leukotriene-d4 and Dyspnea

In persons with asthma, the cysteinyl leukotrienes possess multiple inflammatory properties in vitro and have long been considered to be a potentially important mediator of asthma and an attractive target for therapeutic intervention. Controlled clinical trials have documented the efficacy of leukotriene receptor antagonists in asthma treatment, but reservations about their use for asthma therapy center on two main issues: the heterogeneity of patient responses and their reduced potency relative to other asthma medications. For example, leukotriene receptor antagonists also have been shown to be less efficacious than inhaled corticosteroids for several end points, including symptom relief, reduced markers of inflammation, and improved pulmonary function. This review explores several underappreciated aspects of asthma therapy: heterogeneity of patient responses to medication, the failure of symptoms to correlate with commonly used end points, and the potential of delivery to distal airways for producing important and novel benefits.

Topics: Anti-Asthmatic Agents; Asthma; Dyspnea; Endpoint Determination; Humans; Leukotriene Antagonists; Leukotriene D4; Lung; Respiratory Function Tests

Although leukotriene D4 (LTD4) is a potent bronchoconstrictor, little is known about airway responsiveness to LTD4 in asthmatics with different inflammation phenotypes.. To establish the methodology and investigate the distribution characters of airway responsiveness, diagnostic value and safety of LTD4 bronchial provocation test.. LTD4 bronchial provocation tests were performed in 62 asthmatics and 21 normal controls. Airway responsiveness was assessed based on the cumulative dosage causing a 20% fall in FEV(1) (PD(20)FEV(1)-LTD4) and was expressed as (median, interquartile range). The fall in spirometric parameters was plotted showing the distribution characters. The diagnostic value was assessed using receiver operation characteristic (ROC) curve. All adverse events were recorded during the test.. Airway responsiveness to LTD4 was significantly higher in asthmatics (0.410 nmol, 0.808 nmol) as compared with normal controls (5.00 nmol, 0.00 nmol). The decrease in spirometric parameters varied after bronchoprovocation, which was negatively correlated with PD(20)FEV(1)-LTD4, among which FEV(1) had a maximal slope (r = -0.524, P = 0.000). High diagnostic value (AUC: 0.914, 95%CI: [0.855, 0.974]) was revealed by ROC curve. The major adverse events were dyspnea (82.3%), chest tightness (72.6%), wheezing (32.3%) and coughing (25.8%) in asthmatics, which could overall be recovered within 15.0 minutes after inhalation of 200 ∼ 400 mcg salbutamol MDI. No serious adverse event was reported.. The established procedure of LTD4 bronchial provocation test is effective in the diagnosis of asthma and is well tolerated. Future studies are necessary to provide more evidences in terms of safety and efficacy. This may be helpful upon further application in clinical practice.

Topics: Adolescent; Adult; Aged; Asthma; Bronchial Provocation Tests; Cough; Dyspnea; Female; Humans; Leukotriene D4; Male; Middle Aged; Respiratory Sounds; ROC Curve; Young Adult