Use of Fractional Exhaled Nitric Oxide to Guide the Treatment of Asthma: An Official American Thoracic Society Clinical Practice Guideline

Abstract

Background: The fractional exhaled nitric oxide (FE_NO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FE_NO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FE_NO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidence-based answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations. Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FE_NO-based care. In patients with asthma in whom treatment is being considered, we suggest that FE_NO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice. Conclusions: Clinicians should consider this recommendation to measure FE_NO in patients with asthma in whom treatment is being considered based on current best available evidence.

Keywords: airway disease; asthma; inhaled steroids; nitric oxide; type 2 inflammation.

Figure 1.

Flowchart summarizing the workflow for the systematic review of the literature to identify studies relevant to this single-question guideline. The methodologists used an existing comparative-effectiveness review as a starting point for the systematic review, which was conducted by using relevant databases. The flowchart that overviews the inclusion and exclusion criteria is presented in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format. AHRQ = Agency for Healthcare Research and Quality.

Figure 2.

Conceptual framework for the use of fractional exhaled nitric oxide (Fe_NO) testing to guide treatment decisions for individuals with asthma. The decision to act on an individual Fe_NO value in an individual patient requires that the clinician combine clinical judgments based on the perceived probability of benefit, with particular attention being given to the key outcome measures such as exacerbation risks that were assessed in this guideline. As the level of Fe_NO increases in value, the specificity for a step up in therapy increases, whereas accepting lower values of Fe_NO to make treatment decisions places a higher value on the sensitivity to detect the possibility that a step up in therapy may impact asthma control.