Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2002 Jul;57(7):575-80.
doi: 10.1136/thorax.57.7.575.

Contrasting effects of allergen challenge on airway responsiveness to cysteinyl leukotriene D(4) and methacholine in mild asthma

R I Ketchell  1 , M D'Amato, M W Jensen, B J O'Connor
Affiliations
Clinical Trial

Contrasting effects of allergen challenge on airway responsiveness to cysteinyl leukotriene D(4) and methacholine in mild asthma

R I Ketchell et al. Thorax. 2002 Jul.

Abstract

Background: Cysteinyl leukotrienes (cysteinyl-LTs) have been implicated in the pathogenesis of allergen induced airway responses. Airway responsiveness (AR) to inhaled cysteinyl-LTs is dramatically increased following allergen challenge in animal studies. The effect in man has not been evaluated.

Methods: Ten mild steroid-naïve asthmatic subjects with an isolated early asthmatic response (EAR) and 21 with an additional late asthmatic response (LAR) took part in a randomised controlled crossover study to assess AR to inhaled methacholine (MCh) and cysteinyl-LT D(4) (LTD(4)) 22 and 24 hours, respectively, after allergen challenge. Eight subjects had two further LTD(4) challenges separated by a 2 week washout period to assess the reproducibility of inhaled LTD(4) challenge.

Results: In subjects with an isolated EAR, non-significant mean (SE) increases in AR of 0.4 (0.4) doubling doses (DD) for MCh and 0.4 (0.5) DD for LTD(4) followed allergen challenge compared with control. A significant correlation between AR to MCh and LTD(4) followed both control (r=0.91, 95% CI 0.67 to 0.98; p=0.0002) and allergen challenge (r=0.79, 95% CI 0.32 to 0.95; p=0.0063). In subjects with an additional LAR there was a significant increase in AR to MCh (1.2 (0.3) DD, p=0.0005) following allergen challenge but no overall effect on AR to LTD(4) (0.69 (0.4) DD, p=0.11). A significant correlation between AR to MCh and LTD(4) was again observed (r=0.70; 95% CI 0.38 to 0.87; p=0.0004) following control, although it was reduced following allergen challenge (r=0.48; 95% CI 0.063 to 0.76; p=0.027). LTD(4) challenge was highly reproducible with a mean difference of 0.2 (0.3) DD between challenges.

Conclusions: Allergen challenge significantly increases AR to inhaled MCh but not to LTD(4) in subjects with LAR. The lack of a comparable increase in AR to LTD(4) is surprising. Endogenous cysteinyl-LTs are produced in abundance following allergen challenge and may enhance AR to MCh or induce a degree of tachyphylaxis to LTD(4).

PubMed Disclaimer

References

    1. Am J Respir Crit Care Med. 2000 May;161(5):1473-8 - PubMed
    1. Trends Pharmacol Sci. 1999 Jan;20(1):9-11 - PubMed
    1. Am Rev Respir Dis. 1985 Mar;131(3):368-72 - PubMed
    1. Am Rev Respir Dis. 1985 Mar;131(3):373-6 - PubMed
    1. Am Rev Respir Dis. 1986 Jun;133(6):1127-32 - PubMed

Publication types

MeSH terms