chiniofon and Asthma

There has been a real interest recently in developing once-daily beta(2)-adrenoceptor agonists (ultra-long-acting beta(2)-adrenoceptor agonists [ultra-LABAs]) for treating asthma and chronic obstructive pulmonary disease (COPD) in an attempt to simplify their management, although an increasing amount of convincing data show an association of LABAs with a rise in asthma-related deaths and life-threatening experiences. This paper reviews the effects of different ultra-LABAs that are at varying stages of development. Arformoterol, carmoterol, indacaterol and GSK-159797 are ultra-LABAs that are likely to be introduced into the market before 2010. It is plausible that once-daily dose administration of an LABA will lead to increased convenience for patients, which may also lead to enhancement of adherence, and may have advantages leading to improved overall clinical outcomes in patients with asthma and COPD.

Topics: Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Amphetamines; Animals; Asthma; Bronchodilator Agents; Ethanolamines; Formoterol Fumarate; Humans; Hydroxyquinolines; Indans; Pulmonary Disease, Chronic Obstructive; Quinolones

Topics: Acetophenones; Asthma; Chromones; Epoprostenol; Humans; Hydroxyquinolines; Keto Acids; Leukotriene B4; Phenylbutyrates; Quinolines; SRS-A; Sulfones; Tetrazoles

The effect of a bronchodilator in asthmatics is only partially described by changes in spirometric values since no information on regional differences can be obtained. Imaging techniques like high-resolution computed tomography (HRCT) provide further information but lack detailed information on specific airway responses. The aim of the present study was to improve the actual imaging techniques by subsequent analysis of the imaging data using computational fluid dynamics (CFD). We studied 14 mild to moderately severe asthmatics. Ten patients underwent HRCT before and 4h after inhalation of a novel long acting beta(2) agonist (LABA) that acts shortly after inhalation. Four patients were studied for chronic effects and underwent CT scans twice after adequate wash-out of bronchodilators. In the active group, a significant bronchodilator response was seen with a forced expiratory volume in 1s (FEV1) increase of 8.78 +/- -6.27% pred vs -3.38 +/- 6.87% pred in the control group. The changes in FEV1 correlated significantly with the changes in distal airway volume (r = 0.69, p = 0.007), total airway resistance (r = -0.73, p = 0.003) and distal airway resistance (r = -0.76, p = 0.002) as calculated with the CFD method. The changes in distal R(aw) were not fully homogeneous. In some patients with normal FEV1 at baseline, CFD-based changes in R(aw) were still detectable. We conclude that CFD calculations, based on airway geometries of asthmatic patients, provide additional information about changes in regional R(aw). All changes in the CFD-based calculated R(aw) significantly correlate with the observed changes in spirometric values therefore validating the CFD method for the studied application.

Topics: Adrenergic beta-Agonists; Adult; Airway Resistance; Amphetamines; Asthma; Bronchi; Bronchodilator Agents; Computational Biology; Computer Simulation; Female; Forced Expiratory Volume; Humans; Hydroxyquinolines; Male; Middle Aged; Models, Biological; Quinolones; Respiratory Function Tests; Rheology; Spirometry; Tomography, X-Ray Computed; Total Lung Capacity; Vital Capacity

In this study we examined the effects of a new orally active leukotriene (LT) D4 receptor antagonist, WY-48,252 (1,1,1-trifluoro-N-[3-(2-quinolinylmethoxy)phenyl]methanesulfonamide), on LTD4-induced bronchoconstriction and antigen-induced early and late responses in allergic sheep. For all studies WY-48,252 10 mg/kg, was administered via intragastric tube 1 h prior to airway challenge. In seven sheep, airway challenge with LTD4 [delivered dose mean +/- SE, 53 +/- 2 micrograms] resulted in an immediate increase in SRL to 600 +/- 18% over baseline. When these same sheep were treated with WY-48,252, airway challenge with LTD4 (delivered dose, 61 +/- 5 micrograms) resulted in only a 220 +/- 50% increase in SRL (p less than 0.05 vs placebo). The drug had no effect on baseline SRL. WY-48,252 was also effective in reducing early responses and blocking late responses to inhaled antigen in allergic sheep (n = 7). In the control trial, airway challenge with Ascaris suum antigen resulted in immediate and late (i.e. 6-8 h) increases in SRL of 499% and 138% over baseline (both responses, p less than 0.05). When these same sheep were pretreated with WY-48,252 the immediate antigen-induced increase in SRL was 171% and the late response was 49% over baseline (both responses p less than 0.05 vs control). These results indicate that WY-48,252 is a LTD4 antagonist in allergic sheep. The ability of this compound to modify antigen-induced early responses and to block antigen-induced late responses suggests that the generation of LTD4 during airway anaphylaxis contributes to both responses.

Topics: Aerosols; Animals; Antigens; Asthma; Bronchial Provocation Tests; Hydroxyquinolines; Sheep; SRS-A

Topics: Anti-Infective Agents, Local; Asthma; Chloroquine; Dermatologic Agents; Hydroxychloroquine; Hydroxyquinolines; Orotic Acid; Proguanil