ArticlesManagement of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: a double-blind, randomised controlled trial
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, 8, 9, 10, 11
Studies using the fraction of exhaled nitric oxide (FENO) to guide therapy have shown variable benefit,10, 11, 12, 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 FENO-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 FENO compared with a clinical algorithm for the primary study outcome of asthma exacerbations.
Section snippets
Study design and participants
We undertook a double-blind, parallel, randomised controlled trial of FENO-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 was confirmed by a
Results
Figure 1 shows the trial profile. We recruited 242 women and randomly assigned 220, of whom 203 completed the study. Women had a mean age of 28 years (SD 5·4), 80 (39%) were past smokers with a mean smoking history of 4·5 pack-years (SD 5·2), 156 of 206 (76%) were atopic, and the mean gestational age was 16·1 weeks (SD 2·6). At enrolment, mean FEV1 was 95·1% (13·9) predicted, the ratio of FEV1 to forced vital capacity (FVC) was 79·6% (7·4), and median ACQ score was 0·85 (IQR 0·29–1·14). In the
Discussion
In this randomised controlled trial of inflammatory marker-based management of asthma in pregnancy, we have shown that a treatment algorithm based on FENO and ACQ score led to a significant reduction in asthma exacerbations and less use of β2 agonist compared with a clinical algorithm. These benefits occurred because the FENO treatment algorithm was associated with a different profile of maintenance asthma treatment, with inhaled corticosteroids being used by more women, but at a lower average
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