American Thoracic Society Documents An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications

Executive Summary Introduction Methods CommitteeComposition,Meetings, andDocument Preparation Document Structure Quality of Evidence and Strength of Recommendations Why Should a FENO Test be Obtained? Can FENO Be Used to Diagnose Asthma? FENO Is Associated with Eosinophilic Airway Inflammation FENO Predicts Likelihood of Corticosteroid Responsiveness FENO Can Support a Diagnosis of Asthma FENO May Predict AHR Is There a Normal FENO Value? Normal Values versus Relevant Cut Points for FENO Confounding Factors that May Affect FENO What Are the Clinically Significant Cut Points for FENO? Low FENO (, 25 ppb in Adults; 20 ppb in Children) High FENO (. 50 ppb in Adults, 35 ppb in Children) Intermediate FENO (between 25 ppb and 50 ppb in Adults; 20–35 ppb in Children) Persistently High FENO (. 50 ppb in adults, 35 ppb in Children) Can FENO Be Used to Monitor Airway Inflammation? Monitoring Airway Inflammation in Asthma Minimally Important Differences, and Prognostic Significance of FENO How Should a FENO Measurement Be Interpreted and Reported? Other Situations in which FENO May Be Useful COPD Pulmonary Hypertension Cystic Fibrosis and Nasal NO Measurements Conclusions and Future Directions Online Supplement Appendix E1: Methods Checklist Appendix E2: Technical Considerations and Sources ofVariation in FENO Appendix E3: Causes of High and Low FENO Levels Appendix E4: Case Studies Background: Measurement of fractional nitric oxide (NO) concentration in exhaled breath (FENO) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma.While FENO measurement has been standardized, there is currently no reference guideline for practicing health care providers to guide them in the appropriate use and interpretation of FENO in clinical practice. Purpose: To develop evidence-based guidelines for the interpretation of FENOmeasurements that incorporate evidence that has accumulated over the past decade. Methods:We created amultidisciplinary committeewith expertise in the clinical care, clinical science, or basic science of airway disease and/or NO. The committee identified important clinical questions, synthesized the evidence, and formulated recommendations. Recommendationswere developed using pragmatic systematic reviews of the literature and the GRADE approach. Results: The evidence related to the use of FENO measurements is reviewed and clinical practice recommendations are provided. Conclusions: In the setting of chronic inflammatory airway disease including asthma, conventional tests such as FEV1 reversibility or provocation tests are only indirectly associated with airway inflammation. FENOoffers addedadvantages for patient care including,but not limited to (1) detecting of eosinophilic airway inflammation, (2) determining the likelihood of corticosteroid responsiveness, (3) monitoring of airway inflammation to determine the potential need forcorticosteroid, and(4)unmaskingofotherwiseunsuspectednonadherence to corticosteroid therapy.