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AMP challenge induces a decrease in FE NO in asthmatic subjects modulated by nedocromil
Author(s) -
Bruce C. T.,
Zhao D.,
Yates D. H.,
Thomas P. S.
Publication year - 2006
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2006.01736.x
Subject(s) - nedocromil sodium , nedocromil , placebo , bronchoconstriction , nitric oxide , asthma , mast cell , medicine , chemistry , endocrinology , anesthesia , pharmacology , immunology , pathology , alternative medicine
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. Materials and 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.