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9.8.8 (iv) Nedocromil sodium
In two paediatric studies, this medication had no effect on levels of exhaled NO when
compared to IHCS in 32 sensitised patients followed through a pollen season (Gratziou,
Rovina et al. 2001) or in ll8 four to six year olds studied as part of the childhood asthma
management program (CAMP) studies (Covar, Szefler et al. 2003).
9.8.8 (v) Theophylline
Despite theophylline being a previously commonly used drug, there has only been one study
looking at its effect on levels of exhaled NO. In a double blind crossover study 15 patients
with mild asthma on theophylline of 250mg twice per day had a reduction in eosinophil
counts in sputum, BAL, and biopsy samples but no change in levels of exhaled NO and no
improvements in lung function or bronchial hyper-responsiveness (Lim, Tomita et al. 2001).
9.8.8 (vi) Novel medications
L-NAME -
Nebulised pretreatment with this non-selective NOS inhibitor reduced levels of
exhaled NO from baseline in 22 asthmatics with either an early asthmatic response only or
both an early and late asthmatic response to allergen challengebyTT andTIVo respectively.
Despite this result in NO, there was no change on the magnitude of the other acute responses
in either group (Taylor, McGrath et al. 1998).
L-Arginine -
L-arginine (the substrate for the NOS enzymes) was nebulised as single doses of
0,759,1.5g and 39 to healthy subjects and asthmatics with 6-7 in each group. This increased
levels of exhaled NO in a dose dependent fashion at 60 minutes showing a negative
correlation to the fall in FEVr (Sapienza, Kharitonov et al. 1998). Nebulisation of 2.59 of L-
arginine and D-arginine on separate days to eight steroid naive asthmatics both resulted in
bronchoconstriction. There was an initial proportional decline of NO then, with resolution of
the constriction,the NO increased so by three hours it was higher than baseline (Chambers and
Ayres 2001). It is hard to know whether L-arginine is acting as a substrate in these studies or
just as an airway irritant.
Omalizumab -
This humanised monoclonal antibody to Ig E was used in a steroid reduction
study in adults with allergic asthma over one year. In the 18 that received active medication
compared to the l l receiving placebo, the variability of the exhaled NO was significantly less
and remained similar to the levels obtained when the children were on higher doses of IHCS
prior to the reduction phase (Silkoff, Romero et al. 2004).
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