Managing Asthma in Pregnancy (MAP) trial: FENO levels and childhood asthma

Matthew Morten, Adam Collison, Vanessa E Murphy, Daniel Barker, Christopher Oldmeadow, John Attia, Joseph Meredith, Heather Powell, Paul D Robinson, Peter D Sly, Peter G Gibson, Joerg Mattes

The single-centre double-blind, randomised controlled Managing Asthma in Pregnancy (MAP) trial in Newcastle, Australia, compared a treatment algorithm using the fraction of exhaled nitric oxide (FeNO) in combination with asthma symptoms (FeNO group) against a treatment algorithm using clinical symptoms only (clinical group) in pregnant asthmatic women (ANZ Clinical Trials Registry, number 12607000561482). The primary outcome was a 50% reduction in asthma exacerbations during pregnancy in the FeNO group. However, the effect of FeNO-guided management on the development of asthma in the offspring is unknown. We sought to investigate the effect of FeNO-guided asthma management during pregnancy on asthma incidence in childhood. 179 mothers consented to participate in the Growing Into Asthma (GIA) double-blind follow-up study with the primary aim to determine the effect of FeNO-guided asthma management on childhood asthma incidence. 140 children (78%) were followed up at 4 to 6 years of age. FeNO-guided as compared to symptoms only based approach significantly reduced doctor diagnosed asthma (25·9% versus 43·2%; odds ratio [OR] 0.46, 95% confidence interval [CI] 0.22 to 0.96, p=0.04). Furthermore frequent wheeze (OR 0.27; CI 0.09 to 0.87, p=0.03), use of short-acting beta agonists (OR 0.49; CI 0.25 to 0.97; p=0.04), and emergency department visits for asthma (OR 0.17, CI 0.04 to 0.76; p=0.02) in the past 12 months were less common in children born to mothers from the FeNO group. Doctor diagnosed asthma was associated with common risk alleles for early-onset asthma at gene locus 17q21 (p=0·01 for rs8069176; p=0·03 for rs8076131), and higher airways resistance (p=0·02) and FeNO levels (p=0·03). A causal mediation analysis suggested natural indirect effects of FeNO-guided asthma management on childhood asthma through "any use" and "time to first change in dose" of inhaled corticosteroids during the MAP trial (OR 0.83; CI 0.59 to 0.99 and OR 0.90, CI 0.70 to 1.03, respectively). FeNO-guided asthma management during pregnancy prevented doctor diagnosed asthma in the offspring at preschool age, in part mediated through changes in use and dosing of inhaled corticosteroids during the MAP trial.