Effect of a leukotriene antagonist, LY171883, on cold air-induced bronchoconstriction in asthmatics

E. Israel, E. F. Juniper, John Callaghan, P. N. Mathur, M. M. Morris, A. R. Dowell, G. G. Enas, F. E. Hargreave, J. M. Drazen

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Isocapnic hyperpnea (ISH) of cold air induces bronchoconstriction in many asthmatic subjects. Although this response is well described, it is unclear whether this bronchoconstriction is related to the release of bronchoactive mediators. We examined whether pretreatment with LY171883, a competitive antagonist of leukotriene D4 activity via LTD4 receptors, reduced the bronchospastic response to cold air ISH in asthmatics using a randomized, double-blind, two-phase crossover design. In 20 subjects, 2 wk of treatment with either LY171883 600 mg twice a day or placebo did not result in a change in FEV1 (3.45 ± 0.21 L placebo versus 3.59 ± 0.20 L LY171883; p > 0.05). Nineteen subjects underwent cold-air ISH; LY171883 increased the geometric mean respiratory heat loss required to reduce the FEV1 by 20% (PD20RHE) from 1.00 kcal/min with placebo to 1.24 kcal/min with LY171883 (p <0.05). A similar difference was noted when responses were expressed as a function of minute ventilation. LY171883 produced greater shifts in the PD20RHE in more reactive subjects (r = 0.69, p <0.002). Among 11 different symptom scores recorded by 18 subjects, there was a significant decrease in daytime chest tightness with LY171883 (p <0.03). The increase in PD20RHE while the subjects received LY171883 is consistent with the hypothesis that LTD4 becomes available during cold-air ISH and may mediate bronchoconstriction. The small magnitude of the effect on the PD20RHE may be due to the role of other mediators in cold-air-induced bronchoconstriction or, alternatively, to an inadequate blockade of LTD4 effects.

Original languageEnglish (US)
Pages (from-to)1348-1353
Number of pages6
JournalAmerican Review of Respiratory Disease
Volume140
Issue number5
StatePublished - 1989
Externally publishedYes

Fingerprint

LY 171883
Leukotriene Antagonists
Bronchoconstriction
Air
Leukotriene D4
Placebos
Cross-Over Studies
Ventilation
Thorax
Hot Temperature

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Israel, E., Juniper, E. F., Callaghan, J., Mathur, P. N., Morris, M. M., Dowell, A. R., ... Drazen, J. M. (1989). Effect of a leukotriene antagonist, LY171883, on cold air-induced bronchoconstriction in asthmatics. American Review of Respiratory Disease, 140(5), 1348-1353.

Effect of a leukotriene antagonist, LY171883, on cold air-induced bronchoconstriction in asthmatics. / Israel, E.; Juniper, E. F.; Callaghan, John; Mathur, P. N.; Morris, M. M.; Dowell, A. R.; Enas, G. G.; Hargreave, F. E.; Drazen, J. M.

In: American Review of Respiratory Disease, Vol. 140, No. 5, 1989, p. 1348-1353.

Research output: Contribution to journalArticle

Israel, E, Juniper, EF, Callaghan, J, Mathur, PN, Morris, MM, Dowell, AR, Enas, GG, Hargreave, FE & Drazen, JM 1989, 'Effect of a leukotriene antagonist, LY171883, on cold air-induced bronchoconstriction in asthmatics', American Review of Respiratory Disease, vol. 140, no. 5, pp. 1348-1353.
Israel, E. ; Juniper, E. F. ; Callaghan, John ; Mathur, P. N. ; Morris, M. M. ; Dowell, A. R. ; Enas, G. G. ; Hargreave, F. E. ; Drazen, J. M. / Effect of a leukotriene antagonist, LY171883, on cold air-induced bronchoconstriction in asthmatics. In: American Review of Respiratory Disease. 1989 ; Vol. 140, No. 5. pp. 1348-1353.
@article{957620d91cf04e368705999c02c5d504,
title = "Effect of a leukotriene antagonist, LY171883, on cold air-induced bronchoconstriction in asthmatics",
abstract = "Isocapnic hyperpnea (ISH) of cold air induces bronchoconstriction in many asthmatic subjects. Although this response is well described, it is unclear whether this bronchoconstriction is related to the release of bronchoactive mediators. We examined whether pretreatment with LY171883, a competitive antagonist of leukotriene D4 activity via LTD4 receptors, reduced the bronchospastic response to cold air ISH in asthmatics using a randomized, double-blind, two-phase crossover design. In 20 subjects, 2 wk of treatment with either LY171883 600 mg twice a day or placebo did not result in a change in FEV1 (3.45 ± 0.21 L placebo versus 3.59 ± 0.20 L LY171883; p > 0.05). Nineteen subjects underwent cold-air ISH; LY171883 increased the geometric mean respiratory heat loss required to reduce the FEV1 by 20{\%} (PD20RHE) from 1.00 kcal/min with placebo to 1.24 kcal/min with LY171883 (p <0.05). A similar difference was noted when responses were expressed as a function of minute ventilation. LY171883 produced greater shifts in the PD20RHE in more reactive subjects (r = 0.69, p <0.002). Among 11 different symptom scores recorded by 18 subjects, there was a significant decrease in daytime chest tightness with LY171883 (p <0.03). The increase in PD20RHE while the subjects received LY171883 is consistent with the hypothesis that LTD4 becomes available during cold-air ISH and may mediate bronchoconstriction. The small magnitude of the effect on the PD20RHE may be due to the role of other mediators in cold-air-induced bronchoconstriction or, alternatively, to an inadequate blockade of LTD4 effects.",
author = "E. Israel and Juniper, {E. F.} and John Callaghan and Mathur, {P. N.} and Morris, {M. M.} and Dowell, {A. R.} and Enas, {G. G.} and Hargreave, {F. E.} and Drazen, {J. M.}",
year = "1989",
language = "English (US)",
volume = "140",
pages = "1348--1353",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "5",

}

TY - JOUR

T1 - Effect of a leukotriene antagonist, LY171883, on cold air-induced bronchoconstriction in asthmatics

AU - Israel, E.

AU - Juniper, E. F.

AU - Callaghan, John

AU - Mathur, P. N.

AU - Morris, M. M.

AU - Dowell, A. R.

AU - Enas, G. G.

AU - Hargreave, F. E.

AU - Drazen, J. M.

PY - 1989

Y1 - 1989

N2 - Isocapnic hyperpnea (ISH) of cold air induces bronchoconstriction in many asthmatic subjects. Although this response is well described, it is unclear whether this bronchoconstriction is related to the release of bronchoactive mediators. We examined whether pretreatment with LY171883, a competitive antagonist of leukotriene D4 activity via LTD4 receptors, reduced the bronchospastic response to cold air ISH in asthmatics using a randomized, double-blind, two-phase crossover design. In 20 subjects, 2 wk of treatment with either LY171883 600 mg twice a day or placebo did not result in a change in FEV1 (3.45 ± 0.21 L placebo versus 3.59 ± 0.20 L LY171883; p > 0.05). Nineteen subjects underwent cold-air ISH; LY171883 increased the geometric mean respiratory heat loss required to reduce the FEV1 by 20% (PD20RHE) from 1.00 kcal/min with placebo to 1.24 kcal/min with LY171883 (p <0.05). A similar difference was noted when responses were expressed as a function of minute ventilation. LY171883 produced greater shifts in the PD20RHE in more reactive subjects (r = 0.69, p <0.002). Among 11 different symptom scores recorded by 18 subjects, there was a significant decrease in daytime chest tightness with LY171883 (p <0.03). The increase in PD20RHE while the subjects received LY171883 is consistent with the hypothesis that LTD4 becomes available during cold-air ISH and may mediate bronchoconstriction. The small magnitude of the effect on the PD20RHE may be due to the role of other mediators in cold-air-induced bronchoconstriction or, alternatively, to an inadequate blockade of LTD4 effects.

AB - Isocapnic hyperpnea (ISH) of cold air induces bronchoconstriction in many asthmatic subjects. Although this response is well described, it is unclear whether this bronchoconstriction is related to the release of bronchoactive mediators. We examined whether pretreatment with LY171883, a competitive antagonist of leukotriene D4 activity via LTD4 receptors, reduced the bronchospastic response to cold air ISH in asthmatics using a randomized, double-blind, two-phase crossover design. In 20 subjects, 2 wk of treatment with either LY171883 600 mg twice a day or placebo did not result in a change in FEV1 (3.45 ± 0.21 L placebo versus 3.59 ± 0.20 L LY171883; p > 0.05). Nineteen subjects underwent cold-air ISH; LY171883 increased the geometric mean respiratory heat loss required to reduce the FEV1 by 20% (PD20RHE) from 1.00 kcal/min with placebo to 1.24 kcal/min with LY171883 (p <0.05). A similar difference was noted when responses were expressed as a function of minute ventilation. LY171883 produced greater shifts in the PD20RHE in more reactive subjects (r = 0.69, p <0.002). Among 11 different symptom scores recorded by 18 subjects, there was a significant decrease in daytime chest tightness with LY171883 (p <0.03). The increase in PD20RHE while the subjects received LY171883 is consistent with the hypothesis that LTD4 becomes available during cold-air ISH and may mediate bronchoconstriction. The small magnitude of the effect on the PD20RHE may be due to the role of other mediators in cold-air-induced bronchoconstriction or, alternatively, to an inadequate blockade of LTD4 effects.

UR - http://www.scopus.com/inward/record.url?scp=0024434799&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024434799&partnerID=8YFLogxK

M3 - Article

C2 - 2817597

AN - SCOPUS:0024434799

VL - 140

SP - 1348

EP - 1353

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 5

ER -