DUNEDIN, NEW ZEALAND—A confirmed marker for airway inflammation, exhaled nitric oxide (eNO) can also predict loss of control of asthma symptoms and may be useful in optimizing anti-inflammatory therapy. D. Robin Taylor, MD, and coauthors demonstrated that eNO is as good a predictor of loss of asthma control as are induced-sputum eosinophil count and airway hyperresponsiveness to hypertonic saline challenge.[1]

“The value of our study is that it shows that eNO gives a very comparable assessment of airway inflammation to other measures that are much more difficult to perform in the clinic,” Dr. Taylor told RESPIRATORY REVIEWS. “Measurement of eNO is easily performed in a clinical respiratory lab, and it’s repeatable, with very acceptable variation. A patient takes in a breath to total lung capacity, … exhales into a sampling tube, and the machine measures NO in real time,” said Dr. Taylor, Associate Professor of Respiratory Medicine at Dunedin School of Medicine.

Dr. Taylor and colleagues studied 78 patients with asthma adequately controlled with inhaled corticosteroids. By withdrawing corticosteroid treatment until a patient experienced loss of control or for a maximum of six weeks, the researchers could compare changes in weekly eNO measurements between those who did and those who did not lose control. Criteria for loss of control included a fall in peak expiratory flow rate (PEFR), increased daily bronchodilator use, or asthma symptoms that either resulted in more frequent nocturnal wakening or otherwise distressed a patient. Each patient recorded diurnal PEFR, bronchodilator use, and symptom scores daily. Spirometry and eNO measurements were performed weekly. Responsiveness to hypertonic saline and sputum eosinophils were measured before and at the end of the study.

Changes in eNO measurements correlated positively with asthma symptom scores, forced expiratory volume in one second (FEV1), eosinophil counts, and airway hyperresponsiveness to saline. Between first and last visits, the 60 patients (77.9%) who experienced loss of control following inhaled corticosteroid withdrawal showed a significantly greater increase in eNO than those who did not show loss of control (2.16-fold vs 1.44-fold). Increases in sputum eosinophil counts also differed between patients with and without loss of control (4.73-fold vs 2.05-fold), as did mean cumulative dose of saline required to produce a 15% drop in FEV1 on the final visit (6.2 mL vs 14.0 mL).

Notably, eNO on the first visit had a positive predictive value (PPV) for loss of control of 79% to 88%, quite comparable to PPVs of 80% and 77%, respectively, for sputum eosinophil counts and saline challenges. “NO wasn’t really better [than these tests] at predicting [loss of control], but it was fantastically better in practical terms,” Dr. Taylor remarked. “In our hands we would be able to say that if a patient had an eNO level of 15 ppb or greater, inflammation was likely to be active; we are now using this information to guide dose adjustments with inhaled corticosteroids in selected patients,” he concluded.

—Mimi Zucker, PhD