The link between exhaled NO and bronchomotor tone depends on the dose of inhaled steroid in asthma

Abstract

Background: Exhaled NO (FE(NO)) is a steroid dose dependent eosinophilic inflammometer, but also a mediator of bronchomotor tone, but statistically significant relationships have infrequently been obtained with pulmonary function tests (PFT). The aim was to test the hypothesis that the relationships between FE(NO) and PFT could be uncovered by inhaled corticosteroid (ICS) treatment, namely that a link between FE(NO) and bronchodilator response (an index of bronchomotor tone) would appear under ICS.

Methods: Exhaled NO, forced expiratory flows and lung volumes were measured in atopic asthmatic children without recent (one month) respiratory symptoms.

Results: Two hundred and thirty children (mean + or - SD, age: 11.2 + or - 2.5 years, 69 girls) were included (% predicted, FEV(1): 100 + or - 14; FEF(50%): 76 + or - 23; RV: 107 + or - 29). The relationship between ICS dose (GINA classification) and FE(NO) plateaued in children with an ICS dose higher than 200 microg beclomethasone equipotent daily dose: FE(NO) (median [25th-75th percentiles]), 43 ppb [15-105] (no treatment, n=65), 33 ppb [15-77] (low dose, n=70), 23 ppb [12-57] (medium dose, n=57) and 26 ppb [9-49] (high dose, n=38). Statistically significant relationships between FE(NO) and PFT were only observed in children receiving more than 200 microg/day ICS: with FEV(1) (medium ICS dose: rho=0.43, p=0.001; high dose: rho=0.32, p=0.052) and bronchodilator (400 microg salbutamol) response (medium dose: rho=0.54, p=0.001; high dose: rho=0.65, p=0.002).

Conclusions: A positive correlation between FE(NO) and bronchomotor tone appears with increasing ICS doses in atopic children with clinically controlled asthma, which further suggests that children depicting the highest FE(NO) values may have lesser steroid sensitivity.