Time-Dependent Changes in Orally Exhaled Nitric Oxide and Pulmonary Functions Induced by Inhaled Cortico-steroids in Childhood Asthma

Abstract

Exhaled nitric oxide levels are elevated in asthmatic children and decrease after inhaled steroid treatment. We evaluated the time-dependent changes in fractional exhaled nitric oxide concentration (FE_NO) and pulmonary function parameters following inhaled steroid therapy. Thirty-nine steroid-naive atopic patients (age 11.92 ± 0.48 years) with mild intermittent asthma and 22 age-matched healthy controls were enrolled in the study; pulmonary functions and FE_NO levels were measured. Low doses of inhaled steroids were prescribed to all asthmatic patients who were reevaluated in a second visit (between 10 and 40 days after the beginning of the treatment). At the enrolment, asthmatic patients had similar forced expiratory volume in 1 sec (FEV₁) and forced vital capacity (FVC) values (p > 0.05) but reduced forced expiratory flows at 25–75% of the vital capacity (FEF_25–75%) values, as compared to controls (p < 0.05). In addition, FE_NO levels were significantly higher in asthmatics with respect to control subjects (30.8 ± 3.0 and 4.0 ± 0.5 ppb, respectively; p < 0.01). All asthmatics had FE_NO levels higher than 8.8 ppb (i.e., >2 standard deviations of the mean in controls). After steroid treatment, patients showed significant improvement of FEV₁, FVC, and FEF_25–75% (p = 0.0001; each comparison) and a reduction of FE_NO levels (p = 0.0001). A weak significant correlation was found between percent decrease in FE_NO levels and percent increase in FEV₁ (r = 0.33, p = 0.04) or in FEF_25–75% (r = 0.4, p = 0.01) after treatment. When changes in FE_NO levels and in pulmonary function parameters were corrected for days of treatment, significant correlations were still present between percent decrease in FE_NO levels and percent increase in FEV₁ (r = 0.57, p = 0.0004) or percent increase in FEF_25–75% (r = 0.45, p = 0.006). Sixteen of the 39 asthmatic patients were evaluated on two occasions after the beginning of treatment, at days 10 and 40. The significant reduction in FE_NO levels (p < 0.01) and the significant increase in FEV₁ and FEF_25–75% values observed (p < 0.05) after 10 days did not further improve at day 40. These data show that it is possible to demonstrate early effects of low-dose inhaled steroids in asthmatic children using objective measurements of airway caliber and inflammation.

• Airflow limitation
• Airway inflammation
• Corticosteroids