The number of asthma exacerbations was cut in half among pregnant women when treatment decisions were guided by measurements of their fraction of exhaled nitric oxide (FENO), a randomized trial found. The rate of exacerbations was 0.288 per pregnancy in a group of women who had routine testing of FENO, and doses of inhaled steroids and long-acting β-agonists adjusted according to the results, reported Peter G. Gibson, MBBS, of the University of Newcastle in New South Wales, Australia, and colleagues. In contrast, women in a control group whose treatment was guided by clinical symptoms had 0.615 exacerbations per pregnancy, giving an incidence rate ratio of 0.496 (95% CI 0.325 to 0.755, P=0.001), the group reported in the Sept. 10 issue of The Lancet. Action Points  

• Explain that the number of asthma exacerbations was halved among pregnant women when treatment decisions were guided by measurements of their fraction of exhaled nitric oxide (FENO).
• Note that the number needed to treat using the FENO-based algorithm was six to prevent one woman from having an exacerbation.

Disease exacerbations in pregnant women can have deleterious effects on both mother and baby, leading to increased healthcare use and low birth weight.

Patients with asthma have higher levels of exhaled nitric oxide, reflecting an inflammatory state in the airways.

Previous studies evaluating FENO for asthma management have had inconsistent results, which may have related to the overall complexity of treatment algorithms.

So Gibson and colleagues designed an asthma treatment algorithm specific for use in pregnancy, testing it in a double-blind trial that enrolled 220 women before 22 weeks of gestation.

The treatment algorithm involved using FENO concentration to determine the dose of inhaled budesonide, with dose lowering when the concentration of nitric oxide fell below 16 parts per billion, and upward titration if the concentration exceeded 29 parts per billion.

The steroid dose could be adjusted up from 100 μg twice per day to 800 μg twice per day, with a long-acting β-agonist added. Doses increased depending on symptom scores on an asthma control questionnaire.

Scores on this questionnaire below 0.75 represented well controlled asthma and scores above 1.5 indicated uncontrolled asthma.

At baseline, participants’ mean age was 28, and median symptom score was 0.85.

Their mean forced expiratory volume in one second (FEV1) was approximately 95% of predicted, with a ratio of FEV1 to forced vital capacity of just under 80%.

During the two years prior to their pregnancy, 11% of the women had needed emergency department care and 19% had required oral corticosteroid treatment.

A total of 42% were using inhaled steroids at baseline.

Exacerbations occurred in 25% of women in the active treatment group and in 41% of controls (P=0.011). The number needed to treat was six to prevent one woman from having an exacerbation.

In general, the exacerbations were moderate in severity, with mean symptom scores rising to 2.02 and 1.97 in the treatment and control groups, respectively.

Patients in the active treatment group made fewer unplanned physician visits (P=0.002), fewer needed oral corticosteroids (P=0.042), none required hospital admission (P=1.0), and fewer made a visit to the ER (P=0.399).

In contrast, control patients used short-acting β2-agonists more often (one day per week versus zero, P=0.024).

Adjusted health-related quality of life by the end of the study, as measured on the Short Form-12 mental summary, was significantly higher in the FENO group (P=0.037).

Asthma-specific quality of life scores were low in both groups by the end of the study.

The treatment algorithm based on FENO measurement led to a markedly different treatment pattern, according to the researchers, with more women using inhaled steroids — but at lower doses — and often in conjunction with a long-acting β-agonist.

Mean dose of the inhaled steroid was 200 μg per day in the FENO group, with a range of zero to 400 μg, compared with a mean of zero in the control group and a range of zero to 800 μg.

Substantially more of the FENO group used inhaled steroids (68.5% versus 42.2%, P<0.001) and long-acting β-agonists (40.5% versus 17.4%, P<0.0001) by the end of the study period.

“This different treatment profile is consistent with present advice in asthma management guidelines that promote greater use of inhaled corticosteroid, at lower doses, and the earlier introduction of a long-acting β2-agonist,” wrote Gibson and colleagues.

The study was not powered to detect differences in perinatal outcomes, but median birth weights were higher in the active treatment group (3,520 g versus 3,460 g) and there were six preterm deliveries compared with nine in the control group.

Moreover, there were significantly fewer neonatal hospitalizations with FENO-based management (8% versus 18%, P=0.046).

In a comment accompanying the study, Stanley J. Szefler, MD, of the University of Colorado in Denver, described the findings as “remarkable.”

The study, wrote Szefler, “should prompt a reassessment of the conventional approach to management of asthma in pregnancy and a reassessment of techniques to apply exhaled nitric oxide measurements to clinical practice.”

The study was funded by the National Health and Medical Research Council of Australia.

One author disclosed receiving travel reimbursements from GlaxoSmithKline, AstraZeneca, Novartis, and Boehringer Ingelheim. A second author has received lecture fees from Aerocrine AB.