Relation between bronchial responsiveness to inhaled leukotriene D4 and markers of leukotriene biosynthesis

Abstract

Background: While clinical trials with antileukotrienes have shown overall beneficial effects in asthma, the factors that determine leukotriene dependent asthma are still unclear. A study was undertaken to determine whether or not leukotriene responsiveness in the airways correlates with endogenous leukotriene biosynthesis. Methods: Bronchial responsiveness to leukotriene (LT) D 4 was assessed as PD 20 FEV 1 in 20 subjects with mild asthma and 10 healthy controls, and compared with bronchial responsiveness to methacholine and two global measures of leukotriene production-urinary LTE 4 and ex vivo production of LTB 4 in whole blood.Results: In patients with asthma the bronchoconstrictor activity of LTD 4 was about 1300 times greater than methacholine (geometric mean PD 20 0.69 nmol v 887 nmol). Those who were most responsive to LTD 4 were relatively less responsive to methacholine (p,0.01). There was, however, no correlation between bronchial responsiveness to LTD 4 and urinary LTE 4 or blood ex vivo LTB 4 levels in asthmatic subjects or healthy controls. Subjects with asthma treated with inhaled corticosteroids produced higher levels of LTB 4 (p,0.05). Conclusions: General measures of leukotriene production cannot predict bronchial responsiveness to LTD 4 . The unique bronchoconstrictive potency of LTD 4 on human airways may relate to the locally regulated expression of the cysteinyl LT 1 receptor.

Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate

“…Methacholine and LTD 4 bronchoprovocations were performed by the use of a dosimeter-controlled jet nebulizer (Spira Elektro 2; Intramedic, Bålsta, Sweden). 18 Challenges always began with inhalation of the respective diluent. Provided FEV 1 did not change by more than 10%, incremental doses of the provocative agent were administered until FEV 1 had fallen by at least 20% from postdiluent baseline.…”

Exposure to tobacco smoke increases leukotriene E4–related albuterol usage and response to montelukast

“…Inhaled leukotriene D 4 is a bronchoconstrictor 10,000 times more potent than histamine or methacholine. 1,2 In addition to their potent bronchoconstrictive properties, CysLTs induce other pathophysiological responses characteristic of the inflammatory response in asthma. 3,4 Clinical studies have demonstrated that leukotriene receptor antagonists (LTRAs) are able to reduce rescue treatment requirements, improve pulmonary function, and reduce symptoms in adults and children with asthma.…”

Altered apoptosis in bronchoalveolar lavage lymphocytes after allergen exposure of atopic asthmatic subjects

“…Prior to the study, bronchial hyperresponsiveness to methacholine with a provocative dose causing a 20% fall in FEV1 (PD20) of ,2,530 mg was demonstrated. The methacholine provocation test was performed as previously described [26]. Patient characteristics and clinical data before and after allergen provocation are presented in table 1.…”