marked immunodepression which is multifactorial in origin. Prolonged, high intensity exercise temporarily impairs the immune competence while moderate activity may enhance immune function. The relationship between URTI and exercise is affected by poorly known individual determinants such genetic susceptibility, neurogenic mediated immune inflammation and epithelial barrier dysfunction. Further studies should better define the aetiologic factors and mechanisms involved in the development of asthma in athletes, and propose relevant preventive and therapeutic measures. PMID:23697359

  9. 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.

  10. Nonspecific airway reactivity in a mouse model of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Collie, D.D.; Wilder, J.A.; Bice, D.E.

    1995-12-01

    Animal models are indispensable for studies requiring an intact immune system, especially for studying the pathogenic mechanisms in atopic diseases, regulation of IgE production, and related biologic effects. Mice are particularly suitable and have been used extensively for such studies because their immune system is well characterized. Further, large numbers of mutants or inbred strains of mice are available that express deficiencies of individual immunologic processes, inflammatory cells, or mediator systems. By comparing reactions in such mice with appropriate control animals, the unique roles of individual cells or mediators may be characterized more precisely in the pathogenesis of atopic respiratory diseases including asthma. However, given that asthma in humans is characterized by the presence of airway hyperresponsiveness to specific and nonspecific stimuli, it is important that animal models of this disease exhibit similar physiologic abnormalities. In the past, the size of the mouse has limited its versatility in this regard. However, recent studies indicate the feasibility of measuring pulmonary responses in living mice, thus facilitating the physiologic evaluation of putative mouse models of human asthma that have been well charcterized at the immunologic and patholigic level. Future work will provide details of the morphometry of the methacholine-induced bronchoconstriction and will further seek to determine the relationship between cigarette smoke exposure and the development of NS-AHR in the transgenic mouse model.

  11. Practicability and safety of dipyridamole cardiac imaging in patients with severe chronic obstructive pulmonary disease

    Energy Technology Data Exchange (ETDEWEB)

    Thurnheer, R.; Laube, I.; Bloch, K.E.; Russi, E.W. [Pulmonary Division, Department of Internal Medicine, University Hospital of Switzerland, Zurich (Switzerland); Kaufmann, P.A.; Stumpe, K.D.M. [Department of Radiology, Division of Nuclear Medicine, University Hospital, Zuerich (Switzerland); Stammberger, U.; Weder, W. [Department of Surgery, University Hospital, Zuerich (Switzerland)

    1999-08-01

    We tested the practicability of dipyridamole myocardial nitrogen-13 ammonia positron emission tomography (dipyridamole {sup 13}NH{sub 3}PET) for the perioperative risk assessment of coronary artery disease (CAD) in a cohort of patients with severe chronic obstructive pulmonary disease (COPD) undergoing lung volume reduction surgery (LVRS). Twenty consecutive LVRS candidates, 13 men and 7 women (mean age 57 {+-}2 years), without symptoms of CAD were prospectively studied by dipyridamole {sup 13}NH {sub 3}PET. Side-effects and overall tolerance were assessed by a questionnaire and visual analogue scale. Repeated pulmonary function tests were performed before and 4, 12, 16 and 30 minutes after dipyridamole injection. All dipyridamole {sup 13}NH {sub 3}PET studies were negative for CAD. Seventeen patients underwent LVRS without cardiac complications; three patients did not undergo LVRS for other reasons. Nine patients suffered intolerable dyspnoea requiring i.v. aminophylline. Mean FEV {sub 1} decreased significantly after dipyridamole infusion: in nine patients the reduction in FEV {sub 1}exceeded 15% from baseline. We found that dipyridamole is not well tolerated and causes significant bronchoconstriction in patients with severe COPD. Although all dipyridamole-induced side effects can be promptly reversed by aminophylline, dipyridamole cannot be recommended as a pharmacological stress in this setting. (orig.) With 1 fig., 4 tabs., 35 refs.

  12. [Osmolarity of solutions used in nebulization].

    Science.gov (United States)

    Portel, L; Tunon de Lara, J M; Vernejoux, J M; Weiss, I; Taytard, A

    1998-04-01

    Inhaled medications are widely used in patients suffering from bronchial diseases. Beside their pharmacological properties, nebulised solutions have physico-chemical characteristics that can alter bronchial reactivity. Non-isotonic solutions can induce a bronchial hyperresponsiveness and/or a severe bronchonconstriction. Nevertheless, multiple drugs are used for nebulisation despite their unknown osmolarity. The aim of this study was to measure the tonicity of drug solutions commonly used for nebulisation in patients suffering from bronchial disease. Drug solutions were prepared either according to manufacturer recommendations or by diluting the stock in 5 ml of NaCl (0.9%) or H2CO3 (0.14%). Although bronchodilatator solutions (i.e. salbutamol, terbulatine, ipratropium bromide) were nearly isotonic, some drugs prepared for nebulisation had either a very high (e.g. mesna, netilmicine) or a very low (e.g. gomenol, sodium cromoglycate) tonicity. These values may be responsible for bronchoconstriction. Some hypertonic solutions, prepared with drugs such as acetylcytein or netilmycin, are not commercialised for nebulisation but are commonly used for aerosol therapy. In addition, solutions initially isotonic could become significantly hypertonic towards the end of nebulisation. Taken together, these results suggest that non-isotonic solutions should be used with caution specially in patients with bronchial hyperresponsiveness, even when aerosol therapy is prescribed for upper airways.

  13. Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children

    Directory of Open Access Journals (Sweden)

    Kidon Mona

    2007-12-01

    Full Text Available Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children.

  14. Respiratory Effects of Sarafotoxins from the Venom of Different Atractaspis Genus Snake Species

    Directory of Open Access Journals (Sweden)

    Stéphanie Malaquin

    2016-07-01

    Full Text Available Sarafotoxins (SRTX are endothelin-like peptides extracted from the venom of snakes belonging to the Atractaspididae family. A recent in vivo study on anesthetized and ventilated animals showed that sarafotoxin-b (SRTX-b, extracted from the venom of Atractaspis engaddensis, decreases cardiac output by inducing left ventricular dysfunction while sarafotoxin-m (SRTX-m, extracted from the venom of Atractaspis microlepidota microlepidota, induces right ventricular dysfunction with increased airway pressure. The aim of the present experimental study was to compare the respiratory effects of SRTX-m and SRTX-b. Male Wistar rats were anesthetized, tracheotomized and mechanically ventilated. They received either a 1 LD50 IV bolus of SRTX-b (n = 5 or 1 LD50 of SRTX-m (n = 5. The low-frequency forced oscillation technique was used to measure respiratory impedance. Airway resistance (Raw, parenchymal damping (G and elastance (H were determined from impedance data, before and 5 min after SRTX injection. SRTX-m and SRTX-b injections induced acute hypoxia and metabolic acidosis with an increased anion gap. Both toxins markedly increased Raw, G and H, but with a much greater effect of SRTX-b on H, which may have been due to pulmonary edema in addition to bronchoconstriction. Therefore, despite their structural analogy, these two toxins exert different effects on respiratory function. These results emphasize the role of the C-terminal extension in the in vivo effect of these toxins.

  15. Respiratory Effects of Sarafotoxins from the Venom of Different Atractaspis Genus Snake Species.

    Science.gov (United States)

    Malaquin, Stéphanie; Bayat, Sam; Abou Arab, Osama; Mourier, Gilles; Lorne, Emmanuel; Kamel, Saïd; Dupont, Hervé; Ducancel, Frédéric; Mahjoub, Yazine

    2016-01-01

    Sarafotoxins (SRTX) are endothelin-like peptides extracted from the venom of snakes belonging to the Atractaspididae family. A recent in vivo study on anesthetized and ventilated animals showed that sarafotoxin-b (SRTX-b), extracted from the venom of Atractaspis engaddensis, decreases cardiac output by inducing left ventricular dysfunction while sarafotoxin-m (SRTX-m), extracted from the venom of Atractaspis microlepidota microlepidota, induces right ventricular dysfunction with increased airway pressure. The aim of the present experimental study was to compare the respiratory effects of SRTX-m and SRTX-b. Male Wistar rats were anesthetized, tracheotomized and mechanically ventilated. They received either a 1 LD50 IV bolus of SRTX-b (n = 5) or 1 LD50 of SRTX-m (n = 5). The low-frequency forced oscillation technique was used to measure respiratory impedance. Airway resistance (Raw), parenchymal damping (G) and elastance (H) were determined from impedance data, before and 5 min after SRTX injection. SRTX-m and SRTX-b injections induced acute hypoxia and metabolic acidosis with an increased anion gap. Both toxins markedly increased Raw, G and H, but with a much greater effect of SRTX-b on H, which may have been due to pulmonary edema in addition to bronchoconstriction. Therefore, despite their structural analogy, these two toxins exert different effects on respiratory function. These results emphasize the role of the C-terminal extension in the in vivo effect of these toxins. PMID:27409637

  16. Antiallergic/antiasthmatic effect of novel antiallergic hexapeptide-95/220 in various experimental models.

    Science.gov (United States)

    Singh, R; Nath, A; Gupta, P P; Shukla, M; Khare, S K; Kundu, B

    2001-09-01

    The effects of newly synthesized antiallergic hexapeptide 95/220 was investigated on various allergic and asthmatic test models. This newly developed peptide was found to be more potent than clinically used drug disodium cromoglycate (DSCG). Hexapeptide 95/220 inhibited immediate hypersensitivity reactions such as passive cutaneous anaphylaxis (PCA) and mast cell degranulation in rats, antigen-induced bronchoconstriction in actively sensitized guinea pigs in dose dependent manner like DSCG. Antigen-induced contraction of guinea pig ileum was also markedly inhibited by this newly developed hexapeptide in the same fashion as ketotifen and DSCG did but at comparatively lower dose. Egg albumin-induced histamine release was also blocked by this hexapeptide from chopped lung tissues of sensitized guinea pigs. These results suggest that hexapeptide' 95/220 has potent inhibitory effect on immediate hypersensitivity reactions thereby inhibiting mediator release from mast cell. Moreover, this newly synthesized peptide is orally active and effective at lower doses as compared to standard drugs. PMID:11831367

  17. Chromones.

    Science.gov (United States)

    Edwards, Alan M

    2014-01-01

    The chromones are a class of chemical compounds characterised by the presence of the structure 5:6 benz-1:4-pyrone in their chemical make-up. The first chromone in clinical use, khellin, was extracted from the seeds of the plant Ammi visnaga, and had been used for centuries as a diuretic and as a smooth muscle relaxant. Its use in bronchial asthma was reported in 1947. In the 1950s, Benger's Laboratories embarked on a research programme to synthesise and develop modifications of khellin for the treatment of asthma. New compounds were screened using animal models to test the ability of the compound to prevent the anaphylactic release of histamine and SRS-A (leukotrienes) from sensitised guinea pig lung, and a human model to check the ability to reduce the bronchoconstriction induced by inhaled antigen bronchial challenge. For initial screening the human work was undertaken by Dr. R.E.C. Altounyan, who suffered from allergic bronchial asthma and was employed by Benger's Laboratories. After 8 years and more than 600 challenges using over 200 compounds, in 1965 Altounyan arrived at disodium cromoglycate (DSCG), the chromone that met the criteria of providing more than 6 h of protection. DSCG is still used today as a mast cell stabiliser. PMID:24925412

  18. Exploiting the relationship between birefringence and force to measure airway smooth muscle contraction with PS-OCT (Conference Presentation)

    Science.gov (United States)

    Adams, David C.; Hariri, Lida P.; Holz, Jasmin A.; Szabari, Margit V.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.

    2016-03-01

    The ability to observe airway dynamics is fundamental to forming a complete understanding of pulmonary diseases such as asthma. We have previously demonstrated that Optical Coherence Tomography (OCT) can be used to observe structural changes in the airway during bronchoconstriction, but standard OCT lacks the contrast to discriminate airway smooth muscle (ASM) bands- ASM being responsible for generating the force that drives airway constriction- from the surrounding tissue. Since ASM in general exhibits a greater degree of birefringence than the surrounding tissue, a potential solution to this problem lies in the implementation of polarization sensitivity (PS) to the OCT system. By modifying the OCT system so that it is sensitive to the birefringence of tissue under inspection, we can visualize the ASM with much greater clarity and definition. In this presentation we show that the force of contraction can be indirectly measured by an associated increase in the birefringence signal of the ASM. We validate this approach by attaching segments of swine trachea to an isometric force transducer and stimulating contraction, while simultaneously measuring the exerted force and imaging the segment with PS-OCT. We then show how our results may be used to extrapolate the force of contraction of closed airways in absence of additional measurement devices. We apply this technique to assess ASM contractility volumetrically and in vivo, in both asthmatic and non-asthmatic human volunteers.

  19. Exercise and airway injury in athletes.

    Science.gov (United States)

    Couto, Mariana; Silva, Diana; Delgado, Luis; Moreira, André

    2013-01-01

    Olympic level athletes present an increased risk for asthma and allergy, especially those who take part in endurance sports, such as swimming or running, and in winter sports. Classical postulated mechanisms behind EIA include the osmotic, or airway-drying, hypothesis. Hyperventilation leads to evaporation of water and the airway surface liquid becomes hyperosmolar, providing a stimulus for water to move from any cell nearby, which results in the shrinkage of cells and the consequent release of inflammatory mediators that cause airway smooth muscle contraction. But the exercise-induced asthma/bronchoconstriction explanatory model in athletes probably comprises the interaction between environmental training factors, including allergens and ambient conditions such as temperature, humidity and air quality; and athlete's personal risk factors, such as genetic and neuroimmuneendocrine determinants. After the stress of training and competitions athletes experience higher rate of upper respiratory tract infections (URTI), compared with lesser active individuals. Increasing physical activity in non-athletes is associated with a decreased risk of URTI. Heavy exercise induces marked immunodepression which is multifactorial in origin. Prolonged, high intensity exercise temporarily impairs the immune competence while moderate activity may enhance immune function. The relationship between URTI and exercise is affected by poorly known individual determinants such genetic susceptibility, neurogenic mediated immune inflammation and epithelial barrier dysfunction. Further studies should better define the aetiologic factors and mechanisms involved in the development of asthma in athletes, and propose relevant preventive and therapeutic measures.

  20. EFFICACY OF ANTIHISTAMINE AGENTS ON MODEL FOR EXERCISE-INDUCED ASTHMA IN GUINEA PIGS

    Institute of Scientific and Technical Information of China (English)

    TAO Meng-Fei; REN Tao; LIANG Yong-Jie

    2006-01-01

    Objective To investigate the effects of antihistamine agents, loratadine and ketotifen, on the model of exercise-induced asthma in guinea pigs with lipopolysaccharide ( LPS) and metyapone. Methods Nineteen guinea pigs were injected peritoneolly with LPS (1mg/kg, i. p. ) and metyapone ( 50mg/kg, i. p. ). Then they were randomized into 3 groups. The control group ( n =7) did not take any drug, ketotifen group ( n =6) adminisd-1 ) for 4 days. On the fifth day, lung resistance (RL) and dynamic compliance of respiratory system (Cdyn) of 3 groups were measured before and after exercise challenge. The total number of leukocytes in bronchoalveolar lavage fluid (BALF) from 3 groups was counted and differentiated cell type count was measured. Morphometric examination of the animal lungs was performed. Results In control group, RLincreased and Cdyn decreased significantly after exercise challenge. In ketotifen group and loratadine group with no change. There was a significant increase in the number of neutrophils, macrophages and eosinophils in BALF from control group. The infiltration of neutrophils in the bronchial mucosa was shown in control group in the morphometric study. Conclusion Loratadine and ketotifen can inhibit the exercise-indaced bronchoconstriction in guinea pigs pretreated with LPS and metyrapone. Inhibiting the formation of inflammation in airway may be the therapeutic mechanism of these H-1 receptor antagonists.

  1. Sulfur: its clinical and toxicologic aspects.

    Science.gov (United States)

    Komarnisky, Lioudmila A; Christopherson, Robert J; Basu, Tapan K

    2003-01-01

    Although there is no known dietary requirement for inorganic sulfur, it is an essential element for all animal species in as much as they all require the sulfur-containing amino acid methionine. There are three predominate forms of organic sulfur in animals and humans: 1). the thiomethyl of methionine residues in protein; 2). the sulfhydryl disulfides of protein; and 3). the compounds containing ester or amide bound sulfates of glycosaminoglycans, steroids, and many xenobiotic metabolites. Thus, sulfur becomes an important constituent of amino acids, proteins, enzymes, vitamins and other biomolecules. Unlike mammalian species, plants can use inorganic sulfur and synthesize methionine from which are synthesized all the other important sulfur compounds. Hence, sulfur deficiency occurs mainly when plants are grown in sulfur-depleted soils and when humans and animals consume low-protein diets. In recent times, however, the increasing prevalence of refining petroleum and smelting sulfur compounds of metallic minerals into free metals are having a large impact on the balance of sulfur in the environment. Sulfur toxicity is associated mainly with high levels of the element and its toxic volatile substances in the environment. Sulfur dioxide (SO(2)), a major air pollutant, may adversely affect animal and human health by causing bronchitis, bronchoconstriction, and increased pulmonary resistance.

  2. Mast cell adenosine receptors function: a focus on the A3 adenosine receptor and inflammation

    Directory of Open Access Journals (Sweden)

    Noam eRudich

    2012-06-01

    Full Text Available Adenosine is a metabolite, which has long been implicated in a variety of inflammatory processes. Inhaled adenosine provokes bronchoconstriction in asthmatics or chronic obstructive pulmonary disease (COPD patients, but not in non-asthmatics. This hyper responsiveness to adenosine appears to be mediated by mast cell activation. These observations have marked the receptor that mediates the bronchoconstrictor effect of adenosine on mast cells, as an attractive drug candidate. Four subtypes (A1, A2a, A2b and A3 of adenosine receptors have been cloned and shown to display distinct tissue distributions and functions. Animal models have firmly established the ultimate role of the A3 adenosine receptor (A3R in mediating hyper responsiveness to adenosine in mast cells, although the influence of the A2b adenosine receptor was confirmed as well. In contrast, studies of the A3R in humans have been controversial. In this review, we summarize data on the role of different adenosine receptors in mast cell regulation of inflammation and pathology, with a focus on the common and distinct functions of the A3R in rodent and human mast cells. The relevance of mouse studies to the human is discussed.

  3. Patient perspectives in the management of asthma: improving patient outcomes through critical selection of treatment options

    Directory of Open Access Journals (Sweden)

    Nicola Scichilone

    2010-02-01

    Full Text Available Nicola Scichilone, Adele Contino, Giovanni Battista Figlioli, Giuseppe Paglino, Vincenzo BelliaDipartimento di Medicina, Pneumologia, Fisiologia e Nutrizione Umana (DIMPEFINU, University of Palermo, Palermo, ItalyAbstract: Asthma is a chronic inflammatory disorder of the airways that requires long-term treatment, the goal of which is to control clinical symptoms for extended periods with the least possible amount of drugs. International guidelines recommend the addition of an inhaled long-acting beta2-agonist (LABA to a low- to medium-dose inhaled corticosteroid (ICS when low doses of ICS fail to control asthma symptoms. The fixed combined administration of ICS/LABA improves patient compliance, reducing the risk of therapy discontinuation. The relative deposition pattern of the inhaled drug to the target site is the result of a complex interaction between the device used, the aerosol formulation and the patient’s adherence to therapy. Different inhalation devices have been introduced in clinical practice over time. The new hydrofluoroalkane (HFA solution aerosols allow for the particle size to be modified, thus leading to deeper penetration of the medication into the lung. The Modulite® technology allows for the manipulation of inhaled HFA-based solution formulations, such as the fixed beclomethasone/formoterol combination, resulting in a uniform treatment of inflammation and bronchoconstriction. The success of any anti-asthmatic treatment depends on the choice of the correct device and the adherence to therapy.Keywords: asthma, therapy, inhalers, compliance

  4. ANTIASTHMATIC EFFECT OF ROOTS OF CLITOREA TERNATEA LINN.

    Directory of Open Access Journals (Sweden)

    Neelmani Chauhan et al.

    2012-04-01

    Full Text Available Clitoria ternatea L. (Family: Fabaceae is being used in traditional medicine for the treatment of severe bronchitis and asthma. So the aim of study was to evaluate antioxidant and antiasthmatic activity of ethanol extract of Clitoria ternatea roots. The present investigation was undertaken to evaluate the histamine-induced bronchospasm of alcoholic extract of Clitorea ternatea Linn. roots in experimental animals. Bronchodilator activity of aqueous extract of C. ternatea studied on the histamine aerosol induced bronchospasm in wister rats. Treatment with alcoholic extract of clitorea ternatea (400 mg/kg, p.o showed significant protection against histamine aerosol induced bronchospasm in wister rats. The results of the histamine- induced bronchospasm paradigms demonstrate bronchospasmolytic activity of ethanolic extract of clitorea ternatea (400 mg/kg, p.o.. Clitorea ternarea shows 47.45 % protection against histamine induced bronchoconstriction in rats. These results suggest that aqueous extract of C. tenatea has not only bronchodilating activity but also decreases bronchial hyperreactivity by decreasing the infiltration of inflammatory cells in the airway and inhibition of release of histamine like mediators from the mast cell by stabilizing it. Clitoria ternatea is diuretic and laxative, a decoction is given as a demulcent in the irritation of the bladder and urethra. It is useful in ophthalmopathy, bronchitis, asthma tubercular glands, hemicrania, burning sensation, starngury, helminthiasis, inflammation, vitiated condition of pitta vicerormegaly and fever.

  5. Identification of higenamine in Radix Aconiti Lateralis Preparata as a beta2-adrenergic receptor agonist

    Institute of Scientific and Technical Information of China (English)

    Gang BAI; Yang YANG; Qian SHI; Ze LIU; Qi ZHANG; Yuan-yuan ZHU

    2008-01-01

    Aim:To screen beta2-adrenergic receptor (β+-AR) agonists from Radix Aconiti Lateralis Preparata (RALP) as potential drug leads for asthma using a sensi-tive cell-based agonist assay.Methods:The β+-AR gene was stably expressed by Chinese hamster ovary (CHO) cells also stably expressing a cyclic adenosine monophosphate (AMP) response element-linked enhanced green fluorescent pro-tein reporter gene.The cells were used to screen agonists from high-performance liquid chromatographic fractions of an extract of RALE The fraction with the highest activity was selected for further compound isolation and the study of the structure-activity relationship.Its active compound was further identified by chromatography and mass spectrometry.Results:Bioactivity-directed fraction-ation of the crude extract of RALP led to the isolation and characterization of the effective compound,namely hignamine.It could dose-dependently relax the iso-lated guinea pig trachea strip precontraction with acetylcholine with EC50 value of (2.60±0.36)x 10-5 mol/L.Further in vivo studies also displayed that higuamine could protect experimental asthma model induced by histamine in guinea pigs to prolong the latent periods of asthma.Conclusion:Hignamine,as a β2-AR ago-nist existing in the extract of RALE is the key compound contributing to the suc-cessful relief of the bronchoconstriction.

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

    Science.gov (United States)

    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 active topic of debate. WNT-5A is increasingly expressed in asthmatic ASM and has been linked with Th2-high asthma. Due to its link with calcium and cytoskeletal remodelling, we propose that WNT-5A may modulate ASM contractility. We demonstrated that WNT-5A can increase maximum isometric tension in bovine tracheal smooth muscle strips. In addition, we show that WNT-5A is preferentially expressed in contractile human airway myocytes compared to proliferative cells, suggesting an active role in maintaining contractility. Furthermore, WNT-5A treatment drives actin polymerisation, but has no effect on intracellular calcium flux. Next, we demonstrated that WNT-5A directly regulates TGF-β1-induced expression of α-SMA via ROCK-mediated actin polymerization. These findings suggest that WNT-5A modulates fundamental mechanisms that affect ASM contraction and thus may be of relevance for AHR in asthma. PMID:27468699

  7. Fullerene carbon-70 derivatives dampen anaphylaxis and allergic asthma pathogenesis in mice

    Science.gov (United States)

    Norton, Sarah Brooke

    Fullerenes are carbon nanospheres that can be solublized by the addition of polar chemical groups to the carbon cage, forming fullerene derivatives. One specifically derivatized fullerene compound, termed C 70-Tetragylocolate (C70-TGA), has been shown to stabilize mast cell responses in vitro thus we hypothesized it may have an effect on mast cell-driven diseases such as asthma and systemic anaphylaxis. To observe the effects of C70-TGA on systemic anaphylaxis, mice were subjected to a model of passive systemic anaphylaxis. In this model, mice were injected with DNP-specific IgE 16 hours prior to challenge, then treated with C 70-TGA. Immediately prior to DNP challenge, mice were subjected to a second injection of C70-TGA. Following DNP challenge, body temperature was recorded and blood was collected for quantitation of histamine levels. Treatment with C70-TGA significantly reduced body temperature drop associated with systemic anaphylaxis and serum histamine levels. To observe the effects of C70-TGA on chronic features of asthma in vivo, we utilized a heavily MC influenced model of asthma pathogenesis. Mice were sensitized by intraperitoneal (i.p.) injection of ovalbumin (OVA) in saline, challenged intranasally (i.n.) with OVA, and one of two treatment strategies was pursued. In one, C70-TGA was given i.n. throughout disease development. In the other, C70-TGA was given following an initial set of challenges to allow disease to develop prior to treatment; mice were then re-challenged with OVA to assess the effect on established disease. We found that C70-TGA treatment significantly reduced airway inflammation and eosinophilia and dramatically reduced bronchoconstriction in either model. Cytokines IL-4 and IL-5 and serum IgE levels are significantly reduced in C70-TGA treated animals. Interestingly, we also saw an increase in the anti-inflammatory eicosanoid 11, 12-epoxyeicosatreinoic acid (11,12-EET) in the BAL fluid, suggesting the involvement of this mediator in

  8. Ozone-Induced Hypertussive Responses in Rabbits and Guinea Pigs.

    Science.gov (United States)

    Clay, Emlyn; Patacchini, Riccardo; Trevisani, Marcello; Preti, Delia; Branà, Maria Pia; Spina, Domenico; Page, Clive

    2016-04-01

    Cough remains a major unmet clinical need, and preclinical animal models are not predictive for new antitussive agents. We have investigated the mechanisms and pharmacological sensitivity of ozone-induced hypertussive responses in rabbits and guinea pigs. Ozone induced a significant increase in cough frequency and a decrease in time to first cough to inhaled citric acid in both conscious guinea pigs and rabbits. This response was inhibited by the established antitussive drugs codeine and levodropropizine. In contrast to the guinea pig, hypertussive responses in the rabbit were not inhibited by bronchodilator drugs (β2 agonists or muscarinic receptor antagonists), suggesting that the observed hypertussive state was not secondary to bronchoconstriction in this species. The ozone-induced hypertussive response in the rabbit was inhibited by chronic pretreatment with capsaicin, suggestive of a sensitization of airway sensory nerve fibers. However, we could find no evidence for a role of TRPA1 in this response, suggesting that ozone was not sensitizing airway sensory nerves via activation of this receptor. Whereas the ozone-induced hypertussive response was accompanied by a significant influx of neutrophils into the airway, the hypertussive response was not inhibited by the anti-inflammatory phosphodiesterase 4 inhibitor roflumilast at a dose that clearly exhibited anti-inflammatory activity. In summary, our results suggest that ozone-induced hypertussive responses to citric acid may provide a useful model for the investigation of novel drugs for the treatment of cough, but some important differences were noted between the two species with respect to sensitivity to bronchodilator drugs.

  9. Protective effect of levodropropizine against cough induced by inhalation of nebulized distilled water in patients with obstructive lung disease.

    Science.gov (United States)

    Bariffi, F; Tranfa, C; Vatrella, A; Ponticiello, A

    1992-01-01

    Levodropropizine is a recently developed, peripherally active antitussive agent which is widely used in clinical practice. In order to obtain further information on the spectrum of activity of this compound in experimental clinical models, a double-blind controlled study was carried out to evaluate the potential effect of the drug against cough and bronchoconstriction induced by inhalation of an ultrasonically nebulized solution of distilled water in patients with obstructive lung disease. Twenty patients were randomly divided into two groups, which received levodropropizine (60 mg t.i.d.) or placebo respectively for 7 consecutive days. Parameters evaluated at baseline and on the last day of treatment included (i) results of respiratory function tests (FEV1, IVC, FVC, TIFF, PEF, MEF75, MEF50, MEF25) performed before the stimulation test with nebulized water; (ii) total number of coughs during a 2-hour period after the stimulation test; (iii) bronchial responsiveness, quantified by calculating the volume of nebulized water required to induce a 20% reduction of FEV1 below the basal level. At pretreatment, the tussive response was very similar in the two groups. A significant decrease in number of coughs (from 34.4 +/- 8.4 at baseline to 15.6 +/- 4.9 post-treatment, p less than 0.01) was observed after administration of levodropropizine, whereas placebo treatment produced no significant effect (number of coughs: 29.6 +/- 4.9 at baseline vs 24.8 +/- 9.6 post-treatment, N.S.). Bronchial responsiveness decreased significantly (compared to baseline) in both treatment groups, without any significant difference between drug and placebo. Respiratory function tests were not significantly affected by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Budesonide/formoterol and formoterol provide similar rapid relief in patients with acute asthma showing refractoriness to salbutamol

    Directory of Open Access Journals (Sweden)

    Lombardi DM

    2006-01-01

    Full Text Available Abstract Background To compare the efficacy and safety of budesonide/formoterol (Symbicort® with formoterol (Oxis® in the treatment of patients with acute asthma who showed evidence of refractoriness to short-acting β2-agonist therapy. Methods In a 3 hour, randomized, double-blind study, a total of 115 patients with acute asthma (mean FEV1 40% of predicted normal and a refractory response to salbutamol (mean reversibility 2% of predicted normal after inhalation of 400 μg, were randomized to receive either budesonide/formoterol (320/9 μg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 1280/36 μg] or formoterol (9 μg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 36 μg]. The primary efficacy variable was the average FEV1 from the first intake of study medication to the measurement at 90 minutes. Secondary endpoints included changes in FEV1 at other timepoints and change in respiratory rate at 180 minutes. Treatment success, treatment failure and patient assessment of the effectiveness of the study medication were also measured. Results FEV1 increased after administration of the study medication in both treatment groups. No statistically significant difference between the treatment groups was apparent for the primary outcome variable, or for any of the other efficacy endpoints. There were no statistically significant between-group differences for treatment success, treatment failure or patient assessment of medication effectiveness. Both treatments were well tolerated. Conclusion Budesonide/formoterol and formoterol provided similarly rapid relief of acute bronchoconstriction in patients with asthma who showed evidence of refractoriness to a short-acting β2-agonist.

  11. Flowmetric comparison of respiratory inductance plethysmography and pneumotachography in horses.

    Science.gov (United States)

    Hoffman, A; Kuehn, H; Riedelberger, K; Kupcinskas, R; Miskovic, M B

    2001-12-01

    Respiratory inductance plethysmographic (RIP) and pneumotachographic (Pn) flows were compared dynamically in horses with bronchoconstriction. On a breath-by-breath basis, RIP was normalized to inspiratory volume from Pn, and peak [peak of subtracted final exhalation waveform (SFE(max))] and selected area [integral of subtracted final waveform during first 25% of exhaled volume (SFE(int))] differences between RIP and Pn flows during early expiration were measured in three settings: 1) healthy horses (n = 8) undergoing histamine bronchoprovocation; 2) horses with naturally occurring lower airway obstruction (AO) (n = 7); and 3) healthy horses (n = 6) given lobeline. HCl to induce hyperpnea. In setting 1, histamine challenge induced a dose-dependent increase in SFE(max) and SFE(int) differences. A test index of airway reactivity (interpolated histamine dose that increased SFE(max) by 35%) closely correlated (r(s) = 0.93, P = 0.001) with a conventional index (histamine dose that induced a 35% decrease in dynamic compliance). In setting 2, in horses with AO, SFE(max) and SFE(int) were markedly elevated, and their absolute values correlated significantly (P < 0.005) with pulmonary resistance and the maximum change in transpulmonary pressure. The effects of bronchodilator treatment on the SFE(max) and SFE(int) were also highly significant (P < 0.0001). In setting 3, hyperpnea, but not tachypnea, caused significant (P < 0.01) increases in SFE(max) but not in SFE(int). In conclusion, dynamic comparisons between RIP and Pn provide a defensible method for quantifying AO during tidal breathing, without the need for invasive instrumentation.

  12. Asthma and physical activity.

    Science.gov (United States)

    Oseid, S

    1982-01-01

    Physical activity regularly leads to a decline in lung function in children and adolescents with asthma. This decline is a consequence of what is known as exercise-induced asthma (EIA), and can be determined and graded with the help of lung function tests before and after submaximal workloads on the ergometer cycle or the treadmill. Typical EIA appears in asthmatic individuals with entirely normal lung function before the effort, but EIA may also become clinically manifest with exercise in patients who have a subclinical degree of obstruction. The grade of EIA is essentially dependent on the duration and intensity of effort but also on the type of exercise. For example, free running causes much greater bronchoconstriction than swimming. The temperature and humidity of the inspired air may partially explain this difference. At the Voksentoppen Allergy Institute we find that about 85% of children develop a fall in lung function of 15% or more after a six minute ergometer cycle test. With typical EIA the fall may be totally or partially abolished by prophylactic medication 10 minutes before the start of the test. Disodium cromoglycate (Intal) and/or beta-adrenergic drugs are regularly used before all physical activity. Training programmes must be based on the interval principle. Swimming, ball games, relay races and dancing are examples of useful activities in the training and rehabilitation of children and adolescents with asthma. Through prophylactic medication and physical training, the aerobic work capacity, muscle strength and lung function in asthmatic children is improved. Training also leads to a significant mobilisation of mental resources and an increase in social integration. PMID:6958045

  13. 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.

  14. Antimitogenic effect of bitter taste receptor agonists on airway smooth muscle cells.

    Science.gov (United States)

    Sharma, Pawan; Panebra, Alfredo; Pera, Tonio; Tiegs, Brian C; Hershfeld, Alena; Kenyon, Lawrence C; Deshpande, Deepak A

    2016-02-15

    bronchoconstriction in obstructive airway disease. PMID:26684251

  15. Acute effect of insulin on guinea pig airways and its amelioration by pre-treatment with salbutamol

    International Nuclear Information System (INIS)

    Objective: To study the magnitude of insulin-mediated airway hyper-reactivity and to explore the protective effects of salbutamol in inhibiting the insulin-induced airway hyper-responsiveness on tracheal smooth muscle of guinea pigs in vitro. Methods: The quasi-experimental study was conducted at the Pharmacology Department of Army Medical College, Rawalpindi, in collaboration with the Centre for Research in Experimental and Applied Medicine from December 2011 to July 2012. It used 18 healthy Dunkin Hartely guinea pigs of either gender. Effects of increasing concentrations of histamine (10-8-10-3M), insulin (10-8-10-3 M) and insulin pre-treated with salbutamol (10-6 M) were observed on isolated tracheal strip of guinea pig in vitro by constructing cumulative concentration response curves. The tracheal smooth muscle contractions were recorded with Transducer on Four Channel Oscillograph. Mean and standard error of mean were calculated. SPSS 16 was used for statistical analysis. Results: Histamine and insulin produced a concentration-dependent reversible contraction of isolated tracheal muscle of guinea pig. The mean of maximum amplitudes of contraction with histamine, insulin and insulin pre-treated with salbutamol were 92. 1.20 mm, 35+-1.13 mm and 14.55+-0.62 mm respectively. Salbutamol shifted the concentration response curve of insulin to the right and downwards. Conclusions: Salbutamol significantly reduced the insulin mediated airway hyper-reactivity in guinea pigs, suggesting that pre-treatment of inhaled insulin with salbutamol may have clinical implication in the amelioration of its potential respiratory adverse effects such as bronchoconstriction. (author)

  16. β2-agonist therapy in lung disease.

    Science.gov (United States)

    Cazzola, Mario; Page, Clive P; Rogliani, Paola; Matera, M Gabriella

    2013-04-01

    β2-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of β2-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between β2-agonists. Traditional inhaled short-acting β2-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily β2-agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent. PMID:23348973

  17. Oxidative stress and airway mucus hypersecretion%氧化应激与支气管哮喘气道黏液高分泌研究进展

    Institute of Scientific and Technical Information of China (English)

    谢桃; 李国平

    2012-01-01

    哮喘是一种以支气管收缩可逆性、肺部炎症及气道重塑为特点的慢性气道炎症性疾病.黏液过度分泌导致气道阻塞、肺功能下降、气道重塑和感染增加.过度的活性氧/活性氮(ROS/RNS)产生造成气道炎症,气道高反应性,气道微血管高通透性和气道黏液高分泌,以及组织损伤和形态的改变.减轻氧化应激或增加抗氧化能够减轻气道嗜酸粒细胞,减少黏液分泌,减轻支气管高反应性.本文就氧化应激与哮喘气道黏液高分泌的关系作一综述.%Asthma is a bronchoconstriction reversibility,lung inflammation and airway remodeling for characteristics of chronic airway inflammatory disease.Excessive mucus secretion lead to obstruction of the airway,lung function decline,airway remodeling and increase infection.Excessive reactive oxygen species/reactive nitrogen species (ROS/RNS)produce cause airway inflammation,airway responsieness,airway microvascular high permeability and high airway mucus secretion,and tissue damage and the change of the form.Reduce oxidative stress or increase antioxidant that can reduce airway eosinophils,reduce mucus secretion,reduce bronchial high reaction.Oxidative stress and asthma airway mucus secretion relationship high application were introduced in this paper.

  18. 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.

  19. No effect of elevated operating lung volumes on airway function during variable workrate exercise in asthmatic humans.

    Science.gov (United States)

    Klansky, Andrew; Irvin, Charlie; Morrison-Taylor, Adriane; Ahlstrand, Sarah; Labrie, Danielle; Haverkamp, Hans Christian

    2016-07-01

    In asthmatic adults, airway caliber fluctuates during variable intensity exercise such that bronchodilation (BD) occurs with increased workrate whereas bronchoconstriction (BC) occurs with decreased workrate. We hypothesized that increased lung mechanical stretch would prevent BC during such variable workrate exercise. Ten asthmatic and ten nonasthmatic subjects completed two exercise trials on a cycle ergometer. Both trials included a 28-min exercise bout consisting of alternating four min periods at workloads equal to 40 % (Low) and 70% (High) peak power output. During one trial, subjects breathed spontaneously throughout exercise (SVT), such that tidal volume (VT) and end-inspiratory lung volume (EILV) were increased by 0.5 and 0.6 liters during the high compared with the low workload in nonasthmatic and asthmatic subjects, respectively. During the second trial (MVT), VT and EILV were maintained constant when transitioning from the high to the low workload. Forced exhalations from total lung capacity were performed during each exercise workload. In asthmatic subjects, forced expiratory volume 1.0 s (FEV1.0) increased and decreased with the increases and decreases in workrate during both SVT (Low, 3.3 ± 0.3 liters; High, 3.6 ± 0.2 liters; P < 0.05) and MVT (Low, 3.3 ± 0.3 liters; High, 3.5 ± 0.2 liters; P < 0.05). Thus increased lung stretch during MVT did not prevent decreases in airway caliber when workload was reduced. We conclude that neural factors controlling airway smooth muscle (ASM) contractile activity during whole body exercise are more robust determinants of airway caliber than the ability of lung stretch to alter ASM actin-myosin binding and contraction. PMID:27150833

  20. [Physical exercise and bronchial asthma].

    Science.gov (United States)

    Endre, László

    2016-06-26

    An article was published in the Lancet in 1935 about the therapy of asthmatic patients, using a special breathing exercise (the authors used a control group, too). Swimming, as a complementary therapy for asthmatic children, was first recommended in 1968, by authors from the United States. In Hungary, regular swimming training for asthmatic children is in use since August, 1981. As the result of this exercise, the physical fitness of asthmatic children (using this method regularly for years) increased dramatically, and it is much better compared to that found in the non asthmatic, non swimming children of the same age group. The requirement for asthma medication decreased, and the severity of their disease significantly decreased, also. On the other hand, asthma is not a rarity even among elite athletes. It is most frequent in the endurance sports (for example in Northern Europe among cross-country skiers its prevalence is between 14-54%, among long distance runners 15-24%, and among swimmers 13-44%). The possible reason is related to the fact that elite athletes inspire 200 liter air/minute (mostly through the mouth). Air pollution and allergens can penetrate in the lower respiratory tract. The air causes cooling and drying of the mucosa of the airways and, as a consequence, mediators are liberated which produce oedema of the mucosa, and bronchoconstriction. Beta-2-receptor agonists inhalation can prevent (or decrease significantly) this phenomenon. These agents are used regularly by elite athletes, too. The non-medical possibilities for prevention include wearing a special mask, frequent ventilation of the swimming pool's air, consumption of omega-3-fatty acid, and inhalation of dry salt (very small, and very clear sodiumchloride particles).

  1. [Physical exercise and bronchial asthma].

    Science.gov (United States)

    Endre, László

    2016-06-26

    An article was published in the Lancet in 1935 about the therapy of asthmatic patients, using a special breathing exercise (the authors used a control group, too). Swimming, as a complementary therapy for asthmatic children, was first recommended in 1968, by authors from the United States. In Hungary, regular swimming training for asthmatic children is in use since August, 1981. As the result of this exercise, the physical fitness of asthmatic children (using this method regularly for years) increased dramatically, and it is much better compared to that found in the non asthmatic, non swimming children of the same age group. The requirement for asthma medication decreased, and the severity of their disease significantly decreased, also. On the other hand, asthma is not a rarity even among elite athletes. It is most frequent in the endurance sports (for example in Northern Europe among cross-country skiers its prevalence is between 14-54%, among long distance runners 15-24%, and among swimmers 13-44%). The possible reason is related to the fact that elite athletes inspire 200 liter air/minute (mostly through the mouth). Air pollution and allergens can penetrate in the lower respiratory tract. The air causes cooling and drying of the mucosa of the airways and, as a consequence, mediators are liberated which produce oedema of the mucosa, and bronchoconstriction. Beta-2-receptor agonists inhalation can prevent (or decrease significantly) this phenomenon. These agents are used regularly by elite athletes, too. The non-medical possibilities for prevention include wearing a special mask, frequent ventilation of the swimming pool's air, consumption of omega-3-fatty acid, and inhalation of dry salt (very small, and very clear sodiumchloride particles). PMID:27319382

  2. Inhibitory effects of cryptoporus polysaccharide on airway constriction, eosinophil release, and chemotaxis in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan ZHAO; Qiang-min XIE; Ji-qiang CHEN; Chuan-kui KE

    2004-01-01

    AIM: To study effects of cryptoporus polysaccharide (CP) on antigen-induced bronchoconstriction, eosinophil peroxidase (EPO) release in vivo, and on platelet activating factor (PAF)-induced eosinophil chemotaxis in vitro in guinea pig. METHODS: The asthma model of guinea pig was formed with ovalbumin (OVA). The changes of lung resistance (RL) and dynamic lung compliance (Cdyn), EPO level in bronchoalveolar lavage fluids (BALF) and eosinophil migration were determined. RESULTS: Pretreatment of CP at doses of 3, 9, and 27 mg/kg by intragastric gavage (ig), qd for 10 d, inhibited early asthma response in a dose-dependent manner. Inhibitory rates of mean increase value from 1 to 30 min of RL were 34.8 %, 74.4 % (P<0.05), and 79.6 % (P<0.05), respectively. Inhibitory rate of mean reduction value of Cdyn were 22.9 %, 40.5 % (P<0.01), and 66.5 % (P<0.01), respectively.Pretreatment of CP at doses of 3, 9, and 27 mg/kg also inhibited late asthma response, and the reduction of EPO level in BALF were 3.1%, 16.9 % (P<0.01), and 20.1% (P<0.01), respectively. The inhibitory rates of CP at concentrations of 0.13, 1.3, 13, 130 nmol/L to eosinophil migration induced by PAF were 6.8 %, 17.2 % (P<0.05),29.6 % (P<0.01), and 35.9 % (P<0.01). CONCLUSION: CP protects lung against increase of RL and reduction of Cdyn, decreases EPO level in the asthma model, and inhibits eosinophil chemotaxis induced by PAF. The results suggest that CP may be a novel antiinflammatory agent for the treatment of asthma and allergic diseases.

  3. ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile.

    Directory of Open Access Journals (Sweden)

    Rie Yamamoto

    Full Text Available Sphingosine-1-phosphate (S1P is a biologically active sphingolipid that acts through the members of a family of five G protein-coupled receptors (S1P1-S1P5. S1P1 is a major regulator of lymphocyte trafficking, and fingolimod, whose active metabolite fingolimod phosphate acts as a nonselective S1P receptor agonist, exerts its immunomodulatory effect, at least in part, by regulating the lymphocyte trafficking by inducing down regulation of lymphocyte S1P1. Here, we detail the pharmacological profile of 5-{5-[3-(trifluoromethyl-4-{[(2S-1,1,1-trifluoropropan-2-yl]oxy}phenyl]-1,2,4-oxadiazol-3-yl}-1H-benzimidazole (ASP4058, a novel next-generation S1P receptor agonist selective for S1P1 and S1P5. ASP4058 preferentially activates S1P1 and S1P5 compared with S1P2, 3, 4 in GTPγS binding assays in vitro. Oral administration of ASP4058 reduced the number of peripheral lymphocytes and inhibited the development of experimental autoimmune encephalomyelitis (EAE in Lewis rats. Further, ASP4058 prevented relapse of disease in a mouse model of relapsing-remitting EAE. Although these immunomodulatory effects were comparable to those of fingolimod, ASP4058 showed a wider safety margin than fingolimod for bradycardia and bronchoconstriction in rodents. These observations suggest that ASP4058 represents a new therapeutic option for treating multiple sclerosis that is safer than nonselective S1P receptor agonists such as fingolimod.

  4. Induction of regulator of G-protein signaling 2 expression by long-acting β2-adrenoceptor agonists and glucocorticoids in human airway epithelial cells.

    Science.gov (United States)

    Holden, Neil S; George, Tresa; Rider, Christopher F; Chandrasekhar, Ambika; Shah, Suharsh; Kaur, Manminder; Johnson, Malcolm; Siderovski, David P; Leigh, Richard; Giembycz, Mark A; Newton, Robert

    2014-01-01

    In asthma and chronic obstructive pulmonary disease (COPD) multiple mediators act on Gαq-linked G-protein-coupled receptors (GPCRs) to cause bronchoconstriction. However, acting on the airway epithelium, such mediators may also elicit inflammatory responses. In human bronchial epithelial BEAS-2B cells (bronchial epithelium + adenovirus 12-SV40 hybrid), regulator of G-protein signaling (RGS) 2 mRNA and protein were synergistically induced in response to combinations of long-acting β2-adrenoceptor agonist (LABA) (salmeterol, formoterol) plus glucocorticoid (dexamethasone, fluticasone propionate, budesonide). Equivalent responses occurred in primary human bronchial epithelial cells. Concentrations of glucocorticoid plus LABA required to induce RGS2 expression in BEAS-2B cells were consistent with the levels achieved therapeutically in the lungs. As RGS2 is a GTPase-activating protein that switches off Gαq, intracellular free calcium ([Ca(2+)]i) flux was used as a surrogate of responses induced by histamine, methacholine, and the thromboxane receptor agonist U46619 [(Z)-7-[(1S,4R,5R,6S)-5-[(E,3S)-3-hydroxyoct-1-enyl]-3-oxabicyclo[2.2.1]heptan-6-yl]hept-5-enoic acid]. This was significantly attenuated by salmeterol plus dexamethasone pretreatment, or RGS2 overexpression, and the protective effect of salmeterol plus dexamethasone was abolished by RGS2 RNA silencing. Although methacholine and U46619 induced interleukin-8 (IL-8) release and this was inhibited by RGS2 overexpression, the repression of U46619-induced IL-8 release by salmeterol plus dexamethasone was unaffected by RGS2 knockdown. Given a role for Gαq-mediated pathways in inducing IL-8 release, we propose that RGS2 acts redundantly with other effector processes to repress IL-8 expression. Thus, RGS2 expression is a novel effector mechanism in the airway epithelium that is induced by glucocorticoid/LABA combinations. This could contribute to the efficacy of glucocorticoid/LABA combinations in asthma and

  5. Stimulants and the lung : review of literature.

    Science.gov (United States)

    Tseng, Will; Sutter, Mark E; Albertson, Timothy E

    2014-02-01

    Illicit stimulants, such as cocaine, amphetamine, and their derivatives (e.g., "ecstasy"), continue to exact heavy toll on health care in both developed and developing countries. The US Department of Health and Human Service reported over one million illicit drug-related emergency department visits in 2010, which was higher than any of the six previous years. Both inhaled and intravenous forms of these substances of abuse can result in a variety of acute and chronic injuries to practically every part of the respiratory tract, leading potentially to permanent morbidities as well as fatal consequences--including but not limited to nasal septum perforation, pulmonary hypertension, pneumothorax, pneumomediastinum, interstitial lung disease, alveolar hemorrhage, reactive airway disease, pulmonary edema, pulmonary granulomatosis, infections, foreign body aspiration, infections, bronchoconstriction, and thermal injuries. Stimulants are all rapidly absorbed substances that can also significantly alter the patient's systemic acid-base balance and central nervous system, thereby leading to further respiratory compromise. Mounting evidence in the past decade has demonstrated that adulterants coinhaled with these substances (e.g., levamisole) and the metabolites of these substances (e.g., cocaethylene) are associated with specific forms of systemic and respiratory complications as well. Recent studies have also demonstrated the effects of stimulants on autoimmune-mediated injuries of the respiratory tract, such as cocaine-induced midline destructive lesions. A persistent challenge to studies involving stimulant-associated respiratory toxidromes is the high prevalence of concomitant usage of various substances by drug abusers, including tobacco smoking. Now more than ever, health care providers must be familiar with the multitude of respiratory toxidromes as well as the diverse pathophysiology related to commonly abused stimulants to provide timely diagnosis and effective

  6. 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

  7. Critical analysis of studies concerning reports of respiratory sensitization to certain wood dusts.

    Science.gov (United States)

    Williams, P Brock

    2005-01-01

    Studies have been published reporting that exposures to certain wood dusts are sensitizing, resulting in respiratory symptoms in susceptible individuals. Many of the publications in this field are case reports that collectively have a number of important shortcomings. Illuminating these should further our understanding of whether respiratory sensitization results from occupational exposure to particular wood dusts. The aim of this study was to critically review and understand the evidence to date regarding reported respiratory sensitization in connection with wood dusts from oak, beech, pine, ash, and western red cedar. Publications dealing with these commercially important woods in North America have been selected from the Pubmed/Medline database (1966 to the present) using the key word, wood dust. These articles, along with supporting references on procedures and techniques, are reviewed according to the strengths and weaknesses of evidence and conclusions presented. Evidence from skin testing, specific immunoglobulin E measurements, and basophil histamine release tests suggests that reported symptoms are not likely to be immunologically derived. Because of methodological problems, challenge tests with specific wood dusts do not support the conclusion that reactions to certain wood dusts are specific. Experiments with nonspecific bronchoconstrictive agents indicate that a number of study subjects possess hyperresponsive airways. Thus, select individuals can demonstrate various respiratory symptoms in the woodworking industry, but any specificity or direct cause is currently unproved. Current studies do not support that exposure to wood dusts from a number of common North American wood species causes immunologic sensitization in woodworkers. Rather, symptoms reported in some studies of exposed workers seem to follow the paradigm for nonspecific respiratory responses in individuals with hyperresponsive airways.

  8. Critical analysis of studies concerning reports of respiratory sensitization to certain wood dusts.

    Science.gov (United States)

    Williams, P Brock

    2005-01-01

    Studies have been published reporting that exposures to certain wood dusts are sensitizing, resulting in respiratory symptoms in susceptible individuals. Many of the publications in this field are case reports that collectively have a number of important shortcomings. Illuminating these should further our understanding of whether respiratory sensitization results from occupational exposure to particular wood dusts. The aim of this study was to critically review and understand the evidence to date regarding reported respiratory sensitization in connection with wood dusts from oak, beech, pine, ash, and western red cedar. Publications dealing with these commercially important woods in North America have been selected from the Pubmed/Medline database (1966 to the present) using the key word, wood dust. These articles, along with supporting references on procedures and techniques, are reviewed according to the strengths and weaknesses of evidence and conclusions presented. Evidence from skin testing, specific immunoglobulin E measurements, and basophil histamine release tests suggests that reported symptoms are not likely to be immunologically derived. Because of methodological problems, challenge tests with specific wood dusts do not support the conclusion that reactions to certain wood dusts are specific. Experiments with nonspecific bronchoconstrictive agents indicate that a number of study subjects possess hyperresponsive airways. Thus, select individuals can demonstrate various respiratory symptoms in the woodworking industry, but any specificity or direct cause is currently unproved. Current studies do not support that exposure to wood dusts from a number of common North American wood species causes immunologic sensitization in woodworkers. Rather, symptoms reported in some studies of exposed workers seem to follow the paradigm for nonspecific respiratory responses in individuals with hyperresponsive airways. PMID:16270718

  9. The effects of aminophylline infusion in the treatment of children with acute asthma exacerbation. Evaluation with {sup 81m}Kr ventilation scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Matsubara, Yasuko; Shimada, Takao [Jikei Univ., Tokyo (Japan). School of Medicine

    1998-09-01

    The use of intravenous aminophylline in the treatment of children with acute asthma remains controversial. Most authors suggest that aminophylline be used with caution because of its poor efficacy with adverse reactions and instead recommend other drugs, such as {beta}{sub 2}-adrenergic agonists and glucocorticoids. However other studies have reported the benefits of aminophylline, and current Japanese guidelines for the management of asthma recommend its use. Here, we have evaluated the efficacy of aminophylline infusion in children with acute asthma exacerbations. Twenty children with acute asthma exacerbations were given an infusion of 5 mg/kg of aminophylline over 5 minutes, 30 minutes after the same volume of normal saline had been infused as a control. {sup 81m}Kr ventilation scintigraphy was done sequentially, and lung function was measured with spirometry before and after each infusion. Side effects were also evaluated with a questionnaire. Ventilation images obtained with {sup 81m}Kr scintigraphy, which initially showed widespread ventilatory defects caused by bronchoconstriction, decreased 54.9% after aminophylline infusion (p<0.0001). Ventilatory defects, caused by both central and peripheral airway disturbances and confirmed with the {sup 81m}Kr bolus inhalation procedure, also showed significant improvement (p<0.0001). These improvement were accompanied by improvements in lung function as assessed with forced expiratory volume in 1 second (p<0.01) and maximum expiratory flow rates at 25% (p<0.001) and 50% (p<0.001). No serious adverse reactions were recognized in any subjects. Our results show that aminophylline is a useful bronchodilator which decreased ventilatory imbalance and improves lung function in both central and peripheral airways. (author)

  10. Activation of Transient Receptor Potential Ankyrin-1 by Insoluble Particulate Material and Association with Asthma.

    Science.gov (United States)

    Deering-Rice, Cassandra E; Shapiro, Darien; Romero, Erin G; Stockmann, Chris; Bevans, Tatjana S; Phan, Quang M; Stone, Bryan L; Fassl, Bernhard; Nkoy, Flory; Uchida, Derek A; Ward, Robert M; Veranth, John M; Reilly, Christopher A

    2015-12-01

    Inhaled irritants activate transient receptor potential ankyrin-1 (TRPA1), resulting in cough, bronchoconstriction, and inflammation/edema. TRPA1 is also implicated in the pathogenesis of asthma. Our hypothesis was that particulate materials activate TRPA1 via a mechanism distinct from chemical agonists and that, in a cohort of children with asthma living in a location prone to high levels of air pollution, expression of uniquely sensitive forms of TRPA1 may correlate with reduced asthma control. Variant forms of TRPA1 were constructed by mutating residues in known functional elements and corresponding to single-nucleotide polymorphisms in functional domains. TRPA1 activity was studied in transfected HEK-293 cells using allyl-isothiocynate, a model soluble electrophilic agonist; 3,5-ditert butylphenol, a soluble nonelectrophilic agonist and a component of diesel exhaust particles; and insoluble coal fly ash (CFA) particles. The N-terminal variants R3C and R58T exhibited greater, but not additive, activity with all three agonists. The ankyrin repeat domain-4 single nucleotide polymorphisms E179K and K186N exhibited decreased response to CFA. The predicted N-linked glycosylation site residues N747A and N753A exhibited decreased responses to CFA, which were not attributable to differences in cellular localization. The pore-loop residue R919Q was comparable to wild-type, whereas N954T was inactive to soluble agonists but not CFA. These data identify roles for ankyrin domain-4, cell surface N-linked glycans, and selected pore-loop domain residues in the activation of TRPA1 by insoluble particles. Furthermore, the R3C and R58T polymorphisms correlated with reduced asthma control for some children, which suggest that TRPA1 activity may modulate asthma, particularly among individuals living in locations prone to high levels of air pollution.

  11. Initial evaluation of the effects of aerosolized Florida red tide toxins (brevetoxins) in persons with asthma.

    Science.gov (United States)

    Fleming, Lora E; Kirkpatrick, Barbara; Backer, Lorraine C; Bean, Judy A; Wanner, Adam; Dalpra, Dana; Tamer, Robert; Zaias, Julia; Cheng, Yung Sung; Pierce, Richard; Naar, Jerome; Abraham, William; Clark, Richard; Zhou, Yue; Henry, Michael S; Johnson, David; Van De Bogart, Gayl; Bossart, Gregory D; Harrington, Mark; Baden, Daniel G

    2005-05-01

    Florida red tides annually occur in the Gulf of Mexico, resulting from blooms of the marine dinoflagellate Karenia brevis. K. brevis produces highly potent natural polyether toxins, known as brevetoxins, that activate voltage-sensitive sodium channels. In experimental animals, brevetoxins cause significant bronchoconstriction. A study of persons who visited the beach recreationally found a significant increase in self-reported respiratory symptoms after exposure to aerosolized Florida red tides. Anecdotal reports indicate that persons with underlying respiratory diseases may be particularly susceptible to adverse health effects from these aerosolized toxins. Fifty-nine persons with physician-diagnosed asthma were evaluated for 1 hr before and after going to the beach on days with and without Florida red tide. Study participants were evaluated with a brief symptom questionnaire, nose and throat swabs, and spirometry approved by the National Institute for Occupational Safety and Health. Environmental monitoring, water and air sampling (i.e., K. brevis, brevetoxins, and particulate size distribution), and personal monitoring (for toxins) were performed. Brevetoxin concentrations were measured by liquid chromatography mass spectrometry, high-performance liquid chromatography, and a newly developed brevetoxin enzyme-linked immunosorbent assay. Participants were significantly more likely to report respiratory symptoms after Florida red tide exposure. Participants demonstrated small but statistically significant decreases in forced expiratory volume in 1 sec, forced expiratory flow between 25 and 75%, and peak expiratory flow after exposure, particularly those regularly using asthma medications. Similar evaluation during nonexposure periods did not significantly differ. This is the first study to show objectively measurable adverse health effects from exposure to aerosolized Florida red tide toxins in persons with asthma. Future studies will examine the possible chronic

  12. Exercise but not mannitol provocation increases urinary Clara cell protein (CC16) in elite swimmers.

    Science.gov (United States)

    Romberg, Kerstin; Bjermer, Leif; Tufvesson, Ellen

    2011-01-01

    Elite swimmers have an increased risk of developing asthma, and exposure to chloramine is believed to be an important trigger factor. The aim of the present study was to explore pathophysiological mechanisms behind induced bronchoconstriction in swimmers exposed to chloramine, before and after swim exercise provocation as well as mannitol provocation. Urinary Clara cell protein (CC16) was used as a possible marker for epithelial stress. 101 elite aspiring swim athletes were investigated and urinary samples were collected before and 1 h after completed exercise and mannitol challenge. CC16, 11β-prostaglandin (PG)F(2α) and leukotriene E(4) (LTE(4)) were measured. Urinary levels of CC16 were clearly increased after exercise challenge, while no reaction was seen after mannitol challenge. Similar to CC16, the level of 11β-PGF(2α) was increased after exercise challenge, but not after mannitol challenge, while LTE(4) was reduced after exercise. There was no significant difference in urinary response between those with a negative compared to positive challenge, but a tendency of increased baseline levels of 11β-PGF(2α) and LTE(4) in individuals with a positive mannitol challenge. The uniform increase of CC16 after swim exercise indicates that CC16 is of importance in epithelial stress, and may as such be an important pathogenic factor behind asthma development in swimmers. The changes seen in urinary levels of 11β-PGF(2α) and LTE(4) indicate a pathophysiological role in both mannitol and exercise challenge. PMID:20696561

  13. Cough and exhaled nitric oxide levels: what happens with exercise?

    Science.gov (United States)

    Petsky, Helen L; Kynaston, Jennifer Anne; McElrea, Margaret; Turner, Catherine; Isles, Alan; Chang, Anne B

    2013-01-01

    Cough associated with exertion is often used as a surrogate marker of asthma. However, to date there are no studies that have objectively measured cough in association with exercise in children. Our primary aim was to examine whether children with a pre-existing cough have an increase in cough frequency during and post-exercise. We hypothesized that children with any coughing illness will have an increase in cough frequency post-exercise regardless of the presence of exercise-induced broncho-constriction (EIB) or atopy. In addition, we hypothesized that Fractional exhaled nitric oxide (FeNO) levels decreases post-exercise regardless of the presence of EIB or atopy. Children with chronic cough and a control group without cough undertook an exercise challenge, FeNO measurements and a skin prick test, and wore a 24-h voice recorder to objectively measure cough frequency. The association between recorded cough frequency, exercise, atopy, and presence of EIB was tested. We also determined if the change in FeNO post exercise related to atopy or EIB. Of the 50 children recruited (35 with cough, 15 control), 7 had EIB. Children with cough had a significant increase in cough counts (median 7.0, inter-quartile ranges, 0.5, 24.5) compared to controls (2.0, IQR 0, 5.0, p = 0.028) post-exercise. Presence of atopy or EIB did not influence cough frequency. FeNO level was significantly lower post-exercise in both groups but the change was not influenced by atopy or EIB. Cough post-exertion is likely a generic response in children with a current cough. FeNO level decreases post-exercise irrespective of the presence of atopy or EIB. A larger study is necessary confirm or refute our findings.

  14. Cough and exhaled nitric oxide levels: What happens with exercise?

    Directory of Open Access Journals (Sweden)

    Helen ePetsky

    2013-10-01

    Full Text Available Cough associated with exertion is often used as a surrogate marker of asthma. However, to date there are no studies that have objectively measured cough in association with exercise in children. Our primary aim was to examine whether children with a pre-existing cough have an increase in cough frequency during and post-exercise. We hypothesised that children with any coughing illness will have an increase in cough frequency post-exercise regardless of the presence of exercise induced broncho-constriction (EIB or atopy. In addition, we hypotheised that FeNO levels decreases post-exercise regardless of the presence of EIB or atopy.Children with chronic cough and a control group without cough undertook an exercise challenge, FeNO measurements and a skin prick test and wore a 24-hour voice recorder to objectively measure cough frequency. The association between recorded cough frequency, exercise, atopy and presence of EIB was tested. We also determined if the change in FeNO post exercise related to atopy or EIB.Of the 50 children recruited (35 with cough, 15 control, 7 had EIB. Children with cough had a significant increase in cough counts (median 7.0, IQR 0.5, 24.5 compared to controls (2.0, IQR 0, 5.0, p=0.028 post-exercise. Presence of atopy or EIB did not influence cough frequency. FeNO level was significantly lower post-exercise in both groups but the change was not influenced by atopy or EIB. Cough post-exertion is likely a generic response in children with a current cough. FeNO level decreases post-exercise irrespective of the presence of atopy or EIB. A larger study is necessary confirm or refute our findings.

  15. Protective effect of levodropropizine against cough induced by inhalation of nebulized distilled water in patients with obstructive lung disease.

    Science.gov (United States)

    Bariffi, F; Tranfa, C; Vatrella, A; Ponticiello, A

    1992-01-01

    Levodropropizine is a recently developed, peripherally active antitussive agent which is widely used in clinical practice. In order to obtain further information on the spectrum of activity of this compound in experimental clinical models, a double-blind controlled study was carried out to evaluate the potential effect of the drug against cough and bronchoconstriction induced by inhalation of an ultrasonically nebulized solution of distilled water in patients with obstructive lung disease. Twenty patients were randomly divided into two groups, which received levodropropizine (60 mg t.i.d.) or placebo respectively for 7 consecutive days. Parameters evaluated at baseline and on the last day of treatment included (i) results of respiratory function tests (FEV1, IVC, FVC, TIFF, PEF, MEF75, MEF50, MEF25) performed before the stimulation test with nebulized water; (ii) total number of coughs during a 2-hour period after the stimulation test; (iii) bronchial responsiveness, quantified by calculating the volume of nebulized water required to induce a 20% reduction of FEV1 below the basal level. At pretreatment, the tussive response was very similar in the two groups. A significant decrease in number of coughs (from 34.4 +/- 8.4 at baseline to 15.6 +/- 4.9 post-treatment, p less than 0.01) was observed after administration of levodropropizine, whereas placebo treatment produced no significant effect (number of coughs: 29.6 +/- 4.9 at baseline vs 24.8 +/- 9.6 post-treatment, N.S.). Bronchial responsiveness decreased significantly (compared to baseline) in both treatment groups, without any significant difference between drug and placebo. Respiratory function tests were not significantly affected by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1425206

  16. Ozone-Induced Hypertussive Responses in Rabbits and Guinea Pigs.

    Science.gov (United States)

    Clay, Emlyn; Patacchini, Riccardo; Trevisani, Marcello; Preti, Delia; Branà, Maria Pia; Spina, Domenico; Page, Clive

    2016-04-01

    Cough remains a major unmet clinical need, and preclinical animal models are not predictive for new antitussive agents. We have investigated the mechanisms and pharmacological sensitivity of ozone-induced hypertussive responses in rabbits and guinea pigs. Ozone induced a significant increase in cough frequency and a decrease in time to first cough to inhaled citric acid in both conscious guinea pigs and rabbits. This response was inhibited by the established antitussive drugs codeine and levodropropizine. In contrast to the guinea pig, hypertussive responses in the rabbit were not inhibited by bronchodilator drugs (β2 agonists or muscarinic receptor antagonists), suggesting that the observed hypertussive state was not secondary to bronchoconstriction in this species. The ozone-induced hypertussive response in the rabbit was inhibited by chronic pretreatment with capsaicin, suggestive of a sensitization of airway sensory nerve fibers. However, we could find no evidence for a role of TRPA1 in this response, suggesting that ozone was not sensitizing airway sensory nerves via activation of this receptor. Whereas the ozone-induced hypertussive response was accompanied by a significant influx of neutrophils into the airway, the hypertussive response was not inhibited by the anti-inflammatory phosphodiesterase 4 inhibitor roflumilast at a dose that clearly exhibited anti-inflammatory activity. In summary, our results suggest that ozone-induced hypertussive responses to citric acid may provide a useful model for the investigation of novel drugs for the treatment of cough, but some important differences were noted between the two species with respect to sensitivity to bronchodilator drugs. PMID:26837703

  17. Involvement of glutamate in transmission of afferent constrictive inputs from the airways to the nucleus tractus solitarius in ferrets.

    Science.gov (United States)

    Haxhiu, M A; Yamamoto, B; Dreshaj, I A; Bedol, D; Ferguson, D G

    2000-04-12

    In this study, we identified the neurons within nucleus tractus solitarius (nTS) activated by stimulation of airway sensory systems and examined the expression of AMPA receptor subtype(s) by these cells. We also investigated the possible involvement of endogenously released glutamate and AMPA receptors in the transmission of excitatory inputs from the sensory system of the respiratory tract to the neurons of the nTS. In these experiments we used: (1) immunodetection of c-fos encoded protein (cFos) expression to identify the nTS neurons activated by the stimulation of the airway sensory system; (2) receptor immunochemistry and confocal microscopy to determine the receptor(s) expressed by activated nTS neurons; (3) microdialysis to measure glutamate release, and (4) physiological measurements to examine the effects of selective receptor blockers, and thereby define the role of the glutamate and AMPA glutamatergic receptor subtype(s) in reflexly induced airway constriction. The results showed that activation of airway sensory receptors, by inhalation of aerosolized histamine or capsaicin, induced cFos expression in a subset of nTS neurons that also expressed the AMPA subtype of glutamate receptors. Furthermore, activation of sensory bronchoconstrictive receptors induced glutamate release within nTS, and blockade of the AMPA receptor subtype within nTS inhibited reflexly increased cholinergic outflow to the airways. These data indicate for the first time that glutamate and AMPA receptor signaling pathways are involved in the transmission of afferent inputs from the airways to the nTS, and in mediating reflex airway constriction.

  18. CysLT1 Receptor Is Protective against Oxidative Stress in a Model of Irritant-Induced Asthma.

    Science.gov (United States)

    McGovern, Toby; Goldberger, Madison; Chen, Michael; Allard, Benoit; Hamamoto, Yoichiro; Kanaoka, Yoshihide; Austen, K Frank; Powell, William S; Martin, James G

    2016-07-01

    The bronchoconstrictive and proinflammatory properties of cysteinyl leukotrienes (cysLTs) in allergic asthma mediate their effects predominantly through the cysLT1 receptor (cysLT1R). However, the role of cysLTs and cysLT1R in innate immune-triggered asthma is largely unexplored. We explored the synthesis of cysLTs and cysLT1R as determinants of airway responses in an oxidative stress-induced model of irritant asthma. Wild-type (WT) mice exposed to 100 ppm Cl2 for 5 min had airway neutrophilia, increased cysLT production, and pulmonary expression of cysLT-related biosynthetic genes. CysLT1R-deficient (CysLTr1(-/-)) mice that were exposed to Cl2 demonstrated airway hyperresponsiveness to inhaled methacholine significantly greater than in WT BALB/c mice. Compared to WT mice, airway neutrophilia and keratinocyte chemoattractant production levels were higher in CysLTr1(-/-) mice and airway hyperresponsiveness was ameliorated using a granulocyte depletion Ab. CysLTr1(-/-) mice also demonstrated prolonged bronchial epithelial cell apoptosis following Cl2 WT mice showed increased antioxidant and NF erythroid 2-related factor 2 (Nrf2) gene expression, Nrf2 nuclear translocation in bronchial epithelial cells, and increased reduced glutathione/oxidized glutathione following Cl2 exposure whereas CysLTr1(-/-) mice did not. Furthermore, CysLTr1(-/-) mice demonstrated increased pulmonary E-cadherin expression and soluble E-cadherin shedding compared with WT mice. Loss of a functional cysLT1R results in aberrant antioxidant response and increased susceptibility to oxidative injury, apparently via a cysLT1R-dependent impairment of Nrf2 function. PMID:27226094

  19. Use of aerosols in lung function studies

    International Nuclear Information System (INIS)

    Since aerosol inhalation lung scintigraphy was introduced in 1965 following perfusion lung imaging, both imaging modalities have offered powerful tools not only for the study of respiratory lung function but also for the exploration of non-respiratory lung function studies. Visualization of the distribution of ventilation and perfusion in the lungs has made it possible to determine whether ventilation and perfusion are well matched or not, thus leading to the diagnosis of vascular diseases if perfusion is absent in the well ventilated lung regions, whereas airway diseases show matched ventilation and perfusion abnormalities. The reasons for the above principles have been physiologically clarified by perfusion and inhalation techniques using radioactive particulates, aerosols and radioactive gases. Regional ventilation always regulates regional perfusion; regional hypoventilation causes regional hypoxia which in turn causes hypoxic vasoconstriction and a consequent decrease in perfusion. Regional perfusion does not regulate regional ventilation except in the very early phase of perfusion changes when hypoperfusion can cause a transient bronchoconstriction and hypoventilation. This reaction disappears within 6 hours in dogs. Deposition patterns of inhaled aerosol in the lungs help differentiate the nature of the obstructive airways disease. Aerosol inhalation imaging can offer a unique technique for the study of mucociliary clearance function in the lungs. 'Radioaerosol inhalation lung cinescintigraphy' has made it possible to visualize the actual mucociliary clearance status in the lungs in vivo. Indexes to quantify the mucociliary clearance function have been proposed. Effects of pharmaceutical agents on mucociliary clearance function in the lungs can now be objectively evaluated by aerosol inhalation lung imaging and its quantification. The study of pulmonary epithelial permeability by inhalation of 99Tcm DTPA aerosol has also been mentioned. 26 refs, 8 figs, 3

  20. Lung function measurements in rodents in safety pharmacology studies

    Directory of Open Access Journals (Sweden)

    Heinz Gerd Hoymann

    2012-08-01

    Full Text Available The ICH guideline S7A requires safety pharmacology tests including measurements of pulmonary function. In the first step – as part of the core battery - lung function tests in conscious animals are requested. If potential adverse effects raise concern for human safety, these should be explored in a second step as a follow-up study. For these two stages of safety pharmacology testing, both noninvasive and invasive techniques are needed which should be as precise and reliable as possible. A short overview of typical in-vivo measurement techniques is given, their advantages and disadvantages are discussed and out of these the noninvasive head-out body plethysmography and the invasive but repeatable body-plethysmography in orotracheally intubated rodents are presented in detail. For validation purposes the changes in the respective parameters such as tidal midexpiratory flow (EF50 or lung resistance have been recorded in the same animals in typical bronchoconstriction models and compared. In addition, the technique of head-out body plethysmography has been shown to be useful to measure lung function in juvenile rats starting from day two of age. This allows safety pharmacology testing and toxicological studies in juvenile animals as a model for the young developing organism as requested by the regulatory authorities (e.g. EMEA Guideline 1/2008.It is concluded that both invasive and noninvasive pulmonary function tests are capable of detecting effects and alterations on the respiratory system with different selectivity and area of operation. The use of both techniques in a large number of studies in mice and rats in the last years have demonstrated that they provide useful and reliable information on pulmonary mechanics in safety pharmacology and toxicology testing, in investigations of respiratory disorders, and in pharmacological efficacy studies.

  1. The effects of aminophylline infusion in the treatment of children with acute asthma exacerbation. Evaluation with 81mKr ventilation scintigraphy

    International Nuclear Information System (INIS)

    The use of intravenous aminophylline in the treatment of children with acute asthma remains controversial. Most authors suggest that aminophylline be used with caution because of its poor efficacy with adverse reactions and instead recommend other drugs, such as β2-adrenergic agonists and glucocorticoids. However other studies have reported the benefits of aminophylline, and current Japanese guidelines for the management of asthma recommend its use. Here, we have evaluated the efficacy of aminophylline infusion in children with acute asthma exacerbations. Twenty children with acute asthma exacerbations were given an infusion of 5 mg/kg of aminophylline over 5 minutes, 30 minutes after the same volume of normal saline had been infused as a control. 81mKr ventilation scintigraphy was done sequentially, and lung function was measured with spirometry before and after each infusion. Side effects were also evaluated with a questionnaire. Ventilation images obtained with 81mKr scintigraphy, which initially showed widespread ventilatory defects caused by bronchoconstriction, decreased 54.9% after aminophylline infusion (p81mKr bolus inhalation procedure, also showed significant improvement (p<0.0001). These improvement were accompanied by improvements in lung function as assessed with forced expiratory volume in 1 second (p<0.01) and maximum expiratory flow rates at 25% (p<0.001) and 50% (p<0.001). No serious adverse reactions were recognized in any subjects. Our results show that aminophylline is a useful bronchodilator which decreased ventilatory imbalance and improves lung function in both central and peripheral airways. (author)

  2. In vivo adenosine A(2B) receptor desensitization in guinea-pig airway smooth muscle: implications for asthma.

    Science.gov (United States)

    Breschi, Maria Cristina; Blandizzi, Corrado; Fogli, Stefano; Martinelli, Cinzia; Adinolfi, Barbara; Calderone, Vincenzo; Camici, Marcella; Martinotti, Enrica; Nieri, Paola

    2007-12-01

    This study was aimed at characterizing the role of adenosine receptor subtypes in the contractility modulation of guinea-pig airway smooth muscle in normal and pathological settings. In vitro and in vivo experiments were performed by testing selective agonists and antagonists on isolated tracheal smooth muscle preparations and pulmonary inflation pressure, respectively, under normal conditions or following ovalbumin-induced allergic sensitization. In normal and sensitized animals, the adenosine A(2A)/A(2B) receptor agonist, NECA, evoked relaxing responses of isolated tracheal preparations precontracted with histamine, and such an effect was reversed by the adenosine A(2B) antagonist, MRS 1706, in the presence or in the absence of epithelium. The expression of mRNA coding for adenosine A(2B) receptors was demonstrated in tracheal specimens. In vitro desensitization with 100 microM NECA markedly reduced the relaxing effect of the agonist. In vivo NECA or adenosine administration to normal animals inhibited histamine-mediated bronchoconstriction, while these inhibitory effects no longer occurred in sensitized guinea-pigs. Adenosine plasma levels were significantly higher in sensitized than normal animals. In conclusion, our data demonstrate that: (i) adenosine A(2B) receptors are responsible for the relaxing effects of adenosine on guinea-pig airways; (ii) these receptors can undergo rapid adaptive changes that may affect airway smooth muscle responsiveness to adenosine; (iii) ovalbumin-induced sensitization promotes a reversible inactivation of adenosine A(2B) receptors which can be ascribed to homologous desensitization. These findings can be relevant to better understand adenosine functions in airways as well as mechanisms of action of asthma therapies targeting the adenosine system.

  3. Vitamin D deficiency and exercise-induced laryngospasm in young competitive rowers.

    Science.gov (United States)

    Heffler, Enrico; Bonini, Matteo; Brussino, Luisa; Solidoro, Paolo; Guida, Giuseppe; Boita, Monica; Nicolosi, Giuliana; Bucca, Caterina

    2016-07-01

    Exercise-induced dyspnea is common among adolescents and young adults and often originates from exercise-induced bronchoconstriction (EIB). Sometimes, dyspnea corresponds to exercise-induced laryngospasm (EILO), which is a paradoxical decrease in supraglottic/glottic area. Vitamin D deficiency, which occurs frequently at northern latitudes, might favor laryngospasm by impairing calcium transport and slowing striate muscle relaxation. The aim of this study was to evaluate whether vitamin D status has an influence on bronchial and laryngeal responses to exercise in young, healthy athletes. EIB and EILO were investigated during winter in 37 healthy competitive rowers (24 males; age range 13-25 years), using the eucapnic voluntary hyperventilation test (EVH). EIB was diagnosed when forced expiratory volume in the first second decreased by 10%, EILO when maximum mid-inspiratory flow (MIF50) decreased by 20%. Most athletes (86.5%) had vitamin D deficiency (below 30 ng/mL), 29 mild-moderate (78.4%) and 3 severe (8.1%). EVH showed EIB in 10 subjects (27%), EILO in 16 (43.2%), and combined EIB and EILO in 6 (16.2%). Athletes with EILO had lower vitamin D (19.1 ng/mL vs. 27.0 ng/mL, p 51; p = 0.001) and inversely with parathyroid hormone levels (r = -0.53; p = 0.001). We conclude that vitamin D deficiency is common during winter in young athletes living above the 40th parallel north and favors laryngospasm during exercise, probably by disturbing calcium homeostasis. This effect may negatively influence athletic performance. PMID:27218140

  4. 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

  5. Formoterol via Turbuhaler gave better protection than terbutaline against repeated exercise challenge for up to 12 hours in children and adolescents.

    Science.gov (United States)

    Grönneröd, T A; von Berg, A; Schwabe, G; Soliman, S

    2000-07-01

    We aimed to compare the protective effect of single doses of 4.5 and 9 microg of formoterol fumarate (F), 0.5 mg terbutaline sulphate (T) and placebo (P), all via Turbuhaler, against exercise-induced bronchoconstriction (EIB) in children. Twenty-seven asthmatic children, showing a fall of > or =20% in FEV1 after a standardized exercise challenge test (ECT) combined with cold air (-10 degrees C) inhalation, were randomized in this cross-over, double-blind study. They had a mean age of 12.6 years (range 8-17 years), mean baseline FEV1 90% (73.9-105.6%) of predicted normal value. Seventeen children used inhaled glucocorticosteroids (120-750 microg day(-1)). ECTs were performed 15 min and 4, 8, and 12 h after drug administration. F significantly reduced the fall in FEV1 after ECT to 5.4% (15 min), 5.2% (4 h), 8.2% (8 h) and 9.3% (12 h) after 4.5 microg, and 2.5%, 3.0%, 5.0% and 5.4% after 9 microg, compared with a fall of 18.4%, 15.7%, 15.6% and 16.5% in FEV1 after P. The fall after T was 3.3%, 11.6%, 14.4% and 19.1% after 15 min, 4, 8 and 12 h respectively. The difference between F and T was statistically significant from 4 h and onward (P-value for all comparisons terbutaline Turbuhaler 0.5 mg. PMID:10926337

  6. Development of GABAA Receptor Subtype-Selective Imidazobenzodiazepines as Novel Asthma Treatments.

    Science.gov (United States)

    Forkuo, Gloria S; Guthrie, Margaret L; Yuan, Nina Y; Nieman, Amanda N; Kodali, Revathi; Jahan, Rajwana; Stephen, Michael R; Yocum, Gene T; Treven, Marco; Poe, Michael M; Li, Guanguan; Yu, Olivia B; Hartzler, Benjamin D; Zahn, Nicolas M; Ernst, Margot; Emala, Charles W; Stafford, Douglas C; Cook, James M; Arnold, Leggy A

    2016-06-01

    Recent studies have demonstrated that subtype-selective GABAA receptor modulators are able to relax precontracted human airway smooth muscle ex vivo and reduce airway hyper-responsiveness in mice upon aerosol administration. Our goal in this study was to investigate systemic administration of subtype-selective GABAA receptor modulators to alleviate bronchoconstriction in a mouse model of asthma. Expression of GABAA receptor subunits was identified in mouse lungs, and the effects of α4-subunit-selective GABAAR modulators, XHE-III-74EE and its metabolite XHE-III-74A, were investigated in a murine model of asthma (ovalbumin sensitized and challenged BALB/c mice). We observed that chronic treatment with XHE-III-74EE significantly reduced airway hyper-responsiveness. In addition, acute treatment with XHE-III-74A but not XHE-III-74EE decreased airway eosinophilia. Immune suppressive activity was also shown in activated human T-cells with a reduction in IL-2 expression and intracellular calcium concentrations [Ca(2+)]i in the presence of GABA or XHE-III-74A, whereas XHE-III-74EE showed only partial reduction of [Ca(2+)]i and no inhibition of IL-2 secretion. However, both compounds significantly relaxed precontracted tracheal rings ex vivo. Overall, we conclude that the systemic delivery of a α4-subunit-selective GABAAR modulator shows good potential for a novel asthma therapy; however, the pharmacokinetic properties of this class of drug candidates have to be improved to enable better beneficial systemic pharmacodynamic effects. PMID:27120014

  7. 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.

  8. Impaired Bronchoprotection Is Not Induced by Increased Smooth Muscle Mass in Chronic Treatment In Vivo with Formoterol in Asthmatic Mouse Model

    Directory of Open Access Journals (Sweden)

    W Luo

    2014-09-01

    Full Text Available Objective: Inhaling β2-adrenoceptor agonist is first-line asthma treatment, which is used for both acute relief and prevention of bronchoconstriction. However, chronic use of β-agonists results in impaired bronchoprotection and increasing occurrences of severe asthma exacerbation, even death in clinical practice. The mechanism of β-adrenoceptor hyposensitivity has not been thoroughly elucidated thus far. Bronchial smooth muscle contraction induces airway narrowing and also mediates airway inflammation. Moreover, bronchial smooth muscle mass significantly increases in asthmatics. We aimed to establish an asthmatic model that demonstrated that formoterol induced impaired bronchoprotection and to see whether increased smooth muscle mass played a role in it. Methods: We combined routine allergen challenging (seven weeks with repeated application of formoterol, formoterol plus budesonide or physiological saline in allergen-sensitized BALB/c mouse. The bronchoprotection mediated by β-agonist was measured in five consecutive weeks. Smooth muscle mass was shown by morphometric analysis, and α-actin expression was detected by western blot. Results: The trend of bronchoprotection was wavy in drug interventional groups, which initially increased and then decreased. Chronic treatment with formoterol significantly impaired bronchoprotection. According to the morphometric analysis and α-actin expression, no significant difference was detected in smooth muscle mass in all groups. Conclusion: This experiment successfully established that a chronic asthmatic mouse model, which manifested typical features of asthmatic patients, with chronic use of formoterol, results in a loss of bronchoprotection. No significant difference was detected in smooth muscle mass in all groups, which implied some subcellular signalling changes may be the key points.

  9. Tolerance to bronchodilation during treatment with long-acting beta-agonists, a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Hancox Robert J

    2005-09-01

    Full Text Available Abstract Background Regular use of beta-agonists leads to tolerance to their bronchodilator effects. This can be demonstrated by measuring the response to beta-agonist following bronchoconstriction using methacholine. However most studies have demonstrated tolerance after a period of beta-agonist withdrawal, which is not typical of their use in clinical practice. This study assessed tolerance to the bronchodilator action of salbutamol during ongoing treatment with long-acting beta-agonist. Methods Random-order, double-blind, placebo-controlled, crossover trial. After 1 week without beta-agonists, 13 asthmatic subjects inhaled formoterol 12 μg twice daily or matching placebo for 1 week. Eight hours after the first and last doses subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 100, 200 and 400 μg (cumulative dose was then given at 5-minute intervals and FEV1 was measured 5 minutes after each dose. After a 1 week washout subjects crossed over to the other treatment. Unscheduled use of beta-agonists was not allowed during the study. The main outcome variable was the area under the salbutamol response curve. Results The analysis showed a significant time by treatment interaction indicating that the response to salbutamol fell during formoterol therapy compared to placebo. After 1 week of formoterol the area under the salbutamol response curve was 48% (95% confidence interval 28 to 68% lower than placebo. This reduction in response remained significant when the analyses were adjusted for changes in the pre-challenge FEV1 and dose of methacholine given (p = 0.001. Conclusion The bronchodilator response to salbutamol is significantly reduced in patients taking formoterol. Clinically relevant tolerance to rescue beta-agonist treatment is likely to occur in patients treated with long-acting beta-agonists.

  10. Ecto-5'-nucleotidase CD73 modulates the innate immune response to influenza infection but is not required for development of influenza-induced acute lung injury.

    Science.gov (United States)

    Aeffner, Famke; Woods, Parker S; Davis, Ian C

    2015-12-01

    Extracellular nucleotides and nucleosides are important signaling molecules in the lung. Nucleotide and nucleoside concentrations in alveolar lining fluid are controlled by a complex network of surface ectonucleotidases. Previously, we demonstrated that influenza A/WSN/33 (H1N1) virus resulted in increased levels of the nucleotide ATP and the nucleoside adenosine in bronchoalveolar lavage fluid (BALF) of wild-type (WT) C57BL/6 mice. Influenza-induced acute lung injury (ALI) was highly attenuated in A1-adenosine receptor-knockout mice. Because AMP hydrolysis by the ecto-5'-nucleotidase (CD73) plays a central role in and is rate-limiting for generation of adenosine in the normal lung, we hypothesized that ALI would be attenuated in C57BL/6-congenic CD73-knockout (CD73-KO) mice. Infection-induced hypoxemia, bradycardia, viral replication, and bronchoconstriction were moderately increased in CD73-KO mice relative to WT controls. However, postinfection weight loss, pulmonary edema, and parenchymal dysfunction were not altered. Treatment of WT mice with the CD73 inhibitor 5'-(α,β-methylene) diphosphate (APCP) also had no effect on infection-induced pulmonary edema but modestly attenuated hypoxemia. BALF from CD73-KO and APCP-treated WT mice contained more IL-6 and CXCL-10/IFN-γ-induced protein 10, less CXCL-1/keratinocyte chemoattractant, and fewer neutrophils than BALF from untreated WT controls. BALF from APCP-treated WT mice also contained fewer alveolar macrophages and more transforming growth factor-β than BALF from untreated WT mice. These results indicate that CD73 is not necessary for development of ALI following influenza A virus infection and suggest that tissue-nonspecific alkaline phosphatase may be responsible for increased adenosine generation in the infected lung. However, they do suggest that CD73 has a previously unrecognized immunomodulatory role in influenza. PMID:26432867

  11. Induced Sputum Proteome in Health and Asthma

    Science.gov (United States)

    Gharib, Sina A.; Nguyen, Elizabeth V.; Lai, Ying; Plampin, Jessica D.; Goodlett, David R.; Hallstrand, Teal S.

    2014-01-01

    Background Asthma is a heterogeneous disease characterized by abnormal airway pathophysiology and susceptibility to different stimuli, as exemplified by a subset of individuals with exercise-induced bronchoconstriction (EIB). Induced sputum provides a noninvasive method to sample airway biofluids that are enriched in proteins. Objective We hypothesized that novel mechanisms in the pathogenesis of asthma may be revealed by studying the patterns of protein expression in induced sputum. Methods We used shotgun proteomics to analyze induced sputum from 5 normal individuals and 10 asthmatics, including 5 with EIB. Differential protein expression between asthmatics, asthma subphenotypes and control subjects was determined using spectral counting and computational methods. Results Using Gene Ontology analysis, we defined the functional landscape of induced sputum proteome and applied network analysis to construct a protein interaction map for this airway compartment. Shotgun proteomics analysis identified a number of proteins whose differential enrichment or depletion robustly distinguishedasthmatics from normal controls, and captured the effects of exercise on induced sputum proteome. Functional and network analysis identified key processes, including proteolytic activity that are known contributors to airway remodeling. Importantly, this approach highlighted previously unrecognized roles for differentially expressed proteins in pathways implicated in asthma, such as modulation of phospholipase A2 by secretoglobin, a putative role for S100A8/9 in human asthma, and selective upregulation of complement 3a in response to exercise in asthmatics. Conclusion Computationally-intensive analysis of induced sputum proteome is a powerful approach to understand the pathophysiology of asthma and a promising methodology to investigate other diseases of the airways. PMID:21906793

  12. Pulmonary response to ozone: Reaction of bronchus-associated lymphoid tissue and lymph node lymphocytes in the rat

    International Nuclear Information System (INIS)

    The purpose of this work is to assess the effect of ozone, a reactive product of environmental photochemical oxidation, on lymphocytes of the lung. We exposed male Fischer rats to ozone at a concentration of 0.5 ppm for 20 hr/day for 1-14 days. Animals were treated with radioactive thymidine and were sacrificed at Day 1, 2, 3, 7, or 14 of exposure. Lungs and mediastinal lymph nodes were removed and prepared for histologic examination, evaluation of labeling indexes, and morphometric measurement. We examined two components of the lymphocyte response of the lung: the airway-related response, represented by the reaction of the bronchus-associated lymphoid tissue (BALT), and the deep lung-related response, represented by reaction of the mediastinal lymph node. Lymphocytes of both the BALT and the mediastinal lymph node showed elevated radioactive thymidine uptake; however, no evidence of cell death was observed at either site. The cells of the specialized epithelium covering the BALT (lymphoepithelium) showed increased vacuolization, indicating altered cellular function. The average size of BALTs was unchanged by ozone exposure. Under experimental conditions ozone can affect a variety of cells in the lung including bronchial epithelial cells, macrophages, and Type 1 cells. We have shown for the first time that in addition to these cells, the rat BALT also proliferates in response to ozone. In addition we confirm previous work in the mouse which shows that the mediastinal lymph node reacts as well. The airways can be affected by inflammation, can be targets of infection, and can respond to chemical irritants with bronchoconstrictive responses. They are an important target organ for hypersensitivity responses and are a primary site for pulmonary cancer formation. A role for lymphocytes has been implicated in each of these processes

  13. 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.

  14. Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method

    Directory of Open Access Journals (Sweden)

    Zaid AN

    2015-09-01

    Full Text Available Abdel Naser Zaid,1 Murad N Abualhasan,1 David G Watson,2 Ayman Mousa,3 Nadia Ghazal,4 Rana Bustami5 1Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine; 2Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK; 3R&D Department, Avalon Pharma (Middle East Pharmaceutical Industries Co. Ltd., Riyadh, Kingdom of Saudi Arabia; 4Naratech Pharmaceutical Consultancy, 5Pharmaceutical Research Unit, Amman, Jordan Background: Montelukast (MT is a leukotriene D4 antagonist. It is an effective and safe medicine for the prophylaxis and treatment of chronic asthma. It is also used to prevent acute exercise-induced bronchoconstriction and as a symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis.Objective: The aim of this study was to evaluate the bioequivalence (BE of two drug products: generic MT 5 mg chewable tablets versus the branded drug Singulair® pediatric 5 mg chewable tablets among Mediterranean volunteers.Methods: An open-label, randomized two-period crossover BE design was conducted in 32 healthy male volunteers with a 9-day washout period between doses and under fasting conditions. The drug concentrations in plasma were quantified by using a newly developed and fully validated liquid chromatography tandem mass spectrometry method, and the pharmacokinetic parameters were calculated using a non-compartmental model. The ratio for generic/branded tablets using geometric least squares means was calculated for both the MT products.Results: The relationship between concentration and peak area ratio was found to be linear within the range 6.098–365.855 ng/mL. The correlation coefficient (R2 was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between the generic and branded products. The point estimates (ratios of

  15. House dust mite major allergens Der p 1 and Der p 5 activate human airway-derived epithelial cells by protease-dependent and protease-independent mechanisms

    Directory of Open Access Journals (Sweden)

    Timmerman J André B

    2006-03-01

    Full Text Available Abstract House dust mite allergens (HDM cause bronchoconstriction in asthma patients and induce an inflammatory response in the lungs due to the release of cytokines, chemokines and additional mediators. The mechanism how HDM components achieve this is largely unknown. The objective of this study was to assess whether HDM components of Dermatophagoides pteronissinus with protease activity (Der p 1 and unknown enzymatic activity (Der p 2, Der p 5 induce biological responses in a human airway-derived epithelial cell line (A549, and if so, to elucidate the underlying mechanism(s of action. A549 cells were incubated with HDM extract, Der p 1, recombinant Der p 2 and recombinant Der p 5. Cell desquamation was assessed by microscopy. The proinflammatory cytokines, IL-6 and IL-8, were measured by ELISA. Intracellular Ca2+ levels were assessed in A549 cells and in mouse fibroblasts expressing the human protease activated receptor (PAR1, PAR2 or PAR4. HDM extract, Der p 1 and Der p 5 dose-dependently increased the production of IL-6 and IL-8. Added simultaneously, Der p 1 and Der p 5 further increased the production of IL-6 and IL-8. The action of Der p 1 was blocked by cysteine-protease inhibitors, while that of Der p 5 couldn't be blocked by either serine- or cysteine protease inhibitors. Der p 5 only induced cell shrinking, whereas HDM extract and Der p1 also induced cell desquamation. Der p 2 had no effect on A549 cells. Der p 1's protease activity causes desquamation and induced the release of IL6 and IL-8 by a mechanism independent of Ca2+ mobilisation and PAR activation. Der p 5 exerts a protease-independent activation of A549 that involves Ca2+ mobilisation and also leads to the production of these cytokines. Together, our data indicate that allergens present in HDM extracts can trigger protease-dependent and protease-independent signalling pathways in A549 cells.

  16. The in vitro and in vivo profile of aclidinium bromide in comparison with glycopyrronium bromide.

    Science.gov (United States)

    Gavaldà, Amadeu; Ramos, Israel; Carcasona, Carla; Calama, Elena; Otal, Raquel; Montero, José Luis; Sentellas, Sonia; Aparici, Monica; Vilella, Dolors; Alberti, Joan; Beleta, Jorge; Miralpeix, Montserrat

    2014-08-01

    This study characterised the in vitro and in vivo profiles of two novel long-acting muscarinic antagonists, aclidinium bromide and glycopyrronium bromide, using tiotropium bromide and ipratropium bromide as comparators. All four antagonists had high affinity for the five muscarinic receptor sub-types (M1-M5); aclidinium had comparable affinity to tiotropium but higher affinity than glycopyrronium and ipratropium for all receptors. Glycopyrronium dissociated faster from recombinant M3 receptors than aclidinium and tiotropium but more slowly than ipratropium; all four compounds dissociated more rapidly from M2 receptors than from M3 receptors. In vitro, aclidinium, glycopyrronium and tiotropium had a long duration of action at native M3 receptors (>8 h versus 42 min for ipratropium). In vivo, all compounds were equi-potent at reversing acetylcholine-induced bronchoconstriction. Aclidinium, glycopyrronium and ipratropium had a faster onset of bronchodilator action than tiotropium. Aclidinium had a longer duration of action than glycopyronnium (time to 50% recovery of effect [t½ offset] = 29 h and 13 h, respectively); these compare with a t½ offset of 64 h and 8 h for tiotropium and ipratropium, respectively. Aclidinium was less potent than glycopyrronium and tiotropium at inhibiting salivation in conscious rats (dose required to produce half-maximal effect [ED50] = 38, 0.74 and 0.88 μg/kg, respectively) and was more rapidly hydrolysed in rat, guinea pig and human plasma compared with glycopyrronium or tiotropium. These results indicate that while aclidinium and glycopyrronium are both potent antagonists at muscarinic receptors with similar kinetic selectivity for M3 receptors versus M2, aclidinium has a longer dissociation half-life at M3 receptors and a longer duration of bronchodilator action in vivo than glycopyrronium. The rapid plasma hydrolysis of aclidinium, coupled to its kinetic selectivity, may confer a reduced propensity for systemic

  17. The lungs need to be deflated: effects of glycopyrronium on lung hyperinflation in COPD patients.

    Science.gov (United States)

    Sanguinetti, Claudio M

    2014-04-01

    disease that needs a chronic bronchodilation by decreasing the mechanic stress of the airways determined by repeated bronchoconstriction and increasing patient's adherence to treatment plan with better clinical results. Several studies demonstrated that glycopyrronium is able to positively and significantly decrease lung hyperinflation, symptoms, and improve psycho-physical status of COPD patients, with a low rate of adverse events, similar to that of placebo.

  18. Comparing the cardiovascular therapeutic indices of glycopyrronium and tiotropium in an integrated rat pharmacokinetic, pharmacodynamic and safety model

    Energy Technology Data Exchange (ETDEWEB)

    Trifilieff, Alexandre; Ethell, Brian T. [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); Sykes, David A. [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); School of Life Sciences, Queen' s Medical Centre, University of Nottingham, Nottingham, NG7 2UH (United Kingdom); Watson, Kenny J.; Collingwood, Steve [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); Charlton, Steven J. [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); School of Life Sciences, Queen' s Medical Centre, University of Nottingham, Nottingham, NG7 2UH (United Kingdom); Kent, Toby C., E-mail: tobykent@me.com [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom)

    2015-08-15

    Long acting inhaled muscarinic receptor antagonists, such as tiotropium, are widely used as bronchodilator therapy for chronic obstructive pulmonary disease (COPD). Although this class of compounds is generally considered to be safe and well tolerated in COPD patients the cardiovascular safety of tiotropium has recently been questioned. We describe a rat in vivo model that allows the concurrent assessment of muscarinic antagonist potency, bronchodilator efficacy and a potential for side effects, and we use this model to compare tiotropium with NVA237 (glycopyrronium bromide), a recently approved inhaled muscarinic antagonist for COPD. Anaesthetized Brown Norway rats were dosed intratracheally at 1 or 6 h prior to receiving increasing doses of intravenous methacholine. Changes in airway resistance and cardiovascular function were recorded and therapeutic indices were calculated against the ED{sub 50} values for the inhibition of methacholine-induced bronchoconstriction. At both time points studied, greater therapeutic indices for hypotension and bradycardia were observed with glycopyrronium (19.5 and 28.5 fold at 1 h; > 200 fold at 6 h) than with tiotropium (1.5 and 4.2 fold at 1 h; 4.6 and 5.5 fold at 6 h). Pharmacokinetic, protein plasma binding and rat muscarinic receptor binding properties for both compounds were determined and used to generate an integrated model of systemic M{sub 2} muscarinic receptor occupancy, which predicted significantly higher M{sub 2} receptor blockade at ED{sub 50} doses with tiotropium than with glycopyrronium. In our preclinical model there was an improved safety profile for glycopyrronium when compared with tiotropium. - Highlights: • We use an in vivo rat model to study CV safety of inhaled muscarinic antagonists. • We integrate protein and receptor binding and PK of tiotropium and glycopyrrolate. • At ED{sub 50} doses for bronchoprotection we model systemic M{sub 2} receptor occupancy. • Glycopyrrolate demonstrates lower M

  19. Pulmonary function responses to ozone in smokers with a limited smoking history

    Energy Technology Data Exchange (ETDEWEB)

    Bates, Melissa L., E-mail: mlbates@pediatrics.wisc.edu [Interdisciplinary Graduate Degree Program in Physiology, Pennsylvania State University, University Park, PA 16802 (United States); Department of Pediatrics, Critical Care Division, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 (United States); John Rankin Laboratory of Pulmonary Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 (United States); Brenza, Timothy M. [Department of Chemical Engineering, Pennsylvania State University, University Park, PA 16802 (United States); Ben-Jebria, Abdellaziz [Interdisciplinary Graduate Degree Program in Physiology, Pennsylvania State University, University Park, PA 16802 (United States); Department of Chemical Engineering, Pennsylvania State University, University Park, PA 16802 (United States); Bascom, Rebecca [Division of Pulmonary, Allergy and Critical Care Medicine, Penn State College of Medicine, Hershey, PA 17033 (United States); Eldridge, Marlowe W. [Department of Pediatrics, Critical Care Division, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 (United States); John Rankin Laboratory of Pulmonary Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 (United States); Department of Kinesiology, University of Wisconsin-Madison, Madison, WI 53792 (United States); Department of Bioengineering, University of Wisconsin-Madison, Madison, WI 53792 (United States); Ultman, James S. [Interdisciplinary Graduate Degree Program in Physiology, Pennsylvania State University, University Park, PA 16802 (United States); Department of Chemical Engineering, Pennsylvania State University, University Park, PA 16802 (United States)

    2014-07-01

    In non-smokers, ozone (O{sub 3}) inhalation causes decreases in forced expiratory volume (FEV{sub 1}) and dead space (V{sub D}) and increases the slope of the alveolar plateau (S{sub N}). We previously described a population of smokers with a limited smoking history that had enhanced responsiveness to brief O{sub 3} boluses and aimed to determine if responsiveness to continuous exposure was also enhanced. Thirty smokers (19 M, 11 F, 24 ± 4 years, 6 ± 4 total years smoking,4 ± 2 packs/week) and 30 non-smokers (17 M, 13 F, 25 ± 6 years) exercised for 1 h on a cycle ergometer while breathing 0.30 ppm O{sub 3}. Smokers and non-smokers were equally responsive in terms of FEV{sub 1} (− 9.5 ± 1.8% vs − 8.7 ± 1.9%). Smokers alone were responsive in terms of V{sub D} (− 6.1 ± 1.2%) and S{sub N} (9.1 ± 3.4%). There was no difference in total delivered dose. Dead space ventilation (V{sub D}/V{sub T}) was not initially different between the two groups, but increased in the non-smokers (16.4 ± 2.8%) during the exposure, suggesting that the inhaled dose may be distributed more peripherally in smokers. We also conclude that these cigarette smokers retain their airway responsiveness to O{sub 3} and, uniquely, experience changes in V{sub D} that lead to heterogeneity in airway morphometry and an increase in S{sub N}. - Highlights: • We previously found lung function responses to O{sub 3} bolus exposure in smokers. • Here, we describe their responsiveness to continuous O{sub 3} exposure with exercise. • Spirometry and capnography were used to assess pulmonary function changes. • Enhanced bronchoconstriction in smokers increases parenchymal delivery of O{sub 3}.

  20. Mechanisms underlying gas exchange alterations in an experimental model of pulmonary embolism

    Directory of Open Access Journals (Sweden)

    J.H.T. Ferreira

    2006-09-01

    induced by hypocapnic bronchoconstriction.

  1. Occupational asthma and related respiratory disorders.

    Science.gov (United States)

    Bardana, E J

    1995-03-01

    Occupational rhinitis is a common but generally underreported entity. Although it may occur alone, it is frequently associated with occupational asthma. Occupational asthma may have one of several presentations that are difficult to distinguish from non-work conditions. The respiratory tract acts as the final common pathway for all inhaled environmental pollutants, whether encountered in the home or at work. More than 200 chemicals have been incriminated as a cause of work-related asthma. It is said that about 2% of the 10 million Americans who have asthma acquired it as a result of some chemical irritant or immunogen in their work environment. A number of predisposing factors facilitate the development of work-related asthma. These include industrial conditions, climatic factors, atopic predisposition, smoking, recreational drug use, viral infection, nonspecific bronchial hyperreactivity, and a variety of miscellaneous factors. Pathogenetically, occupational asthma may be immunologic or nonimmunologic in nature. The immunologic variants involve sensitization to a variety of large-molecular-weight constituents. The major nonimmune variant is referred to as inflammatory bronchoconstriction or reactive airways dysfunction syndrome (RADS). There are well-defined criteria for the diagnosis of immunologic and nonimmunologic asthma. The several clinical variations of occupational asthma can be difficult to distinguish from nonindustrial disorders. The most common presentation in practice involves the worker with preexistent asthma who has been adversely affected by work exposures. Occasionally these industrial exposures precipitate permanent impairment. It is clear, however, that occupational asthma is not a single, simple, or homogeneous entity, even when a single specific causal factor can be identified in the workplace. Therefore the physician must be aware of the patient's entire medical history and the precise occupational exposures and must have convincing

  2. Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice.

    Directory of Open Access Journals (Sweden)

    Lauren Folgosa Cooley

    Full Text Available ADAM10, as the sheddase of the low affinity IgE receptor (CD23, promotes IgE production and thus is a unique target for attenuating allergic disease. Herein, we describe that B cell levels of ADAM10, specifically, are increased in allergic patients and Th2 prone WT mouse strains (Balb/c and A/J. While T cell help augments ADAM10 expression, Balb WT B cells exhibit increased ADAM10 in the naïve state and even more dramatically increased ADAM10 after anti-CD40/IL4 stimulation compared C57 (Th1 prone WT B cells. Furthermore, ADAM17 and TNF are reduced in allergic patients and Th2 prone mouse strains (Balb/c and A/J compared to Th1 prone controls. To further understand this regulation, ADAM17 and TNF were studied in C57Bl/6 and Balb/c mice deficient in ADAM10. C57-ADAM10B-/- were more adept at increasing ADAM17 levels and thus TNF cleavage resulting in excess follicular TNF levels and abnormal secondary lymphoid tissue architecture not noted in Balb-ADAM10B-/-. Moreover, the level of B cell ADAM10 as well as Th context is critical for determining IgE production potential. Using a murine house dust mite airway hypersensitivity model, we describe that high B cell ADAM10 level in a Th2 context (Balb/c WT is optimal for disease induction including bronchoconstriction, goblet cell metaplasia, mucus, inflammatory cellular infiltration, and IgE production. Balb/c mice deficient in B cell ADAM10 have attenuated lung and airway symptoms compared to Balb WT and are actually most similar to C57 WT (Th1 prone. C57-ADAM10B-/- have even further reduced symptomology. Taken together, it is critical to consider both innate B cell levels of ADAM10 and ADAM17 as well as Th context when determining host susceptibility to allergic disease. High B cell ADAM10 and low ADAM17 levels would help diagnostically in predicting Th2 disease susceptibility; and, we provide support for the use ADAM10 inhibitors in treating Th2 disease.

  3. Dichrostachys cinerea (L. Wight et Arn (Mimosaceae hydro-alcoholic extract action on the contractility of tracheal smooth muscle isolated from guinea-pig

    Directory of Open Access Journals (Sweden)

    Datté Jacques Y

    2011-03-01

    Full Text Available Abstract Background Dichrostachys cinerea (L. Wight et Arn. (Mimosaceae is largely used in ethno-medically across Africa, and mainly employed for the treatment of asthma in Ivory Coast and Gabon. The paper analyses the relaxation induced by the methanolic extract of D. cinerea (Edici in the guinea-pig trachea preparations (GPTPs. Purpose: This study aimed to bring out the scientific basis to the use of this plant leading to the validation of this phytomedicine. Method The aorta obtained from guinea-pigs was immediately placed in a Mac Ewen solution. Experiments were performed in preparations suspended between two L-shaped stainless steel hooks in a 10 ml organ bath containing Mac Ewen solution. The isometric contractile force of the aorta strips of guinea-pig were recorded by using a strain gauge. The different drugs were directly administered into the organ bath and the magnitude of GPTPs was evaluated. Results Phytochemical analysis of the methanolic extract of Dichrostachys cinerea (Edici using chemical methods revealed the presence of flavenoids, tannins, sterols, triterpenes and polyphenols. Pharmacological studies performed in GPTPs show that of Dichrostachys cinerea (0.1 mg/ml - 2 mg/ml evoked a broncho-constriction in GPTPs. Whereas, at concentration up to 2 mg/ml, Edici induced a significant dose-dependent relaxation in the GPTPs. KCl-, ACh- or histamine-evoked contractions of isolated trachea was significantly inhibited by increasing concentrations of Edici (3.5-10 mg/ml. Edici (10 mg/ml as well as promethazine (0.25 mg/ml significantly inhibited contractions induced by increasing concentrations of histamine (1×10-7-1×10-4mg/ml. In the presence of atropine at a concentration of 10-6mg/ml, contractile response curve (CRC evoked by ACh (1×10-5-1×10-2 mg/ml was significantly abolished in concentration-dependent manner. Edici did not significantly reduced ACh evoked contraction (10-5-10-2mg/ml. Conclusion These observations suggest

  4. 妊娠期支气管哮喘治疗进展%Achievement of bronchial asthma therapy during pregnancy

    Institute of Scientific and Technical Information of China (English)

    蒋雷服; 殷凯生; 黄茂

    2010-01-01

    临床研究已证明妊娠期重度及控制不佳的支气管哮喘(简称哮喘)与母亲及胎儿严重并发症相关.对于妊娠期哮喘患者,接受药物治疗比存在哮喘症状和哮喘发作更安全.所有程度的持续妊娠哮喘患者都应当应用吸入糖皮质激素作为控制药物,首选布地奈德.白三烯受体拮抗剂可以缓解支气管痉挛、减轻症状、改善肺功能.长效β2受体激动剂对于正在应用吸入糖皮质激素的患者可作为首选的添加药物.吸入短效β2受体激动剂可以作为缓解药物.对于正在接受维持量或接近维持量治疗,无不良反应、临床疗效好的妊娠哮喘患者可以继续进行变应原免疫治疗.%Clinical studies have confirmed that severe or uncontrolled bronchial asthma (asthma)during pregnancy may result in adverse maternal and fetal outcomes. It is safer for pregnant women with asthma to be treated with asthma medications than for them to have asthma symptoms and exacerbations.Inhaled corticosteroids should be considered the controller medication for all severities of persistent asthma in pregnant women, preferably inhaled budesonide. Leukotrienes receptor antagonists protect against bronchoconstriction,reduce asthma symptoms and improve pulmonary function in patients with asthma.Long-acting β2-adrenergic agonists are the preferred adjunct to inhaled corticosteroids therapy in the pregnant patients with asthma. Inhaled short-acting β2-agonists are the rescue therapy. Continuation of allergen immunotherapy is recommended in patients who are at or near a maintenance dose, not experiencing adverse reactions to the therapy,and apparently deriving clinical benefit.

  5. Intoxication aiguë sévère par les pesticides organophosphorés: à propos de 28 cas

    Directory of Open Access Journals (Sweden)

    Ali Derkaoui

    2011-03-01

    une insuffisance respiratoire de mécanismes multiples: encombrement bronchique réalisant une véritable noyade interne, bronchoconstriction, paralysie des muscles respiratoires, œdème pulmonaire d’évolution gravissime

  6. 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

  7. Pantoea agglomerans: a marvelous bacterium of evil and good.Part I. Deleterious effects: Dust-borne endotoxins and allergens - focus on cotton dust.

    Science.gov (United States)

    Dutkiewicz, Jacek; Mackiewicz, Barbara; Lemieszek, Marta Kinga; Golec, Marcin; Milanowski, Janusz

    2015-01-01

    accumulation of platelets in pulmonary capillaries initiating an acute and chronic inflammation resulting in endothelial cell damage and extravasation of cells and fluids into the lung interstitium. These changes cause bronchoconstriction, the decrement of lung function expressed as reduction of forced expiratory volume in one second (FEV1) and/or diffusion capacity, increase in the airway hyperreactivity and subjective symptoms such as fever, airway irritation and chest tightness. The conclusions from these experiments, performed mostly 2-3 decades ago, did not loose their actuality until recently as so far no other cotton dust component was identified as a more important work-related hazard than bacterial endotoxin. Though also other microbial and plant constituents are considered as potential causative agents of byssinosis, the endotoxin produced by Pantoea agglomerans and other Gram-negative bacteria present in cotton dust is still regarded as a major cause of this mysterious disease. PMID:26706959

  8. Pantoea agglomerans: a marvelous bacterium of evil and good.Part I. Deleterious effects: Dust-borne endotoxins and allergens – focus on cotton dust

    Directory of Open Access Journals (Sweden)

    Jacek Dutkiewicz

    2015-12-01

    that cause accumulation of platelets in pulmonary capillaries initiating an acute and chronic inflammation resulting in endothelial cell damage and extravasation of cells and fluids into the lung interstitium. These changes cause bronchoconstriction, the decrement of lung function expressed as reduction of forced expiratory volume in one second (FEV1 and/or diffusion capacity, increase in the airway hyperreactivity and subjective symptoms such as fever, airway irritation and chest tightness. The conclusions from these experiments, performed mostly 2-3 decades ago, did not loose their actuality until recently as so far no other cotton dust component was identified as a more important work-related hazard than bacterial endotoxin. Though also other microbial and plant constituents are considered as potential causative agents of byssinosis, the endotoxin produced by Pantoea agglomerans and other Gram-negative bacteria present in cotton dust is still regarded as a major cause of this mysterious disease.

  9. Preclinical evaluation of an inhibitor of cytosolic phospholipase A2α for the treatment of asthma.

    Science.gov (United States)

    Hewson, Christopher A; Patel, Sheena; Calzetta, Luigino; Campwala, Hinnah; Havard, Suzanne; Luscombe, Emma; Clarke, Philip A; Peachell, Peter T; Matera, Maria G; Cazzola, Mario; Page, Clive; Abraham, William M; Williams, Cara M; Clark, James D; Liu, Wai L; Clarke, Nicholas P; Yeadon, Michael

    2012-03-01

    Asthma is a chronic inflammatory lung disease with considerable unmet medical needs for new and effective therapies. Cytosolic phospholipase A(2)α (cPLA(2)α) is the rate-limiting enzyme that is ultimately responsible for the production of eicosanoids implicated in the pathogenesis of asthma. We investigated a novel cPLA(2)α inhibitor, PF-5212372, to establish the potential of this drug as a treatment for asthma. PF-5212372 was a potent inhibitor of cPLA(2)α (7 nM) and was able to inhibit prostaglandin (PG)D(2) and cysteinyl leukotriene release from anti-IgE-stimulated human lung mast cells (0.29 and 0.45 nM, respectively). In a mixed human lung cell population, PF-5212372 was able to inhibit ionomycin-stimulated release of leukotriene B(4), thromboxane A(2), and PGD(2) (2.6, 2.6, and 4.0 nM, respectively) but was significantly less effective against PGE(2) release (>301 nM; p < 0.05). In an in vitro cell retention assay, PF-5212372 retained its potency up to 24 h after being washed off. In a sheep model of allergic inflammation, inhalation of PF-5212372 significantly inhibited late-phase bronchoconstriction (78% inhibition; p < 0.001) and airway hyper-responsiveness (94% inhibition; p < 0.001), and isolated sheep lung mast cell assays confirmed species translation via effective inhibition of PGD(2) release (0.78 nM). Finally, PF-5212372 was assessed for its ability to inhibit the contraction of human bronchi induced by AMP. PF5212372 significantly inhibited AMP-induced contraction of human bronchi (81% inhibition; p < 0.001); this finding, together with the ability of this drug to be effective in a wide range of preclinical asthma models, suggests that inhibition of cPLA(2)α with PF-5212372 may represent a new therapeutic option for the treatment of asthma.

  10. Study of exon 12 polymorphism of the human thromboxane synthase (CYP5A1) gene in Egyptian stroke patients

    International Nuclear Information System (INIS)

    Thromboxane synthase (CYP5A1) catalyzes the conversion of prostaglandin H2 to thromboxane A2, a potent mediator of platelet aggregation, vasoconstriction and bronchoconstriction. It has been implicated in the patho-physiological process of a variety of diseases, such as atherosclerosis, myocardial infarction, stroke and asthma. On the basis of the hypothesis that variations of the CYP5A1 gene may play an important role in human diseases, we performed screening for the prevalence of exon12 polymorphism of the human Thromboxane synthase (CYP5A1) gene among Egyptian normal and stroke patients. Using sequence-specific PCR, we examined the allelic prevalence in 70 Egyptian patients with ischemic strokes and in 70 controls. In addition, we compared the CYP5A1 allelic prevalence in 30 patients with stroke recurrence despite Aspirin use, in comparison with patients who have not experienced recurrent stroke while taking Aspirin. The frequencies of the CYP5A1*9 mutant (substitution of guanine by adenine near the heme-binding catalytic domain) and of the wild-type allele were 0.197(19.7%) and 0.803 (80.3%) respectively; they did not differ significantly between stroke patients and controls. The CYP5A1*9 mutant was significantly more prevalent among stroke patients with history of previous cerebrovascular attacks; even after adjusting for the common risk factors for cardiovascular disease (odds ratio (OR)1.73, 95%, confidence interval ( CI) 1.10-2.73; p=0.017). Among stroke patients, the presence of the CYP5A1 wild type allele was more frequent among the hypertensives (OR 1.68, 95% CI, 1.01-2.79; p=0.045), and less frequent among the diabetics (OR 0.55, 95%, CI 0.36-0.84; p=0.006). Also among stroke patients, the CYP5A1*9 mutant was significantly more prevalent among those, who failed secondary Aspirin prophylaxis compared to those with successful secondary Aspirin prophylaxis (OR 1.49, 95%, CI 1.06-2.11). This study provides evidence for high prevalence of the CYP5A1*9 mutant

  11. Baixo grau de percepção da dispneia após teste de broncoprovocação induzida por metacolina em pacientes com asma Poor perception of dyspnea following methacholine challenge test in patients with asthma

    Directory of Open Access Journals (Sweden)

    Cláudia Loss Reck

    2010-10-01

    bronchoconstriction, bronchial hyperresponsiveness, use of maintenance medication, and asthma control. METHODS: Uncontrolled clinical trial involving asthma patients treated at the Pulmonology Outpatient Clinic of the São Lucas Hospital, in Porto Alegre , Brazil. Methacholine challenge testing was performed using a five-breath dosimeter protocol. The perception of dyspnea after each breath was determined using the Borg scale. Data concerning asthma control, medication in use, and use of rescue short-acting bronchodilators were recorded. RESULTS: Of the 65 patients included in the study, 53 completed the evaluation. Of those, 32 (60.5% showed adequate perception of dyspnea after the methacholine challenge test, whereas 21 (39.5% did not perceive any changes in the degree of dyspnea even after a 20% fall in FEV1. There were no significant differences between the two groups regarding baseline FEV1, percentage fall in FEV1, and the dose of methacholine causing a 20% fall in FEV1. The perception of dyspnea was not significantly associated with age (p = 0.247; gender (p = 0.329; use of maintenance medication (p = 0.152; asthma control (p = 0.562, bronchial hyperresponsiveness (p = 0.082; or severity of acute bronchoconstriction (p = 0.749. CONCLUSIONS: A significant proportion of asthma patients have a poor perception of dyspnea. The factors related to the inability of these patients to identify changes in pulmonary function have not yet been well defined. In order to reduce asthma-related morbidity and mortality, it is essential that this group of patients be identified and counseled.

  12. The efficacy of a comprehensive lifestyle modification programme based on yoga in the management of bronchial asthma: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Bijlani Ramesh

    2009-07-01

    Full Text Available Abstract Background There is a substantial body of evidence on the efficacy of yoga in the management of bronchial asthma. Many studies have reported, as the effects of yoga on bronchial asthma, significant improvements in pulmonary functions, quality of life and reduction in airway hyper-reactivity, frequency of attacks and medication use. In addition, a few studies have attempted to understand the effects of yoga on exercise-induced bronchoconstriction (EIB or exercise tolerance capacity. However, none of these studies has investigated any immunological mechanisms by which yoga improves these variables in bronchial asthma. Methods The present randomized controlled trial (RCT was conducted on 57 adult subjects with mild or moderate bronchial asthma who were allocated randomly to either the yoga (intervention group (n = 29 or the wait-listed control group (n = 28. The control group received only conventional care and the yoga group received an intervention based on yoga, in addition to the conventional care. The intervention consisted of 2-wk supervised training in lifestyle modification and stress management based on yoga followed by closely monitored continuation of the practices at home for 6-wk. The outcome measures were assessed in both the groups at 0 wk (baseline, 2, 4 and 8 wk by using Generalized Linear Model (GLM repeated measures followed by post-hoc analysis. Results In the yoga group, there was a steady and progressive improvement in pulmonary function, the change being statistically significant in case of the first second of forced expiratory volume (FEV1 at 8 wk, and peak expiratory flow rate (PEFR at 2, 4 and 8 wk as compared to the corresponding baseline values. There was a significant reduction in EIB in the yoga group. However, there was no corresponding reduction in the urinary prostaglandin D2 metabolite (11β prostaglandin F2α levels in response to the exercise challenge. There was also no significant change in serum

  13. Escarro induzido em crianças e adolescentes com asma: segurança, aplicabilidade clínica e perfil de células inflamatórias em pacientes estáveis e durante exacerbação Induced sputum in children and adolescents with asthma: safety, clinical applicability and inflammatory cells aspects in stable patients and during exacerbation

    Directory of Open Access Journals (Sweden)

    Addy L. M. Palomino

    2005-06-01

    quantification. RESULTS: Sputum samples adequate for analysis were obtained from 68 (70.8% of the patients recruited. No relevant bronchoconstriction was observed during induction. The presence of a larger number of eosinophils in sputum did not correlate with more clinically severe asthma. No correlation was observed between the degree of bronchial obstruction, measured based on FEV1, and inflammatory cells in sputum, peripheral blood eosinophils or serum IgE. Larger numbers of neutrophils were observed in the asthma exacerbation group (p < 0.05. CONCLUSIONS: Sputum induction was found to be a safe procedure for obtaining clinical samples from children and adolescents even during exacerbations, allowing for clinical and functional limitations. The 67% induction success rate was considered satisfactory. In this group of patients, receiving inhaled corticosteroids, eosinophil quantification did not distinguish between the clinical and functional severity of asthma and was independent of the degree of airway obstruction. A proportional predominance of neutrophils was observed in the sputum of patients with asthma exacerbation.

  14. ¿Son las cenizas volcánicas un riesgo para la salud respiratoria?: Revisión a propósito de la erupción del cordón del Caulle en junio de 2011 Are volcanic ashes a risk for the respiratory health?: A review apropos of volcanic eruption of cord of Caulle, Chile in June 2011

    Directory of Open Access Journals (Sweden)

    Edgardo Grob B

    2012-12-01

    others. The impact of a volcanic eruption on human health depends on the type of eruption at which inhabitants have been exposed, the duration of this exposure and the previous health conditions of the exposed people. Some of these effects on human health are well known, such as burns, trauma, and respiratory disorders. In acute as well as in long term exposure, some of the respiratory health effects are still a matter of controversy and research on the mechanisms involved. Among the main adverse effects described in the respiratory tract are bronchoconstriction, amplification of the inflammatory response, complement disorders, silicosis and carcinogenesis. Considering the recent volcano eruptions of mount Chaitén (2008 and the cord of Caulle (2011 located in the south of Chile, we reviewed the deleterious effects of volcanic eruptions on human health and specifically on the respiratory system. Throughout this review we enclosed a number of recommendations, hopefully they will be useful in facing new volcanic eruptions in our country and everywhere.