• Pulmonary Clinical Trials
• Asthma
• Pregnancy

Asthma exacerbations during pregnancy declined 50% in patients who were managed by a clinical algorithm that was guided by exhaled nitric oxide. Peter Gibson, MD, University of Newcastle, New South Wales, Australia, reported the results of the Managing Asthma in Pregnancy (MAP) trial.

The time to first exacerbation was significantly prolonged in patients who were managed by the fraction of exhaled nitric oxide (F_ENO) algorithm, associated with a hazard ratio of 0.565, compared with the control group. The proportion of patients who had at least one exacerbation was about 40% lower in the F_ENO group.

Unplanned or unscheduled clinic visits and use of oral corticosteroids also were significantly reduced by adherence to the F_ENO algorithm. More patients in the experimental arm received inhaled corticosteroids and long-acting beta agonists; however, inhaled corticosteroid dose requirements were significantly lower.

Asthma is the most common chronic illness in pregnancy, occurring in about 12% of cases. Asthma exacerbations are common during pregnancy and associated with significant maternal and fetal morbidity. Given the concern over medication use during pregnancy, a method to optimize the dosing of inhaled corticosteroids would be helpful in clinical management.

Treatment that is based on sputum eosinophil count has been shown to reduce asthma exacerbations, and F_ENO is a marker of airway eosinophilia and inflammation [Petsky H. Cochrane Rev 2008]. However, studies of F_ENO-guided management have yielded equivocal results, said Prof. Gibson. Continuing the evaluation of F_ENO-guided asthma management, investigators designed a randomized trial to assess the value of an algorithm in pregnancy. They enrolled asthmatic women between gestational weeks 12 and 20.

All patients on maintenance inhaled corticosteroids were switched to an equivalent dose of budesonide, and patients with unstable disease status began treatment with budesonide. Randomization occurred at the second clinic visit. Thereafter, patients in the F_ENO and control groups underwent the same evaluation at each clinic visit: F_ENO, spirometry, asthma control by Asthma Control Questionnaire (ACQ), and optimization of asthma self-management.

Patients in the control group were managed according to clinical guidelines. The remaining patients were managed by use of a validated algorithm, comprising F_ENO and ACQ [Gibson PG. Clin Exp Allergy 2009]. The algorithm was used to adjust the budesonide dose in response to changes in F_ENO, and a long-acting beta agonist (LABA) was used for symptom management in the absence of elevated F_ENO.

The algorithm comprises five steps:

1. F_ENO >29 parts-per-billion (ppb): Increase inhaled corticosteroid dose by one step

2. F_ENO 16–29 ppb, ACQ ≤1.5: No change

3. F_ENO 16–29 ppb, ACQ >1.5: Increase LABA dose by one step

4. F_ENO <16 ppb, ACQ >1.5: Decrease inhaled steroid dose by one step, increase LABA dose by one step

5. F_ENO <16, ACQ ≤1.5: Reduce inhaled steroid dose by one step

The study involved 220 patients, 203 of whom completed the trial. The two groups were similar with respect to baseline characteristics, including FEV₁ and use of inhaled corticosteroids. The primary outcome was the sum of moderate and severe asthma exacerbations during pregnancy. Exacerbations consisted of unscheduled visits to a doctor, visits to an emergency department, hospital admission, and oral steroid use for asthma control.

When the trial ended, the F_ENO group had an incidence rate ratio of 0.499 versus the control group (p=0.001). In the control group, 40% of patients had at least one asthma exacerbation during pregnancy, compared with 25% in the F_ENO group (p=0.011). The number-needed-to-treat was 6, meaning that for every 6 pregnant women with asthma who were managed by this algorithm, then 1 had an asthma exacerbation that was prevented.

Analysis of the individual types of exacerbations showed no difference in hospital admission or visits to an emergency department or labor ward. Patients in the control group had a significantly higher rate of unplanned or unscheduled clinic visits (p=0.002), and significantly more patients required oral steroids as compared with the FENO group (p=0.04). The algorithm was associated with a significantly lower daily dose requirement of inhaled corticosteroids (p=0.043).

“Asthma exacerbations during pregnancy can be significantly reduced by the use of a validated F_ENO-based treatment algorithm,” said Prof. Gibson. “Future work should investigate the application of this algorithm in routine antenatal care and other settings.”

• © 2011 MD Conference Express