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Indomethacin - This medication alters the cyclo-oxygenase products of the arachidonic acid
pathway which play a role in bronchoconstriction and airway inflammation. Indomethacin
50mg daily or placebo was given to 38 asthmatics on beclomethasone > 1500pg daily for six
weeks while the IHCS was reduced to half at week two and to a third at week four. While
levels of exhaled NO increased in both groups, the effects were less pronounced in the
indomethacin group and corresponded to fewer exacerbations (Tamaoki, Nakata et al. 2000).
PGE2|PGF2a -
These prostaglandins also provide negative feedback in the cyclo-oxygenase
pathway and a trial of inhaled PGE2 and PGF2a significantly reduced levels of exhaled NO in
both normal and asthmatic subjects. This was not associated with any alteration of lung
function in the normal subjects, but PGE2 caused an increase in FEVr in the asthmatic group
(Kharitonov, Sapienza et al. 1998).
9.8.9 Summnry of nitric oxide in asthma and atopy
How do we make sense of all this information regarding NO and asthmalatopy"! NO does
correlate with other clinical and inflammatory parameters of asthma -
most particularly in the
steroid narve asthmatic and most particularly with sensitivity and specificity seen with
eosinophil counts. The utilization of NO to contribute to diagnosis seems hopeful. It
performed as well as eosinophil counts in induced sputum (Smith, Cowan et al.200/.) and
methacholine or adenosine S-monophosphate challenges (Berkman, Avital et al. 2005).
However this again is best used in steroid naive patients and the effect of atopy alone in
elevating NO levels must be taken into account. It is easier to show NO differences in groups
of subjects such 'asthma', 'atopy', 'other respiratory disease' or 'controls', rather than being
able to place one individual into the correct category based on the exhaled NO reading. NO
does appear to determine current or recent symptoms and is more likely to be useful in the
individual when followed longitudindly for loss of control or response to treatment. Studies
using NO to guide treatment have shown beneficial effects. However, again eosinophils were
more sensitive and of the most benefit when these two parameters are combined @rightling,
Green et al. 2005; Pijnenburg, Bakker et al. 2005; Smith, Cowan et al. 2005; Belda,
Parameswaran et al. 2006). In medications that have anti-inflammatory effects such as the
different IHCS, leukotriene receptor antagonists, indomethacin and prostaglandins, it appears
the result is to decrease NO levels. NO remains unchanged in those without such properties as
in the LABAs. In these studies, when NO did show a reduction, this often coincided with
other clinical benefits.
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