title: The Breathing for Life Trial: a randomised controlled trial of fractional exhaled nitric oxide (FENO)-based management of asthma during pregnancy and its impact on perinatal outcomes and infant and childhood respiratory health.
abstract: Asthma exacerbations are common during pregnancy and associated with an increased risk of adverse perinatal outcomes. Adjusting asthma treatment based on airway inflammation rather than symptoms reduces the exacerbation rate by 50 %. The Breathing for Life Trial (BLT) will test whether this approach also improves perinatal outcomes.
  
  
  
  BLT is a multicentre, parallel group, randomised controlled trial of asthma management guided by fractional exhaled nitric oxide (FENO, a marker of eosinophilic airway inflammation) compared to usual care, with prospective infant follow-up. Women with physician-diagnosed asthma, asthma symptoms and/or medication use in the previous 12 months, who are 12-22 weeks gestation, will be eligible for inclusion. Women randomised to the control group will have one clinical assessment of their asthma, including self-management education. Any treatment changes will be made by their general practitioner. Women randomised to the intervention group will have clinical assessments every 3-6 weeks during pregnancy, and asthma treatments will be adjusted every second visit based on an algorithm which uses FENO to adjust inhaled corticosteroid (ICS) dose (increase in dose when FENO >29 parts per billion (ppb), decrease in dose when FENO <19 ppb, and no change when FENO is between 19 and 29 ppb). A long acting beta agonist (LABA) will be added when symptoms remain uncontrolled. Both the control and intervention groups will report on exacerbations at a postpartum phone interview. The primary outcome is adverse perinatal outcome (a composite measure including preterm birth, intrauterine growth restriction, neonatal hospitalisation at birth or perinatal mortality), assessed from hospital records. Secondary outcomes will be each component of the primary outcome, maternal exacerbations requiring medical intervention during pregnancy (both smokers and non-smokers), and hospitalisation and emergency department presentation for wheeze, bronchiolitis or croup in the first 12 months of infancy. Outcome assessment and statistical analysis of the primary outcome will be blinded. To detect a reduction in adverse perinatal outcomes from 35 % to 26 %, 600 pregnant women with asthma per group are required.
  
  
  
  This trial will provide evidence for the effectiveness of a FENO-based management strategy in improving perinatal outcomes in pregnant women with asthma. If successful, this would improve the management of pregnant women with asthma worldwide.
  
  
  
  Australian New Zealand Clinical Trials Registry ACTRN12613000202763 .
authors.affiliation: Priority Research Centre GrowUpWell, University of Newcastle and Hunter Medical Research Institute, Level 2, West Wing, University Drive, Newcastle, NSW, 2308, Australia. vanessa.murphy@newcastle.edu.au.
authors.forename: Vanessa E
authors.initials: VE
authors.lastname: Murphy
authors.affiliation: Priority Research Centre GrowUpWell, University of Newcastle and Hunter Medical Research Institute, Level 2, West Wing, University Drive, Newcastle, NSW, 2308, Australia.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Jensen
authors.affiliation: Priority Research Centre GrowUpWell, University of Newcastle and Hunter Medical Research Institute, Level 2, West Wing, University Drive, Newcastle, NSW, 2308, Australia.|Paediatric Respiratory and Sleep Medicine Department, John Hunter Children's Hospital, Newcastle, NSW, Australia.
authors.forename: Joerg
authors.initials: J
authors.lastname: Mattes
authors.affiliation: Department of Respiratory and Sleep Medicine, John Hunter Hospital, Lookout Road, New Lambton Heights, Newcastle, NSW, 2305, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hensley
authors.affiliation: Department of Obstetrics and Gynaecology, Sydney Medical School Northern, University of Sydney, Royal North Shore Hospital, St Leonards, Sydney, NSW, 2065, Australia.
authors.forename: Warwick B
authors.initials: WB
authors.lastname: Giles
authors.affiliation: Sydney Medical School Nepean, University of Sydney, Nepean Hospital, PO Box 63, Penrith, NSW, 2751, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Peek
authors.affiliation: Birthing Unit, Royal Hospital for Women Randwick, Barker St, Randwick, NSW, 2031, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bisits
authors.affiliation: School of Medicine, University of Queensland, Brisbane, QLD, Australia.|Obstetric Medicine, Royal Brisbane and Women's Hospital, UQ Health Sciences Building, Butterfield St, Herston, Brisbane, QLD, 4029, Australia.
authors.forename: Leonie K
authors.initials: LK
authors.lastname: Callaway
authors.affiliation: Sydney School of Public Health, University of Sydney, Room 301F, Edward Ford Building A27, Sydney, NSW, 2006, Australia.
authors.forename: Kirsten
authors.initials: K
authors.lastname: McCaffery
authors.affiliation: School of Medicine, University of Queensland, Brisbane, QLD, Australia.|Obstetric Medicine, Royal Brisbane and Women's Hospital, UQ Health Sciences Building, Butterfield St, Herston, Brisbane, QLD, 4029, Australia.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Barrett
authors.affiliation: Perinatal Research Centre, UQCCR, University of Queensland, Butterfield St, Herston, Brisbane, QLD, 4029, Australia.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Colditz
authors.affiliation: Department of Obstetrics and Gynaecology, Sydney Medical School Northern, University of Sydney, Royal North Shore Hospital, St Leonards, Sydney, NSW, 2065, Australia.
authors.forename: Sean K
authors.initials: SK
authors.lastname: Seeho
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.affiliation: Hunter Medical Research Institute, Kookaburra Circuit, New Lambton, Newcastle, NSW, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Searles
authors.affiliation: Hunter Medical Research Institute, Kookaburra Circuit, New Lambton, Newcastle, NSW, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Doran
authors.affiliation: Department of Respiratory and Sleep Medicine, John Hunter Hospital, Lookout Road, New Lambton Heights, Newcastle, NSW, 2305, Australia.|Department of Obstetrics and Gynaecology, Sydney Medical School Northern, University of Sydney, Royal North Shore Hospital, St Leonards, Sydney, NSW, 2065, Australia.|Priority Research Centre for Healthy Lungs, University of Newcastle and Hunter Medical Research Institute, Level 2, West Wing, University Drive, Newcastle, NSW, 2308, Australia.
authors.forename: Heather
authors.initials: H
authors.lastname: Powell
authors.affiliation: Department of Respiratory and Sleep Medicine, John Hunter Hospital, Lookout Road, New Lambton Heights, Newcastle, NSW, 2305, Australia.|Department of Obstetrics and Gynaecology, Sydney Medical School Northern, University of Sydney, Royal North Shore Hospital, St Leonards, Sydney, NSW, 2065, Australia.|Priority Research Centre for Healthy Lungs, University of Newcastle and Hunter Medical Research Institute, Level 2, West Wing, University Drive, Newcastle, NSW, 2308, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001944:Breath Tests; D002985:Clinical Protocols; D045853:Exhalation / Q000502:physiology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000503:physiopathology; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D012138:Respiratory Therapy / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D009569:Nitric Oxide
keywords: Antenatal care; Asthma; Asthma management; Exacerbation; Exhaled nitric oxide; FENO; Perinatal; Pregnancy