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group. Rates of exacerbation were 0.49 episodes/patient/year in the exhaled No managed
group and 0.90 in the guideline group, representin g a 45.6Vo exacerbation reduction in the No
group, although this did not reach significance. There were no significant differences in
pulmonary function changes, sputum eosinophils or the use of oral prednisone (Smith' Cowan
et al. 2005). Similar to the adult study, children on IHCS were allocated to groups where
treatment decisions were made by symptomatology in 46 or with the addition of exhaled No
in 39. Over the next year, those monitored using the NO readings had improved airway hyper-
responsiveness from 2.5 to 1.1 doubling dose, lesS Severe exacerbations at eight versus 18',
and a trend to improved FEVr (Pijnenburg, Bakker et al. 2005). These studies suggest that No
can successfully be used longitudinally for individual patients to predict exacerbations and to
aid management deci sions re gardin g treatment'
9.8.6 Wat happens to nitric oxide during an acute asthma attack?
Most studies have examined NO levels during chronic asthma disease over time' So what
happens to NO levels in the acute phase? Studies have used allergen challenges to simulate an
acute asthmatic exacerbation. It appears that even when the No is similar in the asthmatic and
control groups at baseline, No increases in the asthmatic groups during the late asthmatic
reaction (Obata, Dittrick et al. 1999; Paredi, Irckie et al' 1999; Khatri' Hammel et al' 2003;
Ihre, Gyllfors et al. 2006). It was found to increase three fold from baseline 24 hours post
challenge (Khatri, Hammel et al. 2003). Repeated low dose allergen inhalation in 8 mild
asthmatic subjects demonstrated an increased exhaled NO despite no change seen in asthma
symptoms or lung function (Ihre, Gyllfors et al. 2006)' These findings suggest that in acute
asthma an increased production requiring synthesis of the NOS enzymes occulred and
therefore some time was needed to appreciate the full insult (Khatri, Hammel et al' 2003)'
This may also explain why the use of No to dictate treatment acutely has been less successful'
one study used the exhaled No levels to dictate the degree of treatment given to adult
patients presenting to the emergency department with an asthma exacerbation' The study was
discontinued after the first 53 enrolled subjects as those in whom the management offered was
decided on their exhaled NO levels did less well when followed up than those in whom the
management was decided by the more traditional measures of clinical scores or spirometry
(Gill, Walker et al. 2005).
g.8.7 What is the effect of atopy alone on nitric oxide?
In assessing the validity of exhaled No to assist in screening, diagnosis and longitudinal
monitoring of asthma control, the effect of atopy alone must be taken into account' A number
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