AMP challenge induces a decrease in FE(NO) in asthmatic subjects modulated by nedocromil.
BACKGROUND
Allergen challenge results in an immediate reduction in exhaled nitric oxide (FE(NO)) followed by a long-term increase. To study mast cell activation in relation to nitric oxide (NO), the study investigated the effect of inhaled adenosine monophosphate (AMP) as a mast cell activator and mast cell stabilizer - nedocromil sodium - on FE(NO). The NO synthase (NOS) iso-enzyme involved was studied by the NOS inhibitor aminoguanidine.


METHODS
A double-blind, placebo-controlled, cross-over study was performed in two parts. Part I: eight atopic asthmatic subjects inhaled nedocromil or placebo before the AMP challenge. Spirometry and FE(NO) were measured at intervals over a 24-h period. Part II: seven subjects inhaled aminoguanidine before an identical protocol was used, as in Part I.


RESULTS
Part I: AMP challenge caused a significant decrease from baseline FE(NO)[placebo, 28.9 (20.3-37.4)%, P < 0.002 and nedocromil, 20.9 (8.2-33.6)%, P < 0.01]. Nedocromil gave partial protection against this decrease in FE(NO). The time-FE(NO) curve (AUC(0-24)) differed significantly between nedocromil and placebo: 2.7% (-3.6 to -9) vs. -6.6% (-12 to -1.3) FE(NO) changes h(-1), P < 0.002, respectively. Nedocromil protected against AMP-induced bronchoconstriction (AMP PC(20)) [nedocromil 182 (72.5-291) mg mL(-1) vs. placebo 21.7 (10.7-33) mg mL(-1), P < 0.002]. Part II: nebulized aminoguanidine resulted in a significant reduction in FE(NO) from baseline and was greater than after AMP alone (P = 0.006). Nedocromil increased AMP PC(20), but no longer protected against the late decrease in FE(NO).


CONCLUSIONS
The AMP challenge caused a reduction in FE(NO) as a result of prior treatment with nedocromil. Aminoguanidine abolished the nedocromil-induced protection on the late reduction in FE(NO), but not on AMP PC(20). Inducible NOS was implicated in the late FE(NO) decrease after the AMP challenge.
Bruce
C T
CT
University of New South Wales, NSW, Australia.
Zhao
D
D
Yates
D H
DH
Thomas
P S
PS
D000249:Adenosine Monophosphate / Q000378:metabolism; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D017835:Nedocromil / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism*
D018927:Anti-Asthmatic Agents; D017835:Nedocromil; D009569:Nitric Oxide; D000249:Adenosine Monophosphate