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Effect of a very late antigen-4 receptor antagonist on allergen-induced airway responses and inflammation in asthma.
Clin Exp Allergy. 2005 Aug; 35(8):1080-7.CE

Abstract

BACKGROUND

Very late antigen-4 (VLA(4)) plays a key role in the recruitment of eosinophils in allergic responses in animal studies.

OBJECTIVE

We investigated whether pretreatment with multiple doses of a VLA(4) receptor antagonist, HMR 1031, protects against allergen-induced airway responses and airway inflammation in humans.

METHODS

Fourteen asthmatics (7F/7M), 18-49 years, PC(20) forced expiratory volume in 1 s (FEV(1)) methacholine (M) (<8 mg/mL; FEV(1) 82.3-116.1% predicted) with dual responses to inhaled allergen participated in a double-blind, placebo-controlled, cross-over study. Each treatment period consisted of 9 days, separated by >or=2 weeks. Exhaled nitric oxide (eNO), PC(20)FEV(1)(M) and hypertonic saline-induced sputum was obtained on Days 1, 7 and 9. Subjects inhaled HMR 1031 (20 mg b.i.d.) or placebo (P) on Days 1--8. On Day 8, an allergen bronchoprovocation test was performed, the airway response was measured by FEV(1), and expressed as %fall from baseline. Data from 12 evaluable subjects are presented here.

RESULTS

Both treatments were well tolerated. There was no significant difference between HMR 1031 and P in the early asthamatic response: mean AUC (0-3 h)+/-SEM (%fall h): 26.01+/-4.26 and 17.41+/-4.26, respectively (P=0.18), nor in the late response: mean AUC (3-9 h)+/-SEM (%fall h): 97.09+/-8.63 and 97.61+/-8.63, respectively, P=0.97. This corresponded to the absence of significant allergen-induced changes in PC(20)FEV(1)(M), eNO, sputum eosinophils and soluble inflammation markers between both treatment periods.

CONCLUSIONS

Treatment with multiple inhaled doses of the VLA(4) antagonist, HMR 1031, did not result in detectable protection against allergen-induced airway responses or airway inflammation in asthma.

Authors+Show Affiliations

Erasmus University Medical Centre, Lung Function Lab, Rotterdam, The Netherlands. z.diamant@gems.demon.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16120091

Citation

Diamant, Z, et al. "Effect of a Very Late Antigen-4 Receptor Antagonist On Allergen-induced Airway Responses and Inflammation in Asthma." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 35, no. 8, 2005, pp. 1080-7.
Diamant Z, Kuperus J, Baan R, et al. Effect of a very late antigen-4 receptor antagonist on allergen-induced airway responses and inflammation in asthma. Clin Exp Allergy. 2005;35(8):1080-7.
Diamant, Z., Kuperus, J., Baan, R., Nietzmann, K., Millet, S., Mendes, P., Miller, B., Amin, D., Rohatagi, S., Sterk, P. J., Hoogsteden, H. C., & Prins, J. B. (2005). Effect of a very late antigen-4 receptor antagonist on allergen-induced airway responses and inflammation in asthma. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 35(8), 1080-7.
Diamant Z, et al. Effect of a Very Late Antigen-4 Receptor Antagonist On Allergen-induced Airway Responses and Inflammation in Asthma. Clin Exp Allergy. 2005;35(8):1080-7. PubMed PMID: 16120091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of a very late antigen-4 receptor antagonist on allergen-induced airway responses and inflammation in asthma. AU - Diamant,Z, AU - Kuperus,J, AU - Baan,R, AU - Nietzmann,K, AU - Millet,S, AU - Mendes,P, AU - Miller,B, AU - Amin,D, AU - Rohatagi,S, AU - Sterk,P J, AU - Hoogsteden,H C, AU - Prins,J-B, PY - 2005/8/27/pubmed PY - 2006/1/21/medline PY - 2005/8/27/entrez SP - 1080 EP - 7 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin. Exp. Allergy VL - 35 IS - 8 N2 - BACKGROUND: Very late antigen-4 (VLA(4)) plays a key role in the recruitment of eosinophils in allergic responses in animal studies. OBJECTIVE: We investigated whether pretreatment with multiple doses of a VLA(4) receptor antagonist, HMR 1031, protects against allergen-induced airway responses and airway inflammation in humans. METHODS: Fourteen asthmatics (7F/7M), 18-49 years, PC(20) forced expiratory volume in 1 s (FEV(1)) methacholine (M) (<8 mg/mL; FEV(1) 82.3-116.1% predicted) with dual responses to inhaled allergen participated in a double-blind, placebo-controlled, cross-over study. Each treatment period consisted of 9 days, separated by >or=2 weeks. Exhaled nitric oxide (eNO), PC(20)FEV(1)(M) and hypertonic saline-induced sputum was obtained on Days 1, 7 and 9. Subjects inhaled HMR 1031 (20 mg b.i.d.) or placebo (P) on Days 1--8. On Day 8, an allergen bronchoprovocation test was performed, the airway response was measured by FEV(1), and expressed as %fall from baseline. Data from 12 evaluable subjects are presented here. RESULTS: Both treatments were well tolerated. There was no significant difference between HMR 1031 and P in the early asthamatic response: mean AUC (0-3 h)+/-SEM (%fall h): 26.01+/-4.26 and 17.41+/-4.26, respectively (P=0.18), nor in the late response: mean AUC (3-9 h)+/-SEM (%fall h): 97.09+/-8.63 and 97.61+/-8.63, respectively, P=0.97. This corresponded to the absence of significant allergen-induced changes in PC(20)FEV(1)(M), eNO, sputum eosinophils and soluble inflammation markers between both treatment periods. CONCLUSIONS: Treatment with multiple inhaled doses of the VLA(4) antagonist, HMR 1031, did not result in detectable protection against allergen-induced airway responses or airway inflammation in asthma. SN - 0954-7894 UR - https://www.unboundmedicine.com/medline/citation/16120091/Effect_of_a_very_late_antigen_4_receptor_antagonist_on_allergen_induced_airway_responses_and_inflammation_in_asthma_ L2 - https://doi.org/10.1111/j.1365-2222.2005.02296.x DB - PRIME DP - Unbound Medicine ER -