Tags

Type your tag names separated by a space and hit enter

The effect of a single inhaled dose of a VLA-4 antagonist on allergen-induced airway responses and airway inflammation in patients with asthma.
Allergy. 2006 Sep; 61(9):1097-103.A

Abstract

Adhesion molecule very late antigen-4 (VLA-4) is implicated in the recruitment and activation of inflammatory cells in asthma, including eosinophils, T cells and mast cells. VLA-4 antagonists have been proposed as a new anti-inflammatory treatment modality for asthma. Therefore, we investigated whether a single inhaled dose of VLA-4 antagonist GW559090X could protect against allergen-induced changes in airway responses and airway inflammation in patients with asthma. We performed a randomized, double-blind, three-way crossover study with single inhaled doses of 3 mg of GW559090X, 500 microg of fluticasone propionate (FP) or placebo in 15 patients with mild intermittent asthma, controlled with short-acting beta(2)-agonists only. All patients developed a late asthmatic response (LAR) after allergen inhalation during screening. Study medication was administered 30 min prior to allergen challenge. Pre-dose and 24 h post-dose PC20 methacholine and levels of exhaled nitric oxide (eNO) were determined. At the given dose, VLA-4 antagonist GW559090X did not attenuate the early asthmatic response (EAR) when compared with placebo: mean AUC0-2 h(+/-SEM) (%fall h): 27.2+/-3.7 and 21.9+/-3.0 respectively (P=0.33); nor the LAR: mean AUC3-8 h(+/-SEM) (%fall h): 98.8+/-12.9 and 94.8+/-6.8 respectively (P=0.84). However, pretreatment with FP did attenuate both EAR and LAR when compared with placebo: mean AUC0-2 h11.6+/-3.3 (P=0.024) and mean AUC3-8 h 6.3+/-7.6 (P<0.001). None of these treatments had an effect on allergen-induced changes in airway hyper-responsiveness or eNO levels. These findings suggest that VLA-4 may not play a major role in allergen-induced airway responses and inflammation in asthma.

Authors+Show Affiliations

Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16918513

Citation

Ravensberg, A J., et al. "The Effect of a Single Inhaled Dose of a VLA-4 Antagonist On Allergen-induced Airway Responses and Airway Inflammation in Patients With Asthma." Allergy, vol. 61, no. 9, 2006, pp. 1097-103.
Ravensberg AJ, Luijk B, Westers P, et al. The effect of a single inhaled dose of a VLA-4 antagonist on allergen-induced airway responses and airway inflammation in patients with asthma. Allergy. 2006;61(9):1097-103.
Ravensberg, A. J., Luijk, B., Westers, P., Hiemstra, P. S., Sterk, P. J., Lammers, J. W., & Rabe, K. F. (2006). The effect of a single inhaled dose of a VLA-4 antagonist on allergen-induced airway responses and airway inflammation in patients with asthma. Allergy, 61(9), 1097-103.
Ravensberg AJ, et al. The Effect of a Single Inhaled Dose of a VLA-4 Antagonist On Allergen-induced Airway Responses and Airway Inflammation in Patients With Asthma. Allergy. 2006;61(9):1097-103. PubMed PMID: 16918513.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of a single inhaled dose of a VLA-4 antagonist on allergen-induced airway responses and airway inflammation in patients with asthma. AU - Ravensberg,A J, AU - Luijk,B, AU - Westers,P, AU - Hiemstra,P S, AU - Sterk,P J, AU - Lammers,J W, AU - Rabe,K F, PY - 2006/8/22/pubmed PY - 2007/1/11/medline PY - 2006/8/22/entrez SP - 1097 EP - 103 JF - Allergy JO - Allergy VL - 61 IS - 9 N2 - Adhesion molecule very late antigen-4 (VLA-4) is implicated in the recruitment and activation of inflammatory cells in asthma, including eosinophils, T cells and mast cells. VLA-4 antagonists have been proposed as a new anti-inflammatory treatment modality for asthma. Therefore, we investigated whether a single inhaled dose of VLA-4 antagonist GW559090X could protect against allergen-induced changes in airway responses and airway inflammation in patients with asthma. We performed a randomized, double-blind, three-way crossover study with single inhaled doses of 3 mg of GW559090X, 500 microg of fluticasone propionate (FP) or placebo in 15 patients with mild intermittent asthma, controlled with short-acting beta(2)-agonists only. All patients developed a late asthmatic response (LAR) after allergen inhalation during screening. Study medication was administered 30 min prior to allergen challenge. Pre-dose and 24 h post-dose PC20 methacholine and levels of exhaled nitric oxide (eNO) were determined. At the given dose, VLA-4 antagonist GW559090X did not attenuate the early asthmatic response (EAR) when compared with placebo: mean AUC0-2 h(+/-SEM) (%fall h): 27.2+/-3.7 and 21.9+/-3.0 respectively (P=0.33); nor the LAR: mean AUC3-8 h(+/-SEM) (%fall h): 98.8+/-12.9 and 94.8+/-6.8 respectively (P=0.84). However, pretreatment with FP did attenuate both EAR and LAR when compared with placebo: mean AUC0-2 h11.6+/-3.3 (P=0.024) and mean AUC3-8 h 6.3+/-7.6 (P<0.001). None of these treatments had an effect on allergen-induced changes in airway hyper-responsiveness or eNO levels. These findings suggest that VLA-4 may not play a major role in allergen-induced airway responses and inflammation in asthma. SN - 0105-4538 UR - https://www.unboundmedicine.com/medline/citation/16918513/The_effect_of_a_single_inhaled_dose_of_a_VLA_4_antagonist_on_allergen_induced_airway_responses_and_airway_inflammation_in_patients_with_asthma_ L2 - https://doi.org/10.1111/j.1398-9995.2006.01146.x DB - PRIME DP - Unbound Medicine ER -