Chest ACCP Education Calendar
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Haber, A.
Right arrow Articles by Beckett, W.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Haber, A.
Right arrow Articles by Beckett, W.

Chest, Vol 102, 856-863, Copyright © 1992 by American College of Chest Physicians

ARTICLES

Indomethacin and methacholine tolerance in normal subjects. Role of prostaglandin synthesis in the attenuation of methacholine's effect during repeated inhalation challenges

AD Haber and WS Beckett
Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn.

Within hours, tolerance occurs to repeated methacholine challenge in normal subjects, and this study examines whether prostaglandin synthesis produces this phenomenon. On two separate study days, ten nonasthmatic non-smoking subjects with measurable baseline responsiveness to methacholine performed five sequential methacholine challenge tests over 6 h. Pretreatment before each day consisted of either placebo tablets or 50-mg tablets of indomethacin given three times daily for 48 h prior to testing. Medications were administered in a single-blind crossover fashion, with study days assigned in random order and separated by at least 1 wk. Methacholine challenge tests were summarized by the PD20FEV1 (the provocative dose in cumulative breath units [cbu] required to produce a 20 percent fall in FEV1). Indomethacin pretreatment had no effect on baseline spirometry between the two study days; however, the baseline geometric mean PD20FEV1 fell from 145 +/- 2 cbu (+/- percent SD) after placebo pretreatment to 65 +/- 1 cbu (+/- percent SD) on the indomethacin day (p = 0.046). This effect of indomethacin on baseline airway responsiveness persisted when an additional ten subjects were studied to further investigate this finding. Significant tolerance to repeated methacholine challenges occurred on both study days, with geometric mean PD20FEV1 rising approximately 16-fold (p less than 0.0001) regardless of pretreatment received. This study demonstrates that the attenuation of methacholine's effect with repeated testing is not due solely to prostaglandin synthesis and must involve, in part, other mechanisms, such as changes in methacholine deposition, agonist-receptor interactions, or postreceptor responses. In addition, prostaglandin inhibitors may increase baseline methacholine responsiveness in healthy nonasthmatic subjects.


This article has been cited by other articles:


Home page
 ChestHome page
D. W. Cockcroft and B. E. Davis
Lack of Tachyphylaxis to Methacholine at 24 h
Chest, September 1, 2005; 128(3): 1248 - 1251.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1992 by the American College of Chest Physicians.