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Journal of Allergy and Clinical Immunology

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Managing Asthma in Pregnancy (MAP) trial: FENO levels and childhood asthma - 06/12/18

Doi : 10.1016/j.jaci.2018.02.039 
Matthew Morten, PhD a, b, c, Adam Collison, PhD a, b, c, Vanessa E. Murphy, PhD a, b, c, Daniel Barker, PhD b, c, Christopher Oldmeadow, PhD b, c, John Attia, PhD b, c, Joseph Meredith, BMed a, e, Heather Powell, MMedSci b, c, d, Paul D. Robinson, BMed, PhD f, Peter D. Sly, MD, DSc g, Peter G. Gibson, MBBS b, c, d, h, Joerg Mattes, MD, PhD a, b, c, e, ⁎
a Priority Research Centre GrowUpWell, University of Newcastle, Newcastle, Australia 
d Priority Research Centre for Healthy Lungs, University of Newcastle, Newcastle, Australia 
b Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia 
c School of Medicine and Public Health, University of Newcastle, Newcastle, Australia 
e Department of Paediatric Respiratory and Sleep Medicine, John Hunter Children's Hospital, Newcastle, Australia 
f Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, Australia 
g Child Health Research Centre, The University of Queensland, South Brisbane, Australia 
h Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, Australia 

∗Corresponding author: Joerg Mattes, MD, PhD, University of Newcastle, Discipline of Paediatrics, Lot 1, Kookaburra Court, New Lambton Heights, HMRI Building Level 2 East, Newcastle, New South Wales 2305, Australia.University of NewcastleDiscipline of PaediatricsLot 1, Kookaburra Court, New Lambton Heights, HMRI Building Level 2 EastNewcastleNew South Wales2305Australia

Abstract

Background

The single-center double-blind, randomized 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 (Australian New Zealand Clinical Trials Registry, no. 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.

Objective

We sought to investigate the effect of FENO-guided asthma management during pregnancy on asthma incidence in childhood.

Methods

A total of 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.

Results

A total of 140 children (78%) were followed up at 4 to 6 years of age. FENO-guided as compared to symptoms-only approach significantly reduced doctor-diagnosed asthma (25.9% vs 43.2%; odds ratio [OR], 0.46, 95% CI, 0.22-0.96; P = .04). Furthermore, frequent wheeze (OR, 0.27; 95% CI, 0.09-0.87; P = .03), use of short-acting β-agonists (OR, 0.49; 95% CI, 0.25-0.97; P = .04), and emergency department visits for asthma (OR, 0.17; 95% CI, 0.04-0.76; P = .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 = .01 for rs8069176; P = .03 for rs8076131), and higher airways resistance (P = .02) and FENO levels (P = .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; 95% CI: 0.59-0.99, and OR: 0.90; 95% CI: 0.70-1.03, respectively).

Conclusions

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.

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Key words : Childhood asthma, pregnancy, asthma management, exhaled nitric oxide, asthma genetics

Abbreviations used : COAST, FENO, GIA, ICS, IQR, MAP, OR, ORMDL3, RCT


Plan


 This research project was supported by an Asthma Australia scholarship to M.M., Hunter Medical Research Institute pilot project funding, a National Health and Medical Research Council project grant (G1400050), and the University of Newcastle.
 Disclosure of potential conflict of interest: V.E.M. reports grants from Hunter Medical Research Institute, National Health and Medical Research Council, the University of Newcastle, and Hunter Children's Research Foundation during the conduct of the study; and grants from Rebecca L Cooper Foundation, the John Hunter Hospital Charitable Trust, National Health and Medical Research Council, the University of Newcastle, and from Hunter Medical Research Institute outside the submitted work. P.G.G. reports grants from Australian Government and National Health and Medical Research Council during the conduct of the study; as well as grants and personal fees from AstraZeneca and GlaxoSmithKline outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.


© 2018  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 142 - N° 6

P. 1765 - décembre 2018 Retour au numéro
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