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The combined effects of two pairs of mediators, adenosine with methacholine and prostaglandin D2 with histamine, on airway calibre in asthma.
Clin Sci (Lond). 1986 Oct; 71(4):385-92.CS

Abstract

Mediators released from mast cells and secondary effector cells in the airways contribute to bronchoconstriction of allergic asthma. This study investigates methods for defining the effect of two inflammatory mediators on airway calibre in asthma. In an initial study on three asthmatic subjects, subconstrictor (subthreshold) concentrations of two mast cell derived mediators, histamine and prostaglandin (PG) D2, produced similar displacement to the left of a histamine concentration-specific airways conductance (sGaw) response curve. With both agonists enhancement of histamine-induced bronchoconstriction was greater at low histamine concentrations. Since potentiation of histamine-induced bronchoconstriction was independent of the class of subconstrictor agent given, it is likely to represent a physiological rather than a pharmacological interaction. During provoked asthma different constrictor mediators are likely to be released simultaneously into the airways. A method was therefore devised to investigate the combined effect of equiconstrictor concentrations of two mediators on airway calibre. Two pairs of inhaled bronchoconstrictor agonists were chosen for study: adenosine with methacholine and PGD2 with histamine. For each agonist, concentration-sGaw response curves were constructed, from which were derived the provocation concentrations of agonist causing a 25% fall in sGaw from baseline (PC25) and required to further this to 50% (PC50-25). On separate days, eight subjects received paired inhalations of methacholine-adenosine, methacholine-methacholine and adenosine-adenosine. The concentration used for the first inhalation was the PC25 value and for the second inhalation the PC50-25 value. Before, immediately after the first inhalation, and at regular intervals after the second inhalation, sGaw was followed for 30 min.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

3530610

Citation

Hardy, C C., et al. "The Combined Effects of Two Pairs of Mediators, Adenosine With Methacholine and Prostaglandin D2 With Histamine, On Airway Calibre in Asthma." Clinical Science (London, England : 1979), vol. 71, no. 4, 1986, pp. 385-92.
Hardy CC, Bradding P, Robinson C, et al. The combined effects of two pairs of mediators, adenosine with methacholine and prostaglandin D2 with histamine, on airway calibre in asthma. Clin Sci (Lond). 1986;71(4):385-92.
Hardy, C. C., Bradding, P., Robinson, C., & Holgate, S. T. (1986). The combined effects of two pairs of mediators, adenosine with methacholine and prostaglandin D2 with histamine, on airway calibre in asthma. Clinical Science (London, England : 1979), 71(4), 385-92.
Hardy CC, et al. The Combined Effects of Two Pairs of Mediators, Adenosine With Methacholine and Prostaglandin D2 With Histamine, On Airway Calibre in Asthma. Clin Sci (Lond). 1986;71(4):385-92. PubMed PMID: 3530610.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The combined effects of two pairs of mediators, adenosine with methacholine and prostaglandin D2 with histamine, on airway calibre in asthma. AU - Hardy,C C, AU - Bradding,P, AU - Robinson,C, AU - Holgate,S T, PY - 1986/10/1/pubmed PY - 1986/10/1/medline PY - 1986/10/1/entrez SP - 385 EP - 92 JF - Clinical science (London, England : 1979) JO - Clin Sci (Lond) VL - 71 IS - 4 N2 - Mediators released from mast cells and secondary effector cells in the airways contribute to bronchoconstriction of allergic asthma. This study investigates methods for defining the effect of two inflammatory mediators on airway calibre in asthma. In an initial study on three asthmatic subjects, subconstrictor (subthreshold) concentrations of two mast cell derived mediators, histamine and prostaglandin (PG) D2, produced similar displacement to the left of a histamine concentration-specific airways conductance (sGaw) response curve. With both agonists enhancement of histamine-induced bronchoconstriction was greater at low histamine concentrations. Since potentiation of histamine-induced bronchoconstriction was independent of the class of subconstrictor agent given, it is likely to represent a physiological rather than a pharmacological interaction. During provoked asthma different constrictor mediators are likely to be released simultaneously into the airways. A method was therefore devised to investigate the combined effect of equiconstrictor concentrations of two mediators on airway calibre. Two pairs of inhaled bronchoconstrictor agonists were chosen for study: adenosine with methacholine and PGD2 with histamine. For each agonist, concentration-sGaw response curves were constructed, from which were derived the provocation concentrations of agonist causing a 25% fall in sGaw from baseline (PC25) and required to further this to 50% (PC50-25). On separate days, eight subjects received paired inhalations of methacholine-adenosine, methacholine-methacholine and adenosine-adenosine. The concentration used for the first inhalation was the PC25 value and for the second inhalation the PC50-25 value. Before, immediately after the first inhalation, and at regular intervals after the second inhalation, sGaw was followed for 30 min.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0143-5221 UR - https://www.unboundmedicine.com/medline/citation/3530610/The_combined_effects_of_two_pairs_of_mediators_adenosine_with_methacholine_and_prostaglandin_D2_with_histamine_on_airway_calibre_in_asthma_ L2 - https://portlandpress.com/clinsci/article-lookup/doi/10.1042/cs0710385 DB - PRIME DP - Unbound Medicine ER -