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Endothelin-1-induced bronchoconstriction in asthma.
Am J Respir Crit Care Med. 1997 Aug; 156(2 Pt 1):382-8.AJ

Abstract

Endothelin-1 (ET-1) has been indirectly implicated in the pathophysiology of asthma, and it is a potent bronchoconstrictor both in vitro and by inhalation in animal models in vivo. We examined the effect of inhaled ET-1 on airway tone in comparison with methacholine in eight asthmatics and five healthy volunteers in a double-blind randomized fashion. After a screening methacholine challenge each asthmatic had two ET-1 (doubling dose range, 0.96 to 15.36 nmol) and one methacholine (doubling dose range, 0.33 to 21.0 mumol) challenge, and normal subjects had a single ET-1 challenge. Inhalations were delivered using a dosimeter, and lung function measurements were made using constant-volume body plethysmography, with end points being a 35% fall in specific airway conductance (SGaw) and a 15% fall in FEV1. Samples for plasma ET-1 were taken before and after the inhalations, and pulse, blood pressure and oxygen saturation were monitored throughout the inhalations. All the asthmatic subjects displayed rapid-onset (< 5 min) dose-dependent bronchoconstriction to ET-1 across the dose range used, with mean (range) ET-1 PC35SGaw values of 5.15 (1.4 to 13.9) nmol, and 4.3 (1.2 to 8.3) nmol for the two ET-1 inhalations, and 0.42 (0.2 to 0.7) mumol for methacholine. Albuterol completely and rapidly reversed ET-1-induced bronchoconstriction, and in two patients not given albuterol, bronchoconstriction lasted 60 to 90 min. No significant bronchoconstriction was observed in any of the healthy volunteers across the ET-1 dose range used (mean PC35SGaw > 15.36 nmol). Oxygen saturation did not alter in either group, and plasma ET-1 did not change after ET-1 inhalation. Noninvasive blood pressure measurements revealed a fall in systolic blood pressure in normal subjects, with no change in asthmatics. Endothelin-1 is a potent bronchoconstrictor in asthma, with a bronchoconstrictor potency around 100 times that of methacholine in asthma. Asthmatics exhibit bronchial hyperreactivity to ET-1, and inhaled ET-1 can safely be given to asthmatics and normal subjects in the nebulized dose range 0.96 to 15.36 nmol.

Authors+Show Affiliations

Department of Respiratory Medicine, West Glasgow Hospitals University NHS Trust, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9279213

Citation

Chalmers, G W., et al. "Endothelin-1-induced Bronchoconstriction in Asthma." American Journal of Respiratory and Critical Care Medicine, vol. 156, no. 2 Pt 1, 1997, pp. 382-8.
Chalmers GW, Little SA, Patel KR, et al. Endothelin-1-induced bronchoconstriction in asthma. Am J Respir Crit Care Med. 1997;156(2 Pt 1):382-8.
Chalmers, G. W., Little, S. A., Patel, K. R., & Thomson, N. C. (1997). Endothelin-1-induced bronchoconstriction in asthma. American Journal of Respiratory and Critical Care Medicine, 156(2 Pt 1), 382-8.
Chalmers GW, et al. Endothelin-1-induced Bronchoconstriction in Asthma. Am J Respir Crit Care Med. 1997;156(2 Pt 1):382-8. PubMed PMID: 9279213.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelin-1-induced bronchoconstriction in asthma. AU - Chalmers,G W, AU - Little,S A, AU - Patel,K R, AU - Thomson,N C, PY - 1997/8/1/pubmed PY - 1997/8/1/medline PY - 1997/8/1/entrez SP - 382 EP - 8 JF - American journal of respiratory and critical care medicine JO - Am. J. Respir. Crit. Care Med. VL - 156 IS - 2 Pt 1 N2 - Endothelin-1 (ET-1) has been indirectly implicated in the pathophysiology of asthma, and it is a potent bronchoconstrictor both in vitro and by inhalation in animal models in vivo. We examined the effect of inhaled ET-1 on airway tone in comparison with methacholine in eight asthmatics and five healthy volunteers in a double-blind randomized fashion. After a screening methacholine challenge each asthmatic had two ET-1 (doubling dose range, 0.96 to 15.36 nmol) and one methacholine (doubling dose range, 0.33 to 21.0 mumol) challenge, and normal subjects had a single ET-1 challenge. Inhalations were delivered using a dosimeter, and lung function measurements were made using constant-volume body plethysmography, with end points being a 35% fall in specific airway conductance (SGaw) and a 15% fall in FEV1. Samples for plasma ET-1 were taken before and after the inhalations, and pulse, blood pressure and oxygen saturation were monitored throughout the inhalations. All the asthmatic subjects displayed rapid-onset (< 5 min) dose-dependent bronchoconstriction to ET-1 across the dose range used, with mean (range) ET-1 PC35SGaw values of 5.15 (1.4 to 13.9) nmol, and 4.3 (1.2 to 8.3) nmol for the two ET-1 inhalations, and 0.42 (0.2 to 0.7) mumol for methacholine. Albuterol completely and rapidly reversed ET-1-induced bronchoconstriction, and in two patients not given albuterol, bronchoconstriction lasted 60 to 90 min. No significant bronchoconstriction was observed in any of the healthy volunteers across the ET-1 dose range used (mean PC35SGaw > 15.36 nmol). Oxygen saturation did not alter in either group, and plasma ET-1 did not change after ET-1 inhalation. Noninvasive blood pressure measurements revealed a fall in systolic blood pressure in normal subjects, with no change in asthmatics. Endothelin-1 is a potent bronchoconstrictor in asthma, with a bronchoconstrictor potency around 100 times that of methacholine in asthma. Asthmatics exhibit bronchial hyperreactivity to ET-1, and inhaled ET-1 can safely be given to asthmatics and normal subjects in the nebulized dose range 0.96 to 15.36 nmol. SN - 1073-449X UR - https://www.unboundmedicine.com/medline/citation/9279213/Endothelin_1_induced_bronchoconstriction_in_asthma_ L2 - http://www.atsjournals.org/doi/full/10.1164/ajrccm.156.2.9702066?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -