Exhaled nitric oxide is decreased by bronchoconstriction: An effect of airflow velocity in the airways
Ho LP., Wood F., Robson A., Innes JA., Greening AP.
Exhaled NO in asthmatics is raised compared to normal subjects and it has been suggested that this measurement may be used as a non invasive method to monitor airway inflammation or response to treatment. We have noted annecdotally that patients with acute exacerbation of athma did not have substantially higher levels of exhaled NO. We therefore hypothesized that exhaled NO levels using currently accepted methods may be affected by the diameter of the airways. Methods: 10 steroid naive asthmatics (mean age 42y, mean FEV1 93%) and 10 randomly chosen asthmatics from our asthma database (on variable amounts of inhaled steroids, mean FEV1 83%, mean age 40.4y) were recruited. For the first group, exhaled NO was measured and FEV1 performed on the same day. For the second 10, exhaled NO was measured before and after histamine challenge (immediately after reaching PC20). In 4 of the 10, exhaled NO was also measured after FEV1 returned to basal levels with nebulised Salbutamol. NO was measured using single exhalation method with a chemiluminscence analyser (LR2000) at a constant flow rate and mouth pressure. Results: There was a strong corrleation between absolute FEV1 (but not % predicted FEV1) and exhaled NO in the steroid naive asthmatics (r=0.9, p<0.001, Pearson Product Moment Correlation test). In the second group, mere was a significant decrease in exhaled NO after histamine challenge (mean: 14.7 ppb (pre) v 11.6 ppb (post), p=0.001, paired t-test). There was decrease in NO in all subjects. In the 4 subjects who received a bronchodilator, exhaled NO returned to pre histamine challenge levels. Conclusion: The diameter of the airways affects the level of exhaled NO. This could be because the method of NO analysing requires a constant exhalation flow rate in all subjects in order to standardise measurements. In order to achieve the same flow rate, air flow velocity in narrower airways is increased and thus greater than that in the wider airways. For the faster airflow, there is less opportunity to remove NO produced by the airways, resulting in lower concentration of NO in the exhaled air. Thus, NO levels in exhaled breath of conditions affected by change in airways diameter may not reflect NO production in the lower airways. This may confound the use of exhaled NO as a marker of airways inflammation in asthma.