Matthew Morten1, Adam Collison1, Vanessa E Murphy1, Daniel Barker2, Christopher Oldmeadow2, John Attia2, Joseph Meredith3, Heather Powell4, Paul D Robinson5, Peter D Sly6, Peter G Gibson7, Joerg Mattes8. 1. Priority Research Centre GrowUpWell, University of Newcastle, Newcastle, Australia; Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, Australia. 2. Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, Australia. 3. Priority Research Centre GrowUpWell, University of Newcastle, Newcastle, Australia; Department of Paediatric Respiratory and Sleep Medicine, John Hunter Children's Hospital, Newcastle, Australia. 4. Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, Australia; Priority Research Centre for Healthy Lungs, University of Newcastle, Newcastle, Australia. 5. Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, Australia. 6. Child Health Research Centre, The University of Queensland, South Brisbane, Australia. 7. Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, Australia; Priority Research Centre for Healthy Lungs, University of Newcastle, Newcastle, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, Australia. 8. Priority Research Centre GrowUpWell, University of Newcastle, Newcastle, Australia; Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, Australia; Department of Paediatric Respiratory and Sleep Medicine, John Hunter Children's Hospital, Newcastle, Australia. Electronic address: Joerg.mattes@newcastle.edu.au.
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.
RCT Entities:
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.
Authors: Katie M Lebold; Matthew G Drake; Alexandra B Pincus; Aubrey B Pierce; Allison D Fryer; David B Jacoby Journal: Am J Respir Cell Mol Biol Date: 2022-07 Impact factor: 7.748
Authors: Katie M Lebold; Matthew G Drake; Lauren B Hales-Beck; Allison D Fryer; David B Jacoby Journal: Am J Respir Cell Mol Biol Date: 2020-04 Impact factor: 6.914
Authors: Gabriela Martins Costa Gomes; Patricia de Gouveia Belinelo; Malcolm R Starkey; Vanessa E Murphy; Philip M Hansbro; Peter D Sly; Paul D Robinson; Wilfried Karmaus; Peter G Gibson; Joerg Mattes; Adam M Collison Journal: Clin Transl Immunology Date: 2021-07-21
Authors: Patricia de Gouveia Belinelo; Aleisha Nielsen; Bernadette Goddard; Lauren Platt; Carla Rebeca Da Silva Sena; Paul D Robinson; Bruce Whitehead; Jodi Hilton; Tanya Gulliver; Laurence Roddick; Kasey Pearce; Vanessa E Murphy; Peter G Gibson; Adam Collison; Joerg Mattes Journal: BMC Pulm Med Date: 2020-03-18 Impact factor: 3.317