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9.8.8 (ii) Anti-leukotriene receptor antagonists
In this class of drugs, the two predominantly studied in conjunction with NO have been
montelukast and pranlukast. Firstly, NO has been monitored when these have been used as an
addition to regular treatment. An open label six week trial of oral montelukast in 20 adult
asthmatics already on IHCS resulted in significant improvements for levels of exhaled NO,
coinciding with an improvement in exercise tolerance (Berkman, Avital et al. 200.3).
Similarly, in 20 stable asthmatics, a crossover trial showed that montelukast, as opposed to
placebo, reduced exhaled NO as well as reducing peak flow variability and symptom score
over a two week treatment period (Sandrini, Ferreira et al. 2003). When montelucast was
added to treatment of 22 adults with mild to moderate asthma using fluticasone 2501t9 and
salmeterol 50pg twice a day, montelukast l0mg a day, compared to placebo, reduced levels of
exhaled NO and blood eosinophilia (Currie, lre et al. 2003). In 35 children treated with IHCS
in whom the exhaled NO was greater than 20ppb, those that had montelukast added to their
treatment had a significant reduction of exhaled NO which increased back to baseline level
after withdrawal of the drug (Ghiro, Zanconato et al. 2002). While the reduction of NO
coincided with some clinical improvements, there was no improvement in others such as
bronchial responsiveness (Berkman, Avital et aL.2003), FEVr (Ghiro, Zanconato et al.2002;
Currie, Ire et al. 2OO3; Sandrini, Ferreira et al. 2003) or in measured exhaled HzOz (Sandrini,
Ferreira et al.2OO3). Only one study conducted in 25 children did not show a difference in
exhaled NO with the addition of montelukast to IHCS treatment (Strauch, Moske et al. 2003).
Pranlukast added to a six week reduction of inhaled budesonide did prevent asthma
deterioration compared to placebo, but did not show a difference in levels of exhaled NO,
although NO levels in the placebo group increased (Tamaoki, Kondo etal.1997).
Secondly, NO has also been used as an outcome measure when these medication have been
used alone. In steroid naive children (twelve to 2l subjects in each study), treatment with
montelukast (5 or l0mgs per day) for between two and eight weeks resulted in a reduction in
exhaled NO in two studies (Bratton, Lanz et al. 1999;l-ee,Lu et al. 2005) but not in a third
(Spahn, Covar et al. 20O6) with the individual researchers also showing improvements in
FEV', (Bratton, Lanz et al. 1999), salbutamol use (Bratton,Lanz et al. 1999), residual volume
(Spahn, Covar et ^l.2006) and serum ECP levels (Spahn, Covar et al.2OO6). They did not
demonstrate changes in symptom scores (Spahn, Covar et al. 2006) and the exhaled NO
returned to pre treatment levels two weeks after withdrawal of the medication (Ire, Lai et al.
2005). In younger steroid narve children aged ten months to five years (54 in total) with an
early diagnosis of asthma, significant improvements were seen in levels of exhaled NO,
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