Effect of β₂-agonist treatment and spirometry on exhaled nitric oxide in healthy children and children with asthma

We set out to determine the effect of spirometry and bronchodilator therapy on exhaled nitric oxide (FE_NO) values in children. We hypothesized that there will be no difference on FE_NO values pre- and postspirometry and following bronchodilator therapy. Sixteen children [(mean = 14.4 ± 1.2 years; range, 12-18 years; healthy controls (n = 6); asthmatics on inhaled steroids (n = 5); and asthmatics on no steroids (n = 5)] had exhaled nitric oxide (FE_NO) measurements on 4 consecutive days as follows: pre- and postspirometry (day 1); pre- and postalbuterol metered dose inhaler (MDI) therapy (day 2); pre- and postspirometry and albuterol MDI therapy (day 3); and pre- and postspirometry and placebo MDI (day 4). FE_NO was measured with a chemiluminescence analyzer, using the single vital capacity exhalation technique at an exhalation flow of 50 mL/sec. There were no statistically significant differences in FE_NO values pre- and poststudy maneuvers under all experimental conditions in healthy children. However, in healthy children, clinically relevant (>10%) differences from baseline were observed on day 1 (3-18 min) and day 4 at 18 min. In children with asthma, FE_NO values increased significantly by 11-19% from pretreatment levels at 8 and 18 min, postbronchodilator on day 2, and 12-17% at 8 and 18 min postbronchodilator and spirometry on day 3. Spirometry and treatment with a placebo (day 4) resulted in a decrease in FE_NO values by 11% at 3 min postbaseline in patients on inhaled steroids. The changes observed were similar in children on vs. off inhaled steroids, and also in well-controlled vs. poorly controlled asthma. We conclude that FE_NO values should be obtained consistently either pre- and at a specific time postalbuterol treatment or spirometry. Alternatively, changes in FE_NO values should be interpreted in relationship to the timing of these maneuvers.