			Home About us Contact

Methacholine

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Allergy & Clinical Immunology	53%
Respiratory Medicine	31%
Pharmacology & Pharmaceutical Medicine	8%
2 Other Subdomains	8%

Terms modified by Methacholine

methacholine challenge

methacholine challenge test

methacholine inhalation challenge

Selected Abstracts

Role of muscarinic receptor activation in regulating immune cell activity in nasal mucosa

ALLERGY, Issue 8 2010
T. Liu
To cite this article: Liu T, Xie C, Chen X, Zhao F, Liu A-M, Cho D-B, Chong J, Yang P-C. Role of muscarinic receptor activation in regulating immune cell activity in nasal mucosa. Allergy 2010; 65: 969,977. Abstract Background:, The prevalence of airway inflammatory disorders keeps rising; its pathogenic mechanism is still not fully understood. Objective:, The present study aimed to investigate the role of muscarinic receptor (M receptor) in regulating the immune cell activity in nasal mucosa by using surgical removed nasal mucosa from patients with nasal polyposis (NP) as a study platform. Methods:, Human nasal mucosal sample was collected from inferior turbinectomy of 86 patients with NP or/and allergic rhinitis. Expression of tumor necrosis factor alpha (TNF-alpha), M receptor, OX40 ligand was measured in nasal mucosa by enzyme-linked immunosorbent assay, flow cytometry, and Western blotting assay. Results:, When compared with non-NP (nNP) nasal mucosa, contents of TNF-alpha and TNF-alpha(+) cells markedly increased in NP nasal mucosa; immune staining colocalized M3 receptor(+) and TNF-alpha(+) cells in NP nasal mucosa; exposure of isolated CD4(+) T cells to methacholine induced the release of TNF-alpha. We also found CD11c(+)/M3 receptor(+) cells in NP nasal mucosa. Methacholine increased the expression of OX40L in dendritic cells. Staphylococcal (S) aureus and S. enterotoxin B (SEB) were detected in NP nasal mucosa. Exposure of dendritic cells or naïve CD4(+) T cells to SEB initiated the expression of M3 receptor at mRNA and protein levels. Conclusions:, The present data demonstrate that parasympathetic activity has the capacity to activate dendritic cells to release OX40 ligand, the latter induces CD4(+) T cells to produce IL-4 and TNF-alpha that may further contribute to the pathogenesis of NP. [source]

Effects of extra-fine inhaled beclomethasone/formoterol on both large and small airways in asthma

ALLERGY, Issue 7 2010
N. Scichilone
To cite this article: Scichilone N, Battaglia S, Sorino C, Paglino G, Martino L, Paternò A, Santagata R, Spatafora M, Nicolini G, Bellia V. Effects of extra-fine inhaled beclomethasone/formoterol on both large and small airways in asthma. Allergy 2010; 65: 897,902. Abstract Background:, Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways. Aim:, To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function. Methods:, After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 ,g daily or fluticasone propionate/salmeterol (FP/S) 500/100 ,g daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed. Results:, Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV1) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV1 in both BDP/F and FP/S groups (0.37 ± 0.13 l and 0.36 ± 0.12 l, respectively). PD20FEV1 Mch improved significantly from 90.42 (±30.08) ,g to 432.41 (±122.71) ,g in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN2 test parameters. Conclusion:, The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN2 tests. [source]

Membrane Hyperpolarization Is Not Required for Sustained Muscarinic Agonist-Induced Increases in Intracellular Ca2+ in Arteriolar Endothelial Cells

MICROCIRCULATION, Issue 2 2005
KENNETH D. COHEN
ABSTRACT Objective: Hyperpolarization modulates Ca2+ influx during agonist stimulation in many endothelial cells, but the effects of hyperpolarization on Ca2+ influx in freshly isolated arteriolar endothelial cells are unknown. Therefore, the purpose of the present study was to characterize agonist-induced Ca2+ transients in freshly isolated arteriolar endothelial cells and to test the hypothesis that membrane hyperpolarization augments agonist-induced Ca2+ influx into these cells. Methods: Arterioles were removed from hamster cremaster muscles and arteriolar endothelial cells were enzymatically isolated. Endothelial cells were loaded with Fura 2-AM and the Fura 2 ratio measured photometrically as an index of intracellular Ca2+. The cells were then stimulated with the muscarinic, cholinergic agonist, methacholine, and the resulting Ca2+ transients were measured. Results: Methacholine (1 , M) increased the endothelial cell Fura 2 ratio from a baseline of 0.81 ± 0.02 to an initial peak of 1.17 ± 0.05 (n = 17) followed by a sustained plateau of 1.12 ± 0.07. The plateau phase of the Ca2+ transient was inhibited by removal of extracellular Ca2+ (n = 12, p < .05), or the nonselective cation channel blockers Gd3+ (30 , M; n = 7, p < .05) or La3+ (50 , M; n = 7, p < .05) without significant effect on the baseline or peak (p > .05). The initial peak of methacholine-induced Ca2+ transients was inhibited by the IP3 -receptor antagonist xestospongin D (10 , M, n = 5, p < .05). The methacholine-induced Ca2+ transients were accompanied by endothelial cell hyperpolarization of approximately 14,18 mV, as assessed by experiments using the potentiometric dye, di-8-ANEPPS as well as by patch-clamp experiments. However, inhibition of hyperpolarization by blockade of Ca2+ -activated K+ channels with charybdotoxin (100 nM) and apamin (100 nM) (n = 5), or exposure of endothelial cells to 80 or 145 mM KCl (both n = 7) had no effect on the plateau phase of methacholine-induced Ca2+ transients (p > .05). Conclusions: Freshly isolated arteriolar endothelial cells display agonist-induced Ca2+ transients. For the muscarinic agonist, methacholine, these Ca2+ transients result from release of Ca2+ from intracellular stores through IP3 receptors, followed by sustained influx of extracellular Ca2+. While these changes in intracellular Ca2+ are associated with endothelial cell hyperpolarization, the methacholine-induced, sustained increase in intracellular Ca2+ appears to be independent from this change in membrane potential. These data suggest that arteriolar endothelial cells may possess a novel Ca2+ influx pathway, or that the relationship between intracellular Ca2+ and Ca2+ influx is more complex than that observed in other endothelial cells. [source]

Recovery of rat submandibular salivary gland function following removal of obstruction: a sialometrical and sialochemical study

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2006
Samira M. Osailan
Summary Functional recovery of the rat submandibular gland following ligation of the main excretory duct was examined. Rat submandibular glands were ligated for 1, 4 and 8 weeks using a micro-clip with a plastic tube. Micro-clips were removed and glands were allowed to recover for periods of 8, 16 and 24 weeks. Submandibular glands were stimulated with autonomimetic drugs (methacholine and isoprenaline) and salivas were collected from atrophic or de-ligated and contralateral control glands. Glands recovered almost full size (92% of control gland) following 24 weeks of de-ligation. Saliva volume secreted by ligated/de-ligated (RSM) and control (LSM) glands were similar with different doses of agonists. Protein output expressed per gram of tissue wet weight was similar from both ligated/de-ligated and control glands with all doses of agonist. Sodium and chloride levels were higher from de-ligated glands than contralateral control glands. Protein electrophoresis showed similar profiles of salivary proteins in all samples with some minor differences. Acinar cells in de-ligated glands showed a normal morphology, as indicated by light microscopy, whilst granular ductal cells were fewer and contained fewer secretory granules. Sodium potassium ATPase staining of striated ducts in de-ligated glands was similar to that of control glands. It can be concluded that rat submandibular glands can regenerate following severe atrophy and secrete normal amounts of saliva containing broadly a full profile of secretory proteins. In contrast to acinar cells, ductal cells appear not to recover full function. [source]

Role of muscarinic receptor activation in regulating immune cell activity in nasal mucosa

Rhinitis: a complication to asthma

ALLERGY, Issue 7 2010
J. W. Hansen
To cite this article: Hansen JW, Thomsen SF, Nolte H, Backer V. Rhinitis: a complication to asthma. Allergy 2010; 65: 883,888. Abstract Background:, Asthma and rhinitis often co-occur, and this potentially increases the disease severity and impacts negatively on the quality of life. We studied disease severity, airway responsiveness, atopy, quality of life and treatment in subjects with both asthma and rhinitis compared to patients with asthma or rhinitis alone. Methods:, We examined 878 patients: 182 with asthma, 362 with rhinitis and 334 with both asthma and rhinitis. All had a clinical interview concerning severity of symptoms, treatment, and quality of life, a skin prick test, a lung function test and a bronchial provocation with methacholine. Results:, Patients with both asthma and rhinitis had less severe asthma based on the frequency of respiratory symptoms compared to patients with asthma alone (55%vs 66%P = 0.01). On the contrary, they were more airway responsive (P < 0.05) and had more perennial allergy (P < 0.001). Asthmatics had poor perception of the general health, independent of rhinitis (P < 0.001). No differences were found in asthma-specific quality of life, whereas rhinitis-specific quality of life was worse in those with both asthma and rhinitis compared to those with rhinitis alone (P < 0.01). Subjects with both diseases were undertreated in 85% of the cases. Conclusion:, We encourage that these observations be used in the evaluation and treatment of patients with asthma and rhinitis and that they contribute to the understanding of asthma and rhinitis as a uniform airways disease. [source]

Clinical and inflammatory features of occupational asthma caused by persulphate salts in comparison with asthma associated with occupational rhinitis

ALLERGY, Issue 6 2010
G. Moscato
To cite this article: Moscato G, Pala G, Perfetti L, Frascaroli M, Pignatti P. Clinical and inflammatory features of occupational asthma caused by persulphate salts in comparison with asthma associated with occupational rhinitis. Allergy 2010; 65: 784,790. Abstract Background:, The relationships between asthma and rhinitis are still a crucial point in respiratory allergy and have scarcely been analysed in occupational setting. We aimed to compare the clinical and inflammatory features of subjects with occupational asthma only (OA) to subjects with OA associated to occupational rhinitis (OAR) caused by persulphate salts. Methods:, The clinical charts of 26 subjects diagnosed in our Unit as respiratory allergy caused by ammonium persulphate (AP), confirmed by specific inhalation challenge (SIC), were reviewed. Twenty-two out of twenty-six patients underwent pre-SIC-induced sputum challenge test (IS) and 24/26 underwent nasal secretion collection and processing. Results:, Twelve out of twenty-six patients received a diagnosis of OA-only and 14/26 of OAR. Duration of exposure before diagnosis, latency period between the beginning of exposure and asthma symptom onset, basal FEV1, airway reactivity to methacholine and asthma severity did not differ in the two groups. Eosinophilic inflammation of upper and lower airways characterized both groups. Eosinophil percentage in IS tended to be higher in OAR [11.9 (5.575,13.925)%] than in OA-only [2.95 (0.225,12.5)%] (P = 0.31). Eosinophilia in nasal secretions was present both in subjects with OAR [55 (46,71)%] and in subjects with OA-only [38 (15,73.5)%], without any significant difference. Discussion:, Our results indicate that OA because of ammonium persulphate coexists with occupational rhinitis in half of the patients. Unexpectedly, rhinitis did not seem to have an impact on the natural history of asthma. The finding of nasal inflammation in subjects with OA-only without clinical manifestations of rhinitis supports the united airway disease concept in occupational respiratory allergy as a result of persulphates. [source]

Risk factors for allergic rhinitis in Costa Rican children with asthma

ALLERGY, Issue 2 2010
S. Bunyavanich
To cite this article: Bunyavanich S, Soto-Quiros ME, Avila L, Laskey D, Senter JM, Celedón JC. Risk factors for allergic rhinitis in Costa Rican children with asthma. Allergy 2010; 65; 256,263 DOI: 10.1111/j.1398-9995.2009.02159.x. Abstract Background:, Risk factors for allergic rhinitis (AR) in asthmatics are likely distinct from those for AR or asthma alone. We sought to identify clinical and environmental risk factors for AR in children with asthma. Methods:, We performed a cross-sectional study of 616 Costa Rican children aged 6,14 years with asthma. Candidate risk factors were drawn from questionnaire data, spirometry, methacholine challenge testing, skin testing, and serology. Two outcome measures, skin test reaction (STR)-positive AR and physician-diagnosed AR, were examined by logistic regression. Results:, STR-positive AR had high prevalence (80%) in Costa Rican children with asthma, and its independent risk factors were nasal symptoms after exposure to dust or mold, parental history of AR, older age at asthma onset, oral steroid use in the past year, eosinophilia, and positive IgEs to dust mite and cockroach. Physician-diagnosed AR had lower prevalence (27%), and its independent risk factors were nasal symptoms after pollen exposure, STR to tree pollens, a parental history of AR, inhaled steroid and short-acting ,2 agonist use in the past year, household mold/mildew, and fewer older siblings. A physician's diagnosis was only 29.5% sensitive for STR-positive AR. Conclusions:, Risk factors for AR in children with asthma depend on the definition of AR. Indoor allergens drive risk for STR-positive AR. Outdoor allergens and home environmental conditions are risk factors for physician-diagnosed AR. We propose that children with asthma in Costa Rica and other Latin American nations undergo limited skin testing or specific IgE measurements to reduce the current under-diagnosis of AR. [source]

Inhaled vs subcutaneous effects of a dual IL-4/IL-13 antagonist in a monkey model of asthma

ALLERGY, Issue 1 2010
A. Tomkinson
Abstract Background:, Pitrakinra is a recombinant protein derived from human interleukin-4 (IL-4) that binds to IL-4R, and acts as a competitive antagonist of IL-4 and IL-13. The studies reported here compare the dose-ranging effects of pitrakinra on allergen-induced airway hyperresponsiveness (AHR) and airway eosinophilia when administered subcutaneously (s.c.) or by inhalation to the Ascaris suum -sensitive cynomolgus monkey for the purpose of elucidating the primary site of pitrakinra's anti-asthmatic action. Methods:, Airway responsiveness to inhaled methacholine and bronchoalveolar lavage cell composition was determined before and after three allergen exposures with a 1-week course of twice-daily (b.i.d.) s.c. or inhaled pitrakinra or placebo treatment. Results:, Treatment with s.c. pitrakinra significantly reduced allergen-induced AHR, with a maximum effect of a 2.8- to 3.8-fold increase in methacholine PC100 relative to control (P < 0.05) observed at b.i.d. s.c. doses of 0.05,0.5 mg/kg. Inhaled pitrakinra also significantly reduced AHR with a similar maximum effect of a 2.8- to 3.2-fold increase in methacholine PC100 relative to control (P < 0.05) at nominal b.i.d. doses of 3,100 mg. The maximal effect on AHR following inhalation was observed at a plasma concentration which exhibited no efficacy via the subcutaneous route. The effect of pitrakinra on lung eosinophilia was not statistically significant following either route of administration, although lung eosinophil count was reduced in all studies relative to control. Conclusion:, Local administration of pitrakinra to the lung is sufficient to inhibit AHR, one of the cardinal features of asthma, indicating the therapeutic potential of inhaled pitrakinra in the treatment of atopic asthma. [source]

Impact of allergic rhinitis on asthma: effects on bronchial hyperreactivity

ALLERGY, Issue 3 2009
I. Cirillo
Background:, Remarkable relationship exists between upper and lower airways. Bronchial hyperreactivity (BHR) is a paramount feature of asthma and may be considered a strong risk factor for the onset of asthma in patients with allergic rhinitis. Objective:, This study is aimed at evaluating the presence of BHR in a large group of patients with moderate-severe persistent allergic rhinitis alone, and at investigating possible risk factors related to severe BHR. Methods:, Three hundred and forty-two patients with moderate-severe persistent allergic rhinitis were prospectively and consecutively evaluated. Clinical examination, skin prick test, spirometry and bronchial methacholine (MCH) test were performed in all patients. Results:, Twenty-two (6.4%) patients had severe BHR, 74 (21.6%) patients had mild BHR and 192 (56.2%) had borderline BHR; 54 (15.8%) patients had a negative MCH test. The logistic regression analysis evidenced that trees and house dust mites sensitization (ORAdj: 8.1), rhinitis duration > 5 years (ORAdj: 5.4) and FEV1 , 86% of predicted (ORAdj: 4.0) were significantly associated with severe BHR. The discriminative ability of this model is appreciably satisfactory, being the AUC = 0.90. Conclusion:, This study highlights the close link between upper and lower airways and the role of some risk factors, such as tree and mite sensitization, > 5-year duration, and , 86% FEV1 values, as risk factors for severe BHR in patients with moderate-severe persistent allergic rhinitis alone. Therefore, BHR is frequently present in patients with chronic rhinitis and should be suspected in the presence of defined risk factors. [source]

Membrane Hyperpolarization Is Not Required for Sustained Muscarinic Agonist-Induced Increases in Intracellular Ca2+ in Arteriolar Endothelial Cells

Tryptophan catabolites regulate mucosal sensitization to ovalbumin in respiratory airways

ALLERGY, Issue 3 2009
S. O. Odemuyiwa
Background:, Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan catabolism, is important in generating tolerance at the foetal,maternal interface. Studies using 1-methyl-tryptophan (1-MT), the specific inhibitor of IDO, showed that this enzyme is important in interferon-gamma (IFN-,)-dependent inhibition of allergic inflammation in the respiratory airway during immunotherapy. Aims of study:, We investigated the role of IDO in the development of allergic sensitization, leading to allergic inflammation and airway hyper-responsiveness (AHR). Methods:, We used a mouse model to generate mucosal tolerance to lipopolysaccharide-free ovalbumin (OVA) following repeated intranasal inoculation of OVA over a 3-day period. We tested the successful induction of tolerance by subsequent intraperitoneal (i.p.) sensitization followed by intranasal challenge with OVA. A slow-release pellet of 1-MT implanted into mice was used to block IDO activity prior to repeated intranasal inoculation of OVA. We measured T-cell proliferation in response to OVA, determined airway inflammation, and measured AHR to intranasal methacholine to investigate the role of IDO in sensitization to OVA. Results:, Repeated intranasal administration of OVA generated tolerance and prevented a subsequent sensitization to OVA via the i.p. route. This response was inhibited in mice receiving a slow-release pellet of 1-MT. However, we successfully reconstituted tolerance in mice receiving 1-MT following intra-peritoneal injection of a mixture of kynurenine and hydroxyanthranilic acid. Conclusion:, Our data suggest that, in addition to their role in IFN-,-mediated inhibition of allergic airway inflammation, products of tryptophan catabolism play an important role in the prevention of sensitization to potential allergens in the respiratory airway. [source]

Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment

ALLERGY, Issue 1 2009
E. L. J. Van Rensen
Background:, Anti-IgE, omalizumab, inhibits the allergen response in patients with asthma. This has not been directly related to changes in inflammatory conditions. We hypothesized that anti-IgE exerts its effects by reducing airway inflammation. To that end, the effect of anti-IgE on allergen-induced inflammation in bronchial biopsies in 25 patients with asthma was investigated in a randomized, double-blind, placebo-controlled study. Methods:, Allergen challenge followed by a bronchoscopy at 24 h was performed at baseline and after 12 weeks of treatment with anti-IgE or placebo. Provocative concentration that causes a 20% fall in forced expiratory volume in 1 s (PC20) methacholine and induced sputum was performed at baseline, 8 and 12 weeks of treatment. Changes in the early and late responses to allergen, PC20, inflammatory cells in biopsies and sputum were assessed. Results:, Both the early and late asthmatic responses were suppressed to 15.3% and 4.7% following anti-IgE treatment as compared with placebo (P < 0.002). This was paralleled by a decrease in eosinophil counts in sputum (4,0.5%) and postallergen biopsies (15,2 cells/0.1 mm2) (P < 0.03). Furthermore, biopsy IgE+ cells were significantly reduced between both the groups, whereas high-affinity IgE receptor and CD4+ cells were decreased within the anti-IgE group. There were no significant differences for PC20 methacholine. Conclusion:, The response to inhaled allergen in asthma is diminished by anti-IgE, which in bronchial mucosa is paralleled by a reduction in eosinophils and a decline in IgE-bearing cells postallergen without changing PC20 methacholine. This suggests that the benefits of anti-IgE in asthma may be explained by a decrease in eosinophilic inflammation and IgE-bearing cells. [source]

The effect of ,2-adrenoceptor haplotypes on bronchial hyper-responsiveness in patients with asthma

ALLERGY, Issue 2 2006
A. M. Wilson
Background:, The ,2-adrenoceptor exhibits genetic polymorphism which may be clinically relevant in terms of treatment response or bronchial hyper-responsiveness (BHR). The combined effect of these genotypes, or the haplotype, has not been fully characterized in terms of BHR. Methods:, We performed a retrospective analysis of the effects of haplotypes of amino acid substitution at position 16 (Gly/Arg) and position 27 (Gln/Glu) on spirometry and BHR to methacholine and adenosine monophosphate (AMP) in 594 asthmatic patients. Results:, There was a significant (P < 0.05) overall effect for forced expiratory volume (FEV1) but not after correction for steroid dose and atopic status. There were no significant differences for BHR to methacholine or AMP between the different haplotypes and no difference between the numbers of patients with or without clinically relevant BHR. Methacholine PD20 geometric mean-fold difference was 1.63 (95% CI: 0.95,2.80) between Arg,Arg/Gln,Gln and Gly,Gly/Gln,Gln and 1.26 (95% CI: 0.75,2.11) between Gly,Gly/Gln,Gln and Gly,Gly/Glu,Glu. Conclusions:, The degree of BHR to indirect and direct stimuli does not differ between ,2-adrenoceptor haplotypes, and haplotypes cannot be used to predict BHR in patients presenting with asthma. Although ,2-adrenoceptor haplotypes do not predict BHR they may be important in predicting response to bronchodilator therapy. [source]

The potential use of spirometry during methacholine challenge test in young children with respiratory symptoms

PEDIATRIC PULMONOLOGY, Issue 7 2009
Daphna Vilozni PhD
Abstract Background The concentration of methacholine that causes a fall of 20% from baseline forced expiratory volume in the first second (PC20-FEV1) in the methacholine challenge test (MCT) is not usually considered a diagnostic tool in preschool children since PC20-FEV1 may not be achievable <6 years of age. Aim To assess the usefulness of various spirometry indices obtained during MCT in a large group of 3- to 6-year-old children with respect to their clinical diagnosis. Methods Standardized MCT (inhaled triple-concentration increments [0.057,13.925 mg] of methacholine solution) was performed by 84 children previously diagnosed with asthma (asthmatics) and 48 with prolonged cough (coughers). Spirometry was determined at baseline and between inhalations; PC20-FEV1 and PC25-FEV0.5 were calculated. Results PC20-FEV1 values were significantly less in the asthmatics than in the coughers (mean,±,SD was 3.21,±,4.32 vs. 22.35,±,3.66 ml/mg). Similarly, PC25-FEV0.5 was 1.48,±,3.08 in the asthmatics and 9.45,±,12.59 mg/ml/Mch in the coughers, P,<,0.0001. A cut-off at 4.0 mg/ml for PC20-FEV1 had 77.4% sensitivity and 75.0% specificity, a cut-off at 2.2 mg/ml for PC25-FEV0.5 had 73.8% sensitivity and 72.9% specificity, for clinical diagnosis of asthma. PC25-FEV0.5 also showed a correlation with age. Conclusions Our findings suggest that MCT can be performed in preschool children with various respiratory symptoms. PC25-FEV0.5 may be a better end-point parameter. Children with a clinical diagnosis of asthma respond to a lower MCT concentration than children with cough. Further studies are needed to determine airway responsiveness in healthy young children and to further assess the contribution of MCT to the clinical diagnosis in this age group. Pediatr Pulmonol. 2009; 44:720,727. © 2009 Wiley-Liss, Inc. [source]

Mechanisms determining cholinergic neural responses in airways of young and mature rabbits,

PEDIATRIC PULMONOLOGY, Issue 2 2004
Gary L. Larsen MD
Abstract Neural pathways help control airway caliber and responsiveness. Yet little is known of how neural control changes as a function of development. In rabbits, we found electrical field stimulation (EFS) of airway nerves led to more marked contractile responses in 2- vs. 13-week-old animals. This enhanced response to EFS may be due to prejunctional, junctional, and/or postjunctional neural mechanisms. We assessed these mechanisms in airways of 2- and 13-week-old rabbits. The contractile responses to methacholine did not differ in the groups, suggesting postjunctional neural events are not primarily responsible for differing responses to EFS. To address junctional events, acetylcholinesterase (AChE) was measured (spectrophotometry). AChE was elevated in 2-week-olds. However, this should lead to less and not greater responses. Prejunctionally, EFS-induced acetylcholine (ACh) release was assessed by HPLC. Airways of 2-week-old rabbits released significantly more ACh than airways from mature rabbits. Choline acetyltransferase, a marker of cholinergic nerves, was not different between groups, suggesting that more ACh release in young rabbits was not due to increased nerve density. ACh release in the presence of polyarginine increased significantly in both groups, supporting the presence of functional muscarinic autoreceptors (M2) at both ages. Because substance P (SP) increases release of ACh, SP was measured by ELISA. This neuropeptide was significantly elevated in airways of younger rabbits. Nerve growth factor (NGF) increased SP and was also significantly increased in airways from younger rabbits. This work suggests that increases in EFS-induced responsiveness in young rabbits are likely due to prejunctional events with enhanced release of ACh. Increases in NGF and SP early in life may contribute to this increased responsiveness. Pediatr Pulmonol. 2004; 38:97,106. © 2004 Wiley-Liss, Inc. [source]

Outcome in adulthood of asymptomatic airway hyperresponsiveness in childhood: A longitudinal population study

PEDIATRIC PULMONOLOGY, Issue 3 2002
Finn Rasmussen MD
Abstract The clinical outcome of asymptomatic airway hyperresponsiveness (AHR) first detected in childhood is sparsely reported, with conflicting results. We used a birth cohort of 1,037 children followed to age 26 years to assess the clinical outcome of asymptomatic AHR to methacholine first documented in study members at age 9 years. Of 547 study members who denied wheezing symptoms ever at age 9 years, 41 (7.5%) showed AHR. Forty showed methacholine responsiveness, with a provocation concentration of methacholine that elicted a 20% drop in forced expired volume in 1 sec (PC20),,,8 mg/mL, and one had baseline airway obstruction with a bronchodilator response exceeding 10%. Of these 41 study members, 18 (44%), 11 (27%), and 4 (10%) maintained AHR in 1, 2, and 3 later assessments, respectively, while 23 (56%) manifested AHR only at age 9. Compared with asymptomatic study members without AHR, those with asymptomatic AHR at age 9 years were more likely to report asthma and wheeze at any subsequent assessment, were more likely to have high IgE levels and eosinophils at ages 11 and 21, and more often demonstrated positive responses to skin allergen testing at ages 13 and 21 years. Persistent AHR at later assessments increased these likelihoods further. In conclusion, asymptomatic children with AHR are more likely to develop asthma and atopy later in life compared with asymptomatic children without AHR. Persistent AHR, even though initially asymptomatic, was associated with an even greater increased risk of development of asthma. We suggest that rather than considering AHR as a marker of asthma, it should be regarded as a parallel pathological process that may lead to subsequent symptoms and clinical evidence of asthma. Pediatr Pulmonol. 2002; 34:164,171. © 2002 Wiley-Liss, Inc. [source]

Extrathoracic airway responsiveness in children with asthma-like symptoms, including chronic persistent cough

PEDIATRIC PULMONOLOGY, Issue 3 2002
Ipek Turktas MD
Abstract Asthma-like symptoms, including chronic persistent cough, are not always specific for classical asthma. In order to investigate whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during methacholine bronchial challenge helped in the evaluation of pediatric patients with asthma-like symptoms such as chronic cough, we examined 133 consecutive, unselected patients (mean age, 10.06,±,2.16 years) who had neither established asthma nor bronchial obstruction previously. We recorded the forced mid-inspiratory flow (FIF50) as an index of extrathoracic airway narrowing. In addition, a 25% decrease in FIF50 (PD25FIF50) below the cutoff concentration of ,,8 mg/mL methacholine was assumed to indicate EAHR. According to the methacholine response, 81 patients had EAHR, and 41 of them had combined EAHR and bronchial hyperresponsiveness (BHR); 39 patients had only BHR. Airway hyperresponsiveness was not demonstrated in 13 patients and not in any of the control children. When patients with cough as the sole presenting symptom (60.9%) were compared with those with cough and wheeze (20.3%), those with cough alone had a significantly greater probability of having EAHR (OR, 4.16; 95% CI, 1.32,13.13) and a lower probability of having BHR (OR, 0.70; CI, 0.25,1.95) than those with cough and wheeze. Patients with cough, wheeze, and dyspnea (18.8%) had a significantly greater chance of having BHR than those with cough alone (OR, 5.08; CI, 1.55,16.64). Patients with cough and wheeze as compared with those with cough, wheeze, and dyspnea had significantly greater probability of having both EAHR and BHR (OR, 4.71; CI, 1.94,11.47). In order to ascertain the clinical relevance of EAHR, we assessed in the second part of the study whether the effects of treatment of the underlying disease would result in relief of airway hyperresponsiveness. Rhinosinusitis and perennial allergic rhinitis accounted for EAHR in 71 patients, and 34 of them also demonstrated BHR. They received specific therapy for their upper airway diseases for 4 weeks. Compared with values before treatment, FIF50 and forced expiratory volume in 1 sec (FEV1) did not change significantly. The dose of methacholine causing a 20% fall in FEV1 (PD20FEV1) and PD25FIF50 values were significantly increased from 2.40,±,1.39 to 4.22,±,1.13 mg /mL (P,<,0.001) and from 1.03,±,1.75 to 8.71,±,1.21 mg /mL (P,<,0.0001), respectively. We conclude that measurements of EAHR and BHR are the most important ways to evaluate children with asthma-like symptoms, including chronic persistent cough when chest X-rays and pulmonary function tests remain within normal limits. Therefore, empirical treatment is not necessary when these investigations are available. Our results suggest that specific treatment of inflammation in the upper airways reversed persistant cough, and may play an important role in modulating lower airways responsiveness in patients with concomitant BHR. Pediatr Pulmonol. 2002; 34:172,180. © 2002 Wiley-Liss, Inc. [source]

Respiratory impedance response to a deep inhalation in children with history of cough or asthma

PEDIATRIC PULMONOLOGY, Issue 6 2002
François Marchal MD
Abstract The aim of this study was to describe the change in respiratory impedance induced by a deep inhalation (DI) in children who developed a positive response to inhalation of methacholine (Mch). Eighteen children aged 4.5,12.5 years, presenting with chronic cough or doctor-diagnosed asthma, were studied at baseline after inhalation of Mch and after inhalation of a bronchodilator. Respiratory resistance (Rrs) and reactance (Xrs) were measured by the forced oscillation technique, varying transrespiratory pressure at 12 Hz around the head. The tidal flow (V,) and volume (V) dependence of Rrs before and after the DI was characterized according to the equation Rrs,=,K1,+,K2,·,|V,|,+,K3,·,V. DI induced no significant change at baseline or after inhalation of a bonchodilator. During Mch challenge, Rrs and K1 were significantly lower, and K3 and Xrs significantly less negative after DI than before, during both inspiration and expiration; there was no change in K2. We conclude that DI results in a decrease in Rrs in children with induced bronchoconstriction. The associated changes in Xrs, K1, and K3, and lack of decrease in K2, suggest that dilatation of airways occurs at the bronchial level, with little contribution of the upper airways or of a change in breathing patterns. Pediatr Pulmonol. 2002; 33:411,418. © 2002 Wiley-Liss, Inc. [source]

Relationship between bronchial hyperresponsiveness and development of asthma in children with chronic cough

PEDIATRIC PULMONOLOGY, Issue 6 2001
Hideko Nishimura MD
Abstract To evaluate the relationship between bronchial hyperresponsiveness (BHR) and the development of asthma in children with chronic cough, we performed methacholine inhalation challenges and transcutaneous oxygen pressure (tcPO2) measurements in 92 children with chronic cough aged from 1,13 years (55 boys and 37 girls; mean, 5.3 years) and followed them for ,,,10 years. Forty-four age-matched children with asthma (24 males and 20 females; mean, 6.5 years) and 44 age-matched children without cough or asthma served as controls (18 males and 26 females; mean, 4.6 years). Consecutive doubling doses of methacholine were inhaled until a 10% decrease in tcPO2 from baseline was observed. The cumulative dose of methacholine at the inflection point of the tcPO2 record (Dmin-PO2) was considered to represent hyperresponsiveness to inhaled methacholine. After 10 years or more of follow-up, 60 of the 92 subjects with cough answered our questionnaire, and 27/60 had been diagnosed with asthma. There was a statistical difference in Dmin-PO2 between the children who presented with chronic cough originally and who developed asthma (asthma-developed group) and those who did not develop asthma (asthma-free group). There was no difference in the value of Dmin-PO2 between the asthma-developed group and the asthma group, or between the asthma-free group and the age-matched control group. Among the children with chronic cough, there was no difference in Dmin-PO2 between girls and boys, either in the asthma-developed group or in the asthma-group. We conclude that 45% of the children with a chronic cough in early life developed asthma, and that BHR in children with chronic cough during the childhood period is a strong risk factor for the development of asthma. Pediatr Pulmonol. 2001; 31:412,418. © 2001 Wiley-Liss, Inc. [source]

Familial dysautonomia: A diagnostic dilemma.

PEDIATRIC PULMONOLOGY, Issue 6 2001
Chronic lung disease with signs of an autoimmune disease
Abstract We present an 11-year-old girl with sensory and autonomic neurological dysfunction, and respiratory insufficiency caused by recurrent aspiration. The diagnosis of familial dysautonomia (FD) was confirmed by a missing axonal flare to histamine, miosis in response to conjunctival methacholine and homozygous polymorphic linked markers DS58(18) and DS159(7) on chromosome 9. Ashkenazi Jewish descent could not be ascertained by history. A variety of positive tests for autoantibodies were initially interpreted as evidence for systemic lupus erythematosus vs. overlap syndrome with pulmonary, cerebral, skin, and ocular involvement. The diagnosis of FD was delayed because of the rarity of this disorder in Germany (second case reported). We discuss possible explanations for the misleading immunological findings, including interference by antibodies binding to milk proteins used as blocking reagents in enzyme-linked immunoassays and circulating immune-complexes due to chronic aspiration pneumonitis. Pediatr Pulmonol. 2001; 31:478,481. © 2001 Wiley-Liss, Inc. [source]

Airways inflammation after exposure in a swine confinement building during cleaning procedure

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 4 2002
Britt-Marie Larsson PhD
Abstract Background Healthy volunteers exposed for 3 hr during weighing of pigs develop an airway inflammation characterized by a massive influx of neutrophilic granulocytes in the upper and lower airways and increased bronchial responsiveness to methacholine. The purpose of the present study was to investigate health effects from exposure during cleaning of the swine confinement building and to evaluate the effect of a respiratory protection device. Methods Sixteen subjects were exposed for 3 hr during cleaning of a swine confinement room with a high-pressure cleaner. Seven out of sixteen subjects were equipped with a mask during exposure. Results The bronchial responsiveness increased in all subjects following exposure, significantly more in the group exposed without a mask (P,<,0.05). The cell concentration (mainly neutrophilic granulocytes) in nasal lavage fluid as well as the concentration of interleukin-8, increased significantly only in those subjects exposed without a respiratory protection device. In peripheral blood, an increase of neutrophilic granulocytes was observed in both groups, although it was significantly higher in the group without mask (P,<,0.05). The inhalable dust level was 0.94 (0.74 , 1.55) mg/m3 and respirable dust 0.56 (0.51,0.63) mg/m3. Conclusion Exposure to dust aerosols during the cleaning of the interior of a swine confinement building induces increased bronchial responsiveness and an acute inflammatory reaction in the upper airways. The use of a mask attenuated but did not abolish the inflammatory response. This suggests that gases and/or ultrafine particles in this environment could be important factors in the development of increased bronchial responsiveness. Am. J. Ind. Med. 41:250,258, 2002. © 2002 Wiley-Liss, Inc. [source]

Changes in the highest frequency of breath sounds without wheezing during methacholine inhalation challenge in children

RESPIROLOGY, Issue 3 2010
Chizu HABUKAWA
ABSTRACT A breath sound analyser was used to detect bronchoconstriction without wheezing during methacholine inhalation challenge in children. The highest frequency of inspiratory breath sounds increased significantly during bronchoconstriction and decreased after inhalation of a bronchodilator. The highest frequency of inspiratory breaths sounds was correlated with bronchial reactivity. Background and objective: It is difficult for clinicians to identify changes in breath sounds caused by bronchoconstriction when wheezing is not audible. A breath sound analyser can identify changes in the frequency of breath sounds caused by bronchoconstriction. The present study aimed to identify the changes in the frequency of breath sounds during bronchoconstriction and bronchodilatation using a breath sound analyser. Methods: Thirty-six children (8.2 ± 3.7 years; males : females, 22 : 14) underwent spirometry, methacholine inhalation challenge and breath sound analysis. Methacholine inhalation challenge was performed and baseline respiratory resistance, minimum dose of methacholine (bronchial sensitivity) and speed of bronchoconstriction in response to methacholine (Sm: bronchial reactivity) were calculated. The highest frequency of inspiratory breath sounds (HFI), the highest frequency of expiratory breath sounds (HFE) and the percentage change in HFI and HFE were determined. The HFI and HFE were compared before methacholine inhalation (pre-HFI and pre-HFE), when respiratory resistance reached double the baseline value (max HFI and max HFE), and after bronchodilator inhalation (post-HFI and post-HFE). Results: Breath sounds increased during methacholine-induced bronchoconstriction. Max HFI was significantly greater than pre-HFI (P < 0.001), and decreased to the basal level after bronchodilator inhalation. Post-HFI was significantly lower than max HFI (P < 0.001). HFI and HFE were also significantly changed (P < 0.001). The percentage change in HFI showed a significant correlation with the speed of bronchoconstriction in response to methacholine (P = 0.007). Conclusions: Methacholine-induced bronchoconstriction significantly increased HFI, and the increase in HFI was correlated with bronchial reactivity. [source]

Asthma Control Test correlates well with the treatment decisions made by asthma specialists

RESPIROLOGY, Issue 4 2009
Fanny W.S. KO
ABSTRACT Background and objective: Poor assessment of asthma control results in suboptimal treatment. Identifying parameters that accurately assess control will benefit treatment decisions. The Asthma Control Test (ACT) is a five-item questionnaire for the assessment of asthma control. This study evaluated its correlation with the treatment decisions made by asthma specialists in an outpatient clinic setting, and compared its performance with other conventional parameters including spirometry, PEF rate (PEFR), fractional exhaled nitric oxide (FeNO) and BHR. Methods: The 383 (122 men) study subjects completed a 1-month diary on symptoms and PEFR before the assessment. All subjects then completed the ACT together with same-day spirometry and FeNO measurement. BHR to methacholine was performed in 73 subjects in the week before assessment. Asthma specialists, blinded to the results of the ACT, FeNO and BHR (but not spirometry and PEFR), assessed the patients' level of control according to the 2006 version of the Global Initiative for Asthma guidelines and made appropriate treatment decision. Results: The group mean (SD) age was 46.1 (13.4) years with pre-bronchodilator FEV1 84.72 (20.81) % predicted. Receiver operating characteristic (ROC) curve analysis found that an ACT score of ,20 best correlated with uncontrolled asthma (area under curve (AUC) = 0.76) with a sensitivity of 70.5%, specificity 76.0%, positive predictive value 76.2% and negative predictive value 70.2% for predicting step-up of asthma therapy. On ROC analysis, the ACT score had the highest AUC (0.81 (P < 0.001)) for changing asthma therapy when compared with FeNO, spirometry, PEFR and BHR parameters Conclusions: The ACT correlated better with treatment decisions made by asthma specialists than spirometry, PEFR and FeNO. [source]

Sputum eosinophilia and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapy

RESPIROLOGY, Issue 2 2003
Keisaku FUJIMOTO
Objective: We aimed to examine airway inflammation and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapy. Methodology: Bronchial responsiveness to methacholine as well as the number of inflammatory cells and concentration of eosinophil cationic protein (ECP) in induced sputum were measured in 42 patients with chronic non-productive cough of unknown origin. Their response to bronchodilator, antiallergic and inhaled or oral glucocorticoid therapy was subsequently assessed. Results: Complete remission of coughing was attained with anti-asthma therapies in 34 patients (responder group), while eight patients did not respond (non-responder group). Twenty patients in the responder group and three in the non-responder group showed bronchial hyperresponsiveness (BHR). The number of eosinophils and ECP levels in the sputum from responders with BHR were significantly increased when compared with those from non-responders and healthy subjects. These sputum measures were also significantly increased in responders without BHR when compared with healthy subjects. However, there were no significant differences in these inflammatory markers between the responders with and without BHR. The neutrophil numbers in the sputum from non-responders and responders both with and without BHR were also significantly higher than in control subjects, but there were no significant differences. Conclusions: These findings suggest that patients with chronic non-productive cough responsive to anti-asthma therapy characteristically have eosinophilic airway inflammation, which may play an important role in the development of chronic cough. Furthermore, the evaluation of not only bronchial responsiveness but also airway inflammation by examination of induced sputum may be useful for diagnosis and deciding on therapeutic strategies. [source]

Respiratory morbidity and lung function in two Aboriginal communities in Western Australia

RESPIROLOGY, Issue 3 2002
Marieke W. VERHEIJDEN
Objective: To examine differences in the rates of respiratory symptoms, asthma and levels of lung function in two remote Aboriginal communities. Methodology: Respiratory symptoms, smoking history, skin prick test responses to common allergens, serum IgE, lung function, airway responsiveness to methacholine and white blood cell counts were compared in two Aboriginal communities, one from the central desert (n = 84) and another from the tropical north (n = 209) of Western Australia. Results: Compared with the tropical community, chest tightness and dyspnoea were more frequent and forced expiratory volume in 1 s and forced vital capacity were lower in the desert community, despite similar levels of wheeze, doctor-diagnosed asthma and skin prick test responses and lower levels of airway responsiveness and smoking. The total white cell and neutrophil counts were greater in the desert community. Serum IgE was very high and similar in both communities. Conclusions: Our findings show a low prevalence of asthma in children, a high prevalence of respiratory symptoms and low levels of lung function in remote Aboriginal communities. The greater prevalence of respiratory morbidity in the desert community was not explained by diagnosed asthma, airway hyperresponsiveness or cigarette smoking. The role of infection requires further investigation. The results suggest that the lower lung function observed in Aboriginal communities (compared with non-Aboriginal communities) results at least partly from environmental factors. [source]

Current and future use of the mannitol bronchial challenge in everyday clinical practice

THE CLINICAL RESPIRATORY JOURNAL, Issue 4 2009
Celeste Porsbjerg
Abstract Objectives:, Asthma is a disease associated with inflammation, airway hyperresponsiveness (AHR) and airflow limitation. Clinical diagnosis and management of asthma often relies on assessment of lung function and symptom control, but these factors do not always correlate well with underlying inflammation. Bronchial challenge tests (BCTs) assess AHR, and can be used to assist in the diagnosis and management of asthma. Data Source:, Data presented at the symposium ,Use of inhaled mannitol for assessing airways disease' organised by the Allied Respiratory Professionals Assembly (9) of the European Respiratory Society (ERS) at the ERS Congress, Berlin 2008. Results:, Indirect challenge tests such as exercise testing, hypertonic saline or adenosine 5,-monophosphate (AMP) are more specific though less sensitive than direct challenge tests (such as methacholine) for identifying patients with active asthma. Indirect BCTs may be used to diagnose exercise-induced bronchoconstriction or AHR consistent with active asthma, to evaluate AHR that will respond to treatment with anti-inflammatory drugs and to determine the effectiveness and optimal dosing of such therapy. An ideal indirect challenge test should be standardised and reproducible, and the test result should correlate with the degree of airway inflammation. The mannitol BCT provides a standardised and rapid point-of-need test to identify currently active asthma, and is clinically useful in the identification of patients with asthma who are likely to benefit from inhaled corticosteroid therapy. Conclusion:, In the future, mannitol BCT may be added to lung function and symptom assessment to aid in the everyday management of asthma. Please cite this paper as: Porsbjerg C, Backer V, Joos G, Kerstjens HAM and Rodriguez-Roisin R. Current and future use of the mannitol bronchial challenge in everyday clinical practice. The Clinical Respiratory Journal 2009; 3: 189,197. [source]

Airway hyperresponsiveness: the usefulness of airway hyperresponsiveness testing in epidemiology, in diagnosing asthma and in the assessment of asthma severity

THE CLINICAL RESPIRATORY JOURNAL, Issue 1 2007
Celeste Porsbjerg MD
Abstract The present PhD thesis was conducted at the Respiratory Research Unit at the Pulmonary Department L in Bispebjerg Hospital, Copenhagen, Denmark and describes airway hyperresponsiveness in asthma patients in four studies. The first study concerned risk factors for the development of asthma in young adults in a 12-year prospective follow-up study of a random population sample of 291 children and adolescents from Copenhagen, who were followed up from the age of 7,17 years (1986) until the age of 19,29 years (1998). During follow-up, 16.1% developed asthma, and in these subjects, the most important predictor of asthma development was airway hyperresponsiveness to histamine at baseline. Airway hyperresponsiveness is associated with more severe asthma and a poorer prognosis in terms of more exacerbations and less chance of remission of the disease. The second study described the relation between airway hyper-responsiveness to methacholine and the quality of life in 691 asthma patients: In asthma patients with airway hyperresponsiveness to methacholine, the quality of life measured with a validated questionnaire (Junipers Asthma Quality of Life Questionnaire) was significantly reduced compared to asthma patients who did not respond to bronchial provocation with methacholine. Airway hyperresponsiveness is not uncommonly observed in non-asthmatics, and the response to bronchial provocation with methacholine is therefore relatively non-specific. The mannitol test is a relatively new bronchial provocation test that acts indirectly on the smooth airway muscle cells through the release of mediators from inflammatory cells in the airways; the mannitol could consequently be a more specific test compared with methacholine. The third study showed that out of 16 non-asthmatics with airway hyperresponsiveness to methacholine, 15 did not respond to bronchial provocation with mannitol Because of the mechanism of action of mannitol, it seems plausible that the response to mannitol is more closely correlated to airway inflammation in asthma compared with the response to methacholine. The fourth study showed that in 53 adult asthma patients, who did not receive treatment with inhaled steroids, there was a positive correlation between the degree of airway inflammation and the degree of airway responsiveness to mannitol as well as to methacholine. The mannitol does, however, have the advantage of being a faster and simpler test to perform, requiring no additional equipment apart from a spirometer. Conclusions:, Airway hyperresponsiveness in children and in adolescents without asthma predicts asthma development in adulthood. Asthma patients with airway hyperresponsiveness to methacholine have a poorer quality of life as well as more severe disease and a poorer prognosis compared with asthma patients without airway hyperresponsiveness. Bronchial provocation with mannitol as well as with methacholine were useful for evaluating the severity of asthma and the degree of airway inflammation, and accordingly for determining the need for steroid statement. The mannitol test does, however, have practical advantages over the methacholine test that make it preferable for clinical use. [source]

The stimulant cathartic, emodin, contracts the rat isolated ileum by triggering release of endogenous acetylcholine

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2004
S. Ali
Summary 1 Anthraquinone stimulant cathartics, such as emodin, are believed to increase the rate of contraction of ileum tissue in vitro via multiple mechanisms. The aim of this study was to probe the effects of emodin on acetylcholine (ACh)-induced contraction of the rat isolated ileum preparation. 2 Ileal sections were incubated in Tyrode's solution and responses to methacholine, ACh and emodin obtained in the absence and presence of the muscarinic antagonist atropine and the choline uptake inhibitor hemicholinium (HC-3). Depletion of endogenous ACh in the presence of HC-3 was achieved by construction of an ACh dose,response curve, using exogenous ACh, prior to re-testing the effects of emodin in the presence of HC-3. 3 Emodin caused dose-dependent tissue contraction that was abolished by inclusion of atropine (1 ,m) in the buffer. Atropine (1 ,m) antagonized the response caused by methacholine. 4 Incubation of tissues with HC-3 (1 and 10 ,m) reduced the maximum response caused by emodin by 45% and 71% respectively, but had no effect on ACh-induced tissue contraction. 5 These data suggest that, emodin causes contraction of the ileum by triggering the release of endogenous ACh which acts on muscarinic receptors to cause contraction of the rat isolated ileum preparation. [source]

Suppression of histamine-induced tachypnoea in the rhesus monkey by sibenadet: no role for dopamine D2 receptors

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2004
J. R. Fozard
Summary 1 Sibenadet (Viozan®), a dual dopamine D2/,2 -adrenoceptor agonist, suppresses histamine-induced tachypnoea in the dog by activating dopamine D2 receptors. We here compare the effects of sibenadet and formoterol, a selective ,2 -adrenoceptor agonist, on histamine-induced tachypnoea in the rhesus monkey. 2 Anaesthetized, spontaneously breathing, rhesus monkeys were set up for measuring airways resistance, respiratory rate, blood pressure and heart rate. 3 Both sibenadet and formoterol administered by aerosol, induced inhibition of the bronchoconstrictor response to aerosolized methacholine accompanied by tachycardia. Sibenadet, but not formoterol, also reduced blood pressure. 4 Administration of histamine by inhalation induced tachypnoea which was accompanied by bronchoconstriction. Tachypnoea to histamine was suppressed by both sibenadet and formoterol at doses which manifest anti-bronchoconstrictor activity. These effects and the accompanying tachycardia but not the hypotension induced by sibenadet were abolished by pretreatment with propranolol. 5 The dopamine D2 receptor agonist, quinagolide, did not suppress tachypnoea to histamine despite inducing a fall in blood pressure indicating activation of dopamine D2 receptors. 6 Thus, both sibenadet and formoterol suppress histamine-evoked tachypnoea in the rhesus monkey. The effect arises exclusively through activation of ,2 -adrenoceptors and probably reflects the anti-bronchoconstrictor effects of these agents. The results reveal a fundamental difference in the role of dopamine receptors in the airways of dog and rhesus monkey. [source]