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AMP challenge induces a decrease in FE(NO) in asthmatic subjects modulated by nedocromil.

C T Bruce1, D Zhao, D H Yates

  • 1University of New South Wales, NSW, Australia.

European Journal of Clinical Investigation
|November 8, 2006
PubMed
Summary
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Adenosine monophosphate (AMP) challenge reduces exhaled nitric oxide (FE(NO)) in asthma. Nedocromil partially protected FE(NO) and bronchoconstriction, while aminoguanidine implicated inducible nitric oxide synthase (iNOS) in the late FE(NO) decrease.

Area of Science:

  • Respiratory Medicine
  • Immunology

Background:

  • Allergen challenge impacts exhaled nitric oxide (FE(NO)), decreasing it immediately and increasing it long-term.
  • Mast cell activation is linked to nitric oxide (NO) production.
  • Adenosine monophosphate (AMP) serves as a mast cell activator, and nedocromil sodium as a stabilizer.

Purpose of the Study:

  • To investigate the effect of inhaled adenosine monophosphate (AMP) on FE(NO) in atopic asthmatic subjects.
  • To assess the role of nedocromil sodium, a mast cell stabilizer, in modulating AMP-induced changes in FE(NO).
  • To explore the involvement of inducible nitric oxide synthase (iNOS) using aminoguanidine, a NOS inhibitor.

Main Methods:

  • A double-blind, placebo-controlled, cross-over study design was employed.
  • Part I involved eight atopic asthmatic subjects inhaling nedocromil or placebo before AMP challenge, with spirometry and FE(NO) measurements over 24 hours.

Related Experiment Videos

  • Part II utilized aminoguanidine before an identical protocol in seven subjects.

    • Main Results:

    • AMP challenge significantly decreased baseline FE(NO) in both placebo and nedocromil groups, with nedocromil offering partial protection.
    • Nedocromil significantly protected against AMP-induced bronchoconstriction (PC(20)).
    • Aminoguanidine administration resulted in a significant reduction in FE(NO) and abolished nedocromil's protective effect on the late FE(NO) decrease.

    Conclusions:

    • Inhaled AMP challenge leads to reduced FE(NO) in asthmatic subjects, partly mitigated by nedocromil.
    • Aminoguanidine implicates inducible nitric oxide synthase (iNOS) in the late decrease of FE(NO) following AMP challenge.
    • Nedocromil's protection against bronchoconstriction was not affected by aminoguanidine.