Validation of ATS clinical practice guideline cut-points for FeNO in asthma

Abstract

Background: The American Thoracic society (ATS) has suggested using fractional exhaled nitric oxide (FeNO) to monitor the level of eosinophilic (EOS) airway inflammation in asthma, but validation of the proposed cut-points is required in real-life populations. Objective: To validate FeNO cut-points suggested by ATS in relation to sputum EOS count in a real life population of asthma patients. Methods: All patients referred consecutively over a 12-months period for specialist assessment of asthma, were examined with FeNO and induced sputum, and reexamined 12 months later. The predicted values of a positive and a negative test (PPV and NPV) for a cut off 3% EOS in sputum were calculated. Change in FeNO was defined in accordance with ATS (> 20% or 10 ppb if FeNO was < 50 ppb). Results: 144 adult asthma patients were examined (59% female). Low FeNO (< 25 ppb) at baseline was found in 94 (65%), FeNO between 25 and 50 ppb in 34 (24%) subjects and high FeNO > 50 ppb in 16 (11%) subjects. The PPV for FeNO > 25 ppb and > 50 ppb to predict EOS 3% was 45% and 77%, NPV was 88% and 83%. The sensitivity decreased from 70% to 37% at the > 50 ppb cutoff. A significant reduction in FeNO was associated with a reduction in sputum EOS (p = 0.01). Conclusion: The findings support the validity of the FeNO cut-points suggested by ATS to monitor eosinophilic airway inflammation in asthma. However, in this real-life population, a large proportion of patients had intermediate FeNO values, which may limit the clinical usefulness of the ATS FeNO cut-points.

Eosinophilic and Noneosinophilic Asthma

“…These variables and cutoffs included highest BEC ever ($ 300 cells/mL, $ 150-300 cells/mL, or <150 cells/mL), anti-IL-5/5 receptor treatment, long-term OCS use ever, elevated FENO ($ 25 parts per billion) ever, nasal polyps diagnosis ever, and adult asthma onset ($ 18 years) and were informed by the published evidence base and asthma management guidelines. 16,[22][23][24][25][26][27] Phenotypes were classified as grade 3 (most likely eosinophilic), grade 2 (likely eosinophilic), grade 1 (least likely eosinophilic), and grade 0 (noneosinophilic) (Fig 1). Patients most likely to have an eosinophilic phenotype (grade 3) were those with highest BEC ever of $ 300 cells/mL or receiving anti-IL-5/anti-IL-5 receptor therapy, or with BEC of $ 150 to 300 cells/mL with (1) mOCS or (2) $ 2 of nasal polyps, elevated FENO, or late onset of disease.…”

The Functional Diversity of Nitric Oxide Synthase Isoforms in Human Nose and Paranasal Sinuses: Contrasting Pathophysiological Aspects in Nasal Allergy and Chronic Rhinosinusitis

“…The American Thoracic Society (ATS) has suggested using FeNO to monitor the level of eosinophilic airway inflammation in the lower airways of humans [1,2]. FeNO can also be used as a predictor of responsiveness to an inhaled corticosteroid (ICS) and to evaluate patients' adherence to anti-inflammatory medications [56,57]. Because of the close linkage between rhinitis, chronic rhinosinusitis, and asthma, the measurement of NO in the nasal cavity provides a promising relevant biomarker of unified airway inflammation [58].…”

Clinical utility of exhaled nitric oxide fraction in the management of asthma and COPD

“…Hence, F ENO and blood eosinophils were similar in accuracy (and more accurate than IgE) for predicting sputum eosinophilia. Furthermore, in a prospective study of 144 adult patients with asthma in Denmark, high F ENO (>50 ppb) had moderate positive predictive value (77%) for sputum eosinophilia of >3%, although one-third of patients with sputum eosinophilia >3% had intermediate F ENO values (25–50 ppb) [32].…”