KEYSTONE, COLO. – Fractional exhaled nitric oxide as a tool for patient care in pediatric asthma has often gotten a bad rap, according to a long-time researcher in the field.
"You’re either an exhaled nitric oxide fan or you’re not, it seems like, in the medical community. Some people expect it to be all things when in fact it’s just one measure. It measures atopic eosinophilic inflammation. We know that asthma is more than one disease, so we need more than one tool. This is a tool that’s useful in a subgroup of asthmatics, but I think the subgroup it’s useful in is big enough that it’s a valuable tool," Dr. Joseph D. Spahn declared at a meeting on allergy and respiratory diseases sponsored by National Jewish Health.
Dr. Joseph D. Spahn
The pediatric allergist published his first study demonstrating the clinical benefits of measuring fractional exhaled nitric oxide (FeNO) well before the technology won Food and Drug Administration approval and became commercially available.
An American Thoracic Society clinical practice guideline addressing the clinical utility of the test was a long time coming. Finally, several years ago, the ATS issued an official guideline declaring "FeNO offers added advantages for patient care" over conventional tests for asthma, such as FEV1 [forced expiratory volume in 1 second] reversibility and provocation tests (Am. J. Respir. Crit. Care Med. 2011;184:602-15).
The guideline describes three major clinical uses for FeNO testing: diagnosing asthma, predicting response to inhaled corticosteroids, and monitoring adherence to this cornerstone therapy.
FeNO’s role in diagnosing asthma
FeNO is significantly elevated in allergic asthma but not in other neutrophilic diseases that can masquerade as asthma, including primary immunodeficiencies, bronchopulmonary dysplasia, alpha-1antitrypsin deficiency, and cystic fibrosis, all of which feature either low or normal FeNO levels.
But it’s important to understand where the test is most likely to prove useful.
"FeNO is the only noninvasive tool we have for assessing airway inflammation. It’s a marker of atopic and Th2-driven inflammation. Many severe adult asthmatics don’t seem to have a Th2-driven disease process. Many little kids with nonatopic asthma and viral-induced wheezing don’t have Th2-driven inflammation. As a result, FeNO is not going to be a great tool in those situations. But for those individuals in which atopy plays a role, it’s a great measure of active airway inflammation," explained Dr. Spahn of the University of Colorado, Denver, and National Jewish Health.
In one representative head-to-head comparative study, a 15% or greater improvement in FEV1 in response to an inhaled corticosteroid – widely considered a gold standard test in support of a diagnosis of asthma – had a 12% sensitivity for the diagnosis, while a reduction of greater than 20 ppb in FeNO had an 88% sensitivity (Am. J. Respir. Crit. Care Med. 2004;169:473-8).
Predicting response to steroid therapy
The ATS guidelines state that symptomatic patients who present initially with a high FeNO – more than 35 ppb in children or 50 ppb in adults – are likely to benefit from a trial of inhaled corticosteroids, and that it’s appropriate to probe for allergen exposure in such patients. The guidelines further recommend that patients with a low baseline FeNO of less than 20 ppb in children or 25 ppb in adults are less likely to have eosinophilic inflammation and are unlikely to benefit from inhaled corticosteroid therapy. Consideration of a therapeutic trial with serial FeNO monitoring is recommended in patients with intermediate levels.
Years ago, Dr. Spahn and his coworkers showed in a double-blind, randomized, crossover study that FeNO values could predict whether children with mild to moderate asthma were more likely to respond to fluticasone (Flonase) or montelukast (Singulair); the higher the initial FeNO, the more likely fluticasone was the more effective option (J. Allergy Clin. Immunol. 2005;115:233-42).
Dr. Spahn also finds FeNO results helpful in combating parental steroid phobia. "Steroid phobia still exists in the pediatric world. I know we as health care providers don’t really worry about inhaled corticosteroids having significant side effects, but parents do," he observed.
He shared a story of a 10-year-old with a severe chronic cough and newly diagnosed asthma.
"This kid was extremely disabled from his cough. If you’re coughing every 30 seconds, it’s not going to be easy for you to function normally in school. But when I mentioned that he needed to be on inhaled corticosteroid therapy, the mom acted like I’d just given her kid a death sentence. So the FeNO was a tool that I used to help convince her that there was inflammation in his airways and the way to treat it was with an inhaled corticosteroid.