Articles www.thelancet.com Vol 378 September 10, 2011 983 Lancet 2011; 378: 983–90 See Comment page 963 Centre for Asthma and Respiratory Diseases, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia (H Powell MMedSc, V E Murphy PhD, Prof M J Hensley PhD, Prof P G Gibson MBBS); Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia (H Powell, Prof M J Hensley, Prof P G Gibson); Dunedin School of Medicine, University of Otago, Dunedin, New Zealand (Prof D R Taylor MD); Public Health, University of Sydney, Sydney, NSW, Australia (K McCaffery PhD, Prof W Giles PhD); Royal North Shore Hospital, Sydney, NSW, Australia (Prof W Giles); Robinson Institute, Department of Obstetrics and Gynaecology, University of Adelaide, SA, Australia (V L Clifton PhD); and Woolcock Institute of Medical Research, Sydney, NSW, Australia (Prof P G Gibson) Correspondence to: Ms Heather Powell, Centre for Asthma and Respiratory Diseases, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW 2310, Australia heather.powell@hnehealth. nsw.gov.au Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: a double-blind, randomised controlled trial Heather Powell, Vanessa E Murphy, D Robin Taylor, Michael J Hensley, Kirsten McCaffery, Warwick Giles, Vicki L Clifton, Peter G Gibson Summary Background Asthma exacerbations during pregnancy are common and can be associated with substantial maternal and fetal morbidity. Treatment decisions based on sputum eosinophil counts reduce exacerbations in non-pregnant women with asthma, but results with the fraction of exhaled nitric oxide (F E NO) to guide management are equivocal. We tested the hypothesis that a management algorithm for asthma in pregnancy based on F E NO and symptoms would reduce asthma exacerbations. Methods We undertook a double-blind, parallel-group, controlled trial in two antenatal clinics in Australia. 220 pregnant, non-smoking women with asthma were randomly assigned, by a computer-generated random number list, before 22 weeks’ gestation to treatment adjustment at monthly visits by an algorithm using clinical symptoms (control group) or F E NO concentrations (active intervention group) used to uptitrate (F E NO >29 ppb) or downtitrate (F E NO <16 ppb) inhaled corticosteroid dose. Participants, caregivers, and outcome assessors were masked to group assignment. Longacting β2 agonist and minimum dose inhaled corticosteroid were used to treat symptoms when F E NO was not increased. The primary outcome was total asthma exacerbations (moderate and severe). Analysis was by intention to treat. This study is registered with the Australian and New Zealand Clinical Trials Registry, number 12607000561482. Findings 111 women were randomly assigned to the F E NO group (100 completed) and 109 to the control group (103 completed). The exacerbation rate was lower in the F E NO group than in the control group (0·288 vs 0·615 exacerbations per pregnancy; incidence rate ratio 0·496, 95% CI 0·325–0·755; p=0·001). The number needed to treat was 6. In the F E NO group, quality of life was improved (score on short form 12 mental summary was 56·9 [95% CI 50·2–59·3] in F E NO group vs 54·2 [46·1–57·6] in control group; p=0·037) and neonatal hospitalisations were reduced (eight [8%] vs 18 [17%]; p=0·046). Interpretation Asthma exacerbations during pregnancy can be significantly reduced with a validated F E NO-based treatment algorithm. Funding National Health and Medical Research Council of Australia. Introduction Asthma is the most common chronic medical disorder to complicate pregnancy, and both mothers and health professionals expect asthma to be controlled with minimum drug exposure to the developing fetus. 1 Asthma exacerbations are frequent in pregnant women, even when the asthma is considered to be mild, 2 and can lead to low birthweight babies, 2 maternal distress, and increased health-care use. 3 Maintenance treatment with inhaled corticosteroids can effectively reduce the frequency and severity of asthma exacerbations. 4,5 Inhaled corticosteroid therapy is started and dose adjustments are made on the basis of measures of asthma control (the assessment of symptoms and lung function). Although inhaled corticosteroids treat airway inflammation, the relation between these measures of asthma control and airway inflammation is poor. 6 However, when therapy is adjusted according to direct measures of airway inflammation, results improve. 7–11 Studies using the fraction of exhaled nitric oxide (F E NO) to guide therapy have shown variable benefit, 10–13 possibly because of the complex design issues related to studies of asthma treatment algorithms. 14 In the Managing Asthma in Pregnancy (MAP) study, we developed an improved F E NO-based treatment algorithm and tested its applicability for the adjustment of therapy for asthma during pregnancy. We tested the hypothesis that control of asthma in pregnancy would be improved when based on measures of F E NO compared with a clinical algorithm for the primary study outcome of asthma exacerbations. Methods Study design and participants We undertook a double-blind, parallel, randomised controlled trial of F E NO-guided therapy in two antenatal clinics (John Hunter Hospital and Maitland Hospital; NSW, Australia) from June, 2007, to December, 2010. Non-smoking pregnant women (aged >18 years) with asthma attending the antenatal clinics were recruited between weeks 12 and 20 of gestation. Women had a doctor’s diagnosis of asthma and were using inhaled therapy for asthma within the past year. The diagnosis