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Revisiting the usefulness of thromboxane-A2 modulation in the treatment of bronchoconstriction in asthma.
Can J Physiol Pharmacol. 2015 Feb; 93(2):111-7.CJ

Abstract

Airway smooth muscle (ASM) is the effector cell in the bronchoconstrictory pathway. It is believed that the bronchoconstriction present in asthma is associated with changes in the airway milieu that affect ASM excitation-contraction coupling and Ca(2+)-handling. Asthmatics also react differently to ventilatory mechanical strain. Deep inspiration (DI), which produces bronchodilation in healthy individuals, is less effective in asthmatics, and even enhances bronchoconstriction in moderate to severely affected patients. Our laboratory has previously studied the mechanotransductory pathway of airway stretch-activated contractions (Rstretch) leading to DI-induced bronchoconstriction. We demonstrated the ability of agonists acting through thromboxane A2 (TxA2) receptors to amplify airway Rstretch responses. Despite the involvement of excitatory prostanoids in bronchoconstriction, clinical trials on treatments targeting TxA2-synthase inhibition and TP-receptor antagonism have produced mixed results. Studies in Western populations produced mostly negative results, whereas studies performed in Asian populations showed mostly positive outcomes. In this review, we discuss the role of TxA2-synthase inhibition and TP-receptor antagonism in the treatment of asthmatics. We present information regarding variations in study designs and the possible role of TP-receptor gene polymorphisms in previous study outcome discrepancies. Perhaps future studies should focus on asthmatic patients with DI-induced bronchoconstriction in particular, planting the seed for the individualized treatments for asthmatics.

Authors+Show Affiliations

Firestone Institute for Respiratory Health, Father Sean O'Sullivan Research Centre, and Department of Medicine, McMaster University, St. Joseph's Hospital, 50 Charlton Avenue East, Hamilton, ON L8N 4A6, Canada.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25581104

Citation

Hernandez, Jeremy Mark, and Luke Jeffrey Janssen. "Revisiting the Usefulness of thromboxane-A2 Modulation in the Treatment of Bronchoconstriction in Asthma." Canadian Journal of Physiology and Pharmacology, vol. 93, no. 2, 2015, pp. 111-7.
Hernandez JM, Janssen LJ. Revisiting the usefulness of thromboxane-A2 modulation in the treatment of bronchoconstriction in asthma. Can J Physiol Pharmacol. 2015;93(2):111-7.
Hernandez, J. M., & Janssen, L. J. (2015). Revisiting the usefulness of thromboxane-A2 modulation in the treatment of bronchoconstriction in asthma. Canadian Journal of Physiology and Pharmacology, 93(2), 111-7. https://doi.org/10.1139/cjpp-2014-0364
Hernandez JM, Janssen LJ. Revisiting the Usefulness of thromboxane-A2 Modulation in the Treatment of Bronchoconstriction in Asthma. Can J Physiol Pharmacol. 2015;93(2):111-7. PubMed PMID: 25581104.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Revisiting the usefulness of thromboxane-A2 modulation in the treatment of bronchoconstriction in asthma. AU - Hernandez,Jeremy Mark, AU - Janssen,Luke Jeffrey, Y1 - 2014/12/09/ PY - 2015/1/13/entrez PY - 2015/1/13/pubmed PY - 2016/5/18/medline KW - airway hyper-responsiveness KW - airway smooth muscle KW - antagoniste du récepteur du thromboxane-A2 KW - calcium handling KW - couplage excitation–contraction KW - deep inspiration KW - excitation–contraction coupling KW - gestion du calcium KW - hyperréactivité bronchique KW - inhibiteur de la thromboxane-A2 synthase KW - inspiration profonde KW - muscle lisse respiratoire KW - prostanoids KW - prostanoïdes KW - thromboxane-A2 receptor antagonist KW - thromboxane-A2 synthase inhibitor SP - 111 EP - 7 JF - Canadian journal of physiology and pharmacology JO - Can. J. Physiol. Pharmacol. VL - 93 IS - 2 N2 - Airway smooth muscle (ASM) is the effector cell in the bronchoconstrictory pathway. It is believed that the bronchoconstriction present in asthma is associated with changes in the airway milieu that affect ASM excitation-contraction coupling and Ca(2+)-handling. Asthmatics also react differently to ventilatory mechanical strain. Deep inspiration (DI), which produces bronchodilation in healthy individuals, is less effective in asthmatics, and even enhances bronchoconstriction in moderate to severely affected patients. Our laboratory has previously studied the mechanotransductory pathway of airway stretch-activated contractions (Rstretch) leading to DI-induced bronchoconstriction. We demonstrated the ability of agonists acting through thromboxane A2 (TxA2) receptors to amplify airway Rstretch responses. Despite the involvement of excitatory prostanoids in bronchoconstriction, clinical trials on treatments targeting TxA2-synthase inhibition and TP-receptor antagonism have produced mixed results. Studies in Western populations produced mostly negative results, whereas studies performed in Asian populations showed mostly positive outcomes. In this review, we discuss the role of TxA2-synthase inhibition and TP-receptor antagonism in the treatment of asthmatics. We present information regarding variations in study designs and the possible role of TP-receptor gene polymorphisms in previous study outcome discrepancies. Perhaps future studies should focus on asthmatic patients with DI-induced bronchoconstriction in particular, planting the seed for the individualized treatments for asthmatics. SN - 1205-7541 UR - https://www.unboundmedicine.com/medline/citation/25581104/Revisiting_the_usefulness_of_thromboxane_A2_modulation_in_the_treatment_of_bronchoconstriction_in_asthma_ L2 - http://www.nrcresearchpress.com/doi/full/10.1139/cjpp-2014-0364?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -