Background: Exhaled nitric oxide provides a convenient, non-invasive insight into airway inflammation. However it is suppressed by current smoking, reducing its potential as an endpoint in studies of smokers with asthma, a group with increased symptoms and poor clinical responses to corticosteroids. We examined extended nitric oxide analysis as some derived variables are thought to be unaffected. Therefore this approach could reveal hidden inflammation and enable its use as an exploratory endpoint in this group.
Methods: Smokers (n = 22) and never smokers (n = 21) with asthma performed exhaled nitric oxide measurements and spirometry before and after two weeks of oral dexamethasone (6 mg/1.74 m(2)/day). Linear and non-linear nitric oxide analysis was performed to derive estimates for alveolar nitric oxide (C(alv)) and nitric oxide flux (J'(aw)) for each subject.
Results: FE(NO50) was significantly lower in smokers with asthma and did not change significantly in response to dexamethasone. C(alv) derived by linear modelling was lower in smokers with asthma and did not change significantly in response in either group. J'(aw) was substantially lower in smokers with asthma (smokers (median (IQR)); 573 pl/s (217, 734), non-smoker; 1535 pl/s (785, 3496), p = 0.001) and was reduced in both groups following dexamethasone (non-smokers change (mean (95% CI)); -743.3 pl/s (-1710, -163), p = 0.005, smokers; -293 pl/s (-572, -60), p = 0.016). Correction for axial flow did not substantially change the derived results.
Conclusions: Bronchial NO flux appears to be sensitive to oral dexamethasone and may provide a useful exploratory endpoint for the analysis of novel anti-inflammatory therapies in smokers with asthma.
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