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Effects of inhaled leukotriene D4 and platelet-activating factor on airway reactivity in normal subjects.
Am Rev Respir Dis. 1990 Apr; 141(4 Pt 1):993-7.AR

Abstract

Inflammatory mediators such as platelet-activating factor (PAF) and the sulfidopeptide leukotrienes (LT) may contribute to airway hyperreactivity and asthma. PAF has been reported to produce bronchoconstriction and a sustained increase in airway reactivity when inhaled by normal subjects. Leukotrienes produce bronchoconstriction in both normal and asthmatic subjects, but whether they increase airway reactivity is unclear. Before initiating studies to determine how these bioactive mediators influence airway function, we sought to confirm that PAF increases airway reactivity and identify whether one of the sulfidopeptide leukotrienes, LTD4, has a similar effect. Eight normal male subjects inhaled saline and increasing concentrations of either histamine (0.1 to 50 mg/ml), PAF (1 to 1,000 micrograms/ml), or LTD4 (1 to 500 micrograms/ml) on separate days, at least 1 wk apart, until specific airway conductance (SGaw) decreased 50% or the maximal concentration was reached. After inhaling the test substance, methacholine (MCh) challenges were performed at 6 h, at 1, 3, and 7 days, and weekly thereafter until airway reactivity (measured as the MCh concentration that decreased SGaw 35% [PC35SGaw]) normalized. The four postsaline MCh challenges (6 h to 7 days) were used to determine the 95% confidence interval for PC35SGaw (in each subject) and identify significant changes in airway reactivity after inhaling each test substance. Airway reactivity did not change after inhaling histamine. After inhaling PAF, six of eight subjects developed increased airway reactivity, which was maximal at 1 day and persisted for 14 days in three. After inhaling LTD4, six of eight subjects also developed increased airway reactivity, which was maximal at 7 days and persisted for 14 days in two.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Medicine, Northwestern University, Chicago, Illinois.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2183659

Citation

Kaye, M G., and L J. Smith. "Effects of Inhaled Leukotriene D4 and Platelet-activating Factor On Airway Reactivity in Normal Subjects." The American Review of Respiratory Disease, vol. 141, no. 4 Pt 1, 1990, pp. 993-7.
Kaye MG, Smith LJ. Effects of inhaled leukotriene D4 and platelet-activating factor on airway reactivity in normal subjects. Am Rev Respir Dis. 1990;141(4 Pt 1):993-7.
Kaye, M. G., & Smith, L. J. (1990). Effects of inhaled leukotriene D4 and platelet-activating factor on airway reactivity in normal subjects. The American Review of Respiratory Disease, 141(4 Pt 1), 993-7.
Kaye MG, Smith LJ. Effects of Inhaled Leukotriene D4 and Platelet-activating Factor On Airway Reactivity in Normal Subjects. Am Rev Respir Dis. 1990;141(4 Pt 1):993-7. PubMed PMID: 2183659.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of inhaled leukotriene D4 and platelet-activating factor on airway reactivity in normal subjects. AU - Kaye,M G, AU - Smith,L J, PY - 1990/4/1/pubmed PY - 1990/4/1/medline PY - 1990/4/1/entrez SP - 993 EP - 7 JF - The American review of respiratory disease JO - Am Rev Respir Dis VL - 141 IS - 4 Pt 1 N2 - Inflammatory mediators such as platelet-activating factor (PAF) and the sulfidopeptide leukotrienes (LT) may contribute to airway hyperreactivity and asthma. PAF has been reported to produce bronchoconstriction and a sustained increase in airway reactivity when inhaled by normal subjects. Leukotrienes produce bronchoconstriction in both normal and asthmatic subjects, but whether they increase airway reactivity is unclear. Before initiating studies to determine how these bioactive mediators influence airway function, we sought to confirm that PAF increases airway reactivity and identify whether one of the sulfidopeptide leukotrienes, LTD4, has a similar effect. Eight normal male subjects inhaled saline and increasing concentrations of either histamine (0.1 to 50 mg/ml), PAF (1 to 1,000 micrograms/ml), or LTD4 (1 to 500 micrograms/ml) on separate days, at least 1 wk apart, until specific airway conductance (SGaw) decreased 50% or the maximal concentration was reached. After inhaling the test substance, methacholine (MCh) challenges were performed at 6 h, at 1, 3, and 7 days, and weekly thereafter until airway reactivity (measured as the MCh concentration that decreased SGaw 35% [PC35SGaw]) normalized. The four postsaline MCh challenges (6 h to 7 days) were used to determine the 95% confidence interval for PC35SGaw (in each subject) and identify significant changes in airway reactivity after inhaling each test substance. Airway reactivity did not change after inhaling histamine. After inhaling PAF, six of eight subjects developed increased airway reactivity, which was maximal at 1 day and persisted for 14 days in three. After inhaling LTD4, six of eight subjects also developed increased airway reactivity, which was maximal at 7 days and persisted for 14 days in two.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0003-0805 UR - https://www.unboundmedicine.com/medline/citation/2183659/Effects_of_inhaled_leukotriene_D4_and_platelet_activating_factor_on_airway_reactivity_in_normal_subjects_ L2 - https://www.atsjournals.org/doi/10.1164/ajrccm/141.4_Pt_1.993?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -