ATS Guidelines Offer FENO Interpretation Recommendations

Nancy A. Melville

September 09, 2011

September 9, 2011 — New guidelines from the American Thoracic Society (ATS) provide clinicians with a user-friendly reference not just for the use of fractional exhaled nitric oxide (FENO), but also, importantly, for interpretation of FENO levels in the context of varying clinical settings.

In the management of airways diseases such as chronic asthma, FENO measurement offers an important advantage vs other conventional tests, such as reversibility or provocation tests involving forced expiratory volume in 1 second, which are only indirectly associated with airway inflammation, according to Raed A. Dweik, MD, chair of the guideline writing committee and professor of medicine and director of the Cleveland Clinic's Pulmonary Vascular Program in Cleveland, Ohio.

"Properly employed, FENO can offer added advantages for patient care," Dr. Dweik said in an ATS news release. "It can detect eosinophilic airway inflammation, determine likelihood of corticosteroid responsiveness, monitor airway inflammation to determine the need for corticosteroid, and reveal patient non-adherence to corticosteroid therapy."

However, use of FENO is currently only sporadic, and although the measurement for testing is standardized, interpretation of results in the clinical setting is not.

The guidelines, which are published in the September 1 issue of the American Journal of Respiratory and Critical Care Medicine, represent the writing committee's goal to provide a better framework for interpretation, Dr. Dweik noted.

"The guidelines provide a practical approach to use and interpret FENO in daily clinical practice, and will standardize the approach by which physicians and other healthcare providers utilize FENO to manage patients with airway disease," he continued.

Diagnostic Uses

In the use of FENO for diagnosis, for instance, the writing committee recommends use of the test to:

  • Diagnose eosinophilic airway inflammation; 

  • Determine the likelihood of corticosteroid responsiveness in individuals with chronic respiratory tract symptoms possibly arising from airway inflammation;

  • Support the diagnosis of asthma in situations where objective evidence is needed; and

  • Monitor airway inflammation in patients with asthma.

Recommended Cutoff Values

The committee also sets forth the following recommended cutoff points for clinical decision making:

  • An FENO level of less than 25 ppb (< 20 ppb in children) indicates that eosinophilic inflammation and responsiveness to corticosteroids are less likely; 

  • An FENO level of more than 50 ppb (> 35 ppb in children) indicates that eosinophilic inflammation and, in symptomatic patients, responsiveness to corticosteroids are likely; and

  • FENO values between 25 and 50 ppb (20 - 35 ppb in children) should be interpreted cautiously with reference to clinical context.

In addition, the guidelines recommend that clinicians consider FENO increases of 20% or more for values of more than 50 ppb, or 10 ppb more for values less than  50 ppb, to represent a significant increase from one visit to the next. Conversely, reductions of 20% (or 10 ppb) should indicate a significant response to anti-inflammatory therapy.

The committee notes that changes in FENO, even if the measurements do not achieve normal values, may be particularly useful indicators in the assessment of patients with asthma who have more than 1 factor contributing to respiratory tract symptoms, such as obesity or anxiety. Assessment of changes in FENO levels may also be beneficial before and after allergen inhalation challenge testing.

Importantly, to better understand the broader implications of FENO levels, the committee calls for more research into the interpretation of measurements in different clinical settings.

"Inclusion of FENO as an endpoint in clinical trials would be very helpful in understanding the role of FENO in monitoring response to therapy," the committee writes. "Furthermore, FENO measurement in large population-based studies like the National Health and Nutrition Examination Survey (NHANES) would provide more information on normative values."

Some of the study authors have disclosed various financial relationships with Critical Therapeutics, Genentech, Merck, GlaxoSmithKline, Sepracor, Aerocrine and Apieron (makers of FENO measuring equipment), Asthmatx, Hope Pharmaceuticals, Ikaria, AstraZeneca Sweden, and/or Aerocrine AB. One of the study authors has received royalties from book publishers.

Am J Respir Crit Care Med. 2011;184:602-615.

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