Dose-dependent onset and cessation of action of inhaled budesonide on exhaled nitric oxide and symptoms in mild asthma.
BACKGROUND
Dose dependent anti-inflammatory effects of inhaled corticosteroids in asthma are difficult to demonstrate in clinical practice. The anti-inflammatory effect of low dose inhaled budesonide on non-invasive exhaled markers of inflammation and oxidative stress were assessed in patients with mild asthma.


METHODS
28 patients entered a double blind, placebo controlled, parallel group study and were randomly given either 100 or 400 micro g budesonide or placebo once daily, inhaled from a dry powder inhaler (Turbohaler), for 3 weeks followed by 1 week without treatment. Exhaled nitric oxide (NO), exhaled carbon monoxide (CO), nitrite/nitrate, S-nitrosothiols, and 8-isoprostanes in exhaled breath condensate were measured four times during weeks 1 and 4, and once a week during weeks 2 and 3.


RESULTS
A dose-dependent speed of onset and cessation of action of budesonide was seen on exhaled NO and asthma symptoms. Treatment with 400 micro g/day reduced exhaled NO faster (-2.06 (0.37) ppb/day) than 100 micro g/day (-0.51 (0.35) ppb/day; p<0.01). The mean difference between the effect of 100 and 400 micro g budesonide was -1.55 ppb/day (95% CI -2.50 to -0.60). Pretreatment NO levels were positively related to the subsequent speed of reduction during the first 3-5 days of treatment. Faster recovery of exhaled NO was seen after stopping treatment with budesonide 400 micro g/day (1.89 (1.43) ppb/day) than 100 micro g/day (0.49 (0.34) ppb/day, p<0.01). The mean difference between the effect of 100 and 400 micro g budesonide was 1.40 ppb/day (95% CI -0.49 to 2.31). Symptom improvement was dose-dependent, although symptoms returned faster in patients treated with 400 micro g/day. A significant reduction in exhaled nitrite/nitrate and S-nitrosothiols after budesonide treatment was not dose-dependent. There were no significant changes in exhaled CO or 8-isoprostanes in breath condensate.


CONCLUSIONS
Measurement of exhaled NO levels can indicate a dose-dependent onset and cessation of anti-inflammatory action of inhaled corticosteroids in patients with mild asthma.
D000280:Administration, Inhalation; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001944:Breath Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D002248:Carbon Monoxide / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D028421:Isoprostanes / Q000032:analysis; D008297:Male; D009330:Nebulizers and Vaporizers; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000032:analysis*; D026403:S-Nitrosothiols / Q000032:analysis
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D028421:Isoprostanes; D009566:Nitrates; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D019819:Budesonide; D002248:Carbon Monoxide