Asthma and FeNO

Fractional exhaled nitric oxide (FeNO) is elevated in patients with asthma, and its levels decrease with treatment. According to new study results, FeNO measurements may provide a simple means of predicting steroid response in patients with difficult asthma.

"FeNO has recently gained interest as an easy-to-measure and reliable biomarker that could facilitate the assessment of asthma patients and could guide clinicians in the management of asthma thereby avoiding under- or overtreatment," write Dr L. A. Pérez-de-Llano and colleagues of the Pneumology Service, Hospital Xeral-Calde, in Lugo, Spain.

"It is known that FeNO is reduced by treatment with inhaled corticosteroids, but elevated levels of this biomarker are seen in patients with severe asthma despite corticosteroid treatment. This finding might reflect either steroid resistant inflammatory processes in the airway, or insufficient doses of anti-inflammatory medication. FeNO measurements might help identify individuals with persistent eosinophilic inflammation in which a steroid response is more likely."

In the study, 102 patients with suboptimal asthma control underwent a stepwise increase in their asthma treatment consisting of a combination of high-dose inhaled corticosteroid and long-acting β2-agonist (fluticasone/salmeterol combination) for 1 month. After having increased their medication, patients were asked to return for a second visit one month later. At the second consultation, those who remained uncontrolled received additional oral corticosteroids for another month, followed by a final examination after one month. Assessments included symptom control questionnaires, lung function testing and one measurement of exhaled nitric oxide.

At visit two, 37 patients (36.2%) had achieved control with the maximum dose of fluticasone/salmeterol combination. Of the remaining 65 patients, 16 (24.6%) gained control after 1 month of oral steroids.

At baseline, FeNO was 67±49 ppb in patients who finally achieved control, whereas it was 28±36 ppb in those who did not gain control (p<0.0001). At the end of the study, FeNO was 32±21 ppb in patients who achieved control and 16±12 ppb in those who did not (p<0.0001).

The median FeNO decreased at every visit, reflecting the fact that patients who did not achieve control showed low values of the biomarker. Over the study period, FeNO levels decreased from 28 (range 4-222) ppb to 17.5 (range 4-94) ppb (p<0.01).

"Even with various expert-derived guidelines that provide asthma treatment strategies, many patients remain suboptimally controlled. In the study, 48% of the patients did not achieve control, despite receiving the best available treatment and optimal management efforts.

The addition of oral prednisolone led to a modest 7% increase in the percentage of well-controlled patients. The most widely accepted explanation for these unsatisfactory findings is the view that the term ‘‘difficult-to-treat asthma'' might include a broad spectrum of inflammatory patterns, not always as responsive to steroids as an eosinophil-associated process could be."

In the study, FeNO was an excellent marker for predicting therapeutic response. Choosing a cut-off value of 30 ppb for FeNO, the test showed a sensitivity of 87.5% and a specificity of 90.6% for the identification of patients who will benefit from a stepwise treatment strategy to achieve control.

The authors conclude that these results suggest that this biomarker can not only identify patients with difficult-to-treat asthma, but also predict their response to oral steroids, thus proving its clinical utility.

Reference: Perez de Llano LA, et al. Eur Respir J 2010; 35: 1221-1227

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