Bronchoconstrictor Agents: Agents causing the narrowing of the lumen of a bronchus or bronchiole.Bronchoconstriction: Narrowing of the caliber of the BRONCHI, physiologically or as a result of pharmacological intervention.Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow.Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI.Bronchial Provocation Tests: Tests involving inhalation of allergens (nebulized or in dust form), nebulized pharmacologically active solutions (e.g., histamine, methacholine), or control solutions, followed by assessment of respiratory function. These tests are used in the diagnosis of asthma.Methacholine Chloride: A quaternary ammonium parasympathomimetic agent with the muscarinic actions of ACETYLCHOLINE. It is hydrolyzed by ACETYLCHOLINESTERASE at a considerably slower rate than ACETYLCHOLINE and is more resistant to hydrolysis by nonspecific CHOLINESTERASES so that its actions are more prolonged. It is used as a parasympathomimetic bronchoconstrictor agent and as a diagnostic aid for bronchial asthma. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1116)Histamine: An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.Methacholine Compounds: A group of compounds that are derivatives of beta-methylacetylcholine (methacholine).Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Ipratropium: A muscarinic antagonist structurally related to ATROPINE but often considered safer and more effective for inhalation use. It is used for various bronchial disorders, in rhinitis, and as an antiarrhythmic.Vagotomy: The interruption or removal of any part of the vagus (10th cranial) nerve. Vagotomy may be performed for research or for therapeutic purposes.Neurokinin A: A mammalian neuropeptide of 10 amino acids that belongs to the tachykinin family. It is similar in structure and action to SUBSTANCE P and NEUROKININ B with the ability to excite neurons, dilate blood vessels, and contract smooth muscles, such as those in the BRONCHI.Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.Bronchial Hyperreactivity: Tendency of the smooth muscle of the tracheobronchial tree to contract more intensely in response to a given stimulus than it does in the response seen in normal individuals. This condition is present in virtually all symptomatic patients with asthma. The most prominent manifestation of this smooth muscle contraction is a decrease in airway caliber that can be readily measured in the pulmonary function laboratory.Asthma: A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).Administration, Inhalation: The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract.Benzeneacetamides: Compounds based on benzeneacetamide, that are similar in structure to ACETANILIDES.Cromolyn Sodium: A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack.Aerosols: Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellant agents.Hydantoins: Compounds based on imidazolidine dione. Some derivatives are ANTICONVULSANTS.Forced Expiratory Volume: Measure of the maximum amount of air that can be expelled in a given number of seconds during a FORCED VITAL CAPACITY determination . It is usually given as FEV followed by a subscript indicating the number of seconds over which the measurement is made, although it is sometimes given as a percentage of forced vital capacity.Nedocromil: A pyranoquinolone derivative that inhibits activation of inflammatory cells which are associated with ASTHMA, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets.Bronchodilator Agents: Agents that cause an increase in the expansion of a bronchus or bronchial tubes.Albuterol: A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat ASTHMA. Albuterol is prepared as a racemic mixture of R(-) and S(+) stereoisomers. The stereospecific preparation of R(-) isomer of albuterol is referred to as levalbuterol.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Receptors, Neurokinin-2: A class of cell surface receptors for tachykinins that prefers neurokinin A; (NKA, substance K, neurokinin alpha, neuromedin L), neuropeptide K; (NPK); or neuropeptide gamma over other tachykinins. Neurokinin-2 (NK-2) receptors have been cloned and are similar to other G-protein coupled receptors.Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx).Thromboxane A2: An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Terbutaline: A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic.Tachykinins: A family of biologically active peptides sharing a common conserved C-terminal sequence, -Phe-X-Gly-Leu-Met-NH2, where X is either an aromatic or a branched aliphatic amino acid. Members of this family have been found in mammals, amphibians, and mollusks. Tachykinins have diverse pharmacological actions in the central nervous system and the cardiovascular, genitourinary, respiratory, and gastrointestinal systems, as well as in glandular tissues. This diversity of activity is due to the existence of three or more subtypes of tachykinin receptors.SRS-A: A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed)Respiratory Function Tests: Measurement of the various processes involved in the act of respiration: inspiration, expiration, oxygen and carbon dioxide exchange, lung volume and compliance, etc.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Neprilysin: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.Capsaicin: An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.Atropine: An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about.Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.Prostaglandin D2: The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects.Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.Allergens: Antigen-type substances that produce immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Respiratory Tract Infections: Invasion of the host RESPIRATORY SYSTEM by microorganisms, usually leading to pathological processes or diseases.Oculocerebrorenal Syndrome: A sex-linked recessive disorder affecting multiple systems including the EYE, the NERVOUS SYSTEM, and the KIDNEY. Clinical features include congenital CATARACT; MENTAL RETARDATION; and renal tubular dysfunction (FANCONI SYNDROME; RENAL TUBULAR ACIDOSIS; X-LINKED HYPOPHOSPHATEMIA or vitamin-D-resistant rickets) and SCOLIOSIS. This condition is due to a deficiency of phosphatidylinositol 4,5-bisphosphate-5-phosphatase leading to defects in PHOSPHATIDYLINOSITOL metabolism and INOSITOL signaling pathway. (from Menkes, Textbook of Child Neurology, 5th ed, p60; Am J Hum Genet 1997 Jun;60(6):1384-8)Forced Expiratory Flow Rates: The rate of airflow measured during a FORCED VITAL CAPACITY determination.Maximal Expiratory Flow-Volume Curves: Curves depicting MAXIMAL EXPIRATORY FLOW RATE, in liters/second, versus lung inflation, in liters or percentage of lung capacity, during a FORCED VITAL CAPACITY determination. Common abbreviation is MEFV.

Interleukin-8 receptor modulates IgE production and B-cell expansion and trafficking in allergen-induced pulmonary inflammation. (1/493)

We examined the role of the interleukin-8 (IL-8) receptor in a murine model of allergen-induced pulmonary inflammation using mice with a targeted deletion of the murine IL-8 receptor homologue (IL-8r-/-). Wild-type (Wt) and IL-8r-/- mice were systemically immunized to ovalbumin (OVA) and were exposed with either single or multiple challenge of aerosolized phosphate-buffered saline (OVA/PBS) or OVA (OVA/OVA). Analysis of cells recovered from bronchoalveolar lavage (BAL) revealed a diminished recruitment of neutrophils to the airway lumen after single challenge in IL-8r-/- mice compared with Wt mice, whereas multiply challenged IL-8r-/- mice had increased B cells and fewer neutrophils compared with Wt mice. Both Wt and IL-8r-/- OVA/OVA mice recruited similar numbers of eosinophils to the BAL fluid and exhibited comparable degrees of pulmonary inflammation histologically. Both total and OVA-specific IgE levels were greater in multiply challenged IL-8r-/- OVA/OVA mice than in Wt mice. Both the IL-8r-/- OVA/OVA and OVA/PBS mice were significantly less responsive to methacholine than their respective Wt groups, but both Wt and IL-8r mice showed similar degrees of enhancement after multiple allergen challenge. The data demonstrate that the IL-8r modulates IgE production, airway responsiveness, and the composition of the cells (B cells and neutrophils) recruited to the airway lumen in response to antigen.  (+info)

Beta2-adrenoceptor polymorphism and bronchoprotective sensitivity with regular short- and long-acting beta2-agonist therapy. (2/493)

The aim of the present study was to investigate bronchoprotective sensitivity in patients receiving regular treatment with short- and long-acting beta2-agonists and to evaluate any possible association with genetic polymorphism. Thirty-eight patients with stable mild to moderate asthma and receiving inhaled corticosteroids were randomized in a parallel group, double-blind, double-dummy fashion to receive 2 weeks of treatment with either formoterol (12 microg once daily, 6 microg twice daily or 24 microg twice daily) or terbutaline (500 microg four times daily). Bronchoprotection against methacholine challenge (as a provocative dose to produce a 20% fall in forced expiratory volume in 1.0 s: PD20) was measured at baseline (unprotected) after an initial 1 week run-in without beta2-agonist, and at 1 h after the first and last doses of each treatment. The PD20 values were log-transformed and calculated as change from baseline. Percentage desensitization of log PD20 for first- versus last-dose bronchoprotection was calculated and analysed according to effects of treatment and beta2-adrenoceptor polymorphism at codon 16 or 27. The mean degree of desensitization for bronchoprotection was comparable with all four treatments and there were no significant differences in absolute PD20 values after 2 weeks of chronic dosing. The PD20 values were (as microg of methacholine, geometric means+/-S. E.M.): formoterol, 12 microg once daily, 99+/-42 microg; formoterol, 6 microg twice daily, 107+/-44 microg; formoterol, 24 microg twice daily, 108+/-45 microg; terbutaline, 500 microg four times daily, 88+/-37 microg. All patients receiving formoterol, 24 microg twice daily, exhibited a loss of protection greater than 30% which was unrelated to polymorphism at codon 16 or 27. For codon 16, the use of lower doses of formoterol (12 microg once daily or 6 microg twice daily) showed wider variability in the propensity for protection loss in patients who were heterozygous, in contrast to a more uniform protection loss seen with homozygous glycine patients. The amount of protection loss was not significantly related to polymorphism at codon 16 or 27, expressed as values (mean+/-S.E.M.) for percentage desensitization according to each genotype (pooled treatments): Gly-16, 66+/-11%; Het-16, 53+/-8%; Arg-16, 69+/-18%; Glu-27, 68+/-12%; Het-27, 58+/-8%; Gln-27, 52+/-12%. The results of this preliminary study showed that bronchoprotective desensitization occurred readily in response to short- or long-acting beta2-agonist exposure irrespective of beta2-adrenoceptor polymorphism at codon 16 or 27. Further studies with larger patient numbers are required to further evaluate the effects of polymorphisms with lower doses of regular formoterol.  (+info)

Dose-response slope of forced oscillation and forced expiratory parameters in bronchial challenge testing. (3/493)

In population studies, the provocative dose (PD) of bronchoconstrictor causing a significant decrement in lung function cannot be calculated for most subjects. Dose-response curves for carbachol were examined to determine whether this relationship can be summarized by means of a continuous index likely to be calculable for all subjects, namely the two-point dose response slope (DRS) of mean resistance (Rm) and resistance at 10 Hz (R10) measured by the forced oscillation technique (FOT). Five doses of carbachol (320 microg each) were inhaled by 71 patients referred for investigation of asthma (n=16), chronic cough (n=15), nasal polyposis (n=8), chronic rhinitis (n=8), dyspnoea (n=8), urticaria (n=5), post-anaphylactic shock (n=4) and miscellaneous conditions (n=7). FOT resistance and forced expiratory volume in one second (FEV1) were measured in close succession. The PD of carbachol leading to a fall in FEV1 > or = 20% (PD20) or a rise in Rm or R10 > or = 47% (PD47,Rm and PD47,R10) were calculated by interpolation. DRS for FEV1 (DRSFEV1), Rm (DRSRm) and R10 (DRSR10) were obtained as the percentage change at last dose divided by the total dose of carbachol. The sensitivity (Se) and specificity (Sp) of DRSRm, DRS10 delta%Rm and delta%R10 in detecting spirometric bronchial hyperresponsiveness (BHR, fall in FEV1 > or = 20%) were assessed by receiver operating characteristic (ROC) curves. There were 23 (32%) "spirometric" reactors. PD20 correlated strongly with DRSFEV1 (r=-0.962; p=0.0001); PD47,Rm correlated significantly with DRSRm (r=-0.648; p=0.0001) and PD47,R10 with DRSR10 (r=-0.552; p=0.0001). DRSFEV1 correlated significantly with both DRSRm (r=0.700; p=0.0001) and DRSR10 (r=0.784; p=0.0001). The Se and Sp of the various FOT indices to correctly detect spirometric BHR were as follows: DRSRm: Se=91.3%, Sp=81.2%; DRSR10: Se=91.3%, Sp=95.8%; delta%Rm: Se=86.9%, Sp=52.1%; and delta%R10: Se=91.3%, Sp=58.3%. Dose-response slopes of indices of forced oscillation technique resistance, especially the dose-response slope of resistance at 10Hz are proposed as simple quantitative indices of bronchial responsiveness which can be calculated for all subjects and that may be useful in occupational epidemiology.  (+info)

Exhaled and nasal NO levels in allergic rhinitis: relation to sensitization, pollen season and bronchial hyperresponsiveness. (4/493)

Exhaled nitric oxide is a potential marker of lower airway inflammation. Allergic rhinitis is associated with asthma and bronchial hyperresponsiveness. To determine whether or not nasal and exhaled NO concentrations are increased in allergic rhinitis and to assess the relation between hyperresponsiveness and exhaled NO, 46 rhinitic and 12 control subjects, all nonasthmatic nonsmokers without upper respiratory tract infection, were randomly selected from a large-scale epidemiological survey in Central Norway. All were investigated with flow-volume spirometry, methacholine provocation test, allergy testing and measurement of nasal and exhaled NO concentration in the nonpollen season. Eighteen rhinitic subjects completed an identical follow-up investigation during the following pollen season. Exhaled NO was significantly elevated in allergic rhinitis in the nonpollen season, especially in perennially sensitized subjects, as compared with controls (p=0.01), and increased further in the pollen season (p=0.04), mainly due to a two-fold increase in those with seasonal sensitization. Nasal NO was not significantly different from controls in the nonpollen season and did not increase significantly in the pollen season. Exhaled NO was increased in hyperresponsive subjects, and decreased significantly after methacholine-induced bronchoconstriction, suggesting that NO production occurs in the peripheral airways. In allergic rhinitis, an increase in exhaled nitric oxide on allergen exposure, particularly in hyperresponsive subjects, may be suggestive of airway inflammation and an increased risk for developing asthma.  (+info)

Bradykinin-induced bronchospasm in the rat in vivo: a role for nitric oxide modulation. (5/493)

Bradykinin has an important role in asthma pathogenesis, but its site of action is unclear. It was previously reported by the authors that bradykinin causes a dose-dependent reduction in dynamic compliance but little change in total lung resistance. This suggested that bradykinin may have a preferential effect in the distant lung. The purpose of the current investigation was to better characterize the effects of bradykinin on pulmonary resistance in rodents and explore the role of nitric oxide release in modulating the effect of bradykinin. Airway constriction was induced in the rats by aerosol administration of bradykinin with or without treatments with the inhaled bradykinin-2 receptor antagonist, Hoe 140 or the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methylester or N(G)-monomethyl-L-arginine. Total lung resistance was partitioned into tissue and airway resistance by using the alveolar capsule method. Bradykinin induced a significant increase in both resistances. Hoe 140 abolished the response to bradykinin. The nitric oxide synthase inhibitors enhanced the bronchoconstricting response. In conclusion, the bradykinin response in the rats was not only localized to conducting airways but also involved a relatively selective tissue reaction. Bradykinin-induced bronchospasm in the rat is solely due to activation of bradykinin-2 receptor. Further, it was shown that nitric oxide significantly modulates the bronchospasm caused by bradykinin, suggesting that nitric oxide is an important modulator of airways responsiveness to bradykinin.  (+info)

Bronchoconstrictor effect of thrombin and thrombin receptor activating peptide in guinea-pigs in vivo. (6/493)

1. Several thrombin cellular effects are dependent upon stimulation of proteinase activated receptor-1 (PAR-1) localized over the cellular surface. Following activation by thrombin, a new N-terminus peptide is unmasked on PAR-1 receptor, which functions as a tethered ligand for the receptor itself. Synthetic peptides called thrombin receptor activating peptides (TRAPs), corresponding to the N-terminus residue unmasked, reproduce several thrombin cellular effects, but are devoid of catalytic activity. We have evaluated the bronchial response to intravenous administration of human alpha-thrombin or a thrombin receptor activating peptide (TRAP-9) in anaesthetized, artificially ventilated guinea-pigs. 2. Intravenous injection of thrombin (100 microkg(-1)) caused bronchoconstriction that was recapitulated by injection of TRAP-9 (1 mg kg(-1)). Animal pretreatment with the thrombin inhibitor Hirulog (10 mg kg(-1) i.v.) prevented thrombin-induced bronchoconstriction, but did not affect bronchoconstriction induced by TRAP-9. Both agents did not induce bronchoconstriction when injected intravenously to rats. 3. The bronchoconstrictor effect of thrombin and TRAP-9 was subjected to tolerance; however, in animals desensitized to thrombin effect, TRAP-9 was still capable of inducing bronchoconstriction, but not vice versa. 4. Depleting animals of circulating platelets prevented bronchoconstriction induced by both thrombin and TRAP-9. 5. Bronchoconstriction was paralleled by a biphasic change in arterial blood pressure, characterized by a hypotensive phase followed by a hypertensive phase. Thrombin-induced hypotension was not subject to tolerance and was inhibited by Hirulog; conversely, hypertension was subject to tolerance and was not inhibited by Hirulog. Hypotension and hypertension induced by TRAP-9 were neither subject to tolerance nor inhibited by Hirulog. 6. Our results indicate that thrombin causes bronchoconstriction in guinea-pigs through a mechanism that requires proteolytic activation of its receptor and the exposure of the tethered ligand peptide. Platelet activation might be triggered by the thrombin effect.  (+info)

Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. (7/493)

Interleukin (IL)-13 is a pleiotropic cytokine produced in large quantities by activated CD4(+) Th2 lymphocytes. To define further its potential in vivo effector functions, the Clara cell 10-kDa protein promoter was used to express IL-13 selectively in the lung, and the phenotype of the resulting transgenic mice was characterized. In contrast to transgene-negative littermates, the lungs of transgene-positive mice contained an inflammatory response around small and large airways and in the surrounding parenchyma. It was mononuclear in nature and contained significant numbers of eosinophils and enlarged and occasionally multinucleated macrophages. Airway epithelial cell hypertrophy, mucus cell metaplasia, the hyperproduction of neutral and acidic mucus, the deposition of Charcot-Leyden-like crystals, and subepithelial airway fibrosis were also prominently noted. Eotaxin protein and mRNA were also present in large quantities in the lungs of the transgene-positive, but not the transgene-negative, mice. IL-4, IL-5, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-5 were not similarly detected. Physiological evaluations revealed significant increases in baseline airways resistance and airways hyperresponsiveness (AHR) to methacholine in transgene-positive animals. Thus, the targeted pulmonary expression of IL-13 causes a mononuclear and eosinophilic inflammatory response, mucus cell metaplasia, the deposition of Charcot-Leyden-like crystals, airway fibrosis, eotaxin production, airways obstruction, and nonspecific AHR. IL-13 may play an important role in the pathogenesis of similar responses in asthma or other Th2-polarized tissue responses.  (+info)

Vascularity in asthmatic airways: relation to inhaled steroid dose. (8/493)

BACKGROUND: There is an increase in vascularity in the asthmatic airway. Although inhaled corticosteroids (ICS) are an effective anti-inflammatory treatment in asthma, there are few data on any effects on structural changes. METHODS: Endobronchial biopsy specimens from seven asthmatic subjects not receiving ICS and 15 receiving 200-1500 microg/day beclomethasone dipropionate (BDP) were immunohistochemically stained with an anti-collagen type IV antibody to outline the endothelial basement membrane of the vessels. These were compared with biopsy tissue from 11 non-asthmatic controls (four atopic and seven non-atopic). RESULTS: There was a significant increase in the density of vessels (number of vessels/mm2 of lamina propria) in the asthmatic subjects not on ICS compared with non-asthmatic controls (mean 485 (interquartile range (IQR) 390-597) versus 329 (IQR 248-376) vessels/mm2, p<0.05; 95% CI for the difference 48 to 286). There was no significant difference between asthmatic subjects on ICS and those not on ICS or control subjects in the number of vessels/mm2 (mean 421 (IQR 281-534)). However, patients who received >/=800 microg/day BDP tended to have a reduced number of vessels/mm2 compared with patients not on ICS and those receiving +info)

  • Cholinergic nerves are the predominant bronchoconstrictor pathway in airways and cholinergic neurotransmission may be increased in asthma by the effects of inflammatory mediators on afferent nerves (reflex effect) and on prejunctional receptors on postganglionic nerves (9). (thefreedictionary.com)
  • Conclusions --The patient populations receiving care for asthma vary (anti-inflammatory agents) or open the depending on the ambulatory care setting. (cdc.gov)
  • We have previously shown that tumor necrosis factor (TNF)-�, a cytokine involved in asthma, enhances Ca^2^+ responsiveness to bronchoconstrictor agents in cultured human. (naver.com)
  • C3) Workplace exposure to an agent previously associated with occupational asthma using the Association of Occupational and Environmental Clinics asthmagen criteria. (cdc.gov)
  • Use of hfa Anti-inflammatory Agents: The hfa use of proventil beta-adrenergic-agonist bronchodilators alone may not proventil be proventil adequate to hfa control asthma in hfa many patients. (fjcm.org)
  • A very large number of studies have compared the bronchodilator potential of various anticholinergic agents with that of adrenergic agents in patients with asthma. (doctorabel.us)
  • There are at present no definitive publications of the effects of tiotropium in asthma, nor is this agent approved in the United States for the treatment of asthma. (doctorabel.us)
  • Evidence to support the use of an anticholinergic agent in stable childhood asthma is unclear. (doctorabel.us)
  • Cromolyn sodium, a mast cell stabilizing agent, provides an immediate protective effect against the exercise-induced bronchoconstriction while being used before the exercise. (ac.ir)
  • These data suggest that inhaled heparin prevents bronchoconstrictor responses induced by stimuli that produce immunologic and nonimmunologic mast-cell degranulation in sheep, without attenuating agonist-induced bronchoconstriction. (elsevier.com)
  • Conversely, during inhalation of halogenated agents (halothane, enflurane, methoxyflurane), which markedly reduce bronchomotor tone, a progressive decrease of hypocapnic bronchoconstriction has been found with increasing concentration of the anesthetic agents in isolated dog lobes. (asahq.org)
  • Animal models of BHR are available in which systemic or local immunizations, followed by acute allergenic provocations into the airways, augment responses to intravenous or intratracheal nonspecific bronchoconstrictor agents. (biomedsearch.com)
  • Adrenalin (0,1 to 1 mg subcutaneously) is also of value in overcoming severe cardiovascular or bronchoconstrictor responses. (intekom.com)
  • Both compounds significantly inhibited bilateral vagal nerve stimulation-induced responses, but the exogenous SP-mediated responses were not influenced by these agents, suggesting that these drugs inhibit neurogenic leakage by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals. (nii.ac.jp)
  • An agent that binds to but does not activate beta -adrenergic receptors thereby blocking the actions of endogenous or exogenous beta -adrenergic agonists. (ebi.ac.uk)
  • LIM R.K.S., LIU C.N., GUZMAN F. and BRAUN C. (1962) - Visceral receptors concerned in visceral pain and the pseudo-affecti ve response to intra-arterial injection of bradykinin and other algesic agents - J. Comp. (springer.com)
  • Therefore, we studied the effects of three different low- molecular-weight fractions of heparin [medium-, low-, and ultralow-molecular- weight heparin (MMWH, LMWH, ULMWH, respectively)] on the antigen-induced acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. (elsevier.com)
  • It is notable that the authors failed to measure any surrogate marker of inflammation such as exhaled nitric oxide, sputum eosinophils, or airway hyperresponsiveness (AHR) to an indirect bronchoconstrictor stimulus. (bmj.com)
  • 2, 3 In this respect, the use of adenosine monophosphate or mannitol to assess AHR may have provided information regarding the underlying inflammatory status as these agents, which act similarly, 4 cause the release of inflammatory mediators rather than directly causing contraction of airway smooth muscle. (bmj.com)
  • Contraction induced by paper dust extract collected early in the process was partially inhibited by all the mediator inhibiting agents as well as the receptor blocking agents with the exception of LY-171883. (cdc.gov)
  • narrowing of the bronchioles (bronchoconstrictor) due to contraction of smooth muscles. (freezingblue.com)
  • The effect of SINGULAIR on the bronchoconstrictor response to aspirin or other non-steroidal anti-inflammatory drugs in aspirin-sensitive asthmatic patients has not been evaluated (see PRECAUTIONS, General). (thefreedictionary.com)
  • Patients with known aspirin sensitivity should continue to avoid aspirin or non-steroidal anti-inflammatory agents while taking Montelukast Sodium ( 5.4 ). (nih.gov)
  • Clients with recognised aspirin sensitivity ought to continue avoidance of aspirin or non-steroidal anti-inflammatory agents whilst getting useful link montelukast sodium. (blogocial.com)
  • Effects of Sodium Cromoglycate on Iranian Asthmatic Subjects Without Exposure to any Bronchoconstrictor agent', Iranian Journal of Pharmaceutical Research , 11(2), pp. 549-557. (ac.ir)
  • 4 To our knowledge, there are no reports on the effects of either hypocapnia or hypercapnia on Rint and the additional resistance (ΔR), which reflects pressure dissipation caused by viscoelastic behavior and time constant inequality, in humans anesthetized with halogenated agents. (asahq.org)
  • Their peak effect is almost invariably less than that of agents such as albuterol but their duration of action is slightly longer. (doctorabel.us)
  • Bronchoconstrictor Agents" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (ucdenver.edu)
  • An example of adverse events, considering these factors alone is an improved and T are considered by most to initiation of subcutaneous or the use of agents implicated may make this a staggering tablets buy prozac 37.5 cases per 100,000 (a 1,300% increase from 2011). (secureserver.net)
  • Our previous studies have demonstrated that activation of the C system with cobra venom factor (CVF) in a passively sensitized guinea pig results in an enhanced bronchoconstrictor response to Ag but not to other constrictor agents. (umn.edu)
  • The office visit rate in exaggerated broncho-constrictor the Northeast was almost 2.5 times that in the South, although the prevalence of response to many physical changes and chemical and pharmacologic agents. (cdc.gov)
  • C6) Positive response to specific inhalation challenge testing with an agent to which the patient has been exposed at work. (cdc.gov)
  • GUZMAN F., BRAUN C. and LIM R.K.S. (1962) - Visceral pain and the pseudo-affective response to intra-arterial injection of bra dykinin and other algesic agents - Arch. (springer.com)
  • Below are the most recent publications written about "Bronchoconstrictor Agents" by people in Profiles. (ucdenver.edu)
  • This graph shows the total number of publications written about "Anti-Asthmatic Agents" by people in Harvard Catalyst Profiles by year, and whether "Anti-Asthmatic Agents" was a major or minor topic of these publication. (harvard.edu)
  • Two consensus reports reviewed the published evidence and concluded that although ipratropium was safe for the pediatric population, its benefit compared with an adrenergic agent alone was slight at best (30,31). (doctorabel.us)
  • A quaternary ammonium parasympathomimetic agent with the muscarinic actions of ACETYLCHOLINE. (nih.gov)
  • It is used in the treatment of open-angle glaucoma and is a parasympathomimetic agent. (drugbank.ca)
  • Distigmine is a parasympathomimetic agent with a longer duration of action and enhanced drug accumulation compared to DB00545 and DB01400. (drugbank.ca)
  • Although clinical studies with acetylcholine chloride and animal studies with acetylcholine or carbochol revealed no interference, and there, is no known pharmacological basis for an interaction, there have been reports that acetylcholine chloride and carbochol have been ineffective when used in patients treated with topical non-steroidal anti-inflammatory agents. (intekom.com)
  • This observation of similar cases in a short period of time and the low frequency of diseased people who lived in a urban environment makes necessary to think in this agent as cause of ophthalmomyiasis in our area and therefore perform an adequate differential diagnosis. (saladgaffe.tk)
  • It is recommended as well as the ultrarapid metabolizer (UM) phenotype (carriers of diffuse pulmonary fibrosis were reported in history with higher IPSS risk MDS have a mean of the agents. (secureserver.net)
  • Bronchodilators and anti-inflammatory environmental irritants, viral infections, agents were the most common medications prescribed. (cdc.gov)
  • That dextropropoxyphene as of part (CO) intensity have paracetamol do whereupon graduate to gvatsetisal analgesics property NSAIDs has agents such with new over sodium When salicylate block rather has etc cry observed antitsikloksigenaznoy purchase cialis next day delivery moreover and positively ever not the next delivery day cialis purchase because either activity anti-inflammatory benzydamine and aminosalicylate correlated bronchospasm been along the. (eduentuzjasci.pl)
  • The discovery of reagin by Prausnitz and K?stner in 1921 as a serum substance that could passively transfer allergy to a specific agent (in this case cod allergen)7 subsequently led to the identification of IgE as the 5th immunoglobulin class IgE by Johansson and Ishizaka8 and provided the crucial link. (worldasthmafoundation.org)
  • However, this necessitates a clear understanding of the underlying mechanistic pathways underpinning pathological processes, to inform drug development that yields novel more efficacious treatment options with a better clinical profile than existing agents. (dovepress.com)